Eberhard Kuhlisch

Publications of Eberhard Kuhlisch

• Randomized trial on 14 versus 7 days of esomeprazole, moxifloxacin, and amoxicillin for second-line or rescue treatment of Helicobacter pylori infection.

  Authors: Stephan Miehlke, Susanne Krasz, Wulf Schneider-Brachert, Eberhard Kuhlisch, Marco Berning, Ahmed Madisch, Martin W Laass, Michael Neumeyer, Claus Jebens, Christian Zekorn, Holger Knoth, Michael Vieth, Manfred Stolte, Norbert Lehn, Andrea Morgner

  Helicobacter. 12/2011; 16(6):420-6.

  Triple therapy with a proton pump inhibitor, moxifloxacin, and amoxicillin has been proven effective in first-line treatment of Helicobacter pylori infection. To explore 1, the value of tripleTriple therapy with a proton pump inhibitor, moxifloxacin, and amoxicillin has been proven effective in first-line treatment of Helicobacter pylori infection. To explore 1, the value of triple therapy with esomeprazole, moxifloxacin, and amoxicillin in second-line or rescue treatment of Caucasian patients and 2, the impact of treatment duration on eradication success. H. pylori-infected patients with at least one previous treatment failure were randomized to oral esomeprazole 20 mg b.i.d., moxifloxacin 400 mg o.d., and amoxicillin 1000 mg b.i.d. for either 7 (EMA-7) or 14 days (EMA-14). Eradication was confirmed by 13C urea breath test. Antimicrobial susceptibility testing was performed in all patients at baseline and in patients who failed treatment. Eighty patients were randomized, and 60% had ≥ 2 previous treatment failures. Pretreatment resistance against clarithromycin and metronidazole was found in 70.5 and 61.5% of cases, respectively. The intention-to-treat eradication rate was significantly higher after EMA-14 compared with EMA-7 (95.0 vs 78.9%, p = .036). No independent risk factor for treatment failure could be identified. There were no serious adverse events. Five of the EMA-14 patients (12.5%) compared with none of the EMA-7 patients discontinued prematurely because of adverse events (p = .031). Post-treatment resistance against moxifloxacin was found in one of seven patients with isolated organisms (14.3%). Second-line/rescue H. pylori eradication therapy with esomeprazole, moxifloxacin, and amoxicillin is very effective and well tolerated. Fourteen days of treatment significantly increase the eradication rate but also the rate of adverse events.

• Biological functionalization of dental implants with collagen and glycosaminoglycans-A comparative study.

  Authors: Bernd Stadlinger, Vera Hintze, Susanne Bierbaum, Stephanie Möller, Matthias C Schulz, Ronald Mai, Eberhard Kuhlisch, Sascha Heinemann, Dieter Scharnweber, Matthias Schnabelrauch, Uwe Eckelt

  Journal of biomedical materials research. Part B, Applied biomaterials. 11/2011;

  Biological implant surface coatings are an emerging technology to increase bone formation. Such an approach is of special interest in anatomical regions like the maxilla. In the present study, weBiological implant surface coatings are an emerging technology to increase bone formation. Such an approach is of special interest in anatomical regions like the maxilla. In the present study, we hypothesized that the coating of titanium implants with components of the organic extracellular matrix increases bone formation and implant stability compared to an uncoated reference. The implants were coated using collagen-I with either two different concentrations of chondroitin sulfate (CS) or two differentially sulfated hyaluronans. Implant coatings were characterized biochemically and with atomic force microscopy. Histomorphometry was used to assess bone-implant contact (BIC) and bone-volume density (BVD) after 4 and 8 weeks of submerged healing in the maxilla of 20 minipigs. Further, implant stability was measured by resonance frequency analysis (RFA). Implants containing the lower CS concentration had significantly more BIC, compared to the uncoated reference at both times of interest. No significant increase was measured from week 4 to 8. Differences in BVD and RFA were statistically not significant. A higher concentration of CS and the application of sulfated hyaluronans showed no comparable increase in BIC. This study demonstrates a positive effect of a specific collagen-glycosaminoglycan combination on early bone formation in vivo. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2011.

• RET-protooncogene variants in patients with sporadic neoplasms of the digestive tract and the central nervous system.

  Authors: Felix Rückert, Heike Görgens, Ines Richter, Dietmar Krex, Gabriele Schackert, Eberhard Kuhlisch, Guido Fitze, Hans-Detlev Saeger, Christian Pilarsky, Robert Grützmann, Hans K Schackert

  International journal of colorectal disease. 02/2011; 26(7):835-40.

  The RET protooncogene plays a crucial role in neural crest development; accordingly, mutations of RET cause MEN2A and familial medullary thyroid carcinoma, while the expression deregulation of RET isThe RET protooncogene plays a crucial role in neural crest development; accordingly, mutations of RET cause MEN2A and familial medullary thyroid carcinoma, while the expression deregulation of RET is involved in the pathophysiology of glioblastoma multiforme (GBM) and pancreatic cancer (PDAC). The aim of this study was to evaluate if germline variants of the RET protooncogene are associated with GBM, pancreatic cancer and gastric cancer (GC). Genomic DNA from peripheral blood was isolated from 100 patients with GBM, 65 patients with GC and 54 patients with PDAC. The coding sequence of RET promoter, exon 2 and exon 13 was amplified. Sequence variations at -5 and -1 in the promotor and in exon 2 were determined through a LightCycler assay, and analysis of exon 13 was carried out by genomic sequencing. There was no significant association of the RET-promoter or exon 2 genotypes with the phenotype in the different populations, although there was an increase of the GG genotype of the -5G>A variant in all cancers compared to controls. Sequencing of exon 13 identified mutation c.2372A>T in codon 791 (Y791F) in heterozygous state in one of 100 GBM patients, in two of 65 patients with gastric cancer, in two of 54 PDAC patients and in none of the controls. Although our data did not reach significance in our small cohorts, we cannot rule out the involvement of the -5G promoter allele and the c.2372A>T mutation in the development of the aforementioned tumours.

• X chromosomal recombination-a family study analysing 39 STR markers in German three-generation pedigrees.

  Authors: Sandra Hering, Jeanett Edelmann, Christa Augustin, Eberhard Kuhlisch, Reinhard Szibor

  International journal of legal medicine. 11/2009;

  Typing of polymorphisms on the human chromosome X (ChrX) has become a standard technique in forensic genetics, and a growing number of short tandem repeats (STRs) has been established. Knowledge ofTyping of polymorphisms on the human chromosome X (ChrX) has become a standard technique in forensic genetics, and a growing number of short tandem repeats (STRs) has been established. Knowledge of marker recombination is of great significance especially when ChrX typing is used in forensic kinship testing. It is known that meiotic recombination is not a simple function of physical distance but crossing over events tend to be clustered. Information on genetic distances between markers can be gathered by family studies and by interpolation of gene bank data such as the Rutgers map. We typed DNA samples of pedigrees consisting of mothers with several sons and grandfather-mother-son constellations and report here the recombination characteristics of 39 ChrX STRs in up to 135 meioses.

• Increased bone formation around coated implants.

  Authors: Bernd Stadlinger, Susanne Bierbaum, Silke Grimmer, Matthias C Schulz, Eberhard Kuhlisch, Dieter Scharnweber, Uwe Eckelt, Ronald Mai

  Journal of clinical periodontology. 07/2009;

  Aim: We hypothesized that coating threaded, sandblasted acid-etched titanium implants with collagen and chondroitin sulphate (CS) increases bone formation and implant stability, compared withAim: We hypothesized that coating threaded, sandblasted acid-etched titanium implants with collagen and chondroitin sulphate (CS) increases bone formation and implant stability, compared with uncoated controls. Materials and Methods: Three different implant surface conditions were applied: (1) sandblasted acid-etched (control), (2) collagen/chondroitin sulphate (low-dose - CS1), (3) collagen/chondroitin sulphate (high-dose - CS2). Sixty 9.5 mm experimental implants were placed in the mandible of 20 minipigs. Bone-implant contact (BIC) and relative peri-implant bone-volume density (rBVD - relation to bone-volume density of the host bone) were assessed after 1 and 2 months of submerged healing. Implant stability was measured by resonance frequency analysis (RFA). Results: After 1 month, coated implants had significantly more BIC compared with controls (CS1: 68%, p<0.0001, CS2: 63%, p=0.009, control: 52%). The rBVD was lower for all surface conditions, compared with the hostbone. After 2 months, BIC increased for all surfaces. No significant differences were measured (CS1: 71%, p=0.016, CS2: 68%, p=0.67, control: 63%). The rBVD was increased for coated implants. RFA values were 71-77 at implantation, 67-73 after 1 month and 74-75 after 2 months. Differences in rBVD and RFA were not statistically significant. Conclusions: Data analysis suggests that collagen/CS has a positive influence on bone formation after 1 month of endosseous healing.

• New Aspects in the Clinical Diagnosis of Otosclerosis Using Laser Doppler Vibrometry.

  Authors: Andre Jakob, Matthias Bornitz, Eberhard Kuhlisch, Thomas Zahnert

  Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology. 06/2009;

  HYPOTHESIS:: Laser Doppler vibrometry (LDV) applied to umbo motion measurement in healthy and otosclerotic ears shows statistically tested differences. BACKGROUND:: The LDV is a research tool thatHYPOTHESIS:: Laser Doppler vibrometry (LDV) applied to umbo motion measurement in healthy and otosclerotic ears shows statistically tested differences. BACKGROUND:: The LDV is a research tool that measures middle ear function by registering sound-induced tympanic membrane velocity. Its possible application in the diagnosis of different middle ear disorders, especially otosclerosis, is currently being evaluated. Established diagnosis can identify various ossicular chain pathologies in most cases but is still sometimes contradicted by the findings of surgical middle ear exploration. METHODS:: We used a fractionally modified LDV setting as previously reported to evaluate 150 normal-hearing ears and 49 ears with conductive hearing loss. In a first step, the impact of age variation on the umbo transfer function was investigated by dividing the normal-hearing population into 3 age groups. In a second step, the control group was compared with patients with conductive hearing loss; certain patterns in the umbo transfer function were especially investigated by discriminant analysis. RESULTS:: Mean magnitude of the oldest group was found to be significantly higher than the other 2 groups, but it was not possible to diagnostically classify the 3 groups. Discriminant analysis revealed the linear term of a cubic polynom to significantly best describe the umbo transfer function in normal ears (p < 0.0005; partial eta = 0.866) and in otosclerotic ears (p < 0.0005; partial eta = 0.799). Separating otosclerotic ear from normal-hearing ear evidence suggests a sensitivity of 82% and specificity of 92%. CONCLUSION:: Evaluation of LDV magnitude curve patterns gives helpful information in the diagnosis of otosclerosis but does not suffice as a single diagnostic tool.

• A randomized double-blind placebo-controlled study showing that budesonide is effective in treating lymphocytic colitis.

  Authors: Stephan Miehlke, Ahmed Madisch, Diana Karimi, Susann Wonschik, Eberhard Kuhlisch, Renate Beckmann, Andrea Morgner, Ralph Mueller, Roland Greinwald, Gerhard Seitz, Gustavo Baretton, Manfred Stolte

  Gastroenterology. 04/2009;

  BACKGROUND AND AIMS:: Budesonide is effective in treating collagenous colitis, but there is no established treatment for lymphocytic colitis. We performed a randomized, double-blind,BACKGROUND AND AIMS:: Budesonide is effective in treating collagenous colitis, but there is no established treatment for lymphocytic colitis. We performed a randomized, double-blind, placebo-controlled study to evaluate the effects of budesonide in patients with lymphocytic colitis. METHODS:: 42 patients (median age 61 years) with lymphocytic colitis and chronic diarrhea were randomly assigned to groups that were given oral doses of budesonide (9 mg/day) or placebo for 6 weeks. Non-responders at Week 6 were given open-label budesonide (9 mg/day) for 6 additional weeks. A complete colonoscopy and histological and quality of life analyses were performed at baseline and at Week 6. The primary endpoint was clinical remission at 6 weeks, with last observation carried forward (LOCF). All patients that left the study in clinical remission were followed for relapse. RESULTS:: At Week 6, 86% of patients given budesonide were in clinical remission (with LOCF) compared with 48% of patients given placebo ( P = 0.010). Furthermore, open-label budesonide therapy induced clinical remission in 7 of 8 patients given placebo. Histological remission was observed in 73% of patients given budesonide compared with 31% given placebo ( P = 0.030). Only 1 patient discontinued budesonide therapy prematurely. During a mean follow-up period of 14 months, 15 patients (44.1%) experienced a clinical relapse (after a mean of 2 months); 8 of the relapsing patients were re-treated with and responded again to budesonide. CONCLUSIONS:: Budesonide effectively induces clinical remission in patients with lymphocytic colitis and significantly improves histology results after 6 weeks. Clinical relapses occur but can be treated again with budesonide.

• Open reduction and internal fixation versus closed treatment and mandibulomaxillary fixation of fractures of the mandibular condylar process: a randomized, prospective, multicenter study with special evaluation of fracture level.

  Authors: Matthias Schneider, Francois Erasmus, Klaus Louis Gerlach, Eberhard Kuhlisch, Richard A Loukota, Michael Rasse, Johannes Schubert, Hendrik Terheyden, Uwe Eckelt

  Journal of oral and maxillofacial surgery : official journal of the American Association of Oral and Maxillofacial Surgeons. 01/2009; 66(12):2537-44.

  PURPOSE: This randomized, clinical multicenter trial investigated the treatment outcomes of displaced condylar fractures, and whether radiographic fracture level was a prognostic factor inPURPOSE: This randomized, clinical multicenter trial investigated the treatment outcomes of displaced condylar fractures, and whether radiographic fracture level was a prognostic factor in therapeutic decision-making between open reduction and internal fixation (ORIF) versus closed reduction and mandibulomaxillary fixation (CRMMF). PATIENTS AND METHODS: Sixty-six patients with 79 displaced fractures (deviation of 10 degrees to 45 degrees , or shortening of the ascending ramus >/=2 mm) of the condylar process of the mandible at 7 clinical centers were enrolled. Patients were randomly allocated to CRMMF (n = 30 patients) or ORIF (n = 36 patients) treatment. The following parameters were measured 6 months after the trauma. Clinical parameters included mouth opening, protrusion, and laterotrusion. Radiographic parameters included level of the fracture, deviation of the fragment, and shortening of the ascending ramus. Subjective parameters included pain (according to a visual analogue scale), discomfort, and subjective functional impairment with a mandibular functional impairment questionnaire. RESULTS: The difference in average mouth opening was 12 mm (P </= .001) between both treatment groups. The average pain level (visual analogue scale from 0 to 100) was 25 after CRMMF, and 1 after ORIF (P </= .001). In 53 unilateral fractures, better functional results were observed for ORIF compared with CRMMF, irrespective of fracture level (condylar base, neck, or intracapsular head). Unexpectedly, the subjective discomfort level decreased with ascending level of the fracture. In patients with bilateral condylar fractures, ORIF was especially advantageous. CONCLUSION: Fractures with a deviation of 10 degrees to 45 degrees , or a shortening of the ascending ramus >/=2 mm, should be treated with ORIF, irrespective of level of the fracture.

