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Guido Gerken

Publications and source records attributed to Guido Gerken.

70 records · Page 4Linked to original sources
PubMed2002

Living-related liver transplantation from the view of the donor: a 1-year follow-up survey.

BACKGROUND: In the past, follow-up surveys for living-related liver transplantation (LRLT) mainly focused on the medical outcome of recipients and donors. In this survey the prevalence of personal, familial, or economic problems of the donors and changes of quality of life after donation were studied. METHODS: Questionnaires were sent to 24 donors after right hepatectomy for LRLT (response 92%). The modified EUROTOLD (European Multicenter Study of Transplantation Using Living Donors) questionnaire was used to inquire about the decision-making process, family problems, and economic problems related to the donation. Global quality of life was measured with the SF-36 Health Survey. RESULTS: For most donors the decision to donate was easy or not very difficult (21/22) and was made spontaneously (17/22). The amount of information about the risks of LRLT was limited at the time of decision but increased remarkably immediately before the operation. In 28%, family conflicts occurred (5/22). Retrospectively, all but two donors (91%) would donate again. On average, donors started working after 9 (+/-3.7) weeks and felt fully recovered after 13 (+/-7.3) weeks. Adverse financial affects were experienced by 41% of the donors (9/22) because of the donation, and four of those received a compensation. Importantly, quality of life did not differ between donors and nondonors. CONCLUSION: Donors viewed LRLT positively. Quality of life after donation did not change. However, donors had a prolonged period of physical rehabilitation, and 41% experienced financial disadvantages.

Adolescent↗
PubMed2002

Commensal-associated molecular patterns induce selective toll-like receptor-trafficking from apical membrane to cytoplasmic compartments in polarized intestinal epithelium.

Commensal-associated molecular patterns, the major products of nonpathogenic bacteria, are present at high concentrations at the apical surface of the intestinal epithelium. However, the nature of the interaction of commensal-associated molecular patterns with the lumenal surface of the epithelium has not been defined. We have recently demonstrated that intestinal epithelial cells constitutively express several Toll-like receptors (TLRs) in vitro and in vivo that seem to be the key receptors responsible for immune cell activation in response to various bacterial products. In this study we characterize the subcellular distribution of two major TLRs, TLR2 and TLR4, and their ligand-specific dynamic regulation in the model human intestinal epithelial cell line T84. Immunocytochemical studies indicate that TLR2 and TLR4 are constitutively expressed at the apical pole of differentiated T84 cells. After stimulation with lipopolysaccharide or peptidoglycan, TLRs selectively traffic to cytoplasmic compartments near the basolateral membrane. Thus, we demonstrate that TLRs are positioned at the apical pole where they are poised to monitor the sensitive balance of the lumenal microbial array. The results of this dynamic epithelial surveillance can then be conveyed to the underlying cell populations of the lamina propria via these innate immune pattern recognition receptors.

Cell Membrane↗
PubMed2002

Do changes in visceral sensory function determine the development of dyspepsia during treatment with aspirin?

BACKGROUND & AIMS: We hypothesized that the development of dyspeptic symptoms during treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) would be linked to alterations in gastric mechanosensory function and gastric emptying. METHODS: In the first study, gastric mechanosensory thresholds (barostat technique) and gastric emptying ((13)C-octanoic breath test) were measured and endoscopy was performed at entry and after 5 days of treatment with aspirin (500 mg 3 times daily) in 8 patients with functional dyspepsia (initially without symptoms) and 8 healthy controls. In a second, double-blind, placebo-controlled, cross-over study, 6 new patients with functional dyspepsia and 6 controls were started with either placebo or aspirin for 5 days. Sensory thresholds were tested after the fifth day of aspirin or placebo treatment. Abdominal symptoms were assessed daily. RESULTS: In the first study, 6 of 8 patients and 3 of 8 controls, and in the second trial 6 of 6 patients and 1 of 6 healthy subjects, developed dyspepsia on aspirin (P < 0.005 patients vs. healthy subjects). No symptoms occurred during placebo treatment. Lanza scores were not associated with symptoms. After aspirin, sensory thresholds increased in both studies in subjects without development of symptoms (by 25.9% +/- 7.9%, and 31.0% +/- 4.1%, respectively, all P < 0.05), whereas there was no significant increase in subjects who developed symptoms (-11.2% +/- 5.3% and -3.4% +/- 13.4%, all P > 0.4). Neither thresholds nor symptoms were linked with the severity of mucosal damage, baseline gastric emptying (t1/2), or changes of gastric emptying (all P > 0.4). CONCLUSIONS: Failure to increase sensory thresholds during treatment with aspirin is associated with the development of dyspepsia.

Adult↗
PubMed2002

Albumin dialysis in cirrhosis with superimposed acute liver injury: a prospective, controlled study.

Patients with liver cirrhosis and a superimposed acute injury with progressive hyperbilirubinemia have a high mortality. A prospective, controlled study was performed to test whether hyperbilirubinemia, 30-day survival, and encephalopathy would be improved by extracorporeal albumin dialysis (ECAD). Twenty-four patients were studied; 23 patients had cirrhosis; 1 had a prolonged cholestatic drug reaction and was excluded from per protocol (PP) analysis. Patients had a plasma bilirubin greater than 20 mg/dL and had not responded to prior standard medical therapy (SMT). Patients were randomized to receive SMT with ECAD or without (control). ECAD was performed with an extracorporeal device that dialyzes blood in a hollow fiber dialyzer (MW cutoff < 60 kd) against 15% albumin. Albumin-bound molecules transfer to dialysate albumin that is regenerated continuously by passage through a charcoal and anion exchange column and a conventional dialyzer. ECAD was associated with improved 30-day survival (PP, 11 of 12 ECAD, 6 of 11 controls; log rank P <.05). Plasma bile acids and bilirubin decreased on average by 43% and 29%, respectively, in the ECAD group after 1 week of treatment, but not in the control group. Renal dysfunction and hepatic encephalopathy improved in the ECAD group, but worsened significantly in the control group. ECAD was safe, with adverse events being rare and identical in both groups. In conclusion, ECAD appears to be effective and safe for the short-term treatment of patients with cirrhosis and superimposed acute injury associated with progressive hyperbilirubinemia and may be useful for increasing survival in such patients awaiting liver transplantation.

Adult↗
PubMed2002

[Quality of life in patients before and after kidney transplantation].

The presented study was carried out to differentially assess the quality of life (QOL) of two patient groups with end-stage renal disease (ESRD) with regard to the replacement therapy (dialysis vs. transplantation) and healthy controls. Successfully transplanted patients (n = 149) and patients treated by dialysis (n = 149) on the waiting list for transplantation at the Transplant Center Essen, Germany were enrolled. Additionally, 149 healthy controls were enrolled by an accumulative process starting from employees of the University Hospital Essen. Members of these three groups were strictly matched by age and gender. Medical data were gained from the patient record, QOL was measured by a global inventory, the Munich Quality of Life Dimension List (MLDL), and two specific inventories, the Brief Symptom Inventory (BSI) and the Questionnaire for Social Support - Short Form (K-22). Transplanted patients and healthy controls reported similar QOL, which was significantly higher than in dialysis patients (p < 0.0001). This was particularly true for the physical and the psychological status, but not for the social situation. Both patient groups reported similar social support, which was significantly lower than in controls (p < 0.006). Both ESRD groups described higher satisfaction with social support than the healthy controls (p < 0.0001). Successful kidney transplantation not only improved distinct aspects of QOL, but even put the patients on par with healthy controls regarding physical, psychological and functional QOL. Lower social support and higher satisfaction with social support in both patient groups should be evaluated further. From a clinical viewpoint, the improvement of QOL due to transplantation is impressive, but more attention should be paid to the interpersonal relations of ESRD patients. International multicenter longitudinal studies to investigate QOL in ESRD patients under different treatment modalities are emphasized.

Activities of Daily Living↗
PubMed2002

Effect of transient chemically induced colitis on the visceromotor response to mechanical colorectal distension.

BACKGROUND: Acute mucosal inflammation may initiate alterations of visceral sensory function. However, experimental studies on the potential effects of a transient inflammation on visceral sensitivity are lacking. METHODS: We performed colorectal distensions with a barostat device in fasted, conscious, male Lewis rats (n = 20) and assessed the nociceptive response (visceromotor response; VMR) to tonic colorectal distension (CRD) (60 mmHg/3 min) by abdominal-wall electromyography. Measurements were taken before and 3, 5 and 14 days after induction of a transient and self-limiting colitis by instillation of trinitrobenzenesulphonic acid (TNB)/ethanol (or saline as control). Tissue samples from paired controls were obtained to assess histological tissue alterations. RESULTS: TNB/ethanol but not saline induced an acute colitis, with most severe histological lesions occurring 5 days after instillation. After 14 days, there was no histological evidence for persisting mucosal alterations. Five days after induction of TNB/ethanol colitis, the VMR to CRD reached a transient increase (P < 0.05 v. baseline), which returned to baseline levels by day 14. In control experiments (rectal saline instillation), the VMR to CRD decreased significantly compared with baseline values (P < 0.05). CONCLUSION: Following an acute colitis due to single colorectal instillation of TNB/ethanol, histological changes are associated with an enhanced nociceptive response to CRD.

Animals↗
PubMed2002

Two cases of pancreatic tuberculosis in nonimmunocompromised patients. A diagnostic challenge and a rare cause of portal hypertension.

Pancreatic tuberculosis is very rare, especially in immunocompetent patients, and represents a diagnostic challenge. We describe 2 cases of pancreatic tuberculosis mimicking carcinoma on CT scan. In the first case, explorative laparotomy revealed granulomatous inflammation suggestive of tuberculosis. Cultured smears from the pancreatic tail tested positive for Mycobacterium tuberculosis, and the patient responded well to antituberculous medication. In the second case, fine needle aspirate revealed tuberculosis. This case is unique with regard to development of portal hypertension in pancreatic tuberculosis. Antituberculous medication achieved little improvement, then the patient was lost to follow-up. In suspicion of carcinoma the patient underwent laparotomy in another hospital. Malignancy was excluded, and a purulent necrotic pancreas was resected. The patient finally improved without any antituberculous medication and remains well. Both patients were tested HIV-negative. We summarize the etiology, clinical presentation, diagnosis and treatment of a diagnostic dilemma, which should be considered in clinical practice.

Adult↗
PubMed2002

Lisofylline and lysophospholipids ameliorate experimental colitis in rats.

BACKGROUND: Intestinal inflammatory processes initiate a chain reaction in which membrane-bound lipids generate eicosanoids and phospholipids. Bioactive lipid mediators play a pivotal role in the pathogenesis of intestinal inflammation and colonic mucosa from patients with inflammatory bowel disease contains high levels of phospholipids. Therefore, we investigated the effects of lysophosphatidic acid and lysophosphatidylethanolamine, two natural occurring phospholipids and lisofylline, which decreases lipid peroxidation, in an in-vivo model of intestinal inflammation. METHODS: Colitis was induced by rectal administration of ethanol and trinitrobenzene sulfonic acid in rats. Rats were treated once daily with either lysophosphatidic acid or lysophosphatidylethanolamine rectally or twice daily intraperitoneally with lisofylline following induction of colitis. Rats were sacrificed after 7 days and the effect of lysophosphatidic acid, lysophosphatidylethanolamine, and lisofylline on colonic damage and inflammation were assessed using standardized macroscopical and histological injury scores. RESULTS: Treatment with lysophosphatidic acid, lysophosphatidylethanolamine, and lisofylline significantly reduced the degree of inflammation and necrosis in the distal colon compared to control rats. In addition, the weight loss was significantly less in the treatment groups compared to controls. Histological studies revealed a significant reduction of epithelial damage and colonic inflammation. CONCLUSION: The administration of anti-inflammatory lysophospholipids and suppression of proinflammatory lipid metabolites by lisofylline may provide new approaches to ameliorate intestinal inflammation.

Administration, Topical↗
PubMedDate not supplied

DNA-based immunotherapy: potential for treatment of chronic viral hepatitis?

Persistent HBV and HCV infection represent major causes of chronic liver disease with a high risk of progression to liver cirrhosis and hepatocellular carcinoma (HCC). Conventional protein-based vaccines are highly efficacious in preventing HBV infection; whereas in therapeutic settings with chronically infected patients, results have been disappointing. Prophylactic vaccination against HCV infection has not yet been achieved due to many impediments including frequent spontaneous mutations of the virus with escape from immune system control. Using animal models it has been demonstrated that DNA-based immunisation strategies may overcome this problem because of their potential to induce immunity against multiple viral epitopes. DNA-based vaccines mimic the effect of live attenuated viral vaccines, eliciting cell mediated immunity in addition to inducing humoral responses. Efficacy may further be improved by addition of DNA encoding immunomodulatory cytokines and more recently, direct genetic modulation of antigen-presenting cells, such as dendritic cells (DC), has been shown to increase antigen-specific immune responses. This review focuses on immunological aspects of chronic HBV and HCV infection and on the potential of DNA- and DC-based vaccines for the treatment of chronic viral hepatitis.

Animals↗
PubMedDate not supplied

Pegylated interferon alfa-2b alone or in combination with lamivudine for HBeAg-positive chronic hepatitis B: a randomised trial.

BACKGROUND: Treatment of HBeAg-positive patients with chronic hepatitis B is not effective in most. A combination of immunomodulatory pegylated interferon alfa-2b and antiviral lamivudine might improve the rate of sustained response. METHODS: 307 HBeAg-positive patients with chronic hepatitis B were assigned combination therapy (100 microg/week pegylated interferon alfa-2b and 100 mg/day lamivudine) or monotherapy (100 microg/week pegylated interferon alfa-2b and placebo) for 52 weeks. During weeks 32-52 the pegylated interferon dose was 50 microg/week in both treatment groups. The analyses were based on the modified intention-to-treat population after exclusion of 24 patients from one centre withdrawn for misconduct, ten who lost HBeAg before the study start, and seven who received no study medication. All included patients were followed up for 26 weeks after treatment. FINDINGS: 49 (36%) of 136 patients assigned monotherapy and 46 (35%) of 130 assigned combination therapy had lost HBeAg at the end of follow-up (p=0.91). More of the combination-therapy than of the monotherapy group had cleared HBeAg at the end of treatment (57 [44%] vs 40 [29%]; p=0.01) but relapsed during follow-up. Patterns were similar when response was assessed by suppression of serum hepatitis B virus (HBV) DNA or change in concentrations of alanine aminotransferase. Response rates (HBeAg loss) varied by HBV genotype (p=0.01): A, 42 (47%) patients; B, ten (44%); C, 11 (28%); and D, 26 (25%). INTERPRETATION: Treatment with pegylated interferon alfa-2b is effective for HBeAg-positive chronic hepatitis B. Combination with lamivudine in the regimen used is not superior to monotherapy. HBV genotype is an important predictor of response to treatment.

Adult↗
PubMedDate not supplied

Serum C3 complement concentrations correlate with liver function in patients with liver cirrhosis.

BACKGROUND/AIMS: The aim of this study was to investigate whether C3 and C4 serum complement concentrations have prognostic relevance for patients with liver cirrhosis. METHODOLOGY: Serum complement concentrations of C3 and C4 were measured in 69 patients with liver cirrhosis and correlated with the Child-Pugh score. RESULTS: C3 concentrations were 1.06+/-0.21 g/L in patients with Child-Pugh A liver cirrhosis and significantly lower in Child-Pugh B (0.78+/-0.24 g/L) and even lower Child-Pugh C (0.49+/-0.14 g/L) (p=0.006 B vs. A, p<0.001 C vs. B). Patients with consecutive hepatorenal syndrome (HRS) had the lowest C3 concentrations (0.44+/-0.05 g/L (Child-Pugh C +HRS) vs. 0.54+/-0.06g/dL (Child-Pugh C -HRS); p<0.05). C4 concentrations were 0.21+/-0.08 in Child-Pugh A and significantly lower in Child-Pugh B (0.11+/-0.04) and Child-Pugh C (0.09+/-0.04) patients (p<0.001). There was a negative correlation between C3 (r = -0.81, p<0.001) and C4 (r = -0.51, p<0.05) concentrations and the Child-Pugh score. CONCLUSIONS: Serum complement concentrations of C3 and C4 correlate negatively with the Child-Pugh score in patients with liver cirrhosis. C3 concentrations are lower in those Child-Pugh C cirrhosis patients with consecutive development of HRS.

Bacterial Infections↗
PubMedDate not supplied

Efficacy of transarterial chemoembolization prior to liver transplantation for hepatocellular carcinoma as found in pathology.

BACKGROUND/AIMS: To analyze the efficacy of chemoembolization prior to liver transplantation in liver explants. METHODOLOGY: We reviewed pathological findings in the explanted livers of 21 patients with histologically proven hepatocellular carcinoma and liver cirrhosis who underwent transarterial chemoembolization (TACE) prior to liver transplantation. Nine patients had solitary nodules with a median diameter of 4 cm (range 1.5-7 cm), 7 patients had 2 or 3 tumors with a median total diameter of 5.9 cm (range 3-9 cm) and 5 patients had a multifocal tumor prior to TACE. Pathological up-staging of the clinical tumor classification was documented as "tumor-progression." Concurrence of clinical and pathological findings was documented as "steady disease". "Tumor regression" described those cases in which the pathological classification downgraded the clinical findings. RESULTS: There was no treatment-related morbidity in these patients' group. Tumor regression was proved in 11/21 patients (52.4%) whereas steady disease was observed in 7/21 patients (33.4%). In 5 patients (23.8%) no vital tumor was found by pathological examination. Tumor regression was observed only in one of the five patients having a multifocal tumor prior to TACE. Tumor progression was observed in 3/21 patients (14.3%). CONCLUSIONS: Our data show that TACE provides acceptable local tumor control as bridging treatment before liver transplantation. Although the majority of our patients (15/21, 71.4%) had 2 or more tumor lesions at the beginning of treatment, tumor progression was observed in only a minority (14.3%) of patients. However, multifocal tumors could not be successfully under-staged through this treatment and, furthermore, vital tumor was always observed in pathology; the usefulness of TACE in multifocal disease has to be re-estimated.

Carcinoma, Hepatocellular↗
PubMedDate not supplied

Overweight patients are more susceptible for acute liver failure.

BACKGROUND/AIMS: To determine a potential correlation of gender, age, and/or body mass index (BMI) with the development of acute-on-chronic liver failure (AOC). METHODOLOGY: A retrospective 2.5-year study employed 34 patients (65% females and 35% males, aged 37.9 +/- 12.6 years) fulfilling established criteria for acute liver failure (ALF). Patients were subdivided into ALF (n = 18) and AOC (n = 16) groups, according to a history of prior chronic liver disease. Causes of liver failure included drug toxicity (52.9%), viral hepatitis (26.5%), and acute excessive ethanol abuse (11.8%). all anamneses were thoroughly reviewed. Throughout the course of the study, the patients were monitored for established clinical signs and laboratory parameters indicating acute liver injury. Gender, age, and BMI were correlated with the clinical outcome. RESULTS: Twelve patients (35.3%) received an orthotopic liver allograft, with one re-transplantation. Six patients (17.6%), including two transplanted individuals, died in the course of the study. Of all parameters evaluated, BMIs were significantly higher in AOC vs. ALF (p < 0.002), revealing values of > 25 in 62.5% of the AOC patients. When subjected to acute risk factors, elevated BMI clearly coincided with a higher rate of AOC. Importantly, half of all patients initially classified as ALF by employing current criteria thus suffered from AOC coinciding with increased mortality. CONCLUSIONS: Generally, these results call for a reduction of the BMI. Specifically, our findings argue for a closer BMI monitoring of patients at risk of developing chronic liver disease.

