Publikationen von Jürgen Hedderich
Hoffmann M, Quabius ES, Tribius S, Gebhardt S, Görögh T, Hedderich J, Huber K, Dunst J, Ambrosch P.
Influence of HPV-status on survival of patients with tonsillar carcinomas (TSCC) treated by CO2-laser surgery plus risk adapted therapy - A 10 year retrospective single centre study.Cancer Lett,
413 (2018), 59-68.
[abstract]
Abstract:
The positive prognostic value of HPV-infections in oropharyngeal squamous cell cancer (OSCC) patients has led to the initiation of prospective clinical trials testing the value of treatment de-escalation. It is unclear how to define patients potentially benefiting from de-escalated treatment, whether a positive smoking history impacts survival data and what kind of de-escalation might be best. Here, we investigate the effect of HPV-status, smoking habit and treatment design on overall survival (OS) and progression free survival (PFS) of 126 patients with tonsillar SCC (TSCC) who underwent CO2-laser-surgery and risk adapted adjuvant treatment. HPV-DNA-, HPV-mRNA-, and p16INK4A-expression were analysed and results were correlated to OS and PFS. Factors tested for prognostic value included HPV-status, p16INK4A-protein expression, therapy and smoking habit. Log rank test and p-values ≤0.05 defined significant differences between groups. The highest accuracy of data with highest significance in this study is given when the HPV-RNA-status is considered. Using p16INK4A-expression alone or in combination with HPV-DNA-status, would have misclassified 23 and 7 patients, respectively. Smoking fully abrogates the positive impact of HPV-infection in TSCC on survival. Non-smoking HPV-positive TSCC patients show 10-year OS of 100% and 90.9% PFS when treated with adjuvant RCT. The presented data show that high-precision HPV-detection methods are needed, specifically when treatment decisions are based on the results. Furthermore, smoking habit should be included in all studies and clinical trials testing HPV-associated survival. Adjuvant RCT especially for HPV-positive non-smokers may help to avoid distant failure.
Schimmer C, Gross J, Ramm E, Morfeld BC, Hoffmann G, Panholzer B, Hedderich J, Leyh R, Cremer J, Petzina R.
Prevention of surgical site sternal infections in cardiac surgery: a two-centre prospective randomized controlled study.Eur J Cardiothorac Surg,
51 (2017), 67-72.
[abstract]
Abstract:
The application of InteguSeal® or Genta-Coll® resorb had no significant influence on the incidence of the sternal SSI rate in 996 consecutive cardiac surgery patients but demonstrated a trend towards a benefit from using these prophylactic approaches. Multiple regression analysis demonstrated a preoperative BMI of >30 kg/m2, re-thoracotomy for bleeding and sternum instability as independent predictors for an increased sternal SSI rate.
Purtskhvanidze K, Hillenkamp J, Tode J, Junge O, Hedderich J, Roider J, Treumer F.
Thinning of Inner Retinal Layers after Vitrectomy with Silicone Oil versus Gas Endotamponade in Eyes with Macula-Off Retinal Detachment.Ophthalmologica,
238 (2017), 124-132.
[abstract]
Abstract:
Inner retinal layers in the fovea/parafovea were significantly thinner in the SiO group. Prospective studies are warranted to further elucidate possible retinal adverse effects of SiO tamponade.
Kling C, Hedderich J, Kabelitz D.
Fertility after recurrent miscarriages: results of an observational cohort study.Arch Gynecol Obstet,
(2017).
[abstract]
Abstract:
Although in general, chances to conceive a child are retained after three or more miscarriages, factors related to subfertility of both partners have an important impact on the outcome. Therefore, prolonged time to pregnancy (> 6-9 months) should result in preventive gynaecological care from the first miscarriage on, so that fertility can be preserved as best as possible.
Purtskhvanidze K, Frühsorger B, Bartsch S, Hedderich J, Roider J, Treumer F.
Persistent Full-Thickness Idiopathic Macular Hole: Anatomical and Functional Outcome of Revitrectomy with Autologous Platelet Concentrate or Autologous Whole Blood.Ophthalmologica,
(2017).
[abstract]
Abstract:
Revitrectomy with APC and gas is a very effective treatment in persistent MH after vitrectomy with ILM peeling and gas.
LÜtzen U, Zhao Y, Lucht K, Zuhayra M, Hedderich J, Cascorbi I, Culman J.
Activation of the cell membrane angiotensin AT2 receptors in human leiomyosarcoma cells induces differentiation and apoptosis by a PPARγ - dependent mechanism.Neoplasma,
64 (2017), 395-405.
[abstract]
Abstract:
Angiotensin II (Ang II), the main effector peptide of the renin-angiotensin system (RAS), acting on AT1 and AT2 receptors participates in the regulation of proliferation, differentiation and apoptosis in tumour cells. The peroxisome-proliferator activated receptor γ (PPARγ) and its ligands exert anti-tumour effects in various human cancer cell lines. The present study investigates the effects initiated by AT1- and AT2 receptor stimulation in SK-UT-1 cells, a human leiomyosarcoma cell line, and clarifies the role of the PPARγ in the AT2 receptor-induced differentiation and apoptosis.Selective stimulation of AT1- and AT2 receptors was achieved by incubation of the cells with Ang II (10-6 M) in the presence of the selective AT2 receptor antagonist, PD 123177 (10-6 M) and the AT1 receptor antagonist, losartan (10-5 M), respectively, the selective PPARγ antagonist, GW 9662, was used at concentration 10-6 M. The expression of smooth muscle cell differentiation markers, SM22α and calponin, was analysed at RNA- and protein levels using RT PCR and Western blot, which was also used to quantify Bcl-2-, Bax- and cleaved caspase-3 proteins. The translocation of the AT2-receptor interacting protein 1 (ATIP1) to the nuclei was studied by Western blot and immunofluorescence staining. The mitochondrial status and the metabolic activity in response to AT1- and AT2 receptor activation were assessed by the quantification of 99mTc - sestamibi and 2´-deoxy-2´-[18F]fluoro-D-glucose uptake.AT1 receptor stimulation did not exert any profound effects in quiescent SK-UT-1 cells. The effects induced by Ang II acting on AT2 receptors were time-dependent. A short, 3 - 6 h lasting stimulation promotes differentiation, i.e increases in the mRNA- and protein levels of SM22α and calponin, whereas a sustained stimulation for 48 h activates the intrinsic apoptotic pathway, as evidenced by reduced cell numbers, down-regulation of the anti-apoptotic Bcl-2 protein and increased levels of the Bax protein and cleaved caspase-3. The effects were reversed by the PPARγ antagonist, GW 9662, clearly implying a PPARγ-dependent mechanism. Our results also demonstrate a co-localisation of the AT2-receptor interacting protein, ATIP1, and the PPARγ in nuclei of SK-UT-1 cells and an accumulation of ATIP1 in the nuclear fraction in response to AT2 receptor stimulation. The regulation of the differentiation and apoptosis via the AT2 receptor favours an important functional role of this receptor in quiescent, slow-cycling SK-UT-1 cells and provides the rationale for the use of AT1 receptor antagonists for the treatment of human leiomyosarcomas.
Quabius ES, Merz I, Görögh T, Hedderich J, Haag J, Röcken C, Ambrosch P, Hoffmann M.
miRNA-expression in tonsillar squamous cell carcinomas in relation to HPV infection and expression of the antileukoproteinase SLPI.Papillomavirus Res,
4 (2017), 26-34.
[abstract]
Abstract:
The aim of this study was to determine if micro-(mi-)RNAs are involved in the previously reported inverse correlation between the antileukoproteinase SLPI, HPV, and smoking habit of head and neck squamous cells carcinoma (HNSCC) patients. HPV-status and SLPI-protein expression were determined in tonsillar SCC (TSCC; n=126). Differentially expressed miRNAs dependent on HPV-status and SLPI-expression were detected by microarray; possible binding-sites in SLPI- and HPVE6-mRNAs were determined in silico. Survival rates were estimated testing prognostic values of HPV-status, SLPI- and miRNA-expression. miRNA-array identified 24 up-regulated and 10 down-regulated miRNAs in HPV-positive versus HPV-negative TSCC (p<0.01; HPV-positivity: 42.1%). HPV-positivity resulted in two up-regulated miRNAs in SLPI-positive TSCC. Of 16 further miRNAs, eight miRNAs were up- and eight were down-regulated in SLPI-negative TSCC. RT-q-PCR-validation of the four most differentially expressed miRNAs showed that miR-363 is expressed strongest in SLPI-negative/HPV-positive TSSC. In silico-analysis of all differentially expressed miRNAs identified miR-363, miR-210, miR-130a, and miR-181a with possible binding sites in the HPV16-E6-mRNA, but none were predicted in the SLPI-mRNA. HPV-positivity, low SLPI-levels and high miR-363-levels are significantly associated with better survival rates. The data presented here show that miR-363 is associated with HPV-positive/SPLI-negative TSCC. The prognostic value of miR-363 suggests a role in the assumed inverse correlation of smoking and SPLI-expression in the mode of HPV-infections in tonsillar but possibly also other HNSCC.
Alkatout I, Hübner F, Wenners A, Hedderich J, Wiedermann M, Sánchez C, Röcken C, Mathiak M, Maass N, Klapper W.
In situ localization of tumor cells associated with the epithelial-mesenchymal transition marker Snail and the prognostic impact of lymphocytes in the tumor microenvironment in invasive ductal breast cancer.Exp Mol Pathol,
102 (2017), 268-275.
[abstract]
Abstract:
Based on previous studies concerning the intratumoral heterogeneity of EMT, our results suggest that Snail and FoxP3 are possible prognostic markers for breast cancer. The diverse presence of lymphocytes in the tumor microenvironment (CD3 and CD8) was confirmed. Although the importance of these markers is known, their specific role in tumor invasion and metastasis as well as their hierarchical organization in these tumors remain unclear.
Beck-Broichsitter BE, Huck J, Küchler T, Hauke D, Hedderich J, Wiltfang J, Becker ST.
Self-perception versus professional assessment of functional outcome after ablative surgery in patients with oral cancer.J Cancer Res Clin Oncol,
143 (2017), 305-311.
[abstract]
Abstract:
From the professionals' point of view differences were perceived in more items compared to the patients' self-assessments, who widely experienced a more severe functional impairment. Physicians should take this into account when discussing adverse therapy effects with the patients.
Kling C, Magez J, Hedderich J, von Otte S, Kabelitz D.
Two-year outcome after recurrent first trimester miscarriages: prognostic value of the past obstetric history.Arch Gynecol Obstet,
293 (2016), 1113-23.
[abstract]
Abstract:
Secondary infertility is a feature of RM. Embryonic vital signs in preceding pregnancies are prognostic markers and should be regarded as a strong confounding factor in trials on therapeutic interventions. Prevention may be more appropriate than treatment.
Günther V, Alkatout I, Fuhs C, Salmassi A, Mettler L, Hedderich J, Maass N, Elessawy M, Schmutzler AG, Eckmann-Scholz C.
The Role of Interleukin-18 in Serum and Follicular Fluid during In Vitro Fertilization and Intracytoplasmic Sperm Injection.Biomed Res Int,
2016 (2016), 6379850.
[abstract]
Abstract:
Cytokines are key modulators of the immune system and play an important role in the ovarian cycle. IL-18 levels in serum and follicular fluid were analyzed in women undergoing in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) treatment. The cohort study group consisted of 90 women, who were undergoing IVF or ICSI. The body mass index (BMI) was determined in all patients; IL-18 levels were measured in follicular fluid and serum. IL-18 levels in serum were significantly higher than those in follicular fluid. The median level in serum was 162.75 (80.21) pg/mL and that in follicular fluid, 138.24 (91.78) pg/mL. Women undergoing IVF treatment had lower IL-18 levels in serum (median, 151.19 (90.73) pg/mL) than those treated with ICSI (median, 163.57 (89.97) pg/mL). The correlation between IL-18 levels in serum and BMI was statistically significant, as well as the correlation between IL-18 levels in follicular fluid and ovarian stimulation response (p = 0.003). IL-18 was correlated with the response to ovarian stimulation and was the reason for successful pregnancy after IVF or ICSI treatment. Among other cytokines, IL-18 appears to be a promising prognostic marker of success in reproductive treatment and should be evaluated as such in further prospective studies.
Egberts F, Bohne AS, Krüger S, Hedderich J, Rompel R, Haag J, Röcken C, Hauschild A.
Varying Mutational Alterations in Multiple Primary Melanomas.J Mol Diagn,
18 (2016), 75-83.
[abstract]
Abstract:
In melanoma, the mitogen-activated protein (MAP) kinase pathway plays a crucial oncogenic role. Recent studies identified additional genetic alterations, eg, TERT-promoter mutations. Up to 8% of melanoma patients present with multiple primary melanomas (MPMs). The pathogenesis is not fully understood, and data on the genetic diversity of MPMs are limited. To identify putative diagnostic and therapeutic consequences, we assessed the mutational status of the BRAF and NRAS genes and TERT promoter in patients with MPMs. The study cohort consisted of 96 patients with 237 malignant melanomas. The BRAF, NRAS, and TERT-promoter genotypes were assessed in all MPMs and were correlated with patients' clinicopathological characteristics. BRAF mutations were found in 84 melanomas (35.4%), NRAS mutations, in 33 (14.0%); and TERT-promoter mutations, in 112 (47.3%). Mutation patterns were concordant between first and subsequent primary tumors in 23.9% of patients and were discordant in 61.4% of patients. The genetic alterations were partially different in 14.7% of patients. By Cox regression analysis, only the NRAS mutation had a significant negative prognostic impact on time to progression to stage III (P = 0.016) and on distant metastasis-free survival (P = 0.032). In the majority of primary melanomas in patients with MPMs, BRAF, NRAS, and TERT-promoter genotypes were discordant. Thus, molecular testing for targeted therapy should be performed on metastatic tissue and not on primary tumors.
Bierkarre H, Harder J, Cuthbert R, Emery P, Leuschner I, Mrowietz U, Hedderich J, McGonagle D, Gläser R.
Differential expression of antimicrobial peptides in psoriasis and psoriatic arthritis as a novel contributory mechanism for skin and joint disease heterogeneity.Scand J Rheumatol,
45 (2016), 188-96.
[abstract]
Abstract:
Given that some AMPs, especially hBD-2, are genetically linked to psoriasis and are only expressed in the skin, these findings show how differential AMP expression in innate immune responses may contribute to disease heterogeneity between PsA and psoriasis and provides a genetic basis for the non-progression of psoriasis subgroups to PsA.
Salmassi A, Fattahi A, Nouri M, Hedderich J, Schmutzler AG.
Expression of mRNA and protein of IL-18 and its receptor in human follicular granulosa cells.J Endocrinol Invest,
(2016).
[abstract]
Abstract:
The presence of IL-18 in FF and the expression of IL-18 and its receptor by GCs suggest an important role for this cytokine in ovarian function.
Ghazal M, Hedderich J, Kern M.
An In Vitro Study of Condylar Displacement Caused by Interocclusal Records: Influence of Recording Material, Storage Time, and Recording Technique.J Prosthodont,
(2016).
[abstract]
Abstract:
Based on the results, the vertical displacement of the condyle caused by the interocclusal records was higher than the lateral or the anteroposterior displacement. Elastomers caused statistically significantly less condylar displacement than waxes or uncorrected composite resin. Corrected LuxaBite records with Aluwax showed significantly less condylar displacement than all other materials.
Salmassi A, Mettler L, Hedderich J, Jonat W, Deenadayal A, von Otte S, Eckmann-Scholz C, Schmutzler AG.
Cut-Off Levels of Anti-Mullerian Hormone for The Prediction of Ovarian Response, In Vitro Fertilization Outcome and Ovarian Hyperstimulation Syndrome.Int J Fertil Steril,
9 (2015 Jul-Sep), 157-67.
[abstract]
Abstract:
AMH levels can help to assess ovarian response potential and guide ovarian stimulation while avoiding OHSS.
Doukas A, Maslehaty H, Barth H, Hedderich J, Petridis AK, Mehdorn HM.
A novel simple measure correlates to the outcome in 57 patients with intracerebellar hematomas. Results of a retrospective analysis.Surg Neurol Int,
6 (2015), 176.
[abstract]
Abstract:
We introduced as a new factor that is, the cerebellar hemorrhage/PF ratio and found out that the value >35% was associated to an unfavorable outcome.
Glatz M, Buchner M, von Bartenwerffer W, Schmid-Grendelmeier P, Worm M, Hedderich J, Fölster-Holst R.
Malassezia spp.-specific immunoglobulin E level is a marker for severity of atopic dermatitis in adults.Acta Derm Venereol,
95 (2015), 191-6.
[abstract]
Abstract:
The significance of allergen-specific IgE as marker for severity of atopic dermatitis is controversial. The aim of this study was to determine the frequency of IgE-mediated sensitisation to food and environmental allergens in 132 children and 67 adults with atopic dermatitis, and its correlation to severity of atopic dermatitis (SCORAD). Total IgE was elevated (> 100 kU/l) in 79.7% of adults and 46.8% of children. Sensitisation frequencies to allergens, particularly microbial allergens, were up to 10-fold higher in adults compared to children. Severity of atopic dermatitis correlated with elevated total IgE in adults (r = 0.549, p < 0.001) and children (r = 0.344, p = 0.005) and with Malassezia spp.-specific IgE in adults (r = 0.429, p = 0.007). Total IgE is a marker for severe atopic dermatitis in both age groups. Malassezia spp.-specific IgE is an important allergen-specific marker for severity of atopic dermatitis in adults.
Stark AM, Doukas A, Hugo HH, Hedderich J, Hattermann K, Maximilian Mehdorn H, Held-Feindt J.
Expression of DNA mismatch repair proteins MLH1, MSH2, and MSH6 in recurrent glioblastoma.Neurol Res,
37 (2015), 95-105.
[abstract]
Abstract:
Our data indicate that there may be glioblastoma patient subgroups characterized by MMR-expression changes beyond MGMT promoter methylation. The immunohistochemical expression of MLH1, MSH2, and MSH6 in initial glioblastoma is not associated with patient survival.
Ilies C, Grudev G, Hedderich J, Renner J, Steinfath M, Bein B, Haake N, Hanss R.
Comparison of a continuous noninvasive arterial pressure device with invasive measurements in cardiovascular postsurgical intensive care patients: a prospective observational study.Eur J Anaesthesiol,
32 (2015), 20-8.
[abstract]
Abstract:
Clinical trials.gov identifier NCT01003665.
Quabius ES, Haag J, Kühnel A, Henry H, Hoffmann AS, Görögh T, Hedderich J, Evert M, Beule AG, Maune S, Knecht R, Óvári A, Durisin M, Hoppe F, Tribius S, Röcken C, Ambrosch P, Hoffmann M.
Geographical and anatomical influences on human papillomavirus prevalence diversity in head and neck squamous cell carcinoma in Germany.Int J Oncol,
46 (2015), 414-22.
[abstract]
Abstract:
The increased knowledge regarding HPV-infections in head and neck squamous cell carcinoma (HNSCC) has unexpectedly contributed to several uncertainties related to i) prevalence diversities depending on tumour site and geographical origin of the patients, ii) proportion of HPV-driven tumours among HPV-DNA-positive cases, and iii) identification of patients with HPV-attributed survival benefit. To investigate this heterogeneity, we analysed 307 HNSCC cases (tonsillar, n=135; non-tonsillar, n=172) from eight health care centers mostly from Northern Germany and determined HPV-DNA/mRNA and p16INK4A-status and combined results with the patient outcome. Overall HPV-DNA prevalence rate was 23.5% (72/307); attributed to: 43.7% (59/135) and 7.6% (13/172) tonsillar and non-tonsillar cases, respectively. Among these, 96.6% tonsillar and 38.5% non-tonsillar SCC were HPV-mRNA-positive. Although the study cohort was composed of patients from regions of rather close proximity, prevalence rates showed diversities of up to 40% in HNSCC subsite analysis with the lowest prevalence for tonsillar SCC in metropolitan areas (22.2%) vs. 50.9% in rural areas. Survival analysis identified p16INK4A alone as strongest predictor, followed by HPV-DNA-status alone or in combination with p16INK4A. This survival benefit was shown for tonsillar and non-tonsillar cases. Smoking significantly correlated with HPV-status, however, it does not influence survival when stratified for HPV. In conclusion, the data emphasize the urge for further data on HPV-infection in HNSCC to, e.g. clarify to what extent survival benefits of p16INK4A-positive patients are truly attributed to HPV-infections.
Quabius ES, Görögh T, Fischer GS, Hoffmann AS, Gebhard M, Evert M, Beule A, Maune S, Knecht R, Óvári A, Durisin M, Hoppe F, Röcken C, Hedderich J, Ambrosch P, Hoffmann M.
The antileukoprotease secretory leukocyte protease inhibitor (SLPI) and its role in the prevention of HPV-infections in head and neck squamous cell carcinoma.Cancer Lett,
357 (2015), 339-45.
[abstract]
Abstract:
Recently, we demonstrated a significant inverse correlation between HPV-infection and SLPI-expression suggesting that SLPI protects against HPV-infection of HNSCC. Here we analyzed in a single lab setting 307 formalin-fixed paraffin-embedded HNSCC cases (tonsillar n = 135; non-tonsillar: n = 172) from eight health care centers. Samples were analyzed for SLPI gene- and protein-expression. Annexin A2, its heterotetramer A2t, putatively facilitating HPV- and SLPI-cell entry, was measured to study the correlation between SLPI and annexin A2. Data were correlated with tobacco consumption and HPV-status. Overall, HPV-DNA prevalence was 23.5% (72/307); attributed to: 43.7% (59/135) tonsillar and 7.6% (13/172) non-tonsillar cases. Smoking resulted in 6.44-fold increased and HPV-infection in 3.46-fold decreased SLPI-gene expression in all HNSCC with similar significant results obtained in tonsillar and non-tonsillar SCC separately. Correlating annexin A2- and SLPI-gene expression showed a significant surplus of annexin A2 in HPV-positive tumors (4.21× more annexin A2) and 6.72× more annexin A2 than SLPI in nonsmokers in all HNSCCs and similar significant results for both tumor entities separately. The surplus of annexin A2 in non-smokers and HPV-positive patients supports our hypothesis that decreased SLPI levels facilitate HPV-infection i.e., increased SLPI-expression may protect against HPV-infection of tonsillar and non-tonsillar SCC.
Hagen I, Schulte DM, Müller N, Martinsen J, Türk K, Hedderich J, Schreiber S, Laudes M.
Soluble receptor for advanced glycation end products as a potential biomarker to predict weight loss and improvement of insulin sensitivity by a very low calorie diet of obese human subjects.Cytokine,
73 (2015), 265-9.
[abstract]
Abstract:
Anti-inflammatory sRAGE might be a potential future biomarker to predict weight loss and improvement of insulin resistance by a VLCD whereby lower baseline sRAGE serum levels indicate a better outcome of the dietary intervention.
Schmedt Auf der Günne W, Zhao Y, Hedderich J, Gohlke P, Culman J.
Omapatrilat: penetration across the blood-brain barrier and effects on ischaemic stroke in rats.Naunyn Schmiedebergs Arch Pharmacol,
388 (2015), 939-51.
[abstract]
Abstract:
Omapatrilat (OMA), which simultaneously inhibits the angiotensin-converting enzyme (ACE) and the neutral endopeptidase (neprilysin (NEP)), is widely used in experimental protocols related to hypertension and heart failure. The penetration of OMA across the blood-brain barrier (BBB) and the effects of ACE/NEP inhibition on the recovery from ischaemic stroke have not yet been investigated. Angiotensin (Ang) I injected intracerebroventricularly (ICV) or intravenously (IV) is converted to Ang II by ACE and induces an immediate increase in blood pressure. The pressor responses to OMA administered ICV, orally or IV were studied in male Wistar rats instrumented with an ICV and arterial and venous catheters. OMA infused ICV rapidly appeared in the systemic circulation and more effectively attenuated the systemic than the central pressor responses to Ang I. OMA administered orally (5, 25, 100 μmol/kg body weight) or IV (0.5, 1, 5, 25 μmol/kg body weight) completely abolished increases in blood pressure to IV Ang I up to 2 h after treatment. The pressor responses to ICV Ang I were not altered, indicating that systemically administered OMA does not cross the BBB. To study the effects of ACE and NEP inhibition in the brain on the recovery from ischaemic stroke, OMA was infused ICV over a 5-day period before and 24 h after the occlusion of the middle cerebral artery (MCAO) for 90 min. ICV application of OMA had no effect on infarction volume and marginally improved neurological outcome. We demonstrate for the first time that simultaneous inhibition of ACE and NEP in the brain tissue does not alter the recovery from ischaemic stroke.
von der Brelie C, Schneegans I, van den Boom L, Meier U, Hedderich J, Lemcke J.
Impaired coagulation is a risk factor for clinical and radiologic deterioration in patients with traumatic brain injury and isolated traumatic subarachnoid hemorrhage.J Trauma Acute Care Surg,
79 (2015), 295-300.
[abstract]
Abstract:
Therapeutic study, level IV; prognostic study, level III.
Kulle AE, Riepe FG, Hedderich J, Sippell WG, Schmitz J, Niermeyer L, Holterhus PM.
LC-MS/MS based determination of basal- and ACTH-stimulated plasma concentrations of 11 steroid hormones: implications for detecting heterozygote CYP21A2 mutation carriers.Eur J Endocrinol,
173 (2015), 517-24.
[abstract]
Abstract:
Considering only marginal biochemical effects anticipated from heterozygosity, the stimulated ((17OHP+21S)/F×1000) identifies and excludes heterozygotes remarkably well. Nevertheless, LC-MS/MS cannot replace genetic testing, since sensitivity and specificity did not reach 100%. However, due to the considerably high NPV of the optimal cut-off and to a specificity of even 100% applying a cut-off higher than 14.7, hormonal assessment of heterozygosity can be of significant aid in conditions with limited access to genetic testing, as in some health care systems. The ((17OHP+21S)/F×1000) equation can guide diagnostic considerations in the differential diagnosis of hyperandrogenism.
Günther V, Bauer I, Hedderich J, Mettler L, Schubert M, Mackelenbergh MT, Maass N, Alkatout I.
Changes of salivary estrogen levels for detecting the fertile period.Eur J Obstet Gynecol Reprod Biol,
194 (2015), 38-42.
