Search PubMed⌕ Search

Biomedical subjects

G Gerken

Publications and source records attributed to G Gerken.

At least 19 recordsLinked to original sources
PubMed2006

Disturbed in vitro adrenergic modulation of cytokine production in inflammatory bowel diseases in remission.

OBJECTIVE: Psychological stress has been implicated in the pathophysiology of both inflammatory and functional gastrointestinal (GI) diseases. The goal of this study was to address neuroendocrine modulation of cytokine production by peripheral blood cells in GI diseases. METHODS: We analyzed the in vitro effects of the beta-adrenergic agonist terbutaline and the glucocorticoid agonist dexamethasone on TNF-alpha and IL-10 production by LPS-stimulated monocytes in whole cell blood cultures in patients with inflammatory bowel diseases in remission (N=10), diarrhoea-predominant irritable bowel syndrome (IBS, N=12), patients with a recent gastroenteritis (post-infectious group, N=10), and healthy controls (N=15). RESULTS: In response to terbutaline, there was a significant increase in IL-10 production (concentration effect: p<0.05), which was diminished in IBD (group effect: p<0.01), comparable in IBS and controls, but enhanced in the post-infectious group (group x concentration effect: p<0.05). In contrast, terbutaline resulted in a concentration-dependent suppression of TNF-alpha production, which was comparable in all groups. Dexamethasone suppressed TNF-alpha production in a dose-dependent manner in all groups, but this effect was significantly more pronounced in post-infectious subjects (group effect: p<0.05). CONCLUSIONS: In IBD, disturbed adrenergic regulation of IL-10 could be part of the mechanism(s) underlying the modulation of disease activity by psychological stress. Diarrhoea-predominant IBS was not associated with altered adrenergic or glucocorticoid regulation of cytokine production by peripheral blood cells, whereas a recent history of gastroenteritis was associated with disturbed neuroendocrine modulation of cytokine production, which may play role in the pathophysiology of post-infectious IBS.

Adrenergic beta-Agonists↗
PubMed2006

Visceral pain and public speaking stress: neuroendocrine and immune cell responses in healthy subjects.

Whereas responses to psychological stressors are well-characterized, little is known regarding responses to painful visceral stimuli. We analyzed the emotional, cardiovascular, neuroendocrine, and cellular immune responses to painful rectal stimulation and psychological stress in healthy individuals. Eleven healthy subjects were studied in three conditions on separate days: painful rectal distension, public speaking stress, and rest. Blood was drawn for endocrinological and immunological analyses; heart rate and blood pressure were measured continuously; state anxiety was assessed with a questionnaire (STAI-S). Anxiety scores were highest in the rectal distension condition. This was evident following rectal distension (mean STAI-S scores: 44.2+/-3.5 post-distension vs. 36.6+/-3.8 post-speech, p<.05), but anxiety was also elevated at baseline (41.6+/-3.9 vs. 32+/-3.2 recovery, p<.01). This anticipatory effect was reflected by elevated baseline cortisol (p<.05) and baseline ACTH (p<.01) levels, as well as circulating lymphocytes and lymphocyte subsets, including decreased basal CD3+CD4+ cells (p<.05) and increased CD16+CD56+ cells (p=.06) compared to rest. Both public speech and rectal distension induced cardiovascular activation, but the effect was more pronounced following rectal distension (+63.8+/-9.4 mmHg in response to distension vs. +36.4+/-6.2 mmHg in response to speech for systolic BP, p<.05). Different response patterns were also observed in the distribution of circulating leukocytes and lymphocyte subsets, including CD16+CD56+ cells (p<.05). An acute visceral pain stimulus causes profound emotional, neuroendocrine, and immune cell responses, which are markedly affected by anticipatory anxiety. These findings may have implications for conditions associated with visceral hyperalgesia.

Adult↗
PubMed2006

[The hepato-pulmonary syndrome--where do we stand in the year 2006?].

The hepato-pulmonary syndrome (HPS) is characterized by a combination of liver disease and pulmonary gas exchange abnormalities with arterial hypoxemia, intrapulmonary vasodilatation and arteriovenous shunting in the absence of intrinsic cardiopulmonary disease. The course of the disease is typically progressive. The mortality rate correlates with the pulmonary shunt volume and the degree of hypoxemia at room air. While the patho-physiology of HPS is still not fully understood, a multifactorial etiology is favored. Apart from functional intrapulmonary arteriovenous shunts which appear to represent a major factor in the development of HPS, both ventilation-perfusion mismatch and limited oxygen diffusion contribute to the HPS. Regarding its clinical appearance, pulmonary and hepatic symptoms have to be distinguished. Contrast echocardiography is the primary diagnostic tool. Symptomatically, hypoxemia can be treated with oxygen. So far, the only successful treatment approach which has been tested in larger patient groups, is liver transplantation. Given this background, the aim of this review is to critically discuss current concepts of this serious complication of liver diseases.

Clinical Trials as Topic↗
PubMed2006

Crohn's disease-induced non-alcoholic fatty liver disease (NAFLD) sensitizes for severe acute hepatitis B infection and liver failure.

Non-alcoholic fatty liver disease (NAFLD) commonly is associated with chronic inflammatory bowel disease (CIBD) and usually is considered to be stable and benign. However, NAFLD -- and in particular its subset, non-alcoholic steatohepatitis (NