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Biomedical subjects

G Gerken

Publications and source records attributed to G Gerken.

At least 37 records · Page 2Linked to original sources
PubMed2004

Long-term effects of transient chemically induced colitis on the visceromotor response to mechanical colorectal distension.

Acute gastrointestinal infections with transient mucosal inflammation frequently precede the onset of functional GI disorders with altered visceral sensory function. We hypothesized that an acute inflammation of the mucosa is linked to long-lasting alterations of afferent visceral pathways. Utilizing abdominal wall electromyography, we tested the visceromotor response to tonic rectal distension (60 mm Hg/3 min) in fasted, conscious, male Lewis rats (n = 40) with a barostat device before and 2, 4, 15, and 17 weeks after rectal instillation of saline or trinitrobenzenesulfonic acid plus ethanol. Tissue samples from paired controls were obtained to assess histologic tissue alterations. Inflammatory changes were present up to 2 weeks after acid/ethanol instillation but not after saline instillation. Compared to baseline measurements, the visceromotor response to colorectal distension increased significantly and reached a maximum 17 weeks (P < 0.001) after induction of colitis, while it decreased in control experiments (P < 0.05). In conclusion, these data suggest that an acute inflammation has long-term effects on somatosensory functioning.

Animals↗
PubMed2004

CNI-sparing regimens within the liver transplant setting: experiences of a single center.

One- and 5-year survival rates after liver transplantation have improved with the development of potent immunosuppressive drugs. Thus, attempts have shifted to reduce long-term complications of CNI and prednisone therapy. Minimization of CNI and concomitant introduction of MMF has resulted in a significant improvement of renal function, blood pressure and triglyceride values in our transplant patients. In recipients who develop recurrent or de novo malignancies, SRL therapy might be recommended. In addition, the flexibility to individualize immunosuppression should be favored in selected patients. However, large prospective randomized trials are required in order to determine if SRL/low dose CNI or SRL monotherapy are reasonable options for prolonging patient survival. Moreover, important questions such as the appropriate SRL target dose for prevention of tumor growth need to be answered. Numerous studies investigating distinct immunosuppressive combination therapies and withdrawal or minimization of CNI are available in the literature; however it is not yet clear which treatment regimens will prove to be the most efficacious and least toxic.

Adult↗
PubMed2003

Cardiovascular risk factors and probability for cardiovascular events in HIV-infected patients: part I. Differences due to the acquisition of HIV-infection.

OBJECTIVE: Due to side effects, such as hyperlipidaemia and insulin resistance, there is an increasing concern that antiretroviral drugs lead to an epidemic of cardiovascular diseases in HIV-infected patients. The present study characterizes the cardiovascular risk profile of HIV-infected individuals, due to the acquisition of HIV-infection. METHODS: Cardiovascular risk factors of 309 HIV-infected adults (HIV-acquisition: 59.2% by homosexual contact (group 1), 28.5% by heterosexual contact (group 2), 9.1% by intravenous drug abuse (group 3) and 3.2% by blood transfusion (group 4)) were analysed. Overall 10-years probability for cardiovascular events was analysed by the Framingham algorithm. RESULTS: Tobacco use was more common in group 1 subjects compared with group 2 subjects (67% vs. 52%; p<0.05). Additionally, group 1 subjects exhibited elevated total cholesterol (5.6 +/- 0.1 mmol/L vs. 4.8 +/- 0.3), LDL-cholesterol (3.6 +/- 0.1 mmol/L vs. 2.8 +/- 0.2) and triglyceride concentrations (3.2 +/- 0.3 mmol/L vs. 1.7 +/- 0.2) compared with group 3 (all p<0.05). No significant differences between the groups were detected in glucose metabolism. The overall 10-years probability for cardiovascular events was significantly higher in group 1 compared with group 2 and group 3 (12.2 +/- 0.8% vs. 6.6 +/- 0.9% and 7.9 +/- 1.6%, p<0.05). CONCLUSIONS: The cardiovascular risk profile differs between subgroups of HIV-infected individuals, leading to significant higher probability of cardiovascular events in group 1 subjects. The risk of premature atherosclerosis by HIV-infected individuals and therapeutic options remains to be established.

Adult↗
PubMed2003

[Living organ donor transplantation--the German experience in comparison to others].

Living liver donation is a prominent and innovative method in the therapy of terminal liver disease in children and adults. Live donation of livers was first used in 1989 for children. After only 10 years, the concept was also established for application in adults. Due to the imminent lack of donor organs and the constantly increasing need of liver transplantation, this method will continue to grow in importance.

Adult↗
PubMed2003

Treatment of hepatitis B reinfection after liver transplantation.

Patients with chronic replicative hepatitis B virus (HBV) infection who undergo orthotopic liver transplantation (OLT) in the absence of prophylactic antiviral therapy have a high risk of graft reinfection. Serial monitoring of serum HBV DNA and HBV sequence analysis, especially of the polymerase and the "a" epitope of the surface antigen, may be a requisite diagnostic tool in order to provide optimal therapeutic management for inhibition of viral replication before and after OLT. Combination therapy with hepatitis B immunoglobulin (HBIG) and lamivudine has been widely adopted as an effective prophylactic treatment regimen against recurrent HBV disease. The major issue of concern has been the development of lamivudine resistance due to the emergence of mutations in the YMDD motif of the HBV DNA polymerase gene. Among newer antivirals, adefovir dipivoxil and entecavir have been demonstrated to be effective against both wild-type and lamivudine resistant mutants. Due to the availability of antiviral drugs, outcome of patient and graft survival has dramatically improved and has become similar or even better as compared to patients with non-HBV-related liver diseases.

Drug Therapy, Combination↗
PubMed2002

[Value of laparoscopy and biopsy].

A liver biopsy can provide important information regarding staging, grading, prognosis and management of patients with chronic liver disease including chronic viral hepatitis. A video-minilaparoscopy is the most accurate diagnostic tool to define liver cirrhosis or liver fibrosis, respectively.

Biopsy↗
PubMed2002

Sustained suppression of HCV replication and inflammatory activity after interleukin-2 therapy in patients with HIV/hepatitis C virus coinfection.

OBJECTIVE: There is increasing evidence that coinfection of hepatitis C (HCV) with HIV is associated with accelerated progression of liver cirrhosis. The aim of this pilot study was to investigate toxicity and efficacy of interleukin-2 (IL-2) for treatment of affected patients. DESIGN: Because low-dose, daily IL-2 therapy is well tolerated and can elevate CD4 cell counts and improve immune functions, patients were treated with 1-2 million units (MU) IL-2 subcutaneously daily. METHODS: This pilot trial included 7 HIV/HCV-coinfected individuals. During therapy, clinical, virologic, and laboratory parameters were closely monitored. RESULTS: All patients responded to IL-2 therapy with either improvement of either CD4 cell counts or liver function test results. In 2 patients, HCV-RNA in serum became negative 2 and 4 months, respectively, after cessation of therapy. HCV-RNA has remained undetectable in these 2 patients for 18 and 24 months, respectively. Therapy was well tolerated and no grade III or IV toxicities were observed. CONCLUSIONS: Low-dose, daily IL-2 therapy can improve both CD4 cell counts and liver function test results in patients with HIV/HCV coinfection and may in some cases lead to sustained suppression of viremia of HCV.

Adult↗
PubMed2002

[Atherosclerosis in HIV-positive patients].

Worldwide, human immunodeficiency virus (HIV) infection is one of the main health subjects. Even, the human immunodeficiency virus primarily effects the immune system, HIV infection also has an impact on other organs. Cardiovascular manifestations in HIV-infected patients could occur by the HI-virus itself or by opportunistic infections. Reports of myocardial infarction in young HIV-infected patients, who received protease inhibitors, have raised concerns about premature arteriosclerosis and coronary artery disease in this population. In the pre-protease inhibitor era, autopsy reports were the first to describe an association between coronary artery disease and HIV infection. Long-term antiretroviral therapy, including protease inhibitors, significantly reduced mortality, morbidity and revolutionized the care of HIV-infected patients. However, class-specific metabolic side effects, such as elevated total cholesterol and triglyceride levels and insulin resistance, have been described. These metabolic alterations of antiretroviral therapy impair the cardiovascular risk profile of HIV-infected patients. Even epidemiological studies found no significant effect of antiretroviral treatment type on coronary heart disease or myocardial infarction, an increase of arteriosclerosis in HIV-infected patients is suspected. Recent results of autopsy studies and analyses of endothelial function in patients with HIV infection described an effect of HIV and antiretroviral therapy on premature arteriosclerosis. The present article gives an overview about arteriosclerosis and coronary events in HIV-infected patients and the impact of antiretroviral therapy.