[abstract]
Abstract:
The saliva and the LH test both detect the fertile window of a menstrual cycle. Caused by the different hormones (estrogen for the saliva and LH for the LH test) leading to the respective positive test results, saliva turns positive 24h before LH. Consequently, the saliva test can be used as an ovulation test and help women maximize their chances of conceiving. There is also a high congruence between LH and saliva in the pre- and post-ovulatory period, indicating that the saliva test can also be used for contraception purposes.
Hey M, Hocke T, Hedderich J, Müller-Deile J.
Investigation of a matrix sentence test in noise: reproducibility and discrimination function in cochlear implant patients.Int J Audiol,
53 (2014), 895-902.
[abstract]
Abstract:
As the CI users differed significantly in their SRT and their s50, a unified discrimination function for CI users must not be used. Further tailoring of the procedure may be required, especially for poorer CI performers.
Gierloff M, Nitsche T, Adam-Klages S, Liebs K, Hedderich J, Gassling V, Wiltfang J, Kabelitz D, Açil Y.
In vitro comparison of different carrier materials with rat bone marrow MSCs.Clin Oral Investig,
18 (2014), 247-59.
[abstract]
Abstract:
Tissufleece E may serve as a promising carrier material for chondrogenic MSCs for cartilage tissue engineering attempts.
Quabius ES, Möller P, Haag J, Pfannenschmidt S, Hedderich J, Görögh T, Röcken C, Hoffmann M.
The role of the antileukoprotease SLPI in smoking-induced human papillomavirus-independent head and neck squamous cell carcinomas.Int J Cancer,
134 (2014), 1323-34.
[abstract]
Abstract:
Recently, we showed that increased SLPI levels prevent human papillomavirus (HPV) infections and metastasis in smoking-induced, non-HPV-driven head and neck squamous cell carcinoma (HNSCC). Here, we focus on the role of SLPI in non-HPV-driven HNSCC, investigating tumor tissue and non-neoplastic mucosa from the same patients and from non-HNSCC patients. Gene and protein expression of SLPI and gene expression of annexin 2 (a SLPI receptor), nicotine receptor (α7AChR) and arylhydrocarbon receptor (AhR) were analyzed in HNSCC patients (20 smokers; 16 nonsmokers). SLPI-results were correlated with the patients' HPV status. Non-neoplastic mucosa of HNSCC patients and normal mucosa from non-HNSCC individuals (18 smokers; 20 nonsmokers) was analyzed for the same parameters. Tissue of the inferior turbinate (n = 10) was incubated with nicotine for analysis of the same genes. SLPI gene expression in tumor tissue was 109.26 ± 23.08 times higher in smokers versus nonsmokers. Non-neoplastic mucosa of smokers showed also higher SLPI gene expression (10.49 ± 1.89-fold non-HNSCC; 18.02 ± 3.93-fold HNSCC patients). Annexin 2 gene expression was also increased in smokers. SLPI data were corroborated by immunohistochemistry. A nicotine dependent correlation between SLPI and annexin 2 gene expression (r(2) = 0.15, p < 0.001) was shown ex vivo. Nicotine and smoking increased α7AChR and AhR gene expression. Five patients, showing no/low SLPI expression, were HPV16-positive. A significant correlation between smoking and SLPI expression in tumors and to our knowledge for the first time in mucosa of HNSCC and non-HNSCC patients was established. Together with the finding that all patients with HPV infection showed no/low SLPI expression, these data support our intriguing hypothesis that smoking induced upregulated SLPI prevents HPV infections.
Alkatout I, Mettler L, Beteta C, Hedderich J, Jonat W, Schollmeyer T, Salmassi A.
Combined surgical and hormone therapy for endometriosis is the most effective treatment: prospective, randomized, controlled trial.J Minim Invasive Gynecol,
20 (2013 Jul-Aug), 473-81.
[abstract]
Abstract:
In the quest to find the most effective treatment of genital endometriosis, this clinical randomized study shows the lowest incidence of recurrence with combined surgical and medical treatment and improved pregnancy rate in any medically treated patients with or without surgery. The highest cure rate (Endoscopic Endometriosis Classification stage 0) for endometriosis was also achieved in the combined treatment group.
Purtskhvanidze K, Treumer F, Junge O, Hedderich J, Roider J, Hillenkamp J.
The long-term course of functional and anatomical recovery after macular hole surgery.Invest Ophthalmol Vis Sci,
54 (2013), 4882-91.
[abstract]
Abstract:
Long-term postoperatively, the median thickness of retinal layers remains slightly thickened between the outer plexiform and the ganglion cell layer. The process of gradual recovery may continue for several years after macular hole surgery.
Gassling V, Hedderich J, Açil Y, Purcz N, Wiltfang J, Douglas T.
Comparison of platelet rich fibrin and collagen as osteoblast-seeded scaffolds for bone tissue engineering applications.Clin Oral Implants Res,
24 (2013), 320-8.
[abstract]
Abstract:
Metabolic activity and proliferation of human osteoblast cells in vitro were supported to a significant higher extent by eluates from PRF membranes. Both membranes are suitable as scaffolds for cultivation of human osteoblast cells in vitro; proliferation was significant higher on PRF membranes and on PRF clot than on BioGide(®) membranes.
Voges I, Jerosch-Herold M, Hedderich J, Hart C, Petko C, Scheewe J, Andrade AC, Pham M, Gabbert D, Kramer HH, Rickers C.
Implications of early aortic stiffening in patients with transposition of the great arteries after arterial switch operation.Circ Cardiovasc Imaging,
6 (2013), 245-53.
[abstract]
Abstract:
Reduced aortic bioelasticity and aortic root dilatation are present in transposition of the great artery patients post ASO and are likely to contribute to LV diastolic dysfunction. Impaired aortic bioelasticity was strongly associated with age, suggesting the usefulness of follow-up studies for early onset of degenerative cardiovascular disease.
Hoffmann M, Quabius ES, Tribius S, Hebebrand L, Görögh T, Halec G, Kahn T, Hedderich J, Röcken C, Haag J, Waterboer T, Schmitt M, Giuliano AR, Kast WM.
Human papillomavirus infection in head and neck cancer: the role of the secretory leukocyte protease inhibitor.Oncol Rep,
29 (2013), 1962-8.
[abstract]
Abstract:
We previously showed that secretory leukocyte protease inhibitor (SLPI) gene and protein expression is significantly lower in metastatic versus non-metastatic head and neck squamous cell carcinoma (HNSCC). However, we did not assess the human papillomavirus (HPV) status of these cases. Since SLPI plays a role in HIV and herpes simplex virus (HSV) infections, we hypothesized that SLPI may be involved in HPV-infected HNSCC. In HNSCC tissue (n=54), HPV DNA was determined and correlated with SLPI expression. Additionally, to investigate a possible role of smoking on SLPI expression in clinically normal mucosa, 19 patients treated for non‑malignant diseases (non-HNSCC) were analyzed for SLPI expression and correlated with smoking habits. In HNSCC patients, SLPI expression showed a significant inverse correlation with HPV status. In patients with moderate/strong SLPI expression (n=19), 10.5% were HPV-positive. By contrast, patients with absent/weak SLPI expression (n=35), 45.7% were HPV-positive. Low SLPI expression was correlated with metastasis (P=0.003) independent of HPV status. HPV-positivity was clearly associated with lymph node status (81.3% N1-3 cases). In smoking non-HNSCC patients (n=7), 42.9% showed absent/weak and 57.1% moderate/strong SLPI staining. In non-smoking non-HNSCC patients (n=10) 83.3% showed absent/weak and 16.7% moderate/strong SLPI expression. For the first time, a correlation between SLPI downregulation and HPV infection was demonstrated, suggesting that high levels of SLPI, possibly induced by environmental factors such as tobacco smoking, correlate with protective effects against HPV infection. SLPI may be a potential biomarker identifying head and neck cancer patients not at risk of developing metastases (SLPI-positive), and those at risk to be infected by HPV (SLPI-negative) and likely to develop metastases.
Wittersheim M, Cordes J, Meyer-Hoffert U, Harder J, Hedderich J, Gläser R.
Differential expression and in vivo secretion of the antimicrobial peptides psoriasin (S100A7), RNase 7, human beta-defensin-2 and -3 in healthy human skin.Exp Dermatol,
22 (2013), 364-6.
[abstract]
Abstract:
Antimicrobial peptides (AMP) are key players in the skin's defense system. Previous observations suggest a site- and age-dependent expression of individual AMP. We investigated the expression and secretion patterns of four important AMP in a representative collective of healthy human skin samples. Levels of psoriasin, RNase 7 and hBD-3 expression - assessed by immunohistochemistry - varied between different body localisations. Older individuals expressed hBD-2 more frequently. No gender-related expression was observed. The in vivo secretion of psoriasin, measured in skin washing fluids using ELISA, was related to body localisation and age, whereas RNase 7 secretion showed no significant differences regarding these variables. HBD-2 and -3 secretion could not be detected. Our findings suggest the usage of control samples matching localisation and approximate age (in the case of hBD-2) for comparative immunohistochemical analysis. To avoid bias through great interindividual differences, sufficient large collectives should be used for in vivo secretion analyses.
Rickers C, Voges I, Jerosch-Herold M, Hedderich J, Hart C, Petko C, Scheewe J, Andrade AC, Pham M, Gabbert D, Kramer HH.
Response to letter regarding article, "Implications of early aortic stiffening in patients with transposition of the great arteries after arterial switch operation".Circ Cardiovasc Imaging,
6 (2013), e24.
Garske U, Haack A, Beltrán O, Flores-Suárez LF, Bremer JP, Lamprecht P, Hedderich J, Quetz J, Gross WL, Ambrosch P, Laudien M.
Intra- and inter-rater reliability of endonasal activity estimation in granulomatosis with polyangiitis (Wegener´s).Clin Exp Rheumatol,
30 (2012 Jan-Feb), S22-8.
[abstract]
Abstract:
Intra-rater reliability is high in decision in dichotomy and even in grading activity. There is no difference for experienced or inexperienced physicians. Inter-rater reliability is high in dichotomy, but low for activity grading. Thus, the ENTAS provides a reliable instrument for assessing, documenting and following GPA-related disease activity in the upper respiratory tract. The relationship of activity and following damage needs to be investigated in further studies.
Helwig U, Müller M, Hedderich J, Schreiber S.
Corticosteroids and immunosuppressive therapy influence the result of QuantiFERON TB Gold testing in inflammatory bowel disease patients.J Crohns Colitis,
6 (2012), 419-24.
[abstract]
Abstract:
Steroid treatment and further combination therapy with immunosuppressive agents lead to a high risk of indeterminate QuantiFERON test.
Gassling V, Holterhus PM, Herbers D, Kulle A, Niederberger U, Hedderich J, Wiltfang J, Gerber WD.
Stress-coping and cortisol analysis in patients with non-syndromic cleft lip and palate: an explorative study.PLoS One,
7 (2012), e41015.
[abstract]
Abstract:
German Clinical Trials Organization DRKS00003466.
Ilies C, Bauer M, Berg P, Rosenberg J, Hedderich J, Bein B, Hinz J, Hanss R.
Investigation of the agreement of a continuous non-invasive arterial pressure device in comparison with invasive radial artery measurement.Br J Anaesth,
108 (2012), 202-10.
[abstract]
Abstract:
The CNAP monitor showed an acceptable agreement and was interchangeable with invasive pressure monitoring for MAP during normotensive conditions. During induction of anaesthesia and when the AP was low, the agreement was less good and interchangeability was not achieved. These results suggest that CNAP is not statistically equivalent to invasive monitoring during all periods of anaesthesia but may be a useful additional AP monitor.
Meyer JE, Steffen A, Bienemann M, Hedderich J, Schulz U, Laudien M, Quetz J, Wollenberg B.
Evaluation and development of a predictive model for ultrasound-guided investigation of neck metastases.Eur Arch Otorhinolaryngol,
269 (2012), 315-20.
[abstract]
Abstract:
Ultrasound investigations for the correct identification of lymph node metastases depend on the experience and qualifications of the investigator; thus, model that provides better preoperative evaluation is desired. Data from 290 patients with an upcoming neck dissection were analyzed to compare the preoperative ultrasound assessment of neck metastases with the pathologically proven postoperative neck status. In total, 364 data sets with 200 malignant and 164 benign lymph nodes were explored. The minimal and maximal transverse diameters and their ratio were shown to be especially good parameters for sensitivity, whereas the echostructure and the presence of a hilum were good for specificity. A model incorporating the evaluated markers is presented. The model provides better judgement of neck lymph nodes in a more objective manner. Using logistic regression, five parameters were identified to predict metastases.
Stark AM, van de Bergh J, Hedderich J, Mehdorn HM, Nabavi A.
Glioblastoma: clinical characteristics, prognostic factors and survival in 492 patients.Clin Neurol Neurosurg,
114 (2012), 840-5.
[abstract]
Abstract:
In addition to patient age and performance, we identified multiple lesions and resection status as independent prognostic factors. Radiotherapy, chemotherapy and combined radio-/chemotherapy with temozolomide were significantly associated with prolonged survival.
Fudickar A, Leiendecker J, Köhling A, Hedderich J, Steinfath M, Bein B.
Transcranial Doppler sonography as a potential screening tool for preanaesthetic evaluation: a prospective observational study.Eur J Anaesthesiol,
29 (2012), 471-6.
[abstract]
Abstract:
Neck rotation and/or extension resulted in a significant change of blood flow in the middle cerebral artery.
Wohlers J, Breucker K, Podschun R, Hedderich J, Lamprecht P, Ambrosch P, Laudien M.
Aberrant cytokine pattern of the nasal mucosa in granulomatosis with polyangiitis.Arthritis Res Ther,
14 (2012), R203.
[abstract]
Abstract:
ABSTRACT: INTRODUCTION: In granulomatosis with polyangiitis (GPA), a complex autoimmune small-vessel vasculitis frequently associated with chronic necrotizing inflammation of the nasal mucosa, elevated nasal Staphylococcus (S.) aureus carrier rates are a risk factor for relapse. As cytokines are primarily involved in the regulation of defense against potentially pathogenic microorganisms, the aim of this study was to compare healthy individuals and GPA patients with respect to their baseline cytokine expression of nasal epithelial cells (NEC), which form the first barrier against such triggers. The ability of S. aureus to influence the nasal microenvironment's cytokine secretion was assessed by exemplary stimulation experiments. METHODS: Baseline expression of 19 cytokines of primary NEC of GPA patients and normal controls (NC) was quantified by a multiplex cytokine assay. Stimulation experiments were performed with supernatants of S. aureus and expression of interleukin-8 was determined by ELISA. RESULTS: In GPA, an altered pattern of baseline cytokine expression with significantly up-regulated G-CSF and reduced interleukin (IL)-8 concentrations was observed. Both NEC of GPA patients and NC responded to stimulation with S. aureus, but GPA patients displayed a significantly lower IL-8 secretion and a diminished dynamic range of response towards the stimulus. CONCLUSIONS: The data presented underline the hypothesis of a disturbed epithelial nasal barrier function in GPA. The dysregulated baseline expression of G-CSF and IL-8 and the reduced response to microbial stimulation may facilitate changes in the composition of the nasal flora and favour an imbalanced inflammatory response, which might be relevant for the disease course.
Voges I, Jerosch-Herold M, Hedderich J, Pardun E, Hart C, Gabbert DD, Hansen JH, Petko C, Kramer HH, Rickers C.
Normal values of aortic dimensions, distensibility, and pulse wave velocity in children and young adults: a cross-sectional study.J Cardiovasc Magn Reson,
14 (2012), 77.
[abstract]
Abstract:
This study provides percentile curves for cross-sectional areas, distensibility and pulse wave velocity of the thoracic aorta in children and young adolescents between their 3rd and 29th year of life. These data may serve as a reference for the detection of pathological changes of the aorta in cardiovascular disease.
Wiltfang J, Jätschmann N, Hedderich J, Neukam FW, Schlegel KA, Gierloff M.
Effect of deproteinized bovine bone matrix coverage on the resorption of iliac cortico-spongeous bone grafts - a prospective study of two cohorts.Clin Oral Implants Res,
(2012).
[abstract]
Abstract:
OBJECTIVES: The augmentation of the alveolar ridge using iliac cortico-spongeous bone grafts is routinely used. However, bone grafts show a substantial degree of resorption, which may negatively affect the long-term success of dental implants in the augmented area. The aim of this study was to evaluate the effect of a deproteinized bovine bone matrix coverage on the resorption of iliac bone grafts. MATERIAL AND METHODS: Two cohorts consisting of 40 patients who received a vertical augmentation of the alveolar ridge with onlay grafts from the iliac crest were prospectively investigated over a period of 2 years. In half of the patients (n = 40), the grafts were covered by a thin layer of deproteinized bovine bone matrix (DBBM cohort). The other 40 patients received the identical surgical procedure without a DBBM coverage (non-DBBM cohort). The graft height/resorption was radiographically determined immediately after surgery, 6 months, 1 year, and 2 years postoperatively. RESULTS: The height of the bone graft 6 months after surgery accounted 92.15% of the initial value in the DBBM cohort and 87.76% in the non-DBBM cohort. One year after augmentation, the height reduced to 83.95% in the DBBM cohort and 72.92% in the non-DBBM cohort. Two years after surgery, the resorption slowed down and the height of the grafts accounted 81.27% in the DBBM cohort and 71.43% in the non-DBBM cohort. The difference was statistically significant. CONCLUSION: Deproteinized bovine bone matrix reduces the postoperative resorption of iliac bone block grafts and may therefore enhance the long-term implant prognosis in the augmented area.
Rohr AC, Riedel C, Fruehauf MC, van Baalen A, Bartsch T, Hedderich J, Alfke K, Doerner L, Jansen O.
MR imaging findings in patients with secondary intracranial hypertension.AJNR Am J Neuroradiol,
32 (2011 Jun-Jul), 1021-9.
[abstract]
Abstract:
The combination of cranial and orbital MR imaging and MRV can be highly sensitive and specific in the diagnosis of patients with IH.
Hui Y, Wohlers J, Podschun R, Hedderich J, Lamprecht P, Ambrosch P, Laudien M.
Antimicrobial peptides in nasal secretion and mucosa with respect to S. aureus colonisation in Wegener´s granulomatosis.Clin Exp Rheumatol,
29 (2011 Jan-Feb), S49-56.
[abstract]
Abstract:
The dynamic response towards challenges with microbes is dysregulated in WG, and this might be one reason for higher S. aureus colonisation rates in WG.
Thienhaus ML, Wohlers J, Podschun R, Hedderich J, Ambrosch P, Laudien M.
Antimicrobial peptides in nasal secretion and mucosa with respect to Staphylococcus aureus colonization in chronic rhinosinusitis with nasal polyps.Rhinology,
49 (2011), 554-61.
[abstract]
Abstract:
In NP patients, LL-37 response towards S. aureus colonization is disturbed while the ability of NEC to respond on S. aureus challenge is preserved. This deregulation of the nasal barrier could be involved in the multifactorial pathophysiology of NP.
Alkatout I, Naumann CM, Hedderich J, Hegele A, Bolenz C, Jünemann KP, Klöppel G.
Squamous cell carcinoma of the penis: predicting nodal metastases by histologic grade, pattern of invasion and clinical examination.Urol Oncol,
29 (2011), 774-81.
[abstract]
Abstract:
With a diagnosis of squamous cell carcinoma of the penis, there is still a significant need to define the tumor criteria that allow the disease to be stratified according to the risk of developing lymph node metastases. The histopathology of the primary tumor in 72 consecutive patients with resected squamous cell carcinoma of the penis was reviewed for this study. Tumor tissue was reviewed for (1) histologic grade, (2) invasion pattern, (3) tumor stage, (4) proportion of poorly differentiated tumor cells, (5) invasion depth, (6) proportion of tumor necrosis, (7) angioinvasion, (8) histologic classification, (9) number of lesions, (10) growth pattern, (11) number of mitoses, (12) degree of keratinization, and (13) clinical groin status. It was found that the presence of inguinal lymph node metastases correlated in descending order of frequency with grade G2/G3, clinically positive groin status, reticular invasion, stage pT2/T3, >50% poorly differentiated tumor cells, depth of invasion, and comedolike tumor necrosis. These results revealed that the risk of inguinal lymph node metastasis in penile carcinoma can be predicted on the basis of 3 major factors: histologic grade, pattern of invasion, and clinical groin status.
Stark AM, Stöhring C, Hedderich J, Held-Feindt J, Mehdorn HM.
Surgical treatment for brain metastases: Prognostic factors and survival in 309 patients with regard to patient age.J Clin Neurosci,
18 (2011), 34-8.
[abstract]
Abstract:
Brain metastases are the most common intracranial tumors. Overall, the only accepted prognostic factors are patient age and performance status. However, several other factors are considered before surgery. We performed a retrospective analysis of 309 patients who underwent surgical resection of newly diagnosed brain metastases between 1994 and 2004. Univariate survival analysis revealed age, performance status, extracranial metastases, complete resection, radiotherapy and re-craniotomy as prognostic indicators. Multivariate analysis determined that patient age, performance status, extracranial metastases, radiotherapy and re-craniotomy are independent factors of prolonged survival. We statistically estimated the age threshold separating patients with favorable outcomes from those with unfavorable prognoses. Using the Kaplan-Meier analysis this threshold can be set at 65 years. Multivariate analysis of patients >65 years revealed the presence of co-morbidities, the number of brain metastases, post-operative performance status and radiotherapy as independent prognostic factors.
Mehdorn HM, Schwartz F, Dawirs S, Hedderich J, Dörner L, Nabavi A.
High-field iMRI in glioblastoma surgery: improvement of resection radicality and survival for the patient?.Acta Neurochir Suppl,
109 (2011), 103-6.
[abstract]
Abstract:
Since the first patients underwent intracranial tumor removal with the radicality control of intraoperative MRI (ioMRI) in September 2005 in our department, the majority of operations performed in the ioMRI room have been indicated for high grade gliomas. In order to elucidate the role of ioMRI scanning in patients harboring high-grade gliomas (HGG) on their survival, one hundred ninety three patients with gliomas WHO grades III and IV were operated either in a standard microsurgical neuronavigated fashion or using additionally ioMRI and were included in a follow-up study. The series started with surgeries from September 2005 until October 2007. Patient attribution to the two groups was based on the logistical availability of the ioMRI on a scheduled surgery day, and on the assumed "difficulty" of the surgery based on the location of the glioma in or near to an eloquent area. Surgery was intended to be as radical as possible without reduction of quality of life. First surgery was performed in 103 patients (75 WHO IV and 28 WHO III) and will be the main topic of this paper. In 60 patients, ioMRI was used, while in 43 patients standard microsurgical neuronavigated resection techniques were applied. Patients were followed in regular intervals mostly until death. Statistical analysis showed a median survival time for patients in whom ioMRI had been used of 20, 37 months compared to 10, 3 months in the cohort who had undergone conventional microsurgical removal. Major influencing concomitants were WHO grades and age which were balanced in both groups.
Zimmermann CE, Gierloff M, Hedderich J, Açil Y, Wiltfang J, Terheyden H.
Survival of transplanted rat bone marrow-derived osteogenic stem cells in vivo.Tissue Eng Part A,
17 (2011), 1147-56.
[abstract]
Abstract:
This study was designed to trace bone marrow-derived stromal cells (MSC) after implantation in an ectopic rat model of bone tissue engineering. MSC were isolated from adult donor rats, expanded, seeded on a hydroxyapatite/β-tricalcium phosphate bone graft substitute (Straumann® BoneCeramic), and cultivated until confluent. Before subcutaneous implantation of seeded constructs and controls (unseeded bone graft substitute) in isogenic rats (n = 32), cells were labeled with the fluorescent dye carboxyfluoresceine-diacetate-succinimidyl-ester. Specimens were harvested at sacrifice on day 1, 3, 7, or 14 after implantation (n = 8 per group) and processed for histology (hematoxylin and eosin, CD68, 4',6-diamidino-2-phenylindol). Carboxyfluoresceine-diacetate-succinimidyl-ester-labeled transplanted cells were quantified in decalcified sections (50 fields of view per specimen) at 488 nm. Over time, transplanted cells decreased in number from 31.3 ± 2.3 (day 1) to 9.2 ± 1.1 (day 3) and 0.3 ± 0.1 (day 7) (p < 0.001). Fourteen days postimplantation MSC could no longer be identified. Additionally, starting on day 3 postimplantation, cellular disintegration was noted. Multinucleated giant cells were present in constructs and controls on day 7 and increased to day 14 postimplantation. These results indicate that ectopically transplanted MSC survive for a rather short time after implantation. Possible reasons for early cell death are discussed.
Zimmermann CE, Gierloff M, Hedderich J, Açil Y, Wiltfang J, Terheyden H.
Biocompatibility of bone graft substitutes: effects on survival and proliferation of porcine multilineage stem cells in vitro.Folia Morphol (Warsz),
70 (2011), 154-60.
[abstract]
Abstract:
Bone graft substitutes (BGS) are widely used in clinical practice. For stem cellbased approaches to bone tissue engineering BGS need to show sufficient biocompatibility in the in vitro setting. This study was designed to demonstrate the influence of six different BGS on the proliferation and metabolic activity of porcine mesenchymal multilineage stem cells (pMSC) in vitro. Bone-marrow derived pMSC were cultivated for 24 hours with the eluates of six different BGS. The eluates were generated by incubating the BGS three times in succession for 24 hours with a culture medium and collecting the supernatants. pMSC vitality and proliferation in the presence of eluates from the first, second, and third incubation were assessed by WST-test quantification of metabolically active cells. Culture of pMSC with eluates in all cases resulted in decreased cell numbers in an eluate concentration-dependent manner. At least a 65% loss of cells compared to controls (culture medium without eluates) could be observed in the presence of undiluted eluates. The negative influence of eluates varied significantly among BGS. In all cases, second and third eluates were less potent in their negative effects on cellular vitality/proliferation. In conclusion, the BGS examined here should be submitted to thorough preincubation before in vitro use for cell-based constructs to maximize cell viability for the tissue engineering of bone.
Zorenkov D, Otto S, Böttner M, Hedderich J, Vollrath O, Ritz JP, Buhr H, Wedel T.
Morphological alterations of the enteric nervous system in young male patients with rectal prolapse.Int J Colorectal Dis,
(2011).