• Correlation of BCR/ABL transcript variants with patients' characteristics in childhood chronic myeloid leukaemia.

  Authors: Ronald Adler, Susanne Viehmann, Eberhard Kuhlisch, Yvonne Martiniak, Silja Röttgers, Jochen Harbott, Meinolf Suttorp

  European journal of haematology. 12/2008;

  Abstract Background and objective: The characteristic chromosomal translocation t(9;22)(q34;q11) in chronic myeloid leukaemia (CML) mainly results in the two different BCR/ABL fusion transcripts b2a2Abstract Background and objective: The characteristic chromosomal translocation t(9;22)(q34;q11) in chronic myeloid leukaemia (CML) mainly results in the two different BCR/ABL fusion transcripts b2a2 or b3a2. Both transcript variants can occur simultaneously due to alternative splicing of the b3a2 transcript. Conflicting results have been reported on the influence of the transcripts on haematological findings at diagnosis and the course of the disease in adults while data concerning these topics on childhood CML are still missing. This paper reports on a correlation of BCR/ABL transcript variants with patients' characteristics in childhood CML. Design and methods: Transcript types were determined in 146 paediatric patients with CML enrolled in trial CML-paed-I. Fifty-five patients (38%) expressed b2a2, 53 patients (36%) b3a2 and 38 patients (26%) both transcripts, respectively. These findings were correlated with patients' characteristics (sex, age, WBC, Hb, platelet count, hepatosplenomegaly, etc.) assessed at diagnosis. Results: While the co-expression of both transcripts was evenly distributed among genders [b2a2 + b3a2: 22 females (28%), 16 males (24%)] a highly significant difference (P = 0.007) was found concerning the expression of the b2a2 transcript [34 male (51%) vs. 21 female (27%)] and vice versa of the b3a2 transcript [17 male (25%) vs. 36 female (45%)]. High platelet counts and the combination of high platelet counts in conjunction with pronounced leukocytosis were observed more often in patients expressing the b3a2 transcript. Conclusions: These findings demonstrate that in children like in adults specific BCR/ABL transcript types present at diagnosis are associated with distinct haematological alterations (e.g. a high platelet count with the transcript b3a2). However, the sex-dependent skewed distribution of the BCR/ABL transcript types observed so far in this paediatric cohort only deserves further investigation.

• Clinical and laboratory phenotypes associated with the aspirin-like defect: a study in 17 unrelated families.

  Authors: Nina Rolf, Ralf Knoefler, Peter Bugert, Siegmund Gehrisch, Gabriele Siegert, Eberhard Kuhlisch, Meinolf Suttorp

  British journal of haematology. 12/2008;

  Aspirin-like defect (ALD) is a rare, mostly autosomal dominant inherited dysfunction of the intraplatelet arachidonic acid (AA) pathway leading to impaired thromboxane A(2) signalling. We aimed toAspirin-like defect (ALD) is a rare, mostly autosomal dominant inherited dysfunction of the intraplatelet arachidonic acid (AA) pathway leading to impaired thromboxane A(2) signalling. We aimed to establish diagnostic criteria for ALD diagnosis and present clinical and laboratory phenotypes of 52 individuals from 17 unrelated families. Platelet in vitro function was determined on the basis of platelet aggregation response (PAR) to AA, adenosine diphosphate, collagen and ristocetin as well as PFA-100((R)) closure times (CT). Using impaired PAR to AA (</=10%) as the mandatory diagnostic criterion, ALD could be confirmed in 17 patients. Subsequently, family members were investigated and among 35 individuals an additional 13 ALD patients as well as 4 individuals with mild ALD (PAR to AA: 19-32%) were identified. At least one bleeding symptom was reported by 25 (74%) ALD patients and prolonged CT was detected in 24 (71%) of the cases, both significantly correlated with impaired PAR to AA (P = 0.001 and P = 0.002, respectively). An estimated 0.6% prevalence was determined for ALD in our paediatric patients with suspected coagulation disorders. Due to the mild bleeding symptoms, ALD is probably underdiagnosed. If ALD is suspected, PAR to AA is suitable for the identification of individuals at risk of increased haemorrhage.

• Resection of colorectal liver metastases: is a resection margin of 3 mm enough? : a multicenter analysis of the GAST Study Group.