Antiretroviral Therapy, Highly Active↗
PubMed2002

[Gastrocolic fistula - a rare cause of cachexia and polyneuropathy].

Gastrocolic fistula is a rare clinical disorder which in the past most often occurred after gastric surgery or carcinoma of the gastrointestinal tract. However, during the last decade an increasing number of cases after benign gastric ulcers have been described. Most common symptoms have been weight loss, abdominal pain, diarrhea and copremesis. A 49-year-old cachectic patient presented with a 2-year history of abdominal discomfort and diarrhea. He reported a weight loss of 32 kg during this period and was finally unable to move because of exhaustion. Furthermore, he suffered of burning paresthesia of the legs and the abdomen. His medical history included a Billroth II operation because of recurrent ulcer disease in 1987. Barium enema revealed a gastrocolic fistula which caused small bowel bacterial overgrowth with villous atrophy and malabsorption and development of polyneuropathy. The fistula was surgically resected, and postoperatively, the patient improved and regained his weight. Gastrocolic fistula is a rare cause of diarrhea and should be considered in clinical practice. Barium enema is superior to endoscopy in detecting gastrocolic fistula.

Cachexia↗
PubMed2002

"For whom the bell tolls!" -- innate defense mechanisms and survival strategies of the intestinal epithelium against lumenal pathogens.

The intestinal epithelium serves as an essential defensive barrier of the mucosal immune system that forms a bipolar interface between the diverse populations of microbes of the lumen and subjacent immune cells present in the lamina propria. Intestinal epithelial cells express various pattern recognition receptors -- poised to recognize microbial "pathogen-associated molecular patterns" as "non-self" and to rapidly initiate innate immune responses of survival and active defense strategies against lumenal pathogens. Current understanding of the variety of innate immune features present in intestinal epithelium to maintain homeostasis is summarized and the mechanisms through which dysregulation may play a central role in initiation and perpetuation of inflammatory bowel disease are discussed.

Animals↗
PubMed2002

Capsaicin-sensitive nerve fibres induce epithelial cell proliferation, inflammatory cell immigration and transforming growth factor-alpha expression in the rat colonic mucosa in vivo.

BACKGROUND: Capsaicin-sensitive nerve fibres protect gastrointestinal mucosa in animal models of mucosal injury by modulation of mucosal blood flow and mucus secretion. The aim of our study was to evaluate the effects of capsaicin-sensitive nerve fibres in rat colonic mucosa on epithelial cell proliferation and transforming growth factor-alpha (TGFalpha) expression, which is important in mucosal defence, protection and repair. METHODS: Male Wistar rats received either a capsaicin enema with or without giving antagonists to calcitonin-gene-related-peptide (CGRP) or substance P (SP) i.v. immediately prior to the capsaicin enemas; a capsaicin enema after sensory desensitization as described previously; or a vehicle enema. In all experiments, animals received 50 mg/kg BrdU i.v. and were killed at 2, 4, 8, 12, 24 and 48 h after the various treatments. Colonic mucosal specimens were evaluated microscopically for mucosal damage, changes in the numbers of inflammatory cells and BrdU-immunoreactive epithelial cell nuclei. In the same specimens, TGFalpha-mRNA and -protein expression were evaluated by RT-PCR and Western blot analysis using standardized procedures. RESULTS: A significant increase in the number of mucosal inflammatory cells and an increase in BrdU-immunoreactive nuclei were detected following mucosal exposure to capsaicin. A 2-fold increase of TGFalpha mRNA and a 10-fold increase of TGFalpha protein expression were obtained 2-12 h after capsaicin enemas. The effects on the invading number of inflammatory cells and on the increase in BrdU immunoreactive epithelial cell nuclei were significantly reduced by both CGRP and SP antagonists and were abolished in rats previously sensory-desensitized. CONCLUSION: Capsaicin-sensitive nerve fibres modulate epithelial cell proliferation and TGFalpha expression in colonic mucosa as well as a migration of inflammatory cells into the colonic mucosa. These effects are mediated by the neurotransmitters CGRP and SP.