[abstract]
Abstract:
OBJECTIVES: The pathogenesis of rectal prolapse (RP) defined by a circumferential, full-thickness invagination of the rectal wall into the anal canal is controversial. RP is normally encountered in elderly women and attributed to several etiological factors (e.g., advanced age, pudendal nerve injury, laxity of supporting ligaments). RP affecting young male patients is unlikely to be explained by these factors and may be due to a rectal motility disorder. Therefore, the enteric nervous system (ENS) as key regulator of intestinal motility was evaluated by a systematic morphometric analysis. PATIENTS AND METHODS: Full-thickness rectosigmoid specimens obtained from young male patients with symptomatic RP (n = 5) and male controls (n = 15) were processed for conventional histology and immunohistochemistry using anti-HuC/D as pan-neuronal marker. Enteric ganglia, nerve and glial cells were quantified separately in the myenteric (MP) and submucosal plexus (SMP). RESULTS: Compared to controls, patients with RP showed significantly (p < 0.05) increased mean ganglionic area both in MP and SMP, increased mean neuronal content of submucosal ganglia, and nearly threefold higher frequency of submucosal ganglia containing ≥7 neurons. CONCLUSION: The morphometric analysis reveals distinct quantitative alterations of the ENS in young male patients with RP mainly characterized by submucosal hyperganglionosis similar to histopathological features described in intestinal neuronal dysplasia. The data give evidence that RP in this unusual subgroup is associated with morphological changes of enteric ganglia which may contribute to the development of RP and complement established etiological concepts.
Kapischke M, Friedrich F, Hedderich J, Schulz T, Caliebe A.
Laparoscopic versus open appendectomy--quality of life 7 years after surgery.Langenbecks Arch Surg,
396 (2011), 69-75.
[abstract]
Abstract:
Patients after laparoscopic appendectomy show a higher degree of satisfaction with their body and their scar than patients after open appendectomy.
Laudien M, Gadola SD, Podschun R, Hedderich J, Paulsen J, Reinhold-Keller E, Csernok E, Ambrosch P, Hellmich B, Moosig F, Gross WL, Sahly H, Lamprecht P.
Nasal carriage of Staphylococcus aureus and endonasal activity in Wegener s granulomatosis as compared to rheumatoid arthritis and chronic Rhinosinusitis with nasal polyps.Clin Exp Rheumatol,
28 (2010 Jan-Feb), 51-5.
[abstract]
Abstract:
Endonasal activity in WG is associated with higher nasal S. aureus colonisation rates and subsequent higher relapse rates. The higher frequency of S. aureus colonisation could be a consequence of a recently shown mucosal barrier defect in WG and facilitate chronic inflammation and granuloma formation in the upper respiratory tract.
Rohr A, Jensen U, Riedel C, van Baalen A, Fruehauf MC, Bartsch T, Hedderich J, Doerner L, Jansen O.
MR imaging of the optic nerve sheath in patients with craniospinal hypotension.AJNR Am J Neuroradiol,
31 (2010), 1752-7.
[abstract]
Abstract:
The ISSON in patients with CSH is partially or fully collapsed due to reduced CSF content. In comparison with other anatomic markers, this sign showed the highest sensitivity for the diagnosis of patients with CSH in this study.
Voges I, Jerosch-Herold M, Hedderich J, Westphal C, Hart C, Helle M, Scheewe J, Pardun E, Kramer HH, Rickers C.
Maladaptive aortic properties in children after palliation of hypoplastic left heart syndrome assessed by cardiovascular magnetic resonance imaging.Circulation,
122 (2010), 1068-76.
[abstract]
Abstract:
Adverse aortic properties post palliation of hypoplastic left heart syndrome manifest themselves by aortic dilatation, decreased distensibility, and increased volume of nonviable aortic wall tissue. The negative association between aortic late gadolinium enhancement and right ventricular ejection fraction suggests unfavorable aortic-ventricular coupling. The potential impact of these findings on long-term right ventricular function should be evaluated in future studies.
Welzel M, Schwarz HP, Hedderich J, Dörr HG, Binder G, Brämswig JH, Krude H, Richter-Unruh A, Niedziela M, Gromoll J, Krone N, Riepe FG, Holterhus PM.
No correlation between androgen receptor CAG and GGN repeat length and the degree of genital virilization in females with 21-hydroxylase deficiency.J Clin Endocrinol Metab,
95 (2010), 2443-50.
[abstract]
Abstract:
Neither CAG nor GGn repeat lengths are statistically significant modifiers of genital virilization in females with 21OHD.
Treumer F, Wacker N, Junge O, Hedderich J, Roider J, Hillenkamp J.
Foveal structure and thickness of retinal layers long-term after surgical peeling of idiopathic epiretinal membrane.Invest Ophthalmol Vis Sci,
(2010).
[abstract]
Abstract:
Purpose. To better understand the long-term effect of idiopathic epiretinal membrane (IEM) peeling on retinal anatomy, foveal structure and the thickness of individual retinal layers were analyzed with frequency-domain optical coherence tomography (fdOCT). The long-term postoperative course of macular thickness was followed. Methods. FdOCT scans were obtained from the horizontal midline in 33 eyes long-term (mean 46 ± 13 months) postoperatively and 30 eyes of age-matched controls. Raw images were exported and the thickness of retinal layers was measured with a manual segmentation procedure aided by a customized computer program. Macular thickness was quantified over time with the time-domain (td) OCT Fast Macular Thickness program. Results. Thickness of retinal layers between the outer nuclear and the ganglion cell plus inner plexiform layers in the horizontal midline of the fovea and the nasal parafovea were greater than normal while that of RPE and photoreceptor, and RNFL layers was not different from controls. Twelve of 33 eyes had a foveal pit while the median foveal shape was distorted. Central macular thickness quantified with tdOCT remained increased while the decrease of nasal macular thickness towards normal values was incomplete and delayed to 35 months postoperatively. The superior, temporal, and inferior macular thickness returned to normal after 12-14 months postoperatively. Conclusions. Long-term postoperatively the fovea and the nasal parafovea remain thickened between the outer nuclear and the ganglion cell layer while the superior, temporal, and inferior macular thickness returns to normal. Long-term observations are required in the assessment of macular recovery from mechanical stress.
Schaefer PJ, Kurz B, Schaefer FK, Hedderich J, Strutz A, Heller M, Jahnke T.
Development of a permanently controllable rotating biopsy device, part II: Competitive in-vitro testing of a cannula-like prototype compared to established end-cut and side-notch biopsy devices.Rofo,
182 (2010), 58-65.
[abstract]
Abstract:
Compared to established core biopsy systems, the biopsy-cannula prototype offers diagnostically equivalent biopsy specimen quality in an in-vitro setting in bovine liver, kidney and myocardium.
Gierthmuehlen M, Sommer P, Zuhayra M, Hedderich J, Jaenig U, Faendrich F, Henze E, Kampen WU.
Imaging of acute heart-transplant rejection using 99m-Technetium labelled oligonucleotides against interleukin-2 mRNA in rats.Eur J Cardiothorac Surg,
37 (2010), 1111-6.
[abstract]
Abstract:
Radioactively labelled anti-sense-oligonucleotides against mRNA of IL2 may be a promising approach for the detection of acute transplant rejection in vivo.
Klomp HJ, Eberhard J, Hren S, Hedderich J, Schmidt HG.
The role of pathophysiological explanations in clinical case representations of dental students and experts.Eur J Dent Educ,
13 (2009), 58-65.
[abstract]
Abstract:
INTRODUCTION: Teaching of biomedical knowledge lays the foundations for the understanding and treatment of diseases. However, the representation of pathophysiological explanations in the management of clinical cases differs for various levels of medical expertise and different theories have been proposed to explain this phenomenon. The present study investigated for the first time how biomedical knowledge is used in clinical reasoning in dental medicine. MATERIALS AND METHODS: In an experimental study 20 experts in the field of Periodontology and 61 students of different levels of training produced written pathophysiological explanations after having studied three different clinical cases. By comparing the written protocols to a visualised expert-made 'canonical' explanation the concepts used in the pathophysiological explanation were counted and classified as well as the links between concepts. RESULTS: The statistical analysis by MANOVA showed significant differences between third- and fourth-year students, students of intermediate expertise level (fifth-year) and experts for various parameters qualifying concepts or links of the written pathophysiological explanations. The participants of intermediate expertise level produced a high rate of concepts and links; however, characteristic findings for knowledge encapsulation in the different levels of expertise were not evident. The analysis showed that the design of the clinical cases and of the canonical explanations significantly influenced the outcomes. CONCLUSION: The present study demonstrated the pathophysiological representations of clinical cases in dental students and experts to be different from other medical disciplines. It could be assumed that this observation is based on different contents for teaching of practical skills and diagnostic procedures in dental compared with medical education.
Laudien M, Lamprecht P, Hedderich J, Holle J, Ambrosch P.
Olfactory dysfunction in Wegener's granulomatosis.Rhinology,
47 (2009), 254-9.
[abstract]
Abstract:
Necrotizing granulomatous inflammation of the upper respiratory tract is one of the hallmarks of Wegener's granulomatosis (WG), which may explain the reason for olfactory dysfunction in WG. However, a systematic analysis using modem olfactory testing tools has not been performed and potential causes of dysfunction at different levels of olfactory information processing remain obscure so far. In this study a group of 76 WG-patients was examined with sniffin'sticks screening 12, odour threshold (T)/discrimination (D)/identification (I) TDI-score, active anterior rhinomanometry and a standardized questionnaire for olfactory function. WG-patients were aware of their olfactory dysfunction, as proven by psychophysiological test results. An altered olfactory function was significantly correlated to local administration of mupirocin and to the time interval between first diagnosis and study entry. None of the other variables had a statistical significant effect on the olfactory dysfunction.
Schaefer PJ, Jahnke T, Hedderich J, Andres H, Heller M, Schaefer FK.
Development of a permanently controllable rotating biopsy device, Part I: theoretical considerations and in-vitro results for five different prototypes.Rofo,
181 (2009), 1175-9.
[abstract]
Abstract:
PURPOSE: To develop different prototypes of permanently controllable rotating biopsy devices with determination of the most efficient prototype in biopsies in bovine myocardium. MATERIALS AND METHODS: Five different prototypes of 18-gauge rotating biopsy devices were designed and constructed, four (1 - 4) with various drill-like cutting edges and one (5) cannula type with a lancet-like helically bent cutting edge. Using bovine myocardium as the biopsy tissue, n = 100 specimens per prototype were obtained, and a quantitative analysis including tissue fragmentation, length in mm and weight in mg was carried out. For statistical analysis, the chi-square test for tissue fragmentation and Kruskal-Wallis test for the parameters length and weight were calculated. RESULTS: Prototype 5 showed the highest rate of extraction of one-fragment specimens in n = 66 cases and the lowest rate of failure to obtain tissue in n = 11 cases. The mean length/weight were 4.15 mm/ 3.91 mg for prototype 1, 1.80 mm/ 1.66 mg for prototype 2, 4.61 mm/ 3.28 mg for prototype 3, 5.20 mm/ 3.74 mg for prototype 4, and 9.57 mm/ 6.97 mg for prototype 5. In all three categories, prototype 5 was significantly superior to the prototypes 1 - 4 with p < 0.001. CONCLUSION: The cannula type with a lancet-like helically bent cutting edge proved to be the most efficient prototype and may now be tested competitively against established automated biopsy devices in vitro.
Klomp HJ, Eberhard J, Hren S, Hedderich J, Schmidt HG.
The role of pathophysiological explanations in clinical case representations of dental students and experts.Eur J Dent Educ,
13 (2009), 58-65.
[abstract]
Abstract:
INTRODUCTION: Teaching of biomedical knowledge lays the foundations for the understanding and treatment of diseases. However, the representation of pathophysiological explanations in the management of clinical cases differs for various levels of medical expertise and different theories have been proposed to explain this phenomenon. The present study investigated for the first time how biomedical knowledge is used in clinical reasoning in dental medicine. MATERIALS AND METHODS: In an experimental study 20 experts in the field of Periodontology and 61 students of different levels of training produced written pathophysiological explanations after having studied three different clinical cases. By comparing the written protocols to a visualised expert-made 'canonical' explanation the concepts used in the pathophysiological explanation were counted and classified as well as the links between concepts. RESULTS: The statistical analysis by MANOVA showed significant differences between third- and fourth-year students, students of intermediate expertise level (fifth-year) and experts for various parameters qualifying concepts or links of the written pathophysiological explanations. The participants of intermediate expertise level produced a high rate of concepts and links; however, characteristic findings for knowledge encapsulation in the different levels of expertise were not evident. The analysis showed that the design of the clinical cases and of the canonical explanations significantly influenced the outcomes. CONCLUSION: The present study demonstrated the pathophysiological representations of clinical cases in dental students and experts to be different from other medical disciplines. It could be assumed that this observation is based on different contents for teaching of practical skills and diagnostic procedures in dental compared with medical education.
Hanss R, Roemer T, Hedderich J, Roesler L, Steinfath M, Bein B, Scholz J, Bauer M.
Influence of anaesthesia resident training on the duration of three common surgical operations.Anaesthesia,
64 (2009), 632-7.
[abstract]
Abstract:
We investigated the influence of resident training on anaesthesia workflow of three standard procedures--laparoscopic cholecystectomy, diagnostic gynaecological laparoscopy and transurethral prostate gland resection (TURP)--comparing 259 non-emergency resident vs 341 consultant cases from 20 German hospitals. Each hospital provided 10 random cases for each procedure, yielding 600 cases for analysis. Standard time intervals as documented in the hospital information system were: 'Case Time' (the time from the start of anaesthesia induction to discharge of the patient to the recovery area) and 'Anaesthesia Control Time' (which was the Case Time minus the time from the start of surgery to the end of surgical closure). Case Time was significantly shorter for consultants in all three procedures (p < 0.05, analysis of variance) and Anaesthesia Control Time shorter for consultants only in gynaecological laparoscopy and TURP. Patient comorbidity, patient age and geographical location of the hospital were not influential factors in the analysis of variance. We conclude that resident training significantly increases duration of elective operative times.
Eberhard J, Klomp HJ, Föge M, Hedderich J, Schmidt HG.
The intermediate effect and the diagnostic accuracy in clinical case recall of students and experts in dental medicine.Eur J Dent Educ,
13 (2009), 128-34.
[abstract]
Abstract:
INTRODUCTION: The extensive knowledge of experts facilitates the solving of domain-specific problems. In general, this is due to the fact that experts recall more detailed information than do novices or even advanced students. However, if physicians of different expertise levels are asked to write down the details of a given case, advanced medical students recall more information than experts. This phenomenon was called the 'intermediate effect' and is considered to be a specific feature of medical expertise. The aim of the here presented study was to examine this observation in the domain of dental medicine. MATERIALS AND METHODS: Sixty-one students and 20 specialised dentists participated in this study. Three clinical case descriptions were presented and afterwards the participants were told to write down all concrete information they remembered. Finally, they had to come up with a diagnosis. Interrater agreement, diagnostic accuracy and the recall explanation protocols were analysed statistically in comparison to state-of-the-art (canonical) explanations of the clinical cases. RESULTS: The mean interrater agreement was 96.2 +/- 3.37%. It was shown statistically that the more experienced the participants, the more accurate their diagnoses were (P < 0.001). The statistical analysis using the Games-Howell test demonstrated significant more written recall of the 5th-year students compared with 3rd- and 4th-year students and experts (P < 0.05). CONCLUSION: The results of this study suggest the existence of the intermediate effect in clinical case recall in dental medicine and thereby corroborate its importance and general applicability for different medical domains.
Kommoss S, Schmidt D, Kommoss F, Hedderich J, Harter P, Pfisterer J, du Bois A.
Histological grading in a large series of advanced stage ovarian carcinomas by three widely used grading systems: consistent lack of prognostic significance. A translational research subprotocol of a prospective randomized phase III study (AGO-OVAR 3 protocol).Virchows Arch,
454 (2009), 249-56.
[abstract]
Abstract:
While there is no doubt that histologic grading is applicable in early stage ovarian carcinoma, it is still in controversial discussion concerning advanced stage ovarian carcinoma. It was the aim of this study to assess the three most widely used grading systems for ovarian carcinoma in terms of prognostic significance, concordance rates, and reproducibility in a large number of advanced stage ovarian carcinomas of all types after standardized chemotherapy. Representative hematoxylin and eosin slides from 334 cases of stage IIB-IV ovarian carcinoma (prospective randomized, multi-center, phase III study) were used. The first round was grading of all cases according to FIGO, GOG, and Silverberg by one author. The second round (after 1 year) was 30 randomly selected cases graded by three authors. None of the three grading systems was prognostically significant (FIGO p = 0.38; GOG p = 0.70; Silverberg p = 0.92). The concordance rates between the three systems were as follows: FIGO/GOG 95.5%, kappa = 0.929; Silverberg/FIGO 69.9%, kappa = 0.533; Silverberg/GOG 66.8%, kappa = 0,481. Grading of advanced stage ovarian carcinomas was of no value for estimation of prognosis in this homogeneously treated patient group. Alternative methods should be defined, which might help to separate patients with high risk of tumor progression from others with low risk.
Schaefer FK, Heer I, Schaefer PJ, Mundhenke C, Osterholz S, Order BM, Hofheinz N, Hedderich J, Heller M, Jonat W, Schreer I.
Breast ultrasound elastography-Results of 193 breast lesions in a prospective study with histopathologic correlation.Eur J Radiol,
(2009).
[abstract]
Abstract:
PURPOSE: To evaluate the diagnostic performance of ultrasound elastography in breast masses. MATERIAL AND METHODS: 193 lesions (129 benign, 64 malignant) were analyzed with the EUB 8500 Logos-ultrasonic-unit (Hitachi Medical, Japan) and a linear-array-transducer of 7.5-13-MHz. Standard of reference was cytology (FNAfine needle aspiration) or histology (core biopsy). The elastic-score was classified according to a 6-point colour-scale (Ueno classification; 1-3=benign, 4-5=malignant). Conventional B-mode ultrasound (US) findings were classified according to the BI-RADS classification. Statistical analysis included sensitivity, specificity, ROC-analysis and kappa-values for intra-/interobserver reliability. RESULTS: The mean score for elasticity was 4.1+/-0.9 for malignant lesions, and 2.1+/-1.0 for benign lesions (p<0.001). With a best cut-off point between elasticity scores 3 and 4, sensitivity was 96.9%, and specificity 76%. Setting a best cut-off point for conventional US between BI-RADS 4 and 5, sensitivity was 57.8%, and specificity 96.1%. Elastography provided higher sensitivity and lower specificity than conventional US, but two lesions with elasticity score 1 were false negative, whereas no lesion scored BI-RADS 1-3 were false negative. ROC-curve was 0.884 for elastography, and 0.820 for conventional US (p<0.001). Weighted kappa-values for intra-/interobserver reliability were 0.784/0.634 for BI-RADS classification, and 0.720/0.561 for elasticity scores. CONCLUSION: In our study setting, elastography does not have the potential to replace conventional B-mode US for the detection of breast cancer, but may complement conventional US to improve the diagnostic performance.
Deschner J, Wolff S, Hedderich J, Kreusch T, Jepsen S.
Dimensional changes of periodontal soft tissues after intrasulcular incision.Clin Oral Investig,
13 (2009), 401-8.
[abstract]
Abstract:
In maxillofacial surgery, intrasulcular incisions are often used. This prospective case series was established to evaluate the detrimental effects of intrasulcular incisions on periodontal structures. In 35 patients, measurements of probing depth and crown length before and 10 months postoperatively were performed to calculate changes of attachment level and gingival recession. In a subgroup, surgically treated sites were compared with untreated control sites. A nonparametric test was applied for longitudinal and split-mouth comparisons. Overall, intrasulcular incisions did not induce significant attachment loss. The frequency of sites losing > or = 2 mm of attachment was 5.0%, 2.6%, and 4.7% at mesial, buccal, and distal sites, respectively. Intrasulcular incisions caused only a slight increase in gingival recession by 0.4 +/- 0.5, 0.2 +/- 0.3, and 0.3 +/- 0.4 mm at mesial, buccal, and distal sites, respectively. Within the limitations of the study design, it can be concluded that intrasulcular incisions without additional vertical incisions do not impose a serious risk for attachment loss and/or gingival recession.
Franke A, Balschun T, Karlsen TH, Hedderich J, May S, Lu T, Schuldt D, Nikolaus S, Rosenstiel P, Krawczak M, Schreiber S.
Replication of signals from recent studies of Crohn's disease identifies previously unknown disease loci for ulcerative colitis.Nat Genet,
40 (2008), 713-5.
[abstract]
Abstract:
Following up on recent genome-wide association studies (GWAS) of Crohn's disease, we investigated 50 previously reported susceptibility loci in a German sample of individuals with Crohn's disease (n = 1,850) or ulcerative colitis (n = 1,103) and healthy controls (n = 1,817). Among these loci, we identified variants in 3p21.31, NKX2-3 and CCNY as susceptibility factors for both diseases, whereas variants in PTPN2, HERC2 and STAT3 were associated only with ulcerative colitis in our sample collection.
Franke A, Balschun T, Karlsen TH, Hedderich J, May S, Lu T, Schuldt D, Nikolaus S, Rosenstiel P, Krawczak M, Schreiber S.
Replication of signals from recent studies of Crohn's disease identifies previously unknown disease loci for ulcerative colitis.Nat Genet,
40 (2008), 713-5.
[abstract]
Abstract:
Following up on recent genome-wide association studies (GWAS) of Crohn's disease, we investigated 50 previously reported susceptibility loci in a German sample of individuals with Crohn's disease (n = 1,850) or ulcerative colitis (n = 1,103) and healthy controls (n = 1,817). Among these loci, we identified variants in 3p21.31, NKX2-3 and CCNY as susceptibility factors for both diseases, whereas variants in PTPN2, HERC2 and STAT3 were associated only with ulcerative colitis in our sample collection.
Böning A, Bürger S, Fraund S, Attmann T, Cremer JT, Hedderich J, Lutter G.
Should the aortic valve be replaced in patients with mild aortic stenosis admitted for coronary surgery?.Thorac Cardiovasc Surg,
56 (2008), 467-70.
[abstract]
Abstract:
BACKGROUND: The question whether the aortic valve in patients with mild aortic stenosis undergoing coronary artery bypass grafting (CABG) should be replaced or left alone is still controversial. METHODS: Between 01/1995 and 03/2004, 38 patients (30 male, 8 female, mean age 70.9 +/- 7.8 years) required redo AVR 7.1 +/- 4.8 years after primary CABG, while 202 patients (125 male, 77 female, mean age 72.7 +/- 7.8 years) underwent combined AVR and CABG (1.9 +/- 0.8 grafts/patient). To evaluate the different approaches, the data of the redo-AVR group were compared with the data of a propensity-score matched group of AVR + CABG patients. RESULTS: All patients survived the procedure; the 30-day survival was 94.7 % in both groups. The 1- and 5-year survival rates were 94.7 % and 83.8 % in the AVR after CABG group, and 94.7 % and 86.9 % in the AVR + CABG group, respectively. The late mortality was 28.9 % in the AVR after CABG and 25 % in the AVR + CABG group. Statistically, significant differences regarding perioperative mortality and morbidity could not be detected, neither with nor without propensity score analysis. CONCLUSION: Combined AVR and CABG in patients with coronary artery disease and mild to moderate aortic stenosis seems advisable in an institution with an equally low perioperative risk for both procedures, because the patient will need only one surgical procedure instead of undergoing surgery with all the associated risks twice.
Dommisch H, Peus K, Kneist S, Krause F, Braun A, Hedderich J, Jepsen S, Eberhard J.
Fluorescence-controlled Er:YAG laser for caries removal in permanent teeth: a randomized clinical trial.Eur J Oral Sci,
116 (2008), 170-6.
[abstract]
Abstract:
The aim of this randomized clinical study was to compare the efficacy of a fluorescence-controlled erbium-loaded yttrium aluminum garnet (Er:YAG) laser with conventional bur treatment for caries therapy in adults. Twenty-six patients with 102 carious lesions were treated using either the Er:YAG laser, at threshold levels of 7, 8, 9, and 10 [U], or rotary burs. Both techniques were applied to each lesion at separate locations. After treatment, dentine samples were obtained using a carbide bur. The viable counts of Streptococcus mutans (SM) and lactobacilli (LB) [expressed as colony-forming units (log10 CFUs)], treatment time, pain, vibration, and sound intensity were determined. The median numbers of CFUs for SM and LB were not statistically different between laser and bur treatment at threshold levels 7 and 8 [U]. At threshold levels 9 and 10 [U], the median number of CFUs for LB [1.11 (range: 0.00-2.04)] were significantly higher following laser treatment than following bur treatment [0.30 (range: 0.00-0.60)]. The results indicate that treatment with a fluorescence-controlled Er:YAG laser at threshold levels of 7 and 8 removed caries to a level similar to that achieved using conventional bur treatment, with clinically irrelevant amounts of remaining bacteria. Although more time consuming, laser treatment provided higher patient comfort than bur treatment.
Weise JB, Rudolph P, Heiser A, Kruse ML, Hedderich J, Cordes C, Hoffmann M, Brant O, Ambrosch P, Csiszar K, Görögh T.
LOXL4 is a selectively expressed candidate diagnostic antigen in head and neck cancer.Eur J Cancer,
44 (2008), 1323-31.
[abstract]
Abstract:
Selective up-regulation of the mRNA of LOXL4, a member of the LOX matrix amine oxidase family, significantly correlated with lymph node metastases and higher tumour stages in head and neck squamous cell carcinomas (HNSCC). To evaluate the diagnostic and prognostic value of the protein we produced an antibody specific for LOXL4 and assessed the expression in 317 human HNSCC specimens. The LOXL4 protein was detected in 92.7% of primary tumours, in 97.8% of lymph node metastases and in affected oral mucosa with high-grade dysplasia, but was absent in various non-neoplastic tissues of the head and neck. TNM categories and overall survival did not link to grades of immunoreactivity. Studies in cultured primary hypopharyngeal HTB-43 carcinoma cells detected perinuclear and cell surface expression of LOXL4, but no nuclear localisation. Therefore, its interactive SRCR-domains and catalytic activity combined with tumour cell specific expression and cell surface associated location indicate multiple functions in tumour cell adhesion and interactions with the extracellular matrix. Our data suggest that LOXL4 is useful both as tumour marker and target in the treatment of HNSCC.
Kling C, Schmutzler A, Wilke G, Hedderich J, Kabelitz D.