  Authors: Ralf Konopke, Stephan Kersting, Frank Makowiec, Peter Gassmann, Eberhard Kuhlisch, Norbert Senninger, Ulrich Hopt, Hans-Detlev Saeger

  World journal of surgery. 09/2008; 32(9):2047-56.

  A safety margin of > or =10 mm is generally accepted in surgery for colorectal metastases. It is reasonable that modern methods of liver parenchyma dissection may allow for a reduction in thisA safety margin of > or =10 mm is generally accepted in surgery for colorectal metastases. It is reasonable that modern methods of liver parenchyma dissection may allow for a reduction in this distance. A total of 333 patients were included in a multicenter trial after resection of colorectal liver metastases. Dissection of the liver had been performed with a CUSA, UltraCision, or water-jet dissector. The size of the resection margin was correlated with recurrence risk and survival. The median hepatic recurrence-free survival reached 35 months for all patients; median recurrence-free survival was 24 months and overall survival was 41 months. Univariate analysis of different groups denoting the extent of resection margin (> or =10 mm, 6-9 mm, 3-5 mm, 1-2 mm, 0 mm (R1)) indicated that a margin of 1-2 mm leads to a significantly reduced median hepatic recurrence-free survival of 20 months (p = 0.004) and recurrence-free survival of 19 months (p = 0.011). Patients with R1 resection had the worst prognosis. Overall survival was not influenced by the size of the resection margin. Surgical margins were significantly reduced in simultaneous resections of four or more liver metastases and in cases in which metastatic infiltration of central liver segments was present. At multivariate analysis, resection margins of 1-2 mm and 0 mm were independent predictors of hepatic recurrence and overall recurrence. The indication for resection of metastases can be safely extended to cases in which tumors sit closer than 1 cm to nonresectable structures.

• Microsatellite instability and loss of heterozygosity in squamous cell carcinoma of the head and neck.

  Authors: Susanne Koy, Jens Plaschke, Hella Luksch, Katrin Friedrich, Eberhard Kuhlisch, Uwe Eckelt, Ramon Martinez

  Head & neck. 08/2008; 30(8):1105-1113.

  BACKGROUND.: Microsatellite instability (MSI) in head and neck squamous cell carcinoma (HNSCC) has been reported with a wide range of frequencies. The aim of our study was to disclose the frequencyBACKGROUND.: Microsatellite instability (MSI) in head and neck squamous cell carcinoma (HNSCC) has been reported with a wide range of frequencies. The aim of our study was to disclose the frequency and basis of MSI in HNSCC and to correlate MSI and findings on loss of heterozygosity (LOH) with the clinical data. METHODS.: We analyzed MSI and LOH in 91 tumors. All tumors presenting instability were analyzed for the expression of mismatch repair genes (MMR) proteins. RESULTS.: Low-level microsatellite instability (MSI-L) was seen in 7.7% of the HNSCC. None of the MSI-L tumors had aberrant MMR protein expression. LOH rates up to 57% were identified for different regions on chromosome 3p. For the marker D10S197, we found a significant correlation between LOH and tumor stage IV. CONCLUSION.: Our results indicate that MMR gene inactivation is rare among primary HNSCC. In contrast, the MSI-L phenotype plays a role in a small subset of tumors. LOH on chromosome arm 3p and 10p12 seems to be involved in tumorigenesis and progression HNSCC, respectively. (c) 2008 Wiley Periodicals, Inc. Head Neck 30: 1105-1113, 2008.

• Oral Budesonide for Maintenance Treatment of Collagenous Colitis: A Randomized, Double-Blind, Placebo-Controlled Trial.

  Authors: Stephan Miehlke, Ahmed Madisch, Birgit Bethke, Andrea Morgner, Eberhard Kuhlisch, Christine Henker, Gerfried Vogel, Matthias Andersen, Eberhard Meier, Gustavo Baretton, Manfred Stolte

  Gastroenterology. 08/2008;

  BACKGROUND & AIMS: Oral budesonide effectively induces clinical remission in patients with collagenous colitis, a debilitating illness characterized by chronic watery/loose diarrhea, but there is aBACKGROUND & AIMS: Oral budesonide effectively induces clinical remission in patients with collagenous colitis, a debilitating illness characterized by chronic watery/loose diarrhea, but there is a high rate of relapse after treatment cessation. METHODS: This randomized, double-blind, placebo-controlled, multicenter study evaluated the efficacy and safety of long-term therapy with oral budesonide (Entocort CIR capsules) for maintenance of clinical remission of collagenous colitis. Patients were aged >18 years with histologically proven collagenous colitis and >3 watery/loose stools per day on >/=4 of the prior 7 days. Open-label oral budesonide 9 mg/d was administered to all patients for 6 weeks. Patients in clinical remission (</=3 stools per day) at week 6 were subsequently randomized to double-blind oral treatment with budesonide 6 mg/d or matching placebo for 6 months. Relapse was defined as >3 stools per day on >/=4 consecutive days (and included patients withdrawn because of adverse events). RESULTS: Of 48 enrolled patients, 46 (96%) achieved clinical remission at week 6 and were randomized to maintenance budesonide or placebo. There were 21 relapses during maintenance therapy, and almost all occurred during the first 2 months. Budesonide therapy was associated with a significantly lower cumulative rate of relapse compared with placebo (6/23 [26%] and 15/23 [65%], respectively; P = .022), and high correlation between clinical remission and histologic improvement was observed. Budesonide was well tolerated with no serious adverse events. CONCLUSIONS: Oral budesonide 6 mg/d is efficacious and well tolerated for long-term maintenance of clinical remission in patients with collagenous colitis.