Animals↗
PubMed2001

[Chronic intestinal pseudo-obstruction. Clinical symptomatology and course].

BACKGROUND AND OBJECTIVE: Chronic intestinal pseudoobstruction (CIP) is a motility disorder clinically characterized by recurrent symptoms of small intestinal or large bowel obstruction without organic stenosis. The aim of the present study was to assess the clinical presentation and course of the disease. PATIENTS AND METHODS: During a four year period all available data including the symptoms as assessed by the bowel disease questionnaire (BDQ) of all patients with newly established diagnosis of CIP were analyzed including duration of symptoms and previous surgical interventions due to the abdominal symptoms. RESULTS: Data of nine patients (five females, four males, age 20 - 64 years) with newly diagnosed CIP were available for analysis. Median age at initial onset of symptoms were 24 years. The final diagnosis of CIP was established after a median of 7 years (range 1 - 20). Initially, the majority of patients suffered from uncharacteristic symptoms such as abdominal fullness and abdominal pain. All patients had undergone repeated abdominal surgical interventions for suspected mechanical bowel obstruction. On average, the first surgical intervention was performed 5 years after the onset of symptoms and there was a median number of 10 treatments as in-patients. Suspected acute bowel obstruction occurred between 1 and 14 times and laparotomies were performed in 50 % of these events. CONCLUSION: The diagnosis of CIP is usually preceded by several years with uncharacteristic abdominal symptoms. During this time, most patients undergo multiple surgical interventions. Thus, in patients with repeated suspected acute bowel obstruction without definite proof of mechanical obstruction, CIP has to be taken into consideration as differential diagnosis. In this context, small bowel manometry is an important diagnostic tool.

Adult↗
PubMed2001

Mycophenolate mofetil impairs healing of left-sided colon anastomoses.

INTRODUCTION: Inadequate healing and consequent leakage from bowel anastomoses are a significant cause of postoperative morbidity and mortality. Immunosuppressive drugs are known to disturb healing processes and to impair the mechanical stability of bowel anastomosis. Mycophenolate mofetil (MMF) is an immunosuppressive agent that selectively inhibits the proliferation of T and B lymphocytes and has been shown to be effective in preventing allograft rejection after organ transplantation. Adverse effects are few; however, nothing is known in regard to possible adverse effects of MMF administration on the healing of bowel anastomosis. The aim of the present study was to evaluate the effect of systemic MMF administration on the healing of colon anastomoses in rats. METHODS: Rats underwent laparotomy, division of the left colon, and sigmoidostomy. MMF (25 mg/kg) or vehicle was administered intraperitoneally in two groups (n=21 per group) 3 days before surgery and then once daily until euthanization (7 animals per group; 2, 4, and 6 days after surgery). Bursting pressure measurements, histologic evaluation, morphometric analysis, mucin and collagen staining, and BrdU immunohistochemistry of the anastomotic site were performed. Furthermore, matrix protein expression at the anastomotic site was determined by collagen I and fibronectin Western blots. RESULTS: Administration of MMF significantly decreased anastomotic bursting pressure postoperatively. Accordingly, histology, mucin staining, and BrdU immunohistochemistry and measurements of the colonic crypt depth showed more extended inflammation, a significantly lower proliferation rate, and a significantly thinned mucosal layer in the MMF-treated groups when compared to control animals, whereas matrix synthesis at the anastomotic site was not different. CONCLUSIONS: The administration of the immunosuppressive agent MMF significantly impairs healing and mechanical stability of colon anastomosis in rats during the early postoperative period. MMF act to disturb host reparative processes mainly by impairment of reparative colonic epithelium proliferation and less by a disturbance of matrix synthesis.

Anastomosis, Surgical↗