Two-year outcome after recurrent implantation failure: prognostic factors and additional interventions.Arch Gynecol Obstet,
278 (2008), 135-42.
[abstract]
Abstract:
OBJECTIVES: After recurrent implantation failure (RIF), empirical figures on further prospects are essential for counselling but difficult to estimate within single IVF centres due to high drop-out rates. Alternatively, couples referred to a tertiary unit for RIF were evaluated. MATERIALS AND METHODS: Multi-centre 2-year observational trial of 1,174 eligible couples treated consecutively with adjuvant lymphocyte immunotherapy (LIT) in a university immunological department from 1999 to 2002 after three or more unsuccessful fresh embryo transfers. Acquisition of data was completed in 2005. RESULTS: With another 1.5 oocyte retrievals, delivery rate per couple depended on age (39.3% at <30 years, 16.9% at >39 years, P < 0.005). Prognosis was favourable when frozen embryo transfers had been conducted before (34.4 vs. 25.8%, P < 0.005). The outcome was slightly better in ICSI couples as compared to conventional IVF (31.0 vs. 24.8%, P < 0.05). Birth rates per fresh embryo transfer from the fourth to eighth retrieval were 17.4-18.3-15.0-12.9-12.9% (decline not significant). Apart from LIT, further additional interventions were given more often to couples who had had frozen embryo transfers before (49 vs. 40%, P < 0.005). CONCLUSIONS: Female age and ovarian response are crucial for further IVF prognosis. Previous frozen embryo transfers indicate better chances. Couples with male factor infertility may benefit from intracytoplasmatic sperm injection (ICSI) because underlying female factors are less prevalent. Cycle rank had comparatively little impact. Additional interventions are preferentially offered to couples who have a favourable prognosis anyway. Their multiple use is common practice in RIF, but its value should be considered limited.
Renner J, Gruenewald M, Meybohm P, Hedderich J, Steinfath M, Scholz J, Bein B.
Effect of elevated PEEP on dynamic variables of fluid responsiveness in a pediatric animal model.Paediatr Anaesth,
18 (2008), 1170-7.
[abstract]
Abstract:
BACKGROUND: Previous studies have demonstrated that stroke volume variation (SVV), pulse pressure variation (PPV) and global end-diastolic volume (GEDV) can be used to predict the response to fluid administration. Currently, little information is available whether application of different levels of positive end-expiratory pressure (PEEP), especially in infants and neonates, affects their ability to predict fluid responsiveness. The aim of our study was to assess the effect of increasing PEEP levels on the predictive value of SVV, PPV and GEDV with respect to fluid responsiveness. METHODS: Stroke volume variation and PPV were monitored continously in 22 anesthetized piglets during changing PEEP levels (5 and 10 cmH(2)O) both before and after fluid loading (FL). GEDV was measured by transpulmonary thermodilution; cardiac output and stroke volume (SV) were measured by pulmonary artery thermodilution. A positive response to FL was defined as > or =15% increase in SV. RESULTS: Fluid loading induced significant changes in all hemodynamic variables except of heart rate and systemic vascular resistance. At PEEP 5 cmH(2)O, SVV, PPV and GEDV significantly correlated with volume induced percentage change in SV, whereas at PEEP 10 cmH(2)O, this correlation was abolished for PPV. As assessed by receiver operating characteristic curve analysis, SVV and GEDV, independent of PEEP level applied, were the best predictors of a positive response to FL [area under the curve: SVV = 0.88; GEDV = 0.80]. CONCLUSIONS: In this pediatric animal model, SVV and GEDV were sensitive and specific predictors of fluid responsiveness during increasing PEEP levels.
Ghazal M, Hedderich J, Kern M.
Wear of feldspathic ceramic, nano-filled composite resin and acrylic resin artificial teeth when opposed to different antagonists.Eur J Oral Sci,
116 (2008), 585-92.
[abstract]
Abstract:
The aim of this study was to evaluate the wear of denture teeth and their antagonists produced by two-body and three-body wear tests. Three types of denture teeth, namely feldspathic ceramic (FC), nano-filled composite resin (NCR), and experimental acrylic resin teeth (AR), were tested. For each type two groups of eight upper premolars each were prepared. The first group was tested against cusps from the same material and the second group was tested against human enamel cusps. Each group was loaded with a total of 200,000 chewing cycles (two-body wear 100,000 cycles and three-body wear 100,000 cycles). Wear was analyzed by measuring the maximum depth and volume loss of the denture teeth using a laser scanner and by measuring the vertical loss of the antagonists using an optical macroscope. Statistically, there was no significant difference between the following combinations: FC-FC and NCR-NCR regarding the vertical and volume loss; and FC-enamel and NCR-enamel regarding the total vertical substance loss. The combinations AR-AR and AR-enamel showed higher wear values than the other combinations. For complete dentures, composite resin and ceramic teeth showed similar vertical and volume loss, whereas composite resin teeth seemed to be more suitable for partial dentures opposing natural teeth in terms of wear of teeth and antagonists.
Eberhard J, Bode K, Hedderich J, Jepsen S.
Cavity size difference after caries removal by a fluorescence-controlled Er:YAG laser and by conventional bur treatment.Clin Oral Investig,
12 (2008), 311-8.
[abstract]
Abstract:
To determine the extensions of cavities prepared conventionally by bur or by a fluorescence-controlled Er:YAG laser. Sixty-five human teeth with dentine caries were bisected through the caries lesion and were treated by a fluorescence-controlled Er:YAG laser in a non-contact or a contact mode or by a rotary bur. The specimens were subjected to histological staining and a quantitative evaluation of cavity area (mm(2)) by computer-assisted alignment. Data were tested for statistical significant differences by the Wilcoxon test (p < 0.05). Twenty-three out of 29 cavities were smaller after caries removal with the non-contact laser compared to the bur. For a threshold level of seven, a cavity size difference of 1.63 (1.86) mm(2) was calculated compared to a cavity size difference of 5.35 (5.05) mm(2) after bur excavation. The differences were statistically significant (p = 0.029). No significant differences were observed between the cavity size differences after excavation with the non-contact or the contact laser handpiece. Residual bacteria within the cavity floor were found only in low numbers after all treatments. The present in vitro study indicates that caries removal by a fluorescence-controlled Er:YAG laser using a threshold level of seven resulted in less dentine loss than preparations by a bur.
Rohr A, Riedel C, Reimann G, Alfke K, Hedderich J, Jansen O.
[Pseudotumor cerebri: quantitative in-vivo measurements of markers of intracranial hypertension].Rofo,
180 (2008), 884-90.
[abstract]
Abstract:
PURPOSE: Intracranial hypertension can change the morphology of anatomical structures that are critical in the evaluation of pseudotumor syndromes. The purpose of our study was to establish the normal range of such markers of intracranial hypertension and to consider a dependency on sex, age and body-mass index (BMI). MATERIALS AND METHODS: 123 persons without signs or symptoms of intracranial hypertension (63 females, 60 males, 18- 86-years-old, mean 49.5 SD17.8 years, mean BMI 25.3 SD42) were prospectively enrolled and MRI was performed at 3T. A STIR sequence in the coronal plane was used to measure the width of the optic nerve, the perioptic fluid rim and the total optic nerve sheath diameter in 4 different locations behind the eyeball. The height and width of the pituitary and Meckel's cave were also measured and the area was calculated. RESULTS: The mean width of the optic nerve sheath narrows significantly from anterior (mean 5.3 SD 0.6 mm) to posterior (mean 4.1 SD 0.4 mm), as does the perioptic fluid rim (mean 1.4 SD 0.3 mm vs. mean 1.0 SD 0.2 mm) and--to a lesser extent--the optic nerve itself (mean 2.4 SD 0.4 mm vs. mean 2 SD 0.3 mm, p=0.000 for all). There was no statistically relevant correlation of the width of the optic nerve sheath with age. The coronal area of Meckel's cave was independent of sex, age or BMI (mean 39 SD 9.3 mm2). The height of the pituitary differed little in women (mean 4.4 SD 0.9 mm) and men (mean 4.2 SD 0.8 mm), but we found a significant negative correlation with age in women only (r = -0.38, p = 0.01). CONCLUSION: The presented typical values and their deviations serve as a basis for the evaluation of pathologies in patients suspected of having pseudotumor syndrome.
Ebert A, Hedderich J, Kern M.
Retention of zirconia ceramic copings bonded to titanium abutments.Int J Oral Maxillofac Implants,
22 (2007 Nov-Dec), 921-7.
[abstract]
Abstract:
PURPOSE: The aim of this study was to evaluate the effect of 2 surface conditioning methods and 2 luting-gap sizes on the retention and durability of zirconia ceramic copings bonded to titanium abutments. MATERIALS AND METHODS: Zirconia ceramic copings (Camlog Biotechnologies, Winsheim, Germany) with a luting-gap size of either 30 microm or 60 microm were bonded to titanium abutments (Camlog Biotechnologies) using the composite resin cement Panavia F (Kuraray, Osaka, Japan). The bonding surfaces of the zirconia ceramic copings were either (a) pretreated with airborne particle abrasion and cleaned with alcohol or (b) just cleaned with alcohol, whereas the bonding surfaces of all titanium abutments had been abraded and cleaned. After the specimens had been stressed for either 1, 30, 60, or 150 days by water and thermal cycling, retention was measured. RESULTS: The surface conditioning method, luting-gap size, and storage time significantly (P = .001; 3-way analysis of variance [ANOVA]) influenced retention. Air abrasion increased the retention significantly. Failure modes were predominantly adhesive. Air-abraded copings bonded with 30-microm luting gap achieved significantly greater retention than those bonded with a 60-microm luting gap. CONCLUSION: Surface conditioning methods and the size of the luting gap have a significant influence on the retention of Camlog zirconia ceramic copings bonded to Camlog titanium abutments.
Bauer M, Hanss R, Römer T, Rösler L, Linnemann K, Hedderich J, Scholz J.
Intraoperative Prozesszeiten im prospektiven multizentrischen Vergleich.Deutsches Ärzteblatt,
104 (2007), 3252 - 3258.
[abstract]
Abstract:
Introduction: Suboptimal intra-operative process times can lead to unnecessary binding of human ressources resulting in higher costs than refunding by the system of diagnoses related groups (DRG).
Methods: Process times for laparoscopic cholecystectomies in 10 hospitals with fewer than 15.000 cases per year (group 1) were compared to 10 hospitals with more than 15.000 cases per year (group 2). Parameters relating to case mixed and level of education activity were evaluated.
Results: No differences were found between the two groups in respect of anaesthetic and surgical case mixed. The overall "case length" , defined as the time during which the anaesthesiologist was present, was significantly greater in group 2 than in group 1, as were the surgical parameters "perioperative time" and "surgical case length" and the anaesthesiological parameters "anaesthesia preparation time" and "anaesthesia follow-up time". Group 1 contained significantly more experienced anaesthesiologists and surgeons.
Discussion: Hospitals with more than 15.000 cases per year show prolonged intra-operative process times, which might ba caused by education. Thus, bigger hospitals with a high contribution to education have a significant financial disadvantage which will not be reimbursed by the DRG system.
Hilpert F, du Bois A, Greimel ER, Hedderich J, Krause G, Venhoff L, Loibl S, Pfisterer J.
Feasibility, toxicity and quality of life of first-line chemotherapy with platinum/paclitaxel in elderly patients aged >or=70 years with advanced ovarian cancer--a study by the AGO OVAR Germany.Ann Oncol,
18 (2007), 282-7.
[abstract]
Abstract:
BACKGROUND: The purpose of the study was to evaluate first-line platinum/paclitaxel (Taxol) under phase III trial conditions in ovarian cancer (OC) patients aged >or=70 years. PATIENTS AND METHODS: Phase III results of 779 patients with OC International Federation of Gynecology and Obstetrics (FIGO) stage IIB/IV treated with cisplatin/paclitaxel versus carboplatin/paclitaxel were retrospectively analyzed according to feasibility, toxicity (National Cancer Institute Common Toxicity Criteria) and quality of life (QoL) [European Organization for Research and Treatment of Cancer QoL questionnaire (EORTC QLQ-C30)] in patients aged <70 or >or=70 years. RESULTS: One hundred and three (13%) patients were aged >or=70 years. Patient characteristics (<70 versus >or=70 years) showed significant differences with regard to Eastern Cooperative Oncology Group performance status, residual disease and constitutional factors but not to FIGO stage, histology or grading. Elderly patients received 98%, 100% and 96% of the recommended paclitaxel, carboplatin and cisplatin dose, respectively, per cycle. Early discontinuation was more frequent in elderly, although QoL, nonhematological and hematological toxicity were comparable between elderly and younger patients, except for febrile neutropenia (5% versus <1%, P = 0.005). There were no significant differences with regard to cycle delays, dose reductions or the use of granulocyte colony-stimulating factor and antibiotics. CONCLUSION: Platinum/paclitaxel appeared to be feasible and tolerable in elderly patients under clinical trial conditions, but there seems to be a different investigators' estimation of toxicity and less intention to maintain trial treatment in elderly.
Stark AM, Hedderich J, Held-Feindt J, Mehdorn HM.
Glioblastoma--the consequences of advanced patient age on treatment and survival.Neurosurg Rev,
30 (2007), 56-61; discussion 61-2.
[abstract]
Abstract:
Glioblastoma is the most common primary brain tumor. Recent evidence suggests that aggressive treatment is also effective in elderly patients. However, large patient series are missing. The aim of this retrospective study was to determine prognostic factors in a large series (n=345) of elderly patients surgically treated for newly diagnosed glioblastoma (WHO grade IV) at a single institution between 1991 and 2002. U-tests (Mann Whitney), chi-square tests, log-rank tests/Kaplan-Meier plots and Cox regression models were used for statistical analysis. Based on the maximum difference in median survival, a threshold of 60 years was used to separate younger from older patients. In total, 185 patients (53.6%) were over 60 years old. In these individuals, total tumor resection, radiotherapy and reoperation for tumor recurrence were identified as independent prognostic factors. When total surgical resection was combined with radiotherapy and reoperation, Kaplan-Meier analysis revealed a median survival of up to 64 weeks in elderly patients. Our data indicate that total tumor resection, radiotherapy and reoperation should also be considered in selected elderly patients. Age alone should not generally exclude elderly individuals from aggressive treatment.
Schattschneider J, Zum Buttel I, Binder A, Wasner G, Hedderich J, Baron R.
Mechanisms of adrenosensitivity in capsaicin induced hyperalgesia.Eur J Pain,
11 (2007), 756-63.
[abstract]
Abstract:
It is well known that iontophoresis of norepinephrine in capsaicin treated skin is followed by an increase in thermal hyperalgesia. It is unclear if this action on nocicepitive afferents involves the release of prostaglandins. The aim of the present study was to determine: (1) the effect of norepinephrine iontophoresis on spontaneous and evoked pain in the human skin after topical application of capsaicin; (2) the effect of cyclooxygenase (COX) inhibition on changes in pain perception induced by norepinephrine application. METHODS: Ten volunteers were included in the study. Iontophoresis of norepinephrine or saline was performed in a randomized cross over design on the volar aspect of the forearm after topical application of capsaicin. In the second part of the study single iv. injections of saline or acetylsalicylic acid were performed in a randomized double blind cross over design. After the injection norepinephrine iontophoresis was performed on the skin treated with topical capsaicin. Spontaneous pain, mechanical hyperalgesia as well as warm and heat pain thresholds were measured before and after each iontophoresis. RESULTS: Norepinephrine did enhance spontaneous pain and mechanical and thermal hyperalgesia in capsaicin treated skin. Inhibition of COX I and II had no effect on the norepinephrine induced changes in pain perception. CONCLUSION: The results do not support the assumption that in human skin sensitized by topical capsaicin application of norepinephrine acts on nociceptive afferents via the release of prostaglandins. Thus, a direct action of norepinephrine on adrenergic receptors in the membrane of the afferent fibers is most likely.
Görögh T, Weise JB, Holtmeier C, Rudolph P, Hedderich J, Gottschlich S, Hoffmann M, Ambrosch P, Csiszar K.
Selective upregulation and amplification of the lysyl oxidase like-4 (LOXL4) gene in head and neck squamous cell carcinoma.J Pathol,
212 (2007), 74-82.
[abstract]
Abstract:
Members of the lysyl oxidase family (LOX) are copper and lysyl-tyrosine quinone cofactor-containing amine oxidases that are important for the assembly and maintenance of components of the extracellular matrix. Our previous results demonstrated that a novel member, LOXL4, is overexpressed in head and neck squamous cell carcinoma (HNSCC) compared to normal squamous epithelium. Results of the current study showed overexpression of the LOXL4 transcript in 74% (46 of 62) of invasive HNSCC tumours and 90% of both primary and metastatic HNSCC cell lines. Significant correlation was found between LOXL4 expression and local lymph node metastases versus primary tumour types (p<0.01) and higher tumour stages (p<0.01). Immunocytochemistry demonstrated cellular overexpression of the LOXL4 protein that correlated with the increased mRNA transcription in HNSCC cells. HNSCC cell lines displayed in significant subset of nuclei increased copies of the LOX4 gene locus on chromosome 10q24, demonstrated by fluorescence in situ hybridization (FISH). Extensive metaphase cytogenetic analysis was performed on UTSCC19A cells, identifying an isochromosome i(10)(q10). Taken together, these results highlight LOXL4 expression as a distinctive trait and suggest a functional role for LOXL4 in the molecular pathogenesis of invasive head and neck carcinomas.
Schaefer FK, Kurz B, Schaefer PJ, Fuerst M, Hedderich J, Graessner J, Schuenke M, Heller H.
Accuracy and precision in the detection of articular cartilage lesions using magnetic resonance imaging at 1.5 Tesla in an in vitro study with orthopedic and histopathologic correlation.Acta Radiol,
48 (2007), 1131-7.
[abstract]
Abstract:
BACKGROUND: Magnetic resonance (MR) sequences for cartilage visualization have been the target of numerous studies, and the optimal sequence for cartilage imaging remains a matter of debate in the literature. PURPOSE: To compare MR findings with different MR sequences for the detection of cartilage lesions in fresh deep-frozen human cadaveric patellae in an in vitro setting. MATERIAL AND METHODS: Ten cadaveric patellae were imaged on a 1.5T MR scanner with a 2x2 channel carotid sandwich coil and a conventional knee coil, and compared with orthopedic findings and gold-standard histopathology. MR sequences were: a) fat-saturated (FS) proton density-weighted (PDw) turbo spin-echo (TSE) sequence (TR/TE 4000/39 ms); b) T2-weighted (T2w) double-echo steady-state (DESS) 3D water-excitation (we) sequence (TR/TE 17/4.7 ms); c) 3D-PDw-SPACE (sampling perfection with application-optimized contrasts using different flip-angle evolutions)-we sequence (TR/TE 1800/19 ms). Accuracy, Kendall's tau-b correlation, and weighted kappa coefficients were calculated. RESULTS: Accuracy for cartilage lesion detection with the FS PDw-TSE sequence and the carotid coil was 78.3%, and with the knee coil 73.9%. For the T2wDESS-3D-we sequence, the corresponding values were 69.5% and 65.2%, and for the 3D-PDw-SPACE-we sequence 65.2% and 60.8%, respectively. Kendall's tau-b correlation ranged between 0.508 for the 3D-PDw-SPACE-we sequence (knee coil) and 0.720 for the FS PDw-TSE sequence (carotid and knee coil). Weighted kappa coefficient was lowest for the 3D-PDw-SPACE-we sequence (knee coil) at 0.607, and highest for the carotid coil and FS PDw-TSE sequence at 0.779. CONCLUSION: The evaluated FS PDw-TSE sequences are superior in comparison to the T2wDESS-3D-we and 3D-PDw-SPACE-we sequences in the in vitro setting for the detection of cartilage lesions, and are comparable to results reported in the literature.
Schaefer PJ, Jahnke T, Schaefer FK, Hedderich J, Hinrichsen H, Heller M, Müller-Hülsbeck S.
[Transjugular intrahepatic portosystemic shunt: evaluation of the impact of the stent's configuration on the patency rate].Rofo,
179 (2007), 965-70.
[abstract]
Abstract:
PURPOSE: To evaluate the impact of the configuration of the stent on the patency rate after transjugular intrahepatic portosystemic shunt with a self-expanding stent. MATERIALS AND METHODS: In total, 80 patients (60 male, 20 female; mean age 56 +/- 9.6, range 37 - 81) with a transjugular intrahepatic portosystemic shunt were evaluated. The primary technical success rate, interventional revision rate, and mean patency rate according to Kaplan-Meier were calculated. The angle of deviation of the blood flow at the portal venous inflow and central venous outflow were measured on projected angiograms (valid cases, n = 78). The following five angle groups were established: 1. portal venous inflow, 2. central venous outflow, 3. maximum, angle, 4. minimum angle, and 5. sum of both angles in the shunt system. Within each group, the Mann-Whitney Test and after dichotomic partition using the median Pearson's Chi-Square Test and Fisher's Exact Test were carried out to prove the dependency of the patency on the stent's configuration. RESULTS: The primary technical success rate was 93 %, the interventional revision rate was 28 %, and the mean patency rate was 17.5 months. The mean/standard deviation/median angle were as follows: 1. portal venous inflow 66.5 degrees / 19.2 degrees / 65 degrees , 2. central venous outflow 43.7 degrees / 14.0 degrees / 40 degrees , 3. maximum angle 69.1 degrees / 16.3 degrees / 65 degrees , 4. minimum angle 40.6 degrees / 13.3 degrees / 40 degrees , and 5. sum of both angles 110.2 degrees / 21.8 degrees / 110 degrees . The 2-sided values of significance in the Mann-Whitney Test/Chi-Square Test/Exact-Fisher Test were as follows: 1. portal venous inflow 0.112 / 0.066 / 0.083, 2. central venous outflow 0.960 / 0.919 / 1.000, 3. maximum angle 0.151 / 0.042 / 0.056, 4. minimum angle 0.578 / 0.622 / 0.632, and 5. sum of both angles 0.104 / 0.111 / 0.140. CONCLUSION: The shunt's patency rate when using a self-expanding stent is not dependent on the stent's configuration regarding the deviation of the blood flow at the portal venous inflow and central venous outflow, and the maximum, minimum and total deviation in the shunt.
Ufer M, Meyer SA, Junge O, Selke G, Volz HP, Hedderich J, Gleiter CH.
Patterns and prevalence of antidepressant drug use in the German state of Baden-Wuerttemberg: a prescription-based analysis.Pharmacoepidemiol Drug Saf,
16 (2007), 1153-60.
[abstract]
Abstract:
PURPOSE: Population-based data about patterns and prevalence of antidepressant drug use is limited in Europe and presently unavailable for Germany. Therefore, we have identified patterns and prevalence of antidepressant use among outpatients on a population-based scale in the German state of Baden-Wuerttemberg. METHODS: We conducted a historical cohort study using a computerised prescription database referring to all members of the major German public health insurance company AOK. We assessed the prevalence of antidepressant drug use over a 3-year period, calculated the number of prescription items purchased per patient and compared first-line and second-line treatments. RESULTS: The 1-year prevalence of antidepressant drug use among more than 4,000,000 health insurance members was 7.4% (male: 4.3%; female: 10.2%). Importantly, almost 40% of the patients received only a single prescription item from 2000 to 2002. Though the use of serotonin-reuptake inhibitors (SSRIs) markedly increased by about 65% within the study period, these are primarily used as second-line drugs and still much less frequently than St. John's wort or tricyclic antidepressants such as amitryptiline or doxepin. CONCLUSIONS: The prevalence of antidepressant drug use is higher than previously reported for other European countries. The preferred use of St. John's wort and tricyclics over SSRIs and other modern-type antidepressants in Germany is quite unique in Europe and different from the US. The identified drug use pattern leaves a major room for improvement in view of the numerous single prescription items purchased.
Müller-Hülsbeck S, Gühne A, Tsokos M, Hüsler EJ, Schaffner SR, Paulsen F, Hedderich J, Heller M, Jahnke T.
Stent-protected carotid angioplasty using a membrane stent: a comparative cadaver study.Cardiovasc Intervent Radiol,
29 (2006 Jul-Aug), 630-6.
[abstract]
Abstract:
PURPOSE: To evaluate the performance of a prototype membrane stent, MembraX, in the prevention of acute and late embolization and to quantify particle embolization during carotid stent placement in human carotid explants in a proof of concept study. METHODS: Thirty human carotid cadaveric explants (mild stenoses 0-29%, n = 23; moderate stenoses 30-69%, n = 3; severe stenoses 70-99%, n = 2) that included the common, internal and external carotid arteries were integrated into a pulsatile-flow model. Three groups were formed according to the age of the donors (mean 58.8 years; sample SD 15.99 years) and randomized to three test groups: (I) MembraX, n = 9; (II) Xpert bare stent, n = 10; (III) Xpert bare stent with Emboshield protection device, n = 9. Emboli liberated during stent deployment (step A), post-dilatation (step B), and late embolization (step C) were measured in 100 microm effluent filters. When the Emboshield was used, embolus penetration was measured during placement (step D) and retrieval (step E). Late embolization was simulated by compressing the area of the stented vessel five times. RESULTS: Absolute numbers of particles (median; >100 microm) caught in the effluent filter were: (I) MembraX: A = 7, B = 9, C = 3; (II) bare stent: A = 6.5, B = 6, C = 4.5; (III) bare stent and Emboshield: A = 7, B = 7, C.=.5, D = 8, E = 10. The data showed no statistical differences according to whether embolic load was analyzed by weight or mean particle size. When summing all procedural steps, the Emboshield caused the greatest load by weight (p = 0.011) and the largest number (p = 0.054) of particles. CONCLUSIONS: On the basis of these limited data neither a membrane stent nor a protection device showed significant advantages during ex vivo carotid angioplasty. However, the membrane stent seems to have the potential for reducing the emboli responsible for supposed late embolization, whereas more emboli were observed when using a protection device. Further studies are necessary and warranted.
Grössner-Schreiber B, Herzog M, Hedderich J, Dück A, Hannig M, Griepentrog M.
Focal adhesion contact formation by fibroblasts cultured on surface-modified dental implants: an in vitro study.Clin Oral Implants Res,
17 (2006), 736-45.