• Suitability of differently designed matrix-based implant surface coatings: An animal study on bone formation.

  Authors: Bernd Stadlinger, Eckart Pilling, Matthias Huhle, Evgenij Khavkin, Susanne Bierbaum, Dieter Scharnweber, Eberhard Kuhlisch, Uwe Eckelt, Ronald Mai

  Journal of biomedical materials research. Part B, Applied biomaterials. 06/2008;

  Introduction: The aim of the present study was to assay how bone formation around dental implants is influenced by differently composed collagen matrices and RGD peptide as implant surface coatingsIntroduction: The aim of the present study was to assay how bone formation around dental implants is influenced by differently composed collagen matrices and RGD peptide as implant surface coatings compared to a sandblasted titanium surface. Material and Methods: Five different implant surface coatings were designed: titanium (sandblasted), collagen type I, collagen type I&III, RGD-peptide, and mineralized collagen. Sixty experimental implants of a square-shaped design were inserted into the mandibles of 12 minipigs, 3 months following extraction of the premolar teeth. During the 6-month study period, sequential polyfluorochrome labeling was performed. After sacrifice, bone implant contact (BIC) was evaluated using histologic and histomorphometric methods. Results: New bone formation was observed against all implant surfaces. Polyfluorochrome labeling showed that bone growth started from the host bone in the majority of samples. The highest BIC was measured for collagen I and collagen I/III coated implants; however, significant differences between the coatings could not be found. Conclusion: Osseointegration was achieved for all implant surfaces. Although a statistically significant increase in BIC could not be demonstrated for the experimental coatings after the 6 months study period, there was also no discernible detrimental effect of the coatings in comparison to the uncoated titanium surfaces. (c) 2008 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2008.

• Color Doppler imaging predicts portal invasion by pancreatic adenocarcinoma.

  Authors: Alexander Kern, Frank Dobrowolski, Stephan Kersting, Dag-Daniel Dittert, Hans-Detlev Saeger, Eberhard Kuhlisch, Alfred Bunk

  Annals of surgical oncology. 05/2008; 15(4):1137-46.

  BACKGROUND: Tumor infiltration of the intima of the portal vein (PV) and superior mesenteric vein (SMV) by pancreatic adenocarcinoma is classically considered a criterion for unsuitability forBACKGROUND: Tumor infiltration of the intima of the portal vein (PV) and superior mesenteric vein (SMV) by pancreatic adenocarcinoma is classically considered a criterion for unsuitability for resection and poor prognosis. This study was performed to evaluate modern color duplex imaging (CDI) for the assessment of PV/SMV infiltration by pancreatic adenocarcinomas. METHOD: From 1994 to 2005, Whipple's procedure or pylorus-preserving pancreato-duodenectomy (PPPD) was performed in 303 patients with pancreatic adenocarcinoma; 35 of these underwent partial PV/SMV resection. Applying a previously reported CDI score, we evaluated the integrity of the echogenic border layer between the vein and tumor (mural demarcation) and maximum blood flow velocity (V (max)) in the PV segment in contact with the tumor. The results were compared to the final histological findings in the resected venous walls. RESULTS: CDI findings correlated well with the histological invasion grades. By measuring V (max )and evaluating mural demarcation, we observed a sensitivity of 66.7% and 100% and a specificity of 98.3% and 93.9%, respectively, in predicting full thickness vein invasion, including the intima. V (max) above 80 cm/s and lack of mural demarcation were predictors of PV/SMV invasion. The postoperative survival rates depended on the depth of tumor infiltration into the PV/SMV. CONCLUSIONS: Modern CDI is a reliable and valid technique for evaluation of morphological and hemodynamic parameters in the portal vein segment adjacent to pancreatic adenocarcinoma. Maximal blood-flow velocity in the portal segment in contact with the tumor and absence of the echogenic vessel-parenchymal sonographic interface are parameters predictive of tumor infiltration of the portal intima.

• One-week once-daily triple therapy with esomeprazole, moxifloxacin, and rifabutin for eradication of persistent Helicobacter pylori resistant to both metronidazole and clarithromycin.

  Authors: Stephan Miehlke, Wulf Schneider-Brachert, Christian Kirsch, Andrea Morgner, Ahmed Madisch, Eberhard Kuhlisch, Christian Haferland, Elke Bästlein, Claus Jebens, Christian Zekorn, Holger Knoth, Manfred Stolte, Norbert Lehn

  Helicobacter. 03/2008; 13(1):69-74.