Adult↗
PubMedDate not supplied

Cryoglobulin-associated uptake of hepatitis C virus into human hepatocytes.

AIMS: The mechanisms of binding and uptake of hepatitis C-virus (HCV) are critical determinants of the infection-reinfection cycle but due to ongoing absence of a robust cell culture system, these mechanisms are still largely hypothetical. Cryoglobulins are atypical immunoglobulins, present in 40% of HCV patients. The aim of this study was to determine the role of these HCV-containing cryoglobulins as carrier molecules for viral uptake into primary human hepatocytes. METHODOLOGY: Cryoglobulins were precipitated from serum of chronically HCV-infected patients, labeled with biotin and incubated with freshly prepared hepatocytes from human liver tissue. Binding and endocytosis of HCV-cryoglobulins were studied by specific assays, ligand blot analysis and electron microscopy on hepatocellar plasma membranes. RESULTS: Biotinylated HCV-cryoglobulins specifically bound to hepatocytes and inhibitors of homotypic endosomal fusion reduced their uptake and intracellular trafficking, Ligand-blot and electron microscopy analysis revealed adhesion to hepatocellular plasma membranes. Inoculation of human hepatocytes with HCV-cryoglobulins but not serum from the same patients induced HCV infection in vitro. CONCLUSIONS: HCV may enter hepatocytes in conjunction with cryoglobulins via immunoglobulin or related receptors. We hypothesize, that this mechanism plays a role in chronic hepatitis to support the infection-reinfection cycle of the virus.

Aged↗
PubMedDate not supplied

Resectability of hepatocellular carcinoma: evaluation of 333 consecutive cases at a single hepatobiliary specialty center and systematic review of the literature.

BACKGROUND/AIMS: To determine resectability rates in patients with hepatocellular carcinoma (HCC) evaluated for surgical therapy. Liver resection constitutes a potentially curative treatment for HCC. However, because of the co-existing cirrhosis or the late diagnosis, only a percentage of the patients evaluated can undergo surgery. METHODOLOGY: We evaluated 333 patients with HCC admitted to our center with the intent to treat by means of tumor resection during a 6-year time period. RESULTS: Surgical resection with curative intent was undertaken in 116 patients (35%). In our series, resectability rates were significantly higher in patients with solitary HCCs (p<0.001), unilobar tumor distribution (p=0.03), and no cirrhosis (p <0.001). Transarterial chemoembolization (TACE) was the most frequent approach for nonresectable cases (18% of patients). A systematic literature review was performed in order to estimate resectability rates at other hepatobiliary centers offering multimodal treatment approaches to HCC. Results showed an overall resectability rate of 30%, with 1808 resections reported in 6108 cases. Resectability rates were significantly higher in Japanese and Eastern series when compared to American and Western studies respectively (p<0.001). CONCLUSIONS: Treatment strategies for HCC require a multidisciplinary comprehensive approach encompassing surgeons, hepatologists, radiologists, and oncologists. Surgical resection was possible in only 35% and 30% of patients with HCC evaluated for surgical therapy in our series and in the world literature, respectively. TACE was the primary treatment modality for non-resectable cases. A "no therapy" option was chosen in 21% of cases worldwide.

Carcinoma, Hepatocellular↗