[abstract]
Abstract:
A major consideration in designing dental implants is to create a surface that provides strong attachment of the implant to bone, connective tissue and epithelium. The aim of the present study was to examine the influence of different treatments of titanium (Ti) implant surfaces on focal adhesion contact (FAC) formation in fibroblast cultures. Human gingival fibroblasts were cultured on glass sheets and polished Ti discs with different surface coatings (applied by physical vapor deposition (PVD): Ti, titanium nitride (TiN), zirconium nitride (ZrN)) or on Ti discs with different surface topographies. For characterization of all surfaces, modified estimation of surface roughness and spacing parameter was carried out using a contact stylus profilometer. Contact angle measurements were carried out to calculate surface energy. Fibroblasts were prepared for transmission electron microscopy at day 3 after seeding, and the number of FACs and the ratio FAC/cellular cross-sections was determined at a length of 300 microm in ultrathin sections. To visualize the extracellular fibronectin and vitronectin molecules and the intracellular actin and vinculin in FAC areas, immunogold labeling was performed. The results revealed a strong correlation between the number of FACs and the surface roughness. The highest number of FACs and the majority of the immunogold-labeled intra- and extracellular matrix molecules were counted on surfaces with the lowest surface roughness: glass sheets coated with either Ti, TiN or ZrN (roughness average=0.03-0.1 microm). These surfaces appear to favor cellular attachment of human gingival fibroblasts and moreover in previous studies the hard coatings have been shown to reduce bacterial adhesion.
Falliner A, Schwinzer D, Hahne HJ, Hedderich J, Hassenpflug J.
Comparing ultrasound measurements of neonatal hips using the methods of Graf and Terjesen.J Bone Joint Surg Br,
88 (2006), 104-6.
[abstract]
Abstract:
In a prospective study, 232 neonates were examined sonographically using the methods of Graf and Terjesen. In order to determine the reproducibility of the methods, 50 hips were evaluated by two skilled examiners. In an inter-observer study, five physicians and five medical students evaluated 24 images, which were evaluated on ten occasions at two-weekly intervals by one of the authors. Statistical evaluation used the Bland-Altman approach.The neonates (110 females, 122 males) were less than four days old. The mean alpha angle was 62.4 degrees and mean femoral head cover was 55.4%. According to Graf's method, 1.3% of hips were pathological, compared with 4.1% according to Terjesen. Spearman's correlation coefficient between femoral head cover and alpha angles was 0.552. The Bland-Altman approach shows greater variation for femoral head cover than for alpha, if measured by experienced examiners. The Bland-Altman approach shows almost equal reproducibility for alpha and femoral head cover in the inter-observer test, but better repeatability for alpha in the intra-observer test.The Graf results relate better than Terjesen's to the well-known frequency of 1% to 2% hip dysplasia in the European population. Kappa statistics indicate a fair agreement between the two methods. Inter-observer evaluation shows an equal reproducibility of both methods, whereas intra-observer tests reveal better repeatability with Graf's method.
Warnke PH, Springer IN, Acil Y, Julga G, Wiltfang J, Ludwig K, Russo PA, Sherry E, Sivananthan S, Hedderich J, Terheyden H.
The mechanical integrity of in vivo engineered heterotopic bone.Biomaterials,
27 (2006), 1081-7.
[abstract]
Abstract:
Recent advances in tissue engineering have aroused interest in growth of heterotopic bone for the repair of skeletal defects. This study demonstrates an in vivo method in minipigs of engineering individual human-sized mandible replacements of heterotopic bone with a mechanical integrity similar to natural bone. Ten individualized mandible replacement scaffolds were created using computer-aided design (CAD) techniques. Five had a resorbable external scaffold made of polylactite mesh (test group 1) and five had had a non-resorbable external scaffold of titanium mesh (test group 2). The mesh scaffolds were loaded each with five BioOss blocks serving as internal scaffolds and 3.5 mg recombinant human Bone Morphogenetic Protein-7. The loaded mesh scaffolds were implanted into the latissimus dorsi muscles of five infant minipigs. After 6 weeks the mandible replacements were harvested. Core biopsy cylinders were taken from the replacements of both test groups and from the natural pig mandibles (control 1). Also, core biopsies from plain BioOss Blocks were gained (control 2). The core biopsy cylinders were loaded axially into a compression test device to evaluate the mechanical compression resistance. Additional specimen underwent histological examination. Both test groups resulted in successful bone induction with degrees of compression resistance [Test 1: 1.62 MPa (SD+/-0.73); Test 2: 1.51 MPa (SD+/-0.56)] statistically insignificant when compared to natural porcine mandibular bone [1.75 MPa (SD+/-0.69)]. This differed significantly from the much lower compression resistance seen in the unadulterated BioOss [0.92 MPa (SD+/-0.04)]. Following this, the in vivo engineered bone has a similar mechanical compression stability as natural bone.
Bein B, Hanss R, Hedderich J, Scholz J.
Heart rate variability and inflammation: correlation or coincidence?.Am J Cardiol,
98 (2006), 1298-9.
Kapischke M, Caliebe A, Tepel J, Schulz T, Hedderich J.
Open versus laparoscopic appendicectomy: a critical review.Surg Endosc,
20 (2006), 1060-8.
[abstract]
Abstract:
BACKGROUND: The benefit of laparoscopic appendicectomy remains unclear. We have analysed available randomised studies comparing laparoscopic and open appendicectomy regarding their clinical pitfalls and statistical relevance. METHODS: Thirty eight studies were analysed in terms of the following aspects: A. clinical problems (e.g., expertise of the surgeons, pre- and postoperative antibiotic treatment, definition of complications, blinding of outcomes) and B. statistical problems (e.g., definition of primary and secondary outcomes, power and sample size, statistical methods, confidence intervals, comparability of groups and studies). RESULTS: Most of the studies have clinical and statistical pitfalls. The most important pitfalls are the uncertain expertise of the operating surgeons, blinding, and the exploratory nature of the studies. Our analysis aims at giving useful information for the appraisal of existing studies and the conduct of further studies. It also gives some preliminary results. CONCLUSIONS: More than twenty years after Semm performed the first laparoscopic appendicectomy, it is necessary to clarify the superiority of laparoscopic or open appendectomy with well-defined, carefully designed randomised studies.
Müller-Hülsbeck S, Gühne A, Tsokos M, Hüsler EJ, Schaffner SR, Paulsen F, Hedderich J, Heller M, Jahnke T.
Stent-Protected Carotid Angioplasty Using a Membrane Stent: A Comparative Cadaver Study.Cardiovasc Intervent Radiol,
(2006).
[abstract]
Abstract:
PURPOSE: To evaluate the performance of a prototype membrane stent, MembraX, in the prevention of acute and late embolization and to quantify particle embolization during carotid stent placement in human carotid explants in a proof of concept study. METHODS: Thirty human carotid cadaveric explants (mild stenoses 0-29%, n = 23; moderate stenoses 30-69%, n = 3; severe stenoses 70-99%, n = 2) that included the common, internal and external carotid arteries were integrated into a pulsatile-flow model. Three groups were formed according to the age of the donors (mean 58.8 years; sample SD 15.99 years) and randomized to three test groups: (I) MembraX, n = 9; (II) Xpert bare stent, n = 10; (III) Xpert bare stent with Emboshield protection device, n = 9. Emboli liberated during stent deployment (step A), post-dilatation (step B), and late embolization (step C) were measured in 100 mum effluent filters. When the Emboshield was used, embolus penetration was measured during placement (step D) and retrieval (step E). Late embolization was simulated by compressing the area of the stented vessel five times. RESULTS: Absolute numbers of particles (median; >100 mum) caught in the effluent filter were: (I) MembraX: A = 7, B = 9, C = 3; (II) bare stent: A = 6.5, B = 6, C = 4.5; (III) bare stent and Emboshield: A = 7, B = 7, C.=.5, D = 8, E = 10. The data showed no statistical differences according to whether embolic load was analyzed by weight or mean particle size. When summing all procedural steps, the Emboshield caused the greatest load by weight (p = 0.011) and the largest number (p = 0.054) of particles. CONCLUSIONS: On the basis of these limited data neither a membrane stent nor a protection device showed significant advantages during ex vivo carotid angioplasty. However, the membrane stent seems to have the potential for reducing the emboli responsible for supposed late embolization, whereas more emboli were observed when using a protection device. Further studies are necessary and warranted.
Schaefer D, Meyer JE, Pods R, Pethe W, Hedderich J, Schmidt C, Maune S.
Endothelial and epithelial expression of eotaxin-2 (CCL24) in nasal polyps.Int Arch Allergy Immunol,
140 (2006), 205-14.
[abstract]
Abstract:
BACKGROUND: Nasal polyposis is mostly associated with eosinophilia of mucosal tissue. This points to the implication of CC chemokines in nasal eosinophilia. Recently the CC chemokine eotaxin-2 (CCL24) was identified. This study was initiated to localize the cellular source, analyze expression of mRNA, and quantify protein synthesis of CCL24. METHODS: Specimens of nasal inferior turbinates from controls and polypous tissue from patients suffering from chronic polypous sinusitis were collected. Furthermore, fibroblasts and epithelial cells were cultured. CCL24 protein was analyzed by immunohistochemistry and ELISA, expression of mRNA by SQ-RT-PCR. RESULTS: CCL24 was observed in endothelial and epithelial cells. Specimens from patients expressed significantly (>2fold) more CCL24 mRNA than controls. Fibroblasts and unstimulated cells did not express CCL24 mRNA. Upon stimulation with TNF-alpha, INF-gamma, IL-4, or costimulation with TNF-alpha and INF-gamma CCL24 mRNA was significantly enhanced (3.2-19.6%). In controls, fibroblast, and unstimulated cells CCL24 protein was below detection limit. Most polyps comprised significant amounts of CCL24 (mean 0.24 ng/mg). TNF-alpha, INF-gamma or IL-4 induced CCL24 protein (0.1-0.3 ng/ml) in epithelial cells. Costimulation with TNF-alpha and IL-4 (0.1-30 and 1-30 ng/ml, respectively) synergistically induced synthesis of CCL24 protein (0.18-0.31 ng/ml). CONCLUSION: In nasal polyps endothelial and epithelial cells are obviously the main source of CCL24, which was shown for transcription (mRNA) and production (protein) levels and was associated with diseases. Results gave evidence of CLL24- directed migration of cells from inside (the bloodstream) to the epithelial side (mucosa) in eosinophilic inflammatory diseases, e.g. nasal polyposis.
Priebe M, Müller-Hülsbeck S, Jahnke T, Charalambous N, Hedderich J, Heller M, Paulsen FP.
Influence of various cell-detachment solutions on endothelial cells after catheter abrasion for prosthesis colonization prior to implantation.J Biomed Mater Res A,
78 (2006), 399-406.
[abstract]
Abstract:
We (1) evaluated the effectiveness of different media on the detachment of endothelial cells (ECs) from a catheter brush (Cragg thrombolytic catheter system) that was previously used for endothelial cell abrasion in 10 cm human umbilical vein (HUV) segments; (2) tested the practicability of endovascular catheter brush abrasion followed by EC detachment from the catheter brush, in vitro culture of harvested ECs, and finally endothelialization of a prosthesis; and (3) analyzed the defect created by the catheter brush in HUV segments after endovascular catheter abrasion. Best results in detachment of ECs from the catheter brush were obtained with a mixture of phosphate-buffered saline + 1% human albumin. EC vitality was time-dependent in the collected HUV segments postdelivery. Harvested EC viability decreased from (26.28 +/- 5.76)% (0-3 h postdelivery) to (17.29 +/- 4.56)% (after 4-8 h). ECs were easily cultured ex vivo within 2-3 weeks; seeded on nitinol stents, they grew to confluency and formed a monolayer on the stent surface (determined by scanning electron microscopy - SEM). Histological and SEM analysis of HUV segments that had undergone previous catheter brush abrasion revealed slight disruption of the intima but intact subintimal layers. Our findings indicate an advantageous method of capturing and culturing primary ECs for gene therapy or for the analysis and diagnosis of certain blood vessel diseases, especially in cases in which endovascular intervention is performed anyway. Moreover, and of high relevance to the biomaterial field, theoretically the procedure could be used to endothelialze a prosthesis ex vivo for implantation into the patient from whom the ECs were harvested, to reduce the inherent thrombogenicity of the prosthesis.
Grössner-Schreiber B, Fetter T, Hedderich J, Kocher T, Schreiber S, Jepsen S.
Prevalence of dental caries and periodontal disease in patients with inflammatory bowel disease: a case-control study.J Clin Periodontol,
33 (2006), 478-84.
[abstract]
Abstract:
AIM: Previous reports suggest a higher incidence of dental caries in patients with inflammatory bowel disease (IBD) and similarities in the immunopathogenesis of IBD and periodontitis. This study assessed the prevalence of periodontal disease and caries in patients with IBD. METHODS: In the present case-control study, 62 patients seeking treatment of IBD and 59 matched healthy controls of a dental practice were clinically examined. Oral soft-tissue alterations, the decayed, missing and filled tooth surface (DMF-S) index, dentine caries, plaque index (PI), bleeding on probing (BOP), probing pocket depth (PPD) and clinical attachment loss (CAL) were evaluated in each patient and in the controls. RESULTS: Patients with IBD showed a significantly higher number of oral manifestations compared with controls. The DMF-S index showed no significant differences, but there was a significantly higher number of subjects with dentine caries in patients with IBD. The mean PPD in patients with IBD was 2.08 versus 2.23 mm in controls (p=0.014). Compared with controls, patients with IBD had more sites with CAL of at least 4 mm (81% versus 64% in controls, p=0.07) and 5 mm (63% versus 46%, p=0.07), respectively. CONCLUSIONS: The results of this case-control study demonstrate a higher frequency of dentine caries in patients with IBD but the periodontal findings showed no distinct differences between cases and controls.
Abukishe A, Brandt M, Hedderich J, Hirt S, Lentz S, Schäfer H, Walluscheck K, Cremer J, Bruhn HD.
[Mutation in factor II and factor V gene in patients with peripheral arterial occlusive disease].Hamostaseologie,
26 (2006), 197-200.
[abstract]
Abstract:
Mutations in factor-V- and factor-II-genes are correlated with an increased risk for venous thrombosis according to the literature. The significance of the mutations in factor- II- and factor-V-genes for the development of the peripheral arterial occlusive disease is not known. Therefore, we investigated the presence of these mutations in 152 patients with documented peripheral arterial occlusive disease and 318 controls without peripheral arterial occlusive disease with polymerase chain reaction (PCR). There was no association between factor-II-mutation and peripheral arterial occlusive disease. The factor-V-mutation, however, was increased in patients with peripheral arterial occlusive disease double fold (12 positive cases in 318 controls, 12 positive cases in 152 patients with peripheral arterial occlusive disease). The significance level was reached (p = 0.05) in statistical analysis but the result did not fall below the significance level as necessary to reach statistical significance (odds ratio 2.19). Nevertheless, from these data we have to discuss a biological relevance of factor-V-mutation in the pathogenesis of peripheral arterial occlusive disease.
Bein B, Hanss R, Hedderich J, Scholz J.
Heart rate variability and inflammation: correlation or coincidence?.Am J Cardiol,
98 (2006), 1298-9.
Hellmig S, Von Schöning F, Gadow C, Katsoulis S, Hedderich J, Fölsch UR, Stüber E.
Gastric emptying time of fluids and solids in healthy subjects determined by 13C breath tests: influence of age, sex and body mass index.J Gastroenterol Hepatol,
21 (2006), 1832-8.
[abstract]
Abstract:
BACKGROUND AND AIM: Disturbance of gastric emptying leads to a variety of symptoms. Furthermore, gastric motility disorders might play a role in the pathophysiology of functional dyspepsia. In previous studies 13C breath tests were validated as non-invasive tools in the measurement of gastric emptying time. So far, reliable reference values of healthy subjects are missing and the impact of constitutional traits (age, sex, body mass index [BMI]) needs to be clarified. METHODS: A study was conducted in 90 healthy individuals (45 men, 45 women) that assessed the correlation of parameters of gastric emptying (half gastric emptying time [T1/2] and time of fastest gastric emptying [T(lag)]) with age, sex and BMI for fluid and solid test meals by 13C breath tests. 100 mg of sodium acetate or sodium octanoate, respectively, were used as tracers. Breath probes were analyzed by non-dispersive infrared spectroscopy. RESULTS: The mean +/- SD of half gastric emptying time (T1/2) of a fluid test meal was determined to be 80.5 +/- 22.1 min and for T(lag) to be 40.3 +/- 10.2 min. However, the T1/2 and T(lag) of solid meals did not fit to normal distribution and thus median and percentiles were determined. The median time of T1/2 for solids was 127 min (25-75% percentiles: 112.0-168.3 min) and 81.5 min for T(lag) (25-75% percentiles: 65.5-102.0 min). No significant correlation was found between gastric emptying and age, sex or BMI. CONCLUSION: This is the first study to examine gastric emptying in an adequate number of healthy subjects by 13C breath tests. No significant correlation was found with age, sex and BMI. Although there is considerable standard deviation in gastric emptying time, these results may nevertheless serve as reference values for further studies.
Eberhard J, Eisenbeiss AK, Braun A, Hedderich J, Jepsen S.
Evaluation of selective caries removal by a fluorescence feedback-controlled Er:YAG laser in vitro.Caries Res,
39 (2005 Nov-Dec), 496-504.
[abstract]
Abstract:
AIM: To establish a fluorescence threshold level that could guide a therapeutic Er:YAG laser through a caries lesion to determine a therapeutic endpoint of caries removal. MATERIALS AND METHODS: A total of 65 extracted human teeth, 35 with dentine caries and 30 healthy, were used for this study. An Er:YAG laser system that emitted at a wavelength of 2.94 microm was used. The laser was equipped with a laser fluorescence feedback system, excitation wavelength 655 nm, to control the irradiation by the Er:YAG laser. The evaluated threshold levels of the fluorescence feedback system were 3, 7, 8, 10, 12, 15 and 20. After treatment the teeth were prepared for histological staining according to the method of Brown and Brenn for the identification of bacteria. The specimens were subjected to a quantitative evaluation of residual bacteria on the treated dentine surface. In addition, the internal fluorescence of dentine and potential fluorescence changes of dentine after laser irradiation were evaluated. Results: About 80% of the irradiated dentine surface showed residual bacteria with threshold levels of 20, 15, 12, and 10. Residual bacteria were not found with threshold levels of 7 and 3. The study revealed a significant increase in dentine fluorescence after laser irradiation. Conclusion: The results of the present in vitro study indicate that a fluorescence threshold level of 7 or 8 units can guide an Er:YAG laser to a complete removal of carious dentine.
Amm M, Hedderich J.
[Transpalpebral tonometry with a digital tonometer in healthy eyes and after penetrating keratoplasty].Ophthalmologe,
102 (2005), 70-6.
[abstract]
Abstract:
PURPOSE: The Goldmann applanation technique established itself as gold standard for clinical intraocular pressure (IOP) measurement. But the device measures by corneal touch and presupposes corneal conditions within a normal range. So precise determination of IOP is crucial in corneal disorders and after corneal surgery. This pilot study presents tonometry data of normal and postkeratoplasty eyes measured transpalpebrally with a digital tonometer in comparison to Goldmann tonometry.METHOD: The TGDc-01 tonometer is based on a ballistic principle of measurement. IOP was measured in 50 healthy eyes (group 1) and 40 eyes after penetrating keratoplasty (group 2) first by the TGDc-01 and after 3 minutes by Goldmann tonometry (Haag-Streit). Subjective refraction, keratometry and ultrasonic pachymetry were performed in all eyes. The IOP measurements in the postkeratoplasty eyes were done when corneal epithelium was fully closed and only a medium suture edema could be observed.RESULTS: The Pearson's product-moment correlation was r=0,46 for group 1 and 0,65 for group 2. Using the concordance correlation coefficient the value showed a reproducibility index of r(c)=0,44 in group 1 and r(c)=0,60 in group 2. Following the Bland-Altman-analysis 58% of the cases in group 1 had a difference between the two instruments of maximum 3 mmHg. In group 2, 53,5% of the eyes showed an absolute difference between Goldmann and TDGc-01 of 3 mmHg or less.CONCLUSION: A transpalpebral measurement technique-avoiding corneal contact-seems to be an alternative choice in patients with corneal pathologies and after corneal surgery. The TGDc-01 tonometer provided mostly similar results compared to the Goldmann device, but with fluctuations. Keeping the deviations between the two methods in mind we recommend, however, the use of the transpalpebral approach only in combination with other techniques (palpation, indentation) to obtain enough reliability of IOP information in problem eyes.
Kahlke V, Leutert J, Schafmayer C, Wolfrum F, Hedderich J, Schütze S, Steinmann J, Kremer B.
Importance of Lipopolysaccharide-Binding-Protein (LBP) for diagnosis of infectious complications following abdominal surgery..Surg Infect,
6 (2005), 155.
Jahnke T, Schäfer FK, Bolte H, Rector L, Schäfer PJ, Brossmann J, Fändrich F, Hedderich J, Heller M, Müller-Hülsbeck S.
2005 Dr. Gary J. Becker Young Investigator Award: periprocedural oral administration of the leflunomide analogue FK778 inhibits neointima formation in a double-injury rat model of restenosis.J Vasc Interv Radiol,
16 (2005), 903-10.
[abstract]
Abstract:
PURPOSE: To test the efficacy of limited oral administration of the new leflunomide analogue FK778 for suppression of neointima proliferation in a double-injury restenosis model in the rat. MATERIALS AND METHODS: For induction of aortic lesions, silicon cuffs were placed operatively around the infrarenal aortas of Lewis rats. After 21 days, the aortic cuffs were removed and the lesions were dilated with 2-F Fogarty catheters inserted via the left common carotid artery. The novel immunosuppressant FK778 was administered at a dose of 5 mg/kg body weight (group 1) or 15 mg/kg body weight (group 2) in a total of 38 animals. For both doses, three different periinterventional time periods, each with a 5-day course of oral FK778, were defined as follows: (i) days -2 to 2, (ii) days 1-5, and (iii) days 7-11, with six or seven rats in each group. After 3 weeks, intima/media ratios were assessed morphometrically and immunohistochemistry for quantification of intimal alpha-actin expression was performed. RESULTS: In both dose groups, there was a trend toward inhibition of neointima formation when the 5-day course of FK778 was started before or 1 day after the intervention. However, in the lower-dose group, inhibition of neointima was not statistically significant regardless of the time frame of treatment (groups 1a-c). With the higher dose, suppression of intimal hyperplasia was significant when FK778 was administered between days 1 and 5 after angioplasty (group 2b; P<.01). Expression of alpha-actin in the intima of FK778-treated rats was significantly reduced when the drug was started 2 days before angioplasty in group 1a (P<.05) or 1 day after angioplasty in both dosage groups (group 1b, P<.01; group 2b, P<.05). CONCLUSION: In the double-injury rat model presented, balloon-mediated proliferation of smooth muscle cells in the intima with consecutive intimal thickening was influenced by FK778 in a dose-dependent manner. However, long-term studies are needed to exclude a delay of vascular healing in this particular model.
Salmassi A, Schmutzler AG, Schaefer S, Koch K, Hedderich J, Jonat W, Mettler L.
Is granulocyte colony-stimulating factor level predictive for human IVF outcome?.Hum Reprod,
20 (2005), 2434-40.
[abstract]
Abstract:
BACKGROUND: We investigated granulocyte colony-stimulating factor (G-CSF) in human reproduction. METHODS: From a total sample of 93 patients, we analysed in group 1 (n = 82) the level of G-CSF and estradiol (E(2)) in serum and follicular fluid (FF) on day of follicular puncture (FP). Furthermore, in response to ovarian stimulation, G-CSF levels in serum were compared between low (n = 11), moderate (n = 53) and high (n = 18) response patients. In group 2 (n = 23) serum for G-CSF assessment was collected throughout menstrual cycle until gestation. Group 3 (n = 11) patients with endometriosis were assessed for G-CSF in serum and FF on day of FP without further differentiation. RESULTS: G-CSF in FF was higher than in serum (P < 0.01). G-CSF in serum increased from low through moderate to high response (P < 0.001); pregnancy rates were 0, 24.5 and 33.5% respectively. G-CSF in serum increased throughout stimulation, reached a peak with ovulation induction (P = 0.01) and decreased until embryo transfer (P=0.001). G-CSF level only in pregnant patients (n = 11) increased from embryo transfer to implantation to gestation (P = 0.005). In endometriosis patients G-CSF in serum and FF was lower than in non-endometriosis patients (P < or = 0.03) and corresponded with low response patients. CONCLUSIONS: G-CSF is involved in follicle development and may be a predictor of IVF outcome.
McCune CA, Ravine D, Carter K, Jackson HA, Hutton D, Hedderich J, Krawczak M, Worwood M.
Iron loading and morbidity among relatives of HFE C282Y homozygotes identified either by population genetic testing or presenting as patients.Gut,
(2005).
[abstract]
Abstract:
BACKGROUND AND AIMS: Although most cases of hereditary haemochromatosis are associated with homozygosity for the C282Y mutation of the HFE gene, the clinical penetrance varies and other genes may modify disease expression. If so, relatives from clinically affected families, by inheriting such genes, may accumulate more iron. To seek evidence for this, we compared iron status and morbidity in unselected first- degree relatives of two groups of index cases from South Wales, namely asymptomatic C282Y homozygotes identified by genetic screening of blood donors (n=56) and C282Y homozygous haemochromatosis patients presenting clinically (n=60). METHODS: All participating relatives had a structured interview, clinical assessment and laboratory investigations. Health-related quality of life was measured (SF-36 v2). RESULTS: 92% of 180 eligible first-degree relatives were interviewed in the "screened" family group and 85% of 143 eligible relatives in the "patient" group. Of 59 relatives homozygous for C282Y, 76% of the men and 32% of the women had the "iron phenotype" (raised transferrin saturation and serum ferritin). Logistic regression modelling of the iron phenotype risk showed that 42% of the initial model deviance could be explained by homozygosity for C282Y, another 6% by life style factors and 6 % by being male. Family group membership was not a significant risk factor. Morbidity and SF-36 scores did not differ significantly either between C282Y homozygotes and relatives lacking C282Y, or between C282Y homozygotes from the "screened" and "patient" groups. Serious morbidity (including cirrhosis) was low in both groups of relatives. CONCLUSIONS: HFE C282Y homozygosity has a high penetrance for iron accumulation but a low clinical penetrance. The lack of excess morbidity among C282Y homozygous relatives of index cases who presented clinically suggests that residual unknown genetic or environmental factors do not greatly influence clinical outcome among C282Y homozygotes.