  AIM: To investigate a 1-week once-daily triple therapy with esomeprazole, moxifloxacin, and rifabutin for rescue therapy of Helicobacter pylori infection. METHODS: Consecutive patients (n = 103) withAIM: To investigate a 1-week once-daily triple therapy with esomeprazole, moxifloxacin, and rifabutin for rescue therapy of Helicobacter pylori infection. METHODS: Consecutive patients (n = 103) with at least one previous treatment failure and H. pylori infection resistant to both metronidazole and clarithromycin were treated with esomeprazole 40 mg, moxifloxacin 400 mg, and rifabutin 300 mg, given once daily for 7 days. Eradication was confirmed by histology and culture. CYP2C19 status was determined by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: Intention-to-treat and per-protocol eradication rates were 77.7% (68.4-85.3) and 83.3% (74.4-90.2). Five patients discontinued prematurely (4.8%). Eradication was achieved in 93.1% of poor/intermediate metabolizers and in 78.8% of homozygous extensive metabolizers (p = .14). Eradication rates in patients with one, two, three, and four or more previous failures were 78.3%, 89.6%, 68.6%, and 88.9%, respectively (p = .21). The regimen was effective in seven of nine patients who previously failed quadruple therapy. Post-treatment resistance to moxifloxacin and rifabutin was detected in two (12.5%) and five (31%) patients after treatment failure. CONCLUSION: Once-daily triple therapy with esomeprazole, moxifloxacin, and rifabutin is a promising, safe, and convenient regimen for rescue therapy of H. pylori infection that may serve as a valuable alternative to quadruple therapy, particularly for patients with intolerance to amoxicillin.

• Boswellia serrata extract for the treatment of collagenous colitis. A double-blind, randomized, placebo-controlled, multicenter trial.

  Authors: Ahmed Madisch, Stephan Miehlke, Otto Eichele, Jenny Mrwa, Birgit Bethke, Eberhard Kuhlisch, Elke Bästlein, Georg Wilhelms, Andrea Morgner, Bernd Wigginghaus, Manfred Stolte

  International journal of colorectal disease. 01/2008; 22(12):1445-51.

  BACKGROUND AND AIMS: The objective of this study was to investigate the effect of Boswellia serrata extract (BSE) on symptoms, quality of life, and histology in patients with collagenous colitis.BACKGROUND AND AIMS: The objective of this study was to investigate the effect of Boswellia serrata extract (BSE) on symptoms, quality of life, and histology in patients with collagenous colitis. MATERIALS AND METHODS: Patients with chronic diarrhea and histologically proven collagenous colitis were randomized to receive either oral BSE 400 mg three times daily for 6 weeks or placebo. Complete colonoscopy and histology were performed before and after treatment. Clinical symptoms and quality of life were assessed by standardized questionnaires and SF-36. The primary endpoint was the percentage of patients with clinical remission after 6 weeks (stool frequency<or=3 soft /solid stools per day on average during the last week). Patients of the placebo group with persistent diarrhea received open-label BSE therapy for a further 6 weeks. RESULTS: Thirty-one patients were randomized; 26 patients were available for per-protocol-analysis. After 6 weeks, the proportion of patients in clinical remission was higher in the BSE group than in the placebo group (per protocol 63.6%; 95%CI, 30.8-89.1 vs 26.7%, 95%CI, 7.7-55.1; p=0.04; intention-to-treat 43.8% vs 26.7%, p=0.25). Compared to placebo, BSE treatment had no effect on histology and quality of life. Five patients discontinued BSE treatment prematurely. Discontinuation was due to adverse events (n=1), unwillingness to continue (n=3), or loss to follow-up for unknown reasons (n=1). Seven patients received open-label BSE therapy, five of whom achieved complete remission. CONCLUSIONS: Our study suggests that BSE might be clinically effective in patients with collagenous colitis. Larger trials are clearly necessary to establish the clinical efficacy of BSE.

• Tissue inhibitor of metalloproteinase-1 (TIMP-1) polymorphisms in a Caucasian population with abdominal aortic aneurysm.

  Authors: Irene Hinterseher, Dietmar Krex, Eberhard Kuhlisch, Karl G Schmidt, Christian Pilarsky, Wolfgang Schneiders, Hans D Saeger, Hendrik Bergert

  World journal of surgery. 12/2007; 31(11):2248-54.

  BACKGROUND: The formation of a sporadic abdominal aortic aneurysm (AAA) is explained by the remodeling of the extracellular matrix (ECM) and breakdown of structural components of the vascular wall.BACKGROUND: The formation of a sporadic abdominal aortic aneurysm (AAA) is explained by the remodeling of the extracellular matrix (ECM) and breakdown of structural components of the vascular wall. Matrix metalloproteinases are the principal matrix-degrading proteases and are known to play a major role in the remodeling of the extracellular matrix in arterial vessels. Their activity is controlled by tissue inhibitors of metalloproteinases (TIMPs). Decreased TIMP-1 and TIMP-2 expression in the extracellular matrix of the walls of AAAs has been shown in several studies. This case control study was designed to investigate the possible impact of genetic variants of the TIMP-1 gene in the etiology of AAA. METHODS: TIMP-1 single nucleotide polymorphisms (SNPs) were analyzed in a primary study sample of 50 patients with AAA and 44 controls. Differences in genotype and allele frequencies of identified polymorphisms were determined after sequencing the entire coding region and selected parts of the promoter using the automated laser fluorescence technique. A second sample (96 patients vs. 89 controls) was investigated by single-base sequencing to confirm significant results. RESULTS: Three polymorphisms were identified, one of which, described for the first time in this article, is located in intron 4 (TIMP-1: 328 + 16C > T). A statistically significant difference in allele frequencies for SNP TIMP-1 372T>C was detected in the primary study group. The C allele was more frequent in male patients with AAA than in the control group [23 vs. 4, p = 0.029, OR (95% CI) 4.38 (1.13-20.47)]. However, this result could not be confirmed in a second sample of males [52 vs. 45, p = 0.624, OR (95% CI) 1.16 (0.65-2.06)]. There were no statistically significant differences in genotype or allele frequencies of the other detected SNPs between the two groups. CONCLUSIONS: Our analysis of the entire coding region and selected parts of the promoter of the TIMP-1 gene failed to show an association between genetic polymorphisms and AAA, suggesting that variations in the TIMP-1 gene do not contribute to the development of AAA.

• Effects of professional singing education on vocal vibrato--a longitudinal study.

  Authors: Dirk Mürbe, Thomas Zahnert, Eberhard Kuhlisch, Johan Sundberg

  Journal of voice : official journal of the Voice Foundation. 12/2007; 21(6):683-8.

  Vocal vibrato is regarded as one of the essential characteristics of voice quality in classical singing. Professional singers seem to develop vibrato automatically, without actively striving toVocal vibrato is regarded as one of the essential characteristics of voice quality in classical singing. Professional singers seem to develop vibrato automatically, without actively striving to acquire it. In this longitudinal investigation, the vocal vibrato of 22 singing students was examined at the beginning of and after 3 years of professional singing education. Subjects sang an ascending-descending triad pattern in slow tempo on vowel [a:] at a comfortable pitch level twice at soft (piano) and twice at medium (mezzoforte) loudness. The top note of the triad pattern was sustained for approximately 5s. The mean and the standard deviation (SD) of the vibrato rate were measured for this note. Results revealed that after 3 years of training, voices with vibrato slower than 5.2 Hz were found to have a faster vibrato, and voices with vibrato faster than 5.8 Hz were found to have a slower vibrato. Standard deviation of vibrato rate was higher in soft than in medium loudness, particularly before the education. Also high values of SD of vibrato rate, exceeding 0.65 Hz, had decreased after the education. These findings confirm that vibrato characteristics can be affected by singing education.

• Influence of extracellular matrix coatings on implant stability and osseointegration: an animal study.

  Authors: Bernd Stadlinger, Eckart Pilling, Matthias Huhle, Ronald Mai, Susanne Bierbaum, Ricardo Bernhardt, Dieter Scharnweber, Eberhard Kuhlisch, Ute Hempel, Uwe Eckelt

  Journal of biomedical materials research. Part B, Applied biomaterials. 11/2007; 83(1):222-31.

  Aim of the present study was to test the hypothesis that the application of components of the extracellular matrix such as glycosaminoglycans used as implant surface coatings in combination withAim of the present study was to test the hypothesis that the application of components of the extracellular matrix such as glycosaminoglycans used as implant surface coatings in combination with collagen, with and without growth factor, can lead to enhanced ossification and thus improve implant stability compared with collagen coatings alone. Twenty miniature pigs received 120 experimental titanium implants in the mandible. Three types of surface coatings were created: (1) collagen type I (coll), (2) collagen type I/chondroitin sulphate (coll/CS), (3) collagen type I/chondroitin sulphate/BMP-4 (coll/CS/BMP). Periimplant bone formation was assessed within a defined recess along the length axis of the implant. Bone-implant contact (BIC) and bone volume density (BVD) were determined, using both histomorphometry and synchrotron radiation micro computed tomography (SRmicroCT). To measure implant stability, resonance frequency analysis was applied after implantation and 1, 3, 7, and 22 weeks after placement. BIC was highest for coll/CS coated implants, followed by coll, p = 0.082. Histomorphometric BVD did not significantly change for any coating. SRmicroCT analysis showed an increased BVD for collagen coated implants, compared with the other two surface coatings. Implant stability showed a decrease for all coatings up to the third week. At 22 weeks, all coatings showed an increase in stability without reaching their initial level. Highest stability was reached for coll coated implants, p = 0.051. It was concluded that collagen and coll/CS implant coatings have advantageous characteristics for peri-implant bone formation, compared with the further integration of BMP-4.