Fraund S, Herrmann G, Witzke A, Hedderich J, Lutter G, Brandt M, Böning A, Cremer J.
Midterm follow-up after minimally invasive direct coronary artery bypass grafting versus percutaneous coronary intervention techniques.Ann Thorac Surg,
79 (2005), 1225-31.
[abstract]
Abstract:
BACKGROUND: Revascularization of the left anterior descending coronary artery can be performed by minimally invasive direct coronary artery bypass grafting (MIDCAB) or percutaneous coronary intervention techniques (PCI). The study compared the midterm results of both techniques. METHODS: The outcome of 206 consecutive MIDCAB and 256 PCI patients treated from 1998 until 2001 was retrospectively analyzed. Cardiologists determined the primary patient allocation for the distinct revascularization technique. Periprocedural complications and midterm follow-up, including quality-of-life assessment (SF-36), was reported up to 5.2 years (3.4 +/- 0.7 years). RESULTS: Periprocedural and overall mortality (p = 0.206) showed no differences. Four MIDCAB patients required early reoperation but not for repeated target vessel revascularization. In 16 patients secondary PCI (7.8%) of other coronary vessels was performed. Repeated revascularization of the left anterior descending coronary artery was necessary in 24.2% of patients in the PCI group (p < 0.001), with 4.7% finally requiring surgical revascularization. The incidence of major adverse cardiac events, including myocardial infarction (p = 0.581), repeated target vessel revascularization (p < 0.001), or death (p = 0.206) was higher in the PCI group. This difference consisted basically of the need for repeated target vessel revascularization. Patient-based quality-of-life assessment (SF-36) was independent from the primary chosen revascularization method. CONCLUSIONS: At midterm follow up, MIDCAB resulted in significantly superior results regarding the need for repeated target vessel revascularization compared with PCI, with no significant differences regarding other major cardiac events.
Petersen W, Braun C, Bock W, Schmidt K, Weimann A, Drescher W, Eiling E, Stange R, Fuchs T, Hedderich J, Zantop T.
A controlled prospective case control study of a prevention training program in female team handball players: the German experience.Arch Orthop Trauma Surg,
125 (2005), 614-21.
[abstract]
Abstract:
BACKGROUND: Few authors have investigated the effectiveness of preventive intervention in European team handball. PURPOSE: The aim of the present study was to evaluate the effects of a prevention program on the incidence of injuries in female European team handball players. STUDY DESIGN: Prospective controlled study. METHODS: Ten female handball teams (134 players) took part in the prevention program (1. Information about injury mechanism, 2. Balance-board exercises, 3. Jump training) while 10 other teams (142 players) were instructed to train as usual. Over one season all injuries were documented weekly. RESULTS: Ankle sprain was the most frequent diagnosis in both groups with 11 ankle sprains in the control group and 7 ankle sprains in the intervention group (Odds ratio: 0.55, 95% confidence interval: 0.22-1.43). The knee was the second frequent injury site. In the control group 5 of all knee injuries were anterior cruciate ligament (ACL) ruptures (incidence: 0.21 per 1000 h) in comparison with one in the intervention group (incidence: 0.04 per 1000 h). Odds ratio was 0.17 with 95% confidence interval of 0.02-1.5. CONCLUSIONS: This study confirms that proprioceptive and neuromuscular training is appropriate for the prevention of knee and ankle injuries among female European team handball players.
Valeva A, Walev I, Boukhallouk F, Wassenaar TM, Heinz N, Hedderich J, Lautwein S, Möcking M, Weis S, Zitzer A, Bhakdi S.
Identification of the membrane penetrating domain of Vibrio cholerae cytolysin as a beta-barrel structure.Mol Microbiol,
57 (2005), 124-31.
[abstract]
Abstract:
Vibrio cholerae cytolysin (VCC) is an oligomerizing pore-forming toxin that is related to cytolysins of many other Gram-negative organisms. VCC contains six cysteine residues, of which two were found to be present in free sulphydryl form. The positions of two intramolecular disulphide bonds were mapped, and one was shown to be essential for correct folding of protoxin. Mutations were created in which the two free cysteines were deleted, so that single cysteine substitution mutants could be generated for site-specific labelling. Employment of polarity-sensitive fluorophores identified amino acid side-chains that formed part of the pore-forming domain of VCC. The sequence commenced at residue 311, and was deduced to form a beta-barrel in the assembled oligomer with the subsequent odd-numbered residues facing the lipid bilayer and even-numbered residues facing the lumen. Pro328/Lys329 were tentatively identified as the position at which the sequence turns back into the membrane and where the antiparallel beta-strand commences. This was deduced from fluorimetric analyses combined with experiments in which the pore was reversibly occluded by derivatization of sulphydryl groups with a bulky moiety. Our data support computer-based predictions that the membrane-permeabilizing amino acid sequence of VCC is homologous to the beta-barrel-forming sequence of staphylococcal cytolysins and identify the beta-barrel as a membrane-perforating structure that is highly conserved in evolution.
Müller-Hülsbeck S, Stolzmann P, Liess C, Hedderich J, Paulsen F, Jahnke T, Heller M.
Vessel wall damage caused by cerebral protection devices: ex vivo evaluation in porcine carotid arteries.Radiology,
235 (2005), 454-60.
[abstract]
Abstract:
PURPOSE: To determine the extent of vessel wall damage caused by cerebral protection devices designed for carotid angioplasty by using ex vivo porcine carotid arteries. MATERIALS AND METHODS: The local animal experimentation committee did not require its approval for this study. With a benchtop vascular model (flow rate, 470 mL/min; dicrotic pulsatile flow, 76 pulses per minute; pressure, 115/67 mm Hg [mean pressure, 91 mm Hg]) into which 85 porcine internal carotid arteries (ICAs) were inserted, five different protection devices (Angioguard [Cordis/Johnson & Johnson, Miami, Fla], Filterwire EX [Boston Scientific, Natick, Mass], Trap [Microvena, White Bear Lake, Minn], Neuroshield [Abbott Laboratories, Redwood City, Calif], and Percusurge [Abbott Laboratories]) were evaluated. Adverse movement (1 cm up, 2 cm down, and 1 cm up again) of the activated devices (deployed filters or inflated balloons [Percusurge only]) was simulated, and the device was retrieved. For each of these steps (deployment, movement, retrieval) the amount of debris from the vessel wall in the effluent of the ICA was determined by using a 100-microm filter. The Mann-Whitney test was used to test for differences, and a correction for multiple comparisons was made. P < .05 was considered to indicate a significant difference. The authors attempted to determine whether there was a notable association between the total amount of debris captured and the classification of damage at microscopy. Carotid arteries were analyzed histologically with light and scanning electron microscopy. RESULTS: All examined protection devices caused dislodged debris, which was captured in the effluent filter. There were significant differences among the devices in terms of the total amount of debris captured in the filters (lowest amounts of debris, 4.75 mg [Angioguard] and 5.02 mg [Filterwire EX]; highest amount, 7.51 mg [Trap]; P < or = .001 for all). All devices caused histologically visible wall damage, with the degree of intimal denudation correlating with the mass of the debris. The Trap device caused the most severe intimal and subintimal wall damage. Adverse movement resulted in no increased debris dislodgment as compared with the debris dislodged during deployment and retrieval of the devices. CONCLUSION: On the basis of the data obtained, cerebral protection devices themselves have a potential influence on embolization rates by causing debris to be dislodged during carotid stent placement.
Jepsen S, Ayna M, Hedderich J, Eberhard J.
Significant influence of scaler tip design on root substance loss resulting from ultrasonic scaling: a laserprofilometric in vitro study.J Clin Periodontol,
31 (2004), 1003-6.
[abstract]
Abstract:
OBJECTIVES: Ultrasonic scalers have become increasingly popular for subgingival debridement. The aim of the present study was to investigate the influence of different working tip designs (narrow versus wide) on root substance loss caused by either magnetostrictive or piezoelectric ultrasonic devices. METHODS: In this in vitro study, a magnetostrictive ultrasonic system with either Slimline or TFI-10 inserts and a piezoelectric ultrasonic system with either Perioprobe or Type-A inserts were compared at different application forces. Loss of root dentin was determined by defect width, defect depth and defect volume resulting from standardized instrumentation using laser profilometry. RESULTS: There were consistent and statistically significant differences between all groups. The mean observed dentin alterations for the magnetostrictive ultrasonic device operating a Slimline insert at a lateral force of 0.3 N were 254.4 microm, 6.3 microm and 22.5 microm3 and for the TFI-10 tip 759.0 microm, 23.5 microm and 160.2 microm3 for the parameters defect width, depth and volume, respectively. For the piezoelectric ultrasonic system operating a Perioprobe insert, the corresponding mean values were 352.0 microm/12.1 microm/56.4 microm3 and for the universal Type-A insert they were 402.4 microm/14.0 microm/133.4 microm3. With application forces of 0.7 N, root substance removal increased up to twofold. CONCLUSION: The present investigation could demonstrate that the aggressiveness of magnetostrictive and piezoelectric ultrasonic devices to root substance was significantly influenced by the scaler tip designs, increasing for wider scaler tips as compared with narrow, probe-shaped inserts.
Falliner A, Hahne HJ, Hedderich J, Brossmann J, Hassenpflug J.
Comparable ultrasound measurements of ten anatomical specimens of infant hip joints by the methods of Graf and Terjesen.Acta Radiol,
45 (2004), 227-35.
[abstract]
Abstract:
The fact that caudal tilts of the transducer are associated with reduced alpha angles and FHC values should be kept in mind in clinical ultrasound investigations. It is recommended that the transducer should be put on the greater trochanter perpendicular to the transverse axis of the body.
Salmassi A, Schmutzler AG, Huang L, Hedderich J, Jonat W, Mettler L.
Detection of granulocyte colony-stimulating factor and its receptor in human follicular luteinized granulosa cells.Fertil Steril,
81 Suppl 1 (2004), 786-91.
[abstract]
Abstract:
OBJECTIVE: To evaluate concentration of granulocyte colony-stimulating factor (G-CSF) in serum and follicular fluid (FF) at the time of oocyte retrieval and to detect expression of G-CSF and its receptor by luteinized granulosa cells (GCs). DESIGN: Collection of serum and FF at the time of oocyte retrieval. SETTING: A university IVF-ICSI program. PATIENT(S): Serum and FF were obtained from 82 women undergoing oocyte retrieval. INTERVENTION(S): Serum and FF were obtained from 82 women. Granulosa cells were pooled from 15 patients (three experiments with five patients each; 3-14 oocytes each). MAIN OUTCOME MEASURE(S): Granulocyte colony-stimulating factor concentration was determined by ELISA, the expression of G-CSF, and its receptor by the immunocytochemical technique and reverse transcriptase polymerase chain reaction analysis. Additionally, G-CSF expression was investigated by cell culture time course studies. RESULT(S): The median G-CSF level in FF (117.98 pg/mL) was significantly higher than that in serum (67.5 pg/mL). Granulocyte colony-stimulating factor and its receptor were expressed by GCs. CONCLUSION(S): The significantly higher level of G-CSF in FF than in serum and the expression of G-CSF and its receptor in FF by GCs suggest an important role for this growth factor in ovarian function.
Bein B, Worthmann F, Tonner PH, Paris A, Steinfath M, Hedderich J, Scholz J.
Comparison of esophageal Doppler, pulse contour analysis, and real-time pulmonary artery thermodilution for the continuous measurement of cardiac output.J Cardiothorac Vasc Anesth,
18 (2004), 185-9.
[abstract]
Abstract:
OBJECTIVE: Continuous measurement of cardiac output (CCO) is of great importance in the critically ill. However, pulmonary artery thermodilution has been questioned for possible complications associated with right heart catheterization. Furthermore, measurements are delayed in the continuous mode during rapid hemodynamic changes. A new pulmonary artery catheter CCO device (Aortech, Bellshill, Scotland) enabling real-time update of cardiac output was compared with 2 different, less-invasive methods of CCO determination, esophageal Doppler and pulse contour analysis. DESIGN: Prospective, observational study. SETTING: University hospital, single institution. PARTICIPANTS: Patients scheduled for elective coronary artery bypass grafting (CABG). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: CCO measurements were analyzed using a Bland-Altman plot. Bias between CCO and pulse contour cardiac output (PCCO), and Doppler-derived cardiac output (UCCO) was (mean +/- 1 SD) -0.71 +/- 1 L/min versus -0.15 +/- 1.09 L/min, and between UCCO and PCCO -0.58 +/- 1.06 L/min. Bias was not significantly different among methods, nor were comparative values before and after cardiopulmonary bypass (p > 0.05). CONCLUSIONS: Agreement between the CCO method and both less-invasive measurements was clinically acceptable. There were no adverse events associated with the use of either device.
Springer IN, Terheyden H, Geiss S, Härle F, Hedderich J, Açil Y.
Particulated bone grafts--effectiveness of bone cell supply.Clin Oral Implants Res,
15 (2004), 205-12.
[abstract]
Abstract:
OBJECTIVE: The objective of this study was to measure the amount of viable bone cells present in different types of bone graft. MATERIAL AND METHODS: Bone chips were harvested from the trabecular or cortical bone of the mandible or the iliac crest and either milled or not. The average size of unmilled bone particles was 5 x 5 x 5 mm and that of milled was 2 x 2 x 2 mm. Drill sludge was obtained using either a ball reamer, a diamond ball or an implant drill (the latter from mandibular bone and of average dimension 1 x 1 x 1 mm). A measure of 0.5 g of each category was cultured in Dulbecco's modified Eagle's medium with additives for four weeks. Cell counts were performed. An analysis of the osteocalcin synthesis, the alkaline phosphatase (ALP) activity, the collagen types and the concentration of bone-specific collagen cross-links in medium supernatants was performed. RESULTS: Cells stained positively for osteocalcin and ALP in all groups. Bone-specific collagen cross-links could be quantified and collagen of types I and V was present with no difference in all groups. Unmilled spongy bone chips revealed greater cell counts than milled (P<0.05). Spongy bone chips revealed greater cell counts than cortical bone chips (P<0.05). Drill sludge obtained by hard alloy ball reamer showed the least amount of viable cells (P<0.05). CONCLUSIONS: Bone milling reduces the quantity of osteoblasts. Bone obtained by the ball reamer supplies a smaller number of cells than bone obtained by other methods. Unmilled spongy bone chips appear to offer the greatest amount of viable osteoblasts.
Falliner A, Hahne HJ, Hedderich J, Brossmann J, Hassenpflug J.
Comparable ultrasound measurements of ten anatomical specimens of infant hip joints by the methods of Graf and Terjesen.Acta Radiol,
45 (2004), 227-35.
[abstract]
Abstract:
PURPOSE: To define which sonographic section planes relative to the acetabular inlet plane will produce analyzable images with the methods of Graf and Terjesen. MATERIAL AND METHODS: Anatomical specimens of infant hip joints were investigated in a water bath using the methods of Graf and Terjesen. Acetabular position was varied in defined increments with respect to the ultrasound beam. The alpha angles and the femoral head coverage (FHC) were measured. RESULTS: To obtain images analyzable by the two methods, the ultrasound beam had to intersect with the acetabular inlet plane at defined angles. The acetabular notch had to be anteriorly rotated from the ultrasound beam plane by at least 20 degrees. Beam entry within a 50 degrees sector posterior to the perpendicular on the inlet plane resulted in analyzable images. The stepwise multiple linear regression analysis showed that alpha angles and FHC were much affected by the coronal-plane transducer tilt. CONCLUSION: The fact that caudal tilts of the transducer are associated with reduced alpha angles and FHC values should be kept in mind in clinical ultrasound investigations. It is recommended that the transducer should be put on the greater trochanter perpendicular to the transverse axis of the body.
Sipos B, Hahn D, Carceller A, Piulats J, Hedderich J, Kalthoff H, Goodman SL, Kosmahl M, Klöppel G.
Immunohistochemical screening for beta6-integrin subunit expression in adenocarcinomas using a novel monoclonal antibody reveals strong up-regulation in pancreatic ductal adenocarcinomas in vivo and in vitro.Histopathology,
45 (2004), 226-36.
[abstract]
Abstract:
AIMS: To analyse the expression of alphavbeta6, an epithelial integrin involved in wound healing and tumorigenesis, in various human carcinoma types. METHODS AND RESULTS: A new monoclonal antibody to the human beta6 subunit, 5C4, was used to locate alphavbeta6 in 157 cancers of gastroenteropancreatic and 21 of lung origin. The data were validated by analysis of alphavbeta6 extracted from histological sections. Alphavbeta6 integrin showed strongest expression in 34 pancreatic ductal adenocarcinomas (mean score 2.88 +/- 0.52), followed by 24 intestinal-type gastric carcinomas (1.45 +/- 1.06) and eight lung adenocarcinomas (1.37 +/- 1.1). Moderate expression was found in 31 diffuse-type gastric carcinomas (0.94 +/- 0.83), seven duodenal adenocarcinomas (0.8 +/- 1.34) and 26 colorectal adenocarcinomas (0.76 +/- 0.71). Little alphavbeta6 was seen in seven liver cell carcinomas and six neuroendocrine tumours. Well-differentiated carcinomas expressed more beta6 than poorly differentiated tumours. Peritumoral epithelial tissues where alphavbeta6-expressing tumours arose also expressed alphavbeta6. There was no correlation between expression of alphavbeta6 and its ligands tenascin and fibronectin in pancreatic and gastric carcinomas. Spheroid formation by pancreatic carcinoma cell lines led to alphavbeta6 up-regulation, but appeared independent of classical ligand binding to alphavbeta6. CONCLUSIONS: Our findings indicate that: (i) alphavbeta6 is overexpressed in pancreatic adenocarcinomas; (ii) alphavbeta6-positive carcinomas originate from alphavbeta6-expressing tissues; (iii) alphavbeta6 expression in tumours seems to be regulated independently from that of its ligands tenascin and fibronectin; and (iv) in-vitro overexpression of alphavbeta6 in pancreatic carcinoma cell lines accompanies spheroid formation.
Zantop T, Welbers B, Weimann A, Rümmler M, Hedderich J, Musahl V, Petersen W.
Biomechanical evaluation of a new cross-pin technique for the fixation of different sized bone-patellar tendon-bone grafts.Knee Surg Sports Traumatol Arthrosc,
12 (2004), 520-7.
[abstract]
Abstract:
To overcome the disadvantages of interference-screw fixation of bone-patellar tendon-bone (BPTB) grafts, new fixation techniques for anterior cruciate ligament (ACL) grafts using biodegradable pins have been developed. The hypothesis of the present study was that cross-pin fixation techniques provide a primary stability that is comparable to that of interference screws. A biomechanical in vitro study was discussed. Human BPTB grafts of 8, 9 and 10 mm diameter were fixed in bovine knees with biodegradable cross pins (diameter: 2.0, 2.7 or 3.2 mm) or biodegradable interference screws. Stiffness and ultimate load were evaluated. For 9 and 10 mm BPTB grafts, no statistically significant difference in maximum load and stiffness was found between the four fixation techniques tested. For 8 mm bone blocks the maximum load of the 3.2 mm pins (274.2 N) was significantly lower than for the 2.0 mm pins (479.8 N) and the interference screws (504.0 N). Predominant failure mode in this group was bone-block fracture. Thicker grafts (9 and 10 mm) fixed with the 2.0 mm pins predominantly failed by implant fracture. Femoral fixation of 8, 9 and 10 mm BPTB grafts using cross pins leads to biomechanical properties that are comparable to biodegradable interference screws when tested by a single-cycle load to failure. Cross pins provide a rigid fixation for 9 and 10 mm BPTB grafts.
Müller-Hülsbeck S, Dimitte DN, Jahnke T, Hedderich J, Grimm J, Heller M.
[In-vitro comparison of the effectiveness of different high-speed rotatory catheters].Rofo,
175 (2003), 406-12.
[abstract]
Abstract:
OBJECTIVE: To determine the in vitro effectiveness of the Amplatz and Rotarex catheters for thrombus fragmentation and combined thrombus fragmentation and aspiration. MATERIALS AND METHODS: Clots (n = 100) from 5-day-old porcine blood (8.5 g) were fragmented with the 8F Rotarex trade mark catheter (RR; 40.000 rpm), which was directed with or without a coaxial guide wire (GW 0.020 inch [8 F RR(GW)], GW 0.014 inch [6 F RR(GW)]), and with the 7 F Amplatz catheter (ATD; 150.000 rpm), in an artery flow model (pulsed flow of 700 ml/min) simulating the superficial femoral artery. To increase the wall adherence of the thrombus, an additional equal number of silicon tubes (with an inner diameter of 7 mm) were fitted inside with a metallic mesh (wall-adherent thrombus [WAT]; 6 F RR(WAT), 8 F RR(WAT), 6 F R(WAT-GW), 8 F RR(WAT-GW), ATD(WAT) ). The effluent was passed through a three-step filter system (10 to 1000 micro m; pressure gradient 35 mmHg). RESULTS: Highest effectiveness was found for 8 F RR (no remaining thrombus detectable) compared to 6 F RR (0.08 g) and ATD (0.07 g), with a p < 0.001 for both methods. The aspirated volume was significantly lower when 6 F and 8 F RR were used with a coaxial guide wire (p < 0.001). The total emboli rate for 8 F RR was significantly lower compared to ATD (p < 0.001). Even when working without a guide wire, 8 F RR caused the lowest proportion of emboli (depending on the modification 0.12 % to 1.76 %; compared to all p < 0.05). Emboli rates reached 7.99 % for 6 F RR (compared to all p < 0.001) and were maximal 5.61 % for ATD. CONCLUSIONS: The tested mechanical thrombectomy catheters have a high potential for in vitro thrombectomy with moderate performance differences. In contrast to the guidewire-directed Rotarex fragmentation-aspiration device, the ATD trade mark fragmentation catheter and prototype Rotarex 6 F catheter have a considerable peripheral embolization rate of particles larger than 1000 micro m, probably requiring additional measures for in vivo thrombectomy.
Horan M, Millar DS, Hedderich J, Lewis G, Newsway V, Mo N, Fryklund L, Procter AM, Krawczak M, Cooper DN.
Human growth hormone 1 (GH1) gene expression: complex haplotype-dependent influence of polymorphic variation in the proximal promoter and locus control region.Hum Mutat,
21 (2003), 408-23.
[abstract]
Abstract:
The proximal promoter region of the human pituitary expressed growth hormone (GH1) gene is highly polymorphic, containing at least 15 single nucleotide polymorphisms (SNPs). This variation is manifest in 40 different haplotypes, the high diversity being explicable in terms of gene conversion, recurrent mutation, and selection. Functional analysis showed that 12 haplotypes were associated with a significantly reduced level of reporter gene expression whereas 10 haplotypes were associated with a significantly increased level. The former tend to be more prevalent in the general population than the latter (p<0.01), possibly as a consequence of selection. Although individual SNPs contributed to promoter strength in a highly interactive and non-additive fashion, haplotype partitioning was successful in identifying six SNPs as major determinants of GH1 gene expression. The prediction and functional testing of hitherto unobserved super-maximal and sub-minimal promoter haplotypes was then used to test the efficacy of the haplotype partitioning approach. Electrophoretic mobility shift assays demonstrated that five SNP sites exhibit allele-specific protein binding. An association was noted between adult height and the mean in vitro expression value corresponding to an individual's GH1 promoter haplotype combination (p=0.028) although only 3.3% of the variance of adult height was found to be explicable by reference to this parameter. Three additional SNPs, identified within sites I and II of the upstream locus control region (LCR), were ascribed to three distinct LCR haplotypes. A series of LCR-GH1 proximal promoter constructs were used to demonstrate that 1) the LCR enhanced proximal promoter activity by up to 2.8-fold depending upon proximal promoter haplotype, and that 2) the activity of a given proximal promoter haplotype was also differentially enhanced by different LCR haplotypes. The genetic basis of inter-individual differences in GH1 gene expression thus appears to be extremely complex.
Springer IN, Terheyden H, Dunsche A, Czech N, Suhr MA, Tiemann M, Hedderich J, Açil Y.
Collagen crosslink excretion and staging of oral cancer.Br J Cancer,
88 (2003), 1105-10.
[abstract]
Abstract:
Lysylpyridinoline (LP) and hydroxylysylpyridinoline (HP) are collagen crosslink residues of which the urinary concentration reflects the level of connective-tissue turnover. HP is ubiquitous in tissue, whereas LP is specific for bone. The purpose of this investigation was to assess the sensitivity and specificity of an increased urinary concentration of both HP and LP in indicating infiltration of mandibular bone by an oral squamous cell carcinoma (OSCC) or recurrence of the disease after successful therapy. We investigated the history and urine levels in 116 adult patients, who were divided into the following groups. Group 1: patients with OSCC with bone infiltration (n=17); group 2: patients with confirmed OSCC (n=12) without evidence of bone infiltration; group 3: patients with recurrence of an OSCC (n=13); group 4: patients without clinical evidence of disease (n=74). The range and upper limit of normal values (HP(max) and LP(max)) were measured from the normal controls in group 4. Levels of LP and HP were measured by HPLC and fluorescence detection. There was a significant difference in the average urinary levels of LP and HP between groups 1-4 (P<0.001). The presence of mandibular bone infiltration could be detected with a sensitivity and specificity of 100% when comparing groups 1 and 2. Presence of tumour tissue could be detected with a sensitivity of 90%. In conclusion, a normal LP concentration in patients with an OSCC strongly suggests that bone invasion by the disease has not taken place. If both urinary HP and LP are elevated, disease recurrence is highly likely.
Boening A, Friedrich C, Hedderich J, Schoettler J, Fraund S, Cremer JT.
Early and medium-term results after on-pump and off-pump coronary artery surgery: a propensity score analysis.Ann Thorac Surg,
76 (2003), 2000-6.
[abstract]
Abstract:
BACKGROUND: Comparative publications on beating-heart off-pump coronary artery bypass grafting (OPCAB) surgery versus conventional coronary artery bypass grafting (CCAB) surgery frequently do not offer conclusive information because of investigator bias. METHODS: Trying to eliminate this problem, a propensity score analysis of the data of all CCAB patients (n = 517) and OPCAB patients (n = 133) operated on by the same surgeons during the same time period (1998 to 2001) was applied. After matching patients with similar propensity score values, 97 CCAB patients and 72 OPCAB patients entered the final analysis. RESULTS: Early results were similar in both groups: the 30-day mortality reached 1.4% in the CCAB group and 2.8% in the OPCAB group; strokes did not happen. Perioperative myocardial infarctions occurred in 4.1% of the CCAB patients and 4.3% of the OPCAB patients. Drainage blood loss in the first 24 hours after surgery (830 +/- 687 mL, CCAB group; and 909 +/- 678 mL, OPCAB group) was similar (p = 0.06) in both groups. Medium term results (freedom from percutaneous transluminal coronary angioplasty or reoperation, freedom from myocardial infarction, freedom from stroke, and the quality of life) also were not significantly different between the off-pump and on-pump groups after a mean follow-up of 27 +/- 11 months. CONCLUSIONS: Our results suggest that elective-surgery patients with coronary artery disease can be operated on either on-pump or off-pump with the same early and late mortality and morbidity.
Ayub M, Thale AB, Hedderich J, Tillmann BN, Paulsen FP.
The cavernous body of the human efferent tear ducts contributes to regulation of tear outflow.Invest Ophthalmol Vis Sci,
44 (2003), 4900-7.
[abstract]
Abstract:
PURPOSE: To test the hypothesis that the surrounding vascular plexus of the lacrimal sac and the nasolacrimal duct contributes to the regulation of tear outflow. METHODS: Experiments in 30 probands aged between 15 and 37 years were performed in both nasolacrimal systems of each subject by observing with an endoscope the transit time of an applied tear drop containing fluorescein dye until its entry into the inferior meatus of the nose. Four different experiments were performed to determine the median transit time under normal conditions and the influence on transit time of a decongestant drug, a foreign body on the ocular surface, and a decongestant drug applied together with a foreign body on the ocular surface. Comparisons were made between the right and left nasolacrimal system, in males and females, eyeglass wearers and non-eyeglass wearers, and the different experiments and the results statistically analyzed. RESULTS: The tear transit time was independent of side (right or left), gender, or eyeglass wear. It showed great individual variability. Application of a decongestant drug or placement of a foreign body on the ocular surface both prolonged the dye transit time significantly. Application of a decongestant drug simultaneously with placement of a foreign body shortened the dye transit time significantly compared with the effect of the decongestant drug alone but revealed no significant difference compared with application of a foreign body alone. CONCLUSIONS: The cavernous body of the lacrimal sac and nasolacrimal duct plays an important role in the physiology of tear outflow regulation. It is subject to autonomic control and is integrated into a complex neuronal reflex feedback mechanism starting with the dense innervation of the cornea. Moreover, its function can be pharmacologically influenced.
Açil Y, Springer I, Behrens P, Ullrich KP, Hedderich J, Bruns J.
Differential enhancement of collagen crosslink excretion in cases of osteosarcoma and chondrosarcoma.J Cancer Res Clin Oncol,
129 (2003), 583-8.
[abstract]
Abstract:
Hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP) are markers of collagen absorption and LP is specific for collagen type I in bone. In the present study we evaluated the concentration of HP and LP in urine of patients with osteosarcoma ( n=20; age range 16-49 years) and chondrosarcoma ( n=15; age range 18-70 years). The values were compared with those obtained from 74 healthy controls (age range 16-83 years). The range and upper limit of normal values (HP(max) and LP(max)) were measured in our control group. High performance liquid chromatography (HPLC) was used to determine concentrations of HP and LP (nmol/mmol creatinine). The average urinary HP concentrations were significantly increased in patients with osteosarcoma ( p=0.001) and chondrosarcoma ( p<0.001), whereas HP remained within the normal range in approximately half of the patients. The average urinary LP concentrations were not increased in osteosarcoma and chondrosarcoma patients as compared with the control group. Further studies in a large group of patients are necessary to evaluate whether HP might be a valuable marker of prognosis, and if its urinary concentration can be correlated to tumour burden.
Jepsen S, Eberhard J, Fricke D, Hedderich J, Siebert R, Açil Y.
Interleukin-1 gene polymorphisms and experimental gingivitis.J Clin Periodontol,
30 (2003), 102-6.
[abstract]
Abstract:
BACKGROUND: Recently, an association between the severity of periodontitis and specific variations in the interleukin-1 (IL1) alpha and beta genes has been demonstrated. AIM: : The purpose of this study was to evaluate the relationship of the IL1 genotype to the development of experimental gingivitis. MATERIALS AND METHODS: Twenty young adult subjects presenting with healthy gingival conditions participated after giving their informed consent. The group included 10 risk genotype positive (P+) and 10 risk genotype negative (P-) individuals. The IL1 genotypes were determined on DNA samples from peripheral blood using PCR-RFLP analyses for the IL1alpha and IL1beta polymorphisms. Experimental gingivitis was allowed to develop in two posterior sextants per subject. Bleeding on probing (BOP%) and gingival crevicular fluid volume (GCF) were assessed at baseline and days 2, 7, 9, 14, 16 and 21. The day 21 results for BOP and GCF as well as the rate of increase of these parameters - mean area under the curve (AUC) and mean increase per day (slope) - were evaluated using risk analyses for IL1 genotype, smoking status and gender. RESULTS: Experimental gingivitis developed with a gradual increase in BOP scores and GCF values (expressed as Periotron units=PU) from baseline to day 21 (BOP, P+: 0.5 to 26.0%; P-: 1.0 to 28.1%; GCF, P+: 36.8 to 138.5 PU, P-: 43.1 to 143.4 PU). No significant risk was associated with P+ and P- for day 21 results, AUC or slope. CONCLUSION: The results of this study failed to provide evidence that the IL1 risk genotype was associated with higher GCF volume and percentage BOP during the development of experimental gingivitis.
Jepsen S, Springer IN, Buschmann A, Hedderich J, Açil Y.
Elevated levels of collagen cross-link residues in gingival tissues and crevicular fluid of teeth with periodontal disease.Eur J Oral Sci,
111 (2003), 198-202.
[abstract]
Abstract:
Lysylpyridinoline (LP) and hydroxylysylpyridinoline (HP) are collagen cross-link residues. Lysylpyridinoline is present in most tissues, whereas LP is present mainly in mineralized tissue. Both are elevated in tissue with increased collagen resorption. The purpose of this investigation was to assess if the concentrations of LP and HP are elevated in gingiva and gingival crevicular fluid (GCF) of teeth with advanced periodontitis (AP). We investigated human gingival biopsies of healthy teeth (n = 19) and teeth with AP (n = 43) in 49 individuals. Samples of GCF from 54 teeth with AP were collected in seven patients and compared with samples from 11 patients with experimentally induced gingivitis. Levels of LP and HP were measured by HPLC and fluorescence detection. Gingival concentrations of HP but not LP around teeth with advanced periodontitis were significantly elevated compared with teeth with healthy periodontium. While significant amounts of HP and LP were measurable in the GCF of teeth with AP, no HP and LP was identified 3 months following non-surgical periodontal therapy of the teeth or in fluid from teeth subjected to experimentally induced gingivitis. Elevated concentrations of HP and LP in GCF may serve as indicators of ongoing destruction of periodontal tissues and alveolar bone in advanced periodontitis.
Müller-Hülsbeck S, Grimm J, Liess C, Hedderich J, Bergmeyer M, Heller M.
Comparison and modification of two cerebral protection devices used for carotid angioplasty: in vitro experiment.Radiology,
225 (2002), 289-94.
[abstract]
Abstract:
The effectiveness of two basic cerebral protection devices designed for carotid angioplasty with and without additional aspiration techniques was compared in an in vitro model. During carotid angioplasty, embolization was simulated by injecting polyvinyl alcohol particles of different sizes into the model system. None of the tested devices, all of which were positioned in the internal carotid artery, was able to completely prevent embolization. In the internal carotid artery, the rate of particle capture did not vary among protection devices. However, embolization into the external carotid artery was more frequent with use of the GuideWire, as compared with that with use of the Angioguard.
Zhu XL, Hamel W, Schrader B, Weinert D, Hedderich J, Herzog J, Volkmann J, Deuschl G, Müller D, Mehdorn HM.
Magnetic resonance imaging-based morphometry and landmark correlation of basal ganglia nuclei.Acta Neurochir (Wien),
144 (2002), 959-69; discussion 968-9.
[abstract]
Abstract:
The two principle targets for deep brain stimulation or lesioning in patients with Parkinson's disease, the subthalamic nucleus (STN) and the globus pallidus internus (GPi), reveal a high degree of individual variability which is relevant to the planning of stereotactic operations. Both nuclei can clearly be delineated in T2WI spin echo MRI which was acquired under stereotactic conditions in general anesthesia before surgery. Such images of 35 patients served for retrospective morphometric analysis of different basal ganglia nuclei (STN, GP, red nucleus, and substantia nigra) and several anatomical landmarks (anterior and posterior commissure, maximum width of third ventricle, brain length and width). The average AC-PC distance was 25.74 mm (range 21 to 29 mm) and is in agreement with previous studies. On average, the center of the STN was located 12.65 mm (+/-1.3) lateral from the midline as determined 3 mm ventral to the intercommissural plane. The average width of the third ventricle was 7.05 mm (+/-2.41). The width of the third ventricle correlated with the laterality of the STN (r(right)=.78; r(left)=.83) and GP (r(right)=.76; r(left)=.68). Although to a lesser extent, significant correlations were also observed between the laterality of the STN and brain width, improving prediction of STN laterality by multiple linear regression analysis (r(right)=.82; r(left)=.87). Similarly, the laterality of GP correlated with brain width. In addition, gender-specific differences were detected. The STN and GP was located farther lateral in males which may be due to overall brain anatomy as gender-specific differences were also observed for brain width and length and AC-PC distance. MRI-based in vivo-localization of different basal ganglia nuclei extend statistical information from common histological brain atlases which are based on a limited number of brains. The correlations observed between different basal ganglia nuclei, i.e. the STN and GPi, and anatomical landmarks may be useful for surgical planning.
Cooper DN, Horan M, Millar DS, Hedderich J, Lewis G, Newsway V, Mo N, Fryklund L, Procter AM, Krawczak M.
Human growth hormone I gene expression is influenced in a complex haplotype-dependent fashion by polymorphic variation in both the proximal promoter and the locus control region.J Pediatr Endocrinol Metab,
15 Suppl 5 (2002), 1429.
Boening A, Scheewe J, Heine K, Hedderich J, Regensburger D, Kramer HH, Cremer J.
Long-term results after surgical correction of atrioventricular septal defects.Eur J Cardiothorac Surg,
22 (2002), 167-73.
[abstract]
Abstract:
OBJECTIVE: Review of the results of surgical correction of atrioventricular septal defects (AVSD), identification of risk factors for mortality and failure of left AV valve repair and determination of the impact of cleft closure on postoperative AV valve function. METHODS: Between 1975 and 1995, 121 consecutive patients (55 males, 66 females) underwent surgery for biventricular correction of AVSD with a median age of 1.2 years and a median weight of 7.6 kg. Sixty-five patients had a complete AVSD, 17 patients an intermediate type, and 39 patients a partial AVSD. The left AV valve (MV) cleft was closed in 53 patients (43.8%). The mean follow-up time is 7.2+/-4.6 years. RESULTS: Actuarial survival of the whole group after 1 year was 80%, after 10 and 20 years 78 and 65%, respectively. There were 18 early deaths (7-day mortality, 10.7%; 30-day mortality, 14.9%) and eight late deaths. In a univariate analysis, risk factors for early or late death were diagnosis of complete AVSD (P=0.006), no cleft closure (P=0.024), postoperative complications (P<0.0001), age <1.2 years (P=0.017), weight <7.6 kg (P=0.002), PA/Ao pressure ratio >0.7 (P<0.0001), and ECC time >110 min (P=0.002). In the multivariate analysis, postoperative complications (P=0.003) and PA/Ao pressure ratio >0.7 (P=0.001) had parallel effects on the postoperative risk for mortality. Moderate or severe MV regurgitation was present in six patients (6.0%) in the first evaluation after discharge and in 20 patients (20.4%) in the most recent postoperative control. There were 25 reoperations in 17 patients, of which 15 had to be performed for MV regurgitation and two for MV stenosis. Freedom from reoperation was 91% at 1 year, 79% at 10 years, and 76% at 15 and 20 years. We could not identify a statistically significant risk factor for reoperation. CONCLUSIONS: In patients with AVSD of various morphologies closure of the left AV valve cleft significantly improves outcome without affecting the need for reoperation. Risk factors for early and late death (multivariate analysis) were a pulmonary/aortic pressure ratio >0.7 and the occurrence of any complication after surgery. The concept of an early surgical AVSD correction before an increase in pulmonary vascular resistance and AV valve deformations occur would represent a better surgical option than a late correction as done in our series. Early correction allows for reduction of early mortality, superior long-term survival rates and a high freedom from subsequent valve degeneration.
Açil Y, Springer IN, Prasse JG, Hedderich J, Jepsen S.
Concentration of collagen cross-links in human dentin bears no relation to the individual age.Int J Legal Med,
116 (2002), 340-3.
[abstract]
Abstract:
Lysylpyridinoline (LP) and hydroxylysylpyridinoline (HP) are collagen cross-link residues. HP is present in most tissues, whereas LP is specific for bone and dentin. Based on the current literature there are certain indications that measurement of the concentrations of HP and LP in dentin may be a valuable tool to determine the individual age. The purpose of this investigation was to assess if the concentrations of LP and HP in dentin increase during lifetime. We have investigated 173 molars from 173 individuals (2 through 78 years of age, 31 primary and 142 secondary teeth) in the course of the present study. Levels of LP and HP were measured by HPLC and fluorescence detection. The results show that dentinal concentrations of HP and LP did not increase with age and varied between individuals of the same age and that determination of dentinal concentrations of HP and LP cannot be used to determine the individual age.
Kiechle M, Jacobsen A, Schwarz-Boeger U, Hedderich J, Pfisterer J, Arnold N.
Comparative genomic hybridization detects genetic imbalances in primary ovarian carcinomas as correlated with grade of differentiation.Cancer,
91 (2001), 534-40.
[abstract]
Abstract:
BACKGROUND: In the current study the authors attempted to evaluate genetic alterations in a large set of primary ovarian carcinomas and to compare the genetic findings with clinical parameters such as grade of tumor differentiation. This strategy was applied to identify chromosomal regions containing genes associated with tumor progression. METHODS: Genetic imbalances were assessed in 106 primary ovarian carcinomas using comparative genomic hybridization (CGH). CGH was applied because it is a powerful tool with which to screen the entire genome of a tumor for genetic changes by highlighting regions of altered DNA sequence copy numbers (deletions and amplifications). Multivariate statistical standard procedures were used to determine an association between tumor grading and genetic alterations. RESULTS: One hundred three carcinomas showed aberrant CGH profiles. The most frequent alterations were amplifications of 8q, 1q, 20q, 3q, and 19p, which occurred in 69-53% of tumors, and underrepresentations of 13q, 4q, and 18q, which occurred in 54-50% of tumors. Undifferentiated ovarian carcinomas (World Health Organization Grade 3) were found to be correlated significantly with underrepresentation of 11p and 13q as well as with overrepresentation of 8q and 7p (P = 0.001, 0.001, 0.01, and 0.027, respectively). However, 12p underrepresentation and 18p overrepresentation were significantly more frequent in well and moderately differentiated tumors (P = 0.01 and 0.004, respectively). To facilitate the interpretation and clinical application of the results of the current study, the significant aberrations were translated into a score system. This score system can be used easily for the prediction of an undifferentiated phenotype with a specificity and sensitivity of 79% and 86%, respectively. CONCLUSIONS: The current study data show that primary ovarian carcinomas are based on consistent genetic alterations that most likely are important for the development of this tumor entity. The correlation between certain aberrations and undifferentiated carcinomas may help to discriminate between primary and secondary genetic events and may indicate the location of those genes involved in cellular functions associated with tumor progression and the development of anaplastic and aggressive phenotypes.
Salmassi A, Lü S, Hedderich J, Oettinghaus C, Jonat W, Mettler L.
Interaction of interleukin-6 on human granulosa cell steroid secretion.J Endocrinol,
170 (2001), 471-8.
[abstract]
Abstract:
Numerous studies have shown that a variety of cytokines are involved in the regulation of ovarian function. Interleukin-6 (IL-6), has been found in follicular fluid. In this report we show by immunocytochemical methods the localization of the extracellular domain of the IL-6-receptor and its associated signal transducer glycoprotein gp 130 on the surface of granulosa cells (GCs). The possibility that IL-6 may also influence the basal and FSH-stimulated production of estradiol (E2) and progesterone (Prog) by GCs in vitro was also investigated. GCs were obtained from infertile patients undergoing in vitro fertilization and embryo transfer treatment and cultured for 72 h or were given increasing concentrations of human recombinant IL-6 (8--128 pg/ml) in the absence or presence of FSH (96 U/ml). For the time-course studies, FSH-stimulated GCs were treated in the absence or presence of IL-6 (128 pg/ml) and supernatants were assayed at 24 h intervals (24-96 h) for E2 and Prog productions. The results show that increasing amounts of IL-6 significantly inhibit E2 production in the absence or presence of FSH vs untreated controls (P=0.025 at IL-6=128 pg/ml and P=0.016 at IL-6=16 pg/ml respectively). IL-6 also inhibited FSH-stimulated but not unstimulated Prog release (P=0.038 at IL-6=8 pg/ml). These findings suggest that IL-6 may be one of the factors that plays a local regulatory role in the course of FSH-stimulated E2 and Prog release. The time-course studies of the effect of the absence or presence of IL-6 demonstrated a significant inhibitory effect on both E2 and Prog secretion (P<0.001) by FSH-stimulated GCs. As infections of the female reproductive tract are often accompanied by elevated local IL-6 levels, this factor may be one of the links leading to endocrine reproductive dysfunction during genital infections.
Boening A, Scheewe J, Paulsen J, Regensburger D, Kramer HH, Hedderich J, Cremer JT.
Tetralogy of Fallot: influence of surgical technique on survival and reoperation rate.Thorac Cardiovasc Surg,
49 (2001), 355-60.
[abstract]
Abstract:
BACKGROUND: The influence of different surgical techniques in patients with Tetralogy of Fallot (TOF) on long-term survival and reoperation rate is still a matter of controversy. PATIENTS AND METHODS: The data of 266 patients (152 male, 114 female, mean body weight: 13.4 +/- 11.9 kg, mean age 4.1 +/- 6.0 years) with TOF, including 30 patients (11.2 %) with TOF/pulmonary atresia, were analyzed retrospectively. A palliative surgical procedure preceded definite correction between 1975 and 1999 in 46 patients (17.5 %). The surgical technique consisted of a transannular patch in 103 patients (40.1 %); in 133 patients (51.8 %), a non-transvalvular technique was used. In 33 patients (12.3 %), a conduit was implanted into the right ventricular outflow tract (RVOT). For surgical access to the cardiac defects, a transventricular approach was used in 138 patients, and a transatrial/trans-pulmonary approach in 26 patients. The mean follow-up time of all patients was 6.6 years. RESULTS: Kaplan-Meier survival for the entire group was 86.2 % at one year and remained stable at 85.6 % after 5 years. The 30-day mortality was 10.1 % (27 patients). Fatal risk factors were: previous cardiac surgery, preoperative oxygen saturation (SO(2)) < 80 %, diagnosis of pulmonary atresia, prolonged aortic clamping or bypass time, postoperative infections, and early revisions. Freedom from reoperation was 91.6 % after 5, 84.5 % after 10, and 52.6 % after 20 years. There was no correlation between the different surgical techniques (transannular patch, non-transvalvular techniques, transventricular approach) applied and the mortality or the rate of reoperations. CONCLUSIONS: In our series of TOF patients operated over a period of 25 years, we were unable to assess an influence of the surgical technique used for definite correction on mortality or reoperation rate. Pulmonary atresia in patients with TOF is associated with a higher risk of death and reoperation.
Terheyden H, Lee U, Ludwig K, Kreusch T, Hedderich J.
Sterilization of elastic ligatures for intraoperative mandibulomaxillary immobilization.Br J Oral Maxillofac Surg,
38 (2000), 299-304.
[abstract]
Abstract:
Sterilization can influence the mechanical properties of elastic ligatures used for mandibulomaxillary immobilization. The aim of this study was to compare different sterilization protocols (ethylene oxide, autoclave, irradiation, plasma sterilization, povidone-iodine for 24 hours and 70% isopropyl alcohol for 24 hours) of three elastomers (natural rubber, silicone rubber, and polyurethane). Three mechanical variables were assessed in a testing machine: breaking strength, tensile strength and tensile strength after a 24-hour load (material fatigue). Natural rubber was most susceptible to mechanical alteration by sterilization and lost 46% of its breaking strength and 43% of its tensile strength after autoclaving. Polyurethane was more resistant (multiple comparison, Tukey-Kramer), but polyurethane ligatures stuck together after autoclaving. The protocols for low-temperature sterilization, ethylene oxide, irradiation, and plasma were superior to autoclaving and the disinfecting solutions. These data suggest that polyurethane sterilized with ethylene oxide is the material of choice.
Link S, Häring G, Hedderich J.
[Effect of phacoemulsification and posterior chamber lens implantation on intraocular pressure in patients with and without open-angle glaucoma].Ophthalmologe,
97 (2000), 402-6.
[abstract]
Abstract:
BACKGROUND: Many of the previous studies which dealt with the influence of cataract surgery on intraocular pressure, were performed retrospectively and based on heterogeneous groups of patients. Therefore, the purpose of our study was to prospectively assess the effect of phacoemulsification and posterior chamber intraocular-lens (IOL)-implantation on intraocular pressure (IOP) under standardized conditions in patients with and without open-angle-glaucoma. PATIENTS AND METHODS: Overall 52 patients were recruited for the study. 34 eyes with normal IOP and 16 eyes with open-angle-glaucoma were operated with the same technique. RESULTS: Mean IOP in patients with cataract and without glaucoma was preoperatively 15.1 mmHg. 6 months postoperatively these patients showed a mean decrease of IOP of 11.9% (1.8 mmHg +/- 3.8; p = 0.027); after 12 months IOP showed a decrease of 18.5% (2.8 mmHg +/- 3.5; p = 0.0001). In patients with glaucoma mean IOP was preoperatively 17.3 mmHg. IOP was reduced by 23.7% (4.1 mmHg +/- 6.0; p = 0.017) 6 months after cataract surgery and 22.6% (3.9 mmHg +/- 4.5; p = 0.005) 12 months after the operation. In 6 of 16 eyes the antiglaucoma medication could be suspended. CONCLUSION: Reduction of IOP is a positive side effect of phacoemulsification and posterior chamber IOL implantation and should be considered when indicating cataract surgery in patients with glaucoma and only slight elevation of IOP.
Lüttges J, Schemm S, Vogel I, Hedderich J, Kremer B, Klöppel G.
The grade of pancreatic ductal carcinoma is an independent prognostic factor and is superior to the immunohistochemical assessment of proliferation.J Pathol,
191 (2000), 154-61.
[abstract]
Abstract:
Tumour grade is one of the prognostic factors in pancreatic ductal adenocarcinoma, but its value is controversial. In this study, the predictive value and the reproducibility of the WHO grading system were reconsidered and the possibility of supplementing it with the immunohistochemically assessed proliferative activity was investigated. Seventy resected ductal adenocarcinomas of the head of the pancreas were evaluated. A total of 60 HPF fields on two to four sections per tumour were screened for glandular differentiation, mucin production, mitosis, and nuclear atypia by two observers with different degrees of experience. Each criterion was scored and the grade was calculated from the mean value of all single scores. Corresponding slides were immunohistochemically stained with the proliferation marker Ki-S5. The percentage of positive nuclei was assessed and a proliferation index (PI) assigned (<10%=1; 10-50%=2; >50%=3). Multivariate analysis (Cox regression) identified grade and R stage as the most significant factors for predicting survival. The PI determined on the basis of Ki-S5 staining did not prove to be an independent prognostic factor. In 30 of 70 carcinomas, it correlated with the tumour grade. Within a given tumour grade, the cases with the least favourable prognosis could be distinguished on the basis of their PI. The inter-observer variability was considerable, with the main differences occurring in the group of G1 tumours. According to the refined WHO criteria, the histopathological grade of pancreatic ductal carcinoma is an important independent prognostic factor, but reproducibility depends on the expertise of the observer. Criteria that relate to cellular and structural differentiation seem to be more predictive than those related to proliferation.
Bonatz G, Lüttges J, Hedderich J, Inform D, Jonat W, Rudolph P, Parwaresch R.
Prognostic significance of a novel proliferation marker, anti-repp 86, for endometrial carcinoma: a multivariate study.Hum Pathol,
30 (1999), 949-56.
[abstract]
Abstract:
Traditional prognostic factors often fail to identify a subgroup of endometrial carcinoma (EC) patients with an apparently paradoxical poor outcome. We therefore analyzed tumor cell proliferation immunohistochemically in a series of 164 endometrial carcinomas (EC) and compared its prognostic impact with that of the standard prognostic factors patient age, FIGO stage, FIGO grading, and histopathologic subtype. In addition to the established proliferation markers Ki-S5 (Ki-67) and KiS4 (topoisomerase IIalpha), we used a novel monoclonal antibody (MAb), anti-repp 86, which binds to a recently described proliferation-specific protein (p86) expressed exclusively in the S, G2, and M phases of the cell cycle. anti-repp 86, Ki-S4, and Ki-S5 immunoreactive labeling indices (LI) correlated significantly with FIGO stage, FIGO grade, and myometrial invasion, but not with histopathologic subtype. By univariate analysis, conventional prognostic factors and proliferation indices were all predictive of disease-related mortality. A multivariate Cox regression analysis selected anti-repp 86 LI (P = .002), FIGO stage (P = .02), and histopathologic type as significant prognosticators of recurrence; anti-repp 86 LI (P = .001) and histopathologic type (P = .0106) also emerged as relevant predictors of mortality. A hierarchical forward regression model with the conventional prognosticators entered first and with anti-repp 86 entered next showed that anti-repp 86 and histopathologic subtype were the superior independent prognostic indicators for an increased risk of recurrence and cancer-related death. We conclude that the evaluation of anti-repp 86 immunostaining is an easily performable and exceptionally reliable method for identifying EC patients with adverse prognosis.
Wiechens B, Grammer JB, Johannsen U, Pleyer U, Hedderich J, Duncker GI.
Experimental intravitreal application of ciprofloxacin in rabbits.Ophthalmologica,
213 (1999), 120-8.
[abstract]
Abstract:
BACKGROUND: Ciprofloxacin (CFLX) is a fluoroquinolone antibiotic with a broad antimicrobial spectrum. This study was performed to examine the retinal toxicity of free and liposome-incorporated CFLX in rabbit eyes after intravitreal injection. MATERIALS AND METHODS: Free CFLX in doses of 100, 250, 500, 1,000 and 2,000 microg was injected into the midvitreous of rabbit eyes (n = 28). To prolong the intravitreal antibacterial level, CFLX was incorporated into multilamellar liposomes: 0.1 ml of this suspension ( wedge 273.6 microg CFLX) was injected into the midvitreous of a second group of rabbit eyes (n = 6). The other eye served as a control and received normal saline solution or empty liposomes, respectively. Before injection and at the end of follow-up an electroretinogram (ERG) was obtained. After a follow-up of 1, 14 and 28 days the animals were perfused with glutaraldehyde and the eyes were examined by light and transmission electron microscopy. RESULTS: Significant reduction of the ERG was observed after 2,000 microg free CFLX in 4 out of 6 eyes after 14 days. Fourteen days after injection of 2,000 microg CFLX the central retina showed pigmentary changes in 4 out of 6 eyes. In the second group the ERG as well as the histologic studies did not reveal any pathologic changes after injection of liposome-incorporated CFLX compared to the control eyes. CONCLUSION: In therapeutic doses of 100-500 microg, free CFLX does not have retinal toxicity in rabbit eyes. No retinal toxicity was observed after intravitreal injection of liposome-incorporated CFLX.
Häring G, Gronemeyer A, Hedderich J, de Decker W.
Stereoacuity and aniseikonia after unilateral and bilateral implantation of the Array refractive multifocal intraocular lens.J Cataract Refract Surg,
25 (1999), 1151-6.
[abstract]
Abstract:
PURPOSE: To evaluate stereoacuity and aniseikonia in eyes with unilateral and bilateral implantation of the Allergan Array refractive multifocal intraocular lens (MIOL). SETTING: Department of Ophthalmology, University Hospital, Kiel, Germany. METHODS: This study comprised 31 patients with a unilateral MIOL and a phakic fellow eye and 29 patients with bilateral MIOLs. In all pseudophakic eyes, an Array MIOL had been implanted between 1991 and 1994 during a prospective clinical trial. In the present study, patients were re-examined. Near and distance visual acuity were tested; binocular functions were assessed using Bagolini lenses, the Worth 4-dot test, the Lang random-dot test, and the Titmus fly chart. Aniseikonia was evaluated using Aulhorn's phase-difference haploscope. Mean follow-up was 43 months in both groups. RESULTS: After unilateral implantation 87.1% of patients and after bilateral implantation 93.1% of patients correctly perceived the stereograms of the Lang random-dot test. The mean subjective height of the measured Titmus fly was 4.2 cm after unilateral and 4.3 cm after bilateral implantation. The stereoacuity tests revealed no statistically significant differences between the groups. Distance and near aniseikonia were significantly less after bilateral than after unilateral implantation. CONCLUSION: Despite the simultaneous formation of multiple retinal images, the Array MIOL allowed good binocular vision including random-dot stereopsis. Functional aniseikonia developed but did not interfere with normal binocular vision.
Wiechens B, Neumann D, Grammer JB, Pleyer U, Hedderich J, Duncker GI.
Retinal toxicity of liposome-incorporated and free ofloxacin after intravitreal injection in rabbit eyes.Int Ophthalmol,
22 (1998-99), 133-43.
[abstract]
Abstract:
BACKGROUND: Ofloxacin (OFLX) is a fluoroquinolone-antibiotic with a broad antimicrobial spectrum that may have a potential role in the treatment of bacterial endophthalmitis. However, its elimination half life after intravitreal injection is short. To prolong the intravitreal antibacterial level OFLX was incorporated into liposomes. This study was performed to investigate the retinal toxicity of liposome-incorporated and free OFLX. MATERIALS AND METHODS: OFLX was incorporated into multilamellar large vesicles. 0.1 ml of this suspension (= 180.2 microg OFLX) was injected into the midvitreous of rabbit eyes (n = 6). Free OFLX in doses of 100 microg, 500 microg and 1,000 microg was injected into the midvitreous of a second group of rabbit eyes (n = 18). The other eye served as a control and received empty liposomes or normal saline solution, respectively. Before injection and at the end of follow-up an ERG was obtained. After a follow-up of 1 day, 14 and 28 days the animals were perfused with glutaraldehyde and the eyes were examined by light- and transmission electron microscopy. RESULTS: The ERG as well as the histologic studies did not reveal any pathological changes after injection of liposome-incorporated OFLX compared to the control eyes. Significant reduction of the ERG was observed after 500 microg free OFLX in 2 out of 6 eyes after 1 and 14 days, respectively, and in 2 eyes 1 day after 1,000 microg free OFLX. Three days after injection of 1,000 microg OFLX the retina showed focal destruction in 1 out of 6 eyes. In another eye with the same dose 14 days after injection the photoreceptor outer segments showed disorganisation. CONCLUSION: This study shows that liposome-incorporated OFLX did not have any retinal toxicity in this animal model. Free OFLX appears to have no retinal toxicity in rabbit eyes at a dose of 100 microg after intravitreal injection. Injection of higher doses resulted in ERG changes and marked retinal damage.
Bonatz G, Lehmann-Willenbrock E, Hedderich J, Semm K.
[Follow-up of beta-hCG after pelviscopic linear salpingotomy for therapy of tubal pregnancy].Geburtshilfe Frauenheilkd,
55 (1995), 37-40.
[abstract]
Abstract:
From 1987 until 1993 a total of 337 patients underwent a therapy for tubal pregnancy at the Department of Gynaecology and Obstetrics of the University of Kiel. The percentage of cases treated by tubal-preserving pelviscopic linear salpingotomy and subsequent extraction of the conceptus, increased from 59% in 1987 to 88% in 1993. In 6.5% a second look pelviscopy was performed for suspected remnants of trophoblastic tissue. Remaining trophoblastic cells can be recognised by serial determination of serum beta-hCG titers postoperatively. However, the interval of the postoperative beta-hCG decline reveals considerable interindividual variation. A regression following the "Cox Proportional Hazard" model shows that the period of the beta-hCG decline depends on the initial titer. The Kaplan Meier curve obtained via beta-hCG determination in 98 patients following pelviscopic linear salpingotomy until values reached 20 mIU/ml or less, shows that 50% of the patients had to be controlled for more than 7 days, 10% for more than 28 days and individual patients even for more than 70 days. The relative beta-hCG titers differ significantly from the unresolved group compared to the group with resolved ectopic pregnancy starting at postoperative day 2 (p < 0.01). At postoperative day 3/4 10% of the initial beta-hCG value is attained in 50% of cases. Even then a serial beta-hCG follow-up should be obtained down to the detection limit to ensure complete resolution of viable trophoblastic cells.
Pröhl A, Alsen-Hinrichs C, Hedderich J, Kruse H, Wassermann O.
[Regional distribution of stomach and colon cancer mortality in the Dithmarschen and Nordfriesland districts--cartographic presentation].Gesundheitswesen,
57 (1995), 274-84.
[abstract]
Abstract:
In two counties (Dithmarschen and Nordfriesland) of the Federal State of Schleswig-Holstein (in the northern part of Germany) the cancer mortality rates, especially those of stomach and colon cancer, were evaluated for the time period 1980-1991. For this purpose the corresponding death certificates collected in these counties were analysed. The counties were subdivided into 16 and 17 smaller areas, respectively. The age-adjusted mortality rates were calculated and the obtained data scaled into eight sections, which were graphically mapped over the smaller areas of the two counties. The frequency of these cancer mortality rates reflects a wide range of distribution pattern in the smaller areas of the two counties, which greatly differ from the cancer mortality values calculated for the two counties as a whole. In comparison with the frequency of stomach cancer mortality for men published in the German Cancer Atlas in 1984 it could be demonstrated that this cancer mortality further decreased in these counties. However, in some smaller areas of these counties, especially in rural areas, the mortality rates of stomach cancer in men were still rather high. The opposite seems to be reflected regarding the frequency of colon cancer mortality. Here higher frequencies of mortality were seen in the small cities of these counties. We suggest that a more subtile cancer mortality mapping can be performed easily without any risk of hurting the requirements of personal data securities, because cancer mortality data are already continuously evaluated by a trained staff at the offices of statistical affairs. These data may be transferred and used for cancer mortality mapping as described in the present paper. In order to guarantee that there will be no violation of personal data secrecy the cancer mortality mapping must be restricted to cancer sites with high frequencies of mortality. All published data should be supervised by an official with special knowledge of the requirements of personal data protection. This study underlines the necessity for higher resolution (smaller areas) in cancer registries as essential prerequisite for systematical exploration of the origins of cancer mortality and as a basis for preventive measures.
Bonatz G, Lehmann-Willenbrock E, Kunstmann P, Semm I, Hedderich J, Semm K.
Management of patients with persistent beta-hCG values following laparoscopic surgical and local drug treatment for ectopic pregnancy.Int J Gynaecol Obstet,
47 (1994), 33-8.
[abstract]
Abstract:
OBJECTIVES: To show that the beta-human chorionic gonadotropin (hCG) decline following tubal-preserving techniques for ectopic pregnancy (EP) can take a longer course than currently believed, indicating expectant management; and to define the indications for a second-look laparoscopy if beta-hCG persists. METHODS: Three hundred thirty-seven patients treated for EP were retrospectively reviewed. In order to define the 'normal' beta-hCG decline following tubal-preserving techniques we acquired a Kaplan-Meier curve for 98 patients treated by laparoscopic linear salpingotomy, the main method performed for EP (253 patients). The Mann-Whitney U-test served as a statistical test. The patient population requiring a second-look laparoscopy for proliferating trophoblastic remnants is described. RESULTS: Twenty-eight patients (8.3%) required a second-look laparoscopy (acute abdominal pain and sonographically suspect findings combined with increasing beta-hCG values). The majority (15 patients) underwent a preceding laparoscopic linear salpingotomy (6.5% unresolved cases). The relative beta-hCG values differed significantly from the unresolved group compared to the group with resolved EP starting at postoperative day 2 (P < 0.01). A maximal beta-hCG decline period of 77 days postoperatively was observed. CONCLUSIONS: Patients with slowly declining beta-hCG levels following tubal-preserving techniques for EP can be managed expectantly. Increasing beta-hCG values combined with abdominal pain and sonographically suspect observations indicate a second-look laparoscopy.
Hassenpflug J, Hahne HJ, Hedderich J.
[Comments on the use of the "life-table method" in orthopedics].Z Orthop Ihre Grenzgeb,
130 (1992 May-Jun), 223-9.
[abstract]
Abstract:
In the description of long term results, e.g. of joint replacements, survivorship analysis is used increasingly in orthopaedic surgery. The survivorship analysis is more useful to describe the frequency of failure rather than global statements in percentage. The relative probability of failure for fixed intervals is drawn from the number of controlled patients and the frequency of failure. The complementary probabilities of success are linked in their temporal sequence thus representing the probability of survival at a fixed endpoint. Necessary condition for the use of this procedure is the exact definition of moment and manner of failure. It is described how to establish survivorship tables.
Paulsen P, Simon C, Peters O, Hedderich J, Heim P.
Influence of azithromycin and other macrolides on the intracellular killing of Staphylococcus aureus by human polymorphonuclear leucocytes of healthy donors and a patient with Chédiak-Higashi syndrome.Chemotherapy,
38 (1992), 185-90.
[abstract]
Abstract:
A mixture of human blood phagocytes from healthy donors and opsonized staphylococci was incubated in vitro for 30 min. After that time all the bacteria were phagocytosed. The test tubes were further incubated for 2, 4 and 24 h with or without addition of a macrolide (erythromycin, azithromycin, clarithromycin, roxithromycin) and the effect of these drugs on the survival of intracellular staphylococci (Staphylococcus aureus ATCC 25923) was measured. The minimal effective concentration of the antibiotic which killed 80-90% of the bacteria after a 4-hour incubation was 0.1 mg/l for erythromycin, azithromycin and clarithromycin and 1.2 mg/l for roxithromycin. The percentage of surviving bacteria after 2 and 4 h incubation was not significantly different between these macrolides at the minimal effective concentration. Increasing the concentration of each antibiotic above the minimal effective concentration did not alter the killing rate of intracellular staphylococci. The bacterial activity of polymorphonuclear leucocytes (PMNL) from a patient with Chédiak-Higashi syndrome was less in comparison to PMNL from healthy donors, but was improved in vitro by the addition of erythromycin or azithromycin.
Cogliatti SB, Schmid U, Schumacher U, Eckert F, Hansmann ML, Hedderich J, Takahashi H, Lennert K.
Primary B-cell gastric lymphoma: a clinicopathological study of 145 patients.Gastroenterology,
101 (1991), 1159-70.
[abstract]
Abstract:
Resection specimens from 145 patients with primary B-cell gastric lymphoma at stage IE (n = 88) and at stage IIE (n = 57) were investigated. Histologically, low-grade malignant B-cell lymphomas arising from the mucosa-associated lymphoid tissue, including immunocytoma (n = 71), could be distinguished from high-grade malignant B-cell lymphomas with (n = 25) and without (n = 49) evidence of a low-grade component. The very rare low-grade B-cell lymphomas of centroblastic-centrocytic, centrocytic, and plasmacytic type were not considered. All patients had undergone primary gastric resection, and 65 received additional chemotherapy (n = 33), radiotherapy (n = 22), or both (n = 10). Actuarial overall survival rates calculated by the Kaplan-Meier life-table method were 76% after 5 years and 58% after 10 years. According to the Mantel test and a multivariate analysis using the Cox regression method, patients at stage IE had a significantly better survival probability than those at stage IIE (P less than 0.0001); 5-year survival rates were 87% and 61%, respectively. The survival probability for low-grade malignant lymphomas was significantly better than for tumors with secondary high-grade transformation (P less than 0.05) or for primary high-grade lymphomas (P less than 0.0001), whereas the two high-grade groups were not significantly different. Five-year survival rates were 91% for low-grade, 73% for secondary high-grade, and 56% for primary high-grade malignant lymphomas. Retrospectively, no significantly different survival rates were found between patients who had undergone gastric resection alone and patients who had received additional treatment. However, survival analyses showed that classification and grading according to the histopathological concept of mucosa-associated lymphoid tissue-derived gastric lymphomas into low-grade B-cell lymphomas of mucosa-associated lymphoid tissue type and high-grade B-cell lymphomas with or without evidence of a low-grade component has great prognostic relevance.
Horst HA, Horny HP, Gent HJ, Sellschopp C, Hedderich J.
[Biological significance of estrogen receptor status in axillary lymph node metastases of invasive ductal breast cancers].Klin Wochenschr,
66 (1988), 1160-6.
[abstract]
Abstract:
One hundred and fourty-nine axillary lymph node metastases of 35 female patients with invasive breast carcinomas were investigated immunohistochemically for their estrogen receptor (ER)-status. In addition, proliferative activity of the metastatic deposits was determined with the monoclonal antibody Ki-67. Twenty-four primary tumours were ER+ and 11 ER-. Lymph node metastases were ER+ in 21 of the 24 cases where the primary tumour was ER+. In 10 of the 11 cases with ER- primary tumours, the metastases were also ER-. In any given case, the lymph node metastases proved to be either all ER+ or all ER-. Negative ER-status was found to be related to higher numbers of axillary node metastases and higher maximum proliferative activity of the metastatic tumours. Follow-up at 2 years after diagnosis revealed a significantly lower incidence of distant metastases in patients with ER+ primary tumours.
Horst HA, Hedderich J, Bäuning K, Weisner D.
[The tumor registry as an instrument of better management of cancer patients].Dtsch Med Wochenschr,
112 (1987), 1230-4.
Kraus E, Koschorek F, Scheil F, Hedderich J.
Timing and factors influencing operative outcome in intracranial aneurysms.Neurochirurgia (Stuttg),
29 (1986), 215-8.
[abstract]
Abstract:
The results of operation in 851 intracranial aneurysms were statistically analysed. The influence of 22 factors on operative outcome is shown. The importance of the time of intervention for the prognosis of patients is of special interest. It is striking that the outcome of an operation within 48 hours only depends on the neurological status, whereas at operation in the stage of recovery further factors such as vasospasm, arteriosclerosis, brain oedema, ischaemia and blood in the subarachnoid space are of great importance. They lead to a more unfavourable outcome.
Dietl J, Hedderich J, Sprenger E.
[Diagnosis of endometrial cancer by DNA cytophotometry].Geburtshilfe Frauenheilkd,
46 (1986), 796-9.
[abstract]
Abstract:
Cytophotometric determination of nuclear DNA content was performed in 121 cases by examining endometrial preparations. The endometrial cells were obtained by means of a MiMark cell sampler before curetting. A variety of groups (normal endometrium, adenomatous hyperplasia, endometrial carcinoma) were compared with each other and examined under statistical conditions. The differences were statistically significant according to the 3rd quartile (75% of DNA-population in a histogram) between the group of secretory transformed and atrophic endometrium and the group of well and moderately differentiated adenocarcinoma. Determination of the median and deviation index of the DNA population yielded similar results. The group of adenomatous hyperplasia did not differ from the normal endometrium according to all statistical parameters. Obviously it is impossible to distinguish precancerous endometrium from normal endometrium by cytophotometry. Differences between proliferative endometrium and well differentiated adenocarcinoma were seen in individual cases only. On the other hand, moderately differentiated adenocarcinoma could obviously be differentiated and delimitated.
Bruhn HD, Broers H, Euler H, Everding A, Feller AC, Hedderich J, Jostarndt L, Jooss B, Zurborn KH, Löffler H.
[CA-50 in serum of patients with carcinoma. Clinical experiences with a new tumor marker].Dtsch Med Wochenschr,
111 (1986), 1267-72.
[abstract]
Abstract:
Quantitative radioimmunological demonstration of carbohydrate antigen CA-50 in serum achieved a sensitivity of 62.3% for colorectal carcinoma (n = 53), of 64.7% for gastric carcinoma (n = 34), of 33.9% for lung carcinoma (n = 56), and 19.8% for lymphoproliferative diseases (n = 91). The positive results for the latter probably correspond to the immunohistological demonstration of the antigen in dendritic reticulum cells. Occasionally an increased CA-50 level in inflammatory disease presents difficulties in differential diagnosis, but it returns to normal when the inflammatory process has subsided. Methodological scatter of the CA-50 system is satisfactory, with a coefficient of variation of +/- 11%, but unsatisfactory at low values (less than or equal to 10 U/ml) and high ones (greater than or equal to 50 U/ml) with a coefficient of variation of +/- 19%. Further development with the IMRA technique may significantly reduce methodological scatter (coefficient of variation +/- 5%).
Seppelt U, Sprenger E, Hedderich J.
Investigation of automated DNA diagnosis and grading of prostatic cancer.Anal Quant Cytol Histol,
8 (1986), 152-7.
[abstract]
Abstract:
As a preliminary step towards a DNA-related automatic diagnosis and grading, the fine needle aspiration biopsies of 85 patients with prostatic cancer and of 20 patients with benign prostatic hypertrophy were subjected to DNA single-cell fluorescence cytometry. The DNA histograms were analyzed statistically by univariate data description, stepwise linear discriminant analysis and multiple regression analysis. The accuracy of the DNA-based malignancy diagnosis was 85.1%, with 10.6% false-negative and 4.3% false-positive results. The accuracy of the prognosis-related malignancy grading was, however, only 39.5% and thus unsatisfactory. The results indicate that a DNA-related diagnosis of prostatic malignancy is possible but that a similar automatic grading of prostatic cancer is not yet possible.
Voigt J, Hamelmann H, Hedderich J, Seifert J, Buchhammer T, Köhler A.
[Effectiveness and side effects of low-molecular weight heparin-dihydroergotamine in preventing thromboembolism in abdominal surgery].Zentralbl Chir,
111 (1986), 1269-305.
[abstract]
Abstract:
Low-molecular heparin-dihydroergotamine had been applied once a day to 103 patients and heparin-dihydroergotamine twice a day to 97 patients as part of a double-blind, controlled, consecutive, and randomised clinical study, with 200 abdominal surgery patients being involved. High-risk patients above 40 years of age and potentially affected by thrombotically predisposing factors were almost equally represented in both groups. Evidence to postoperative thrombosis was phlebographically produced in either group. No fatal pulmonary embolism was found to be among ten deaths. No significant differences of clinical relevance were found to exist between both groups with regard to coagulative values, intra-operative and postoperative blood and drainage loss, and complications due to bleeding. No accumulated occurrence of major postoperative complications was recordable from either group. The vascular status of all patients was unchanged from beginning to end of the period of observation. The following conclusion was drawn as a result of the study: One single NMH/DHE injection daily is comparable with two HDHE applications per die for action and undesired side-effects.
Seppelt U, Sprenger E, Hedderich J.
[DNA oriented automated malignancy diagnosis and malignancy grading in prostatic cancer].Urol Int,
40 (1985), 76-81.
[abstract]
Abstract:
85 patients with prostate cancer and 20 patients with benign prostatic hypertrophy underwent DNA single-cell fluorescence photometry to investigate the possibility of DNA-related automatic diagnosis and grading of prostate cancer. The DNA histograms were analysed statistically by univariate data description, stepwise linear discriminant analysis and regression analysis. The accuracy for the malignancy diagnosis was 85.1%, with 10.6% false-negative and 4.3% false-positive results. The accuracy of the malignancy grading, however, was very poor with only 39.5%.
Voigt J, Lennert K, Hedderich J.
[5 years' general drug prevention of thromboembolism in general surgery. Comparison of personal experiences with results from the literature].Fortschr Med,
102 (1984), 562-4.
[abstract]
Abstract:
Despite wide use of physical methods the number of fatal postoperative pulmonary embolisms in surgical patients increased in Kiel until 1976. Because of these results, additional general prophylaxis with 2-3 X 5000 i U of heparin-dihydroergotamine was introduced in 1978. The rate of fatal pulmonary embolism in general surgery proven by autopsy decreased to 0,3% between 1979 and 1983. It should be noted that six of the nine patients who died from pulmonary embolism had also suffered from an infaust disease. This is an excellent result since our study also includes high risk patients after emergency surgery, cases which Kakkar and Gruber did not include in their studies. Due to the extensive analysis of medical records and the pertinent post-mortem reports, the high effectivity of drug induced prophylaxis with 2-3 X 5000 i U of heparin-dihydroergotamine in order to reduce fatal pulmonary embolism in general surgery could be proven.
Dietl J, Semm K, Hedderich J, Buchholz F.
CIN and preclinical cervical carcinoma. A study of morbidity trends over a 10-year period.Int J Gynaecol Obstet,
21 (1983), 283-9.
[abstract]
Abstract:
Between 1971 and 1980 1312 cone biopsies were performed at the Department of Gynecology and Obstetrics, Kiel. Comparing the two intervals from 1971 to 1975 and 1976 to 1980 the number of cases with dysplasia and Carcinoma in situ significantly rose in the last 5 years in patients 16-30 years of age. Amongst other reasons for this increase, on the basis of our investigation, the regular gynecological examination in combination with the prescription of the ovulation inhibitors seems to be responsible. The average age of patients (36-44 years) undergoing cone biopsy for the first time decreased in the period between 1971 and 1980 (approx. 8 years). The excision of carcinoma in situ in women under 30 years of age mostly showed margins free of pathological epithelium. With increasing age the cases of not free margins increased to 70%. For the hemostasis of the conization crater up to 1977, the conventional suture technique was applied, since 1977 cone coagulation probe according to Semm was used. In this group (1977-1980) treated with coagulation after cone biopsy, 45% of the cases with carcinoma in situ not free margins had histologically normal epithelium of the extirpated uterus. In patients with the desire for a child or in pregnant women a secondary coagulation of the wound crater is achieved to preserve the uterus.
Strenge H, Hedderich J.
Age-dependent changes in central somatosensory conduction time.Eur Neurol,
21 (1982), 270-6.
[abstract]
Abstract:
Cervical and cortical somatosensory evoked potentials(SEPs) were recorded in 45 normal subjects. Absolute peak latencies and latency differences between the components P7, N9, N11, N13, P17 and N20 were measured. Subjects aged 40-60 years had significantly longer latencies of N13 and N20 than subjects aged 15-39 years. Moreover, statistical analysis revealed a significant prolongation of N9-N13, N11-N13 and N13-N20 transit times in older subjects. Possible connections with known morphological age-related findings are discussed.
Strenge H, Hedderich J, Tackmann W.
[The significance of sex-linked differences for the assessment of somatosensory evoked potentials (author's transl)].EEG EMG Z Elektroenzephalogr Elektromyogr Verwandte Geb,
12 (1981), 120-4.
[abstract]
Abstract:
In 45 healthy volunteers (22 males and 23 females with the same age structure) the peak latencies and inter-peak differences of the cervical and early cortical components of the somatosensory evoked potential were measured. The distribution of the values of the variables and their relationship with arm length were investigated both for the sample as a whole and for each sex separately. Significantly higher average values of the latencies and arm lengths were found in men. The correlations between arm length and latency had consistently higher values for the female sample. On the basis of these results it is concluded that a sufficient assessment of the latencies is only possible with the help of sex-specific normal values.
Griesser G, Hedderich J.
Some considerations of multi-variate hospital statistics.Med Inform (Lond),
5 (1980 Apr-Jun), 131-9.
[abstract]
Abstract:
At the University Hospital in Kiel data on the medical care and administration of individual patients is collected in a hospital information system. The description leads to lists of all cases treated, arranged according to basic data descriptions, and to tabulations of aggregated data. The aim of these statistics is to provide an overview of the collected data. At present the statistics can do little more than offer some general impressions about the frequency of serious diseases requiring hospitalization and health-care needs of a particular region; this is because they are selected and therefore biased and misleading. An accurate epidemiological view of a region to evaluate the quality, efficiency and cost of its health-care system can only be obtained if all the hospitals in that area are producing summarized information. So correlation of population statistics, broken down by patients' residential area and the hospital means for evaluating the health-care demands and consumption of a particular population, and for regional planning when figures for catchment area and attraction rate are produced.
Harms D, Gottschalk I, Griesser H, Hedderich J, Wilke H, Willke E.
[Central tumor registry, Society for Pediatric Oncology. First report (author's transl)].Klin Padiatr,
192 (1980), 99-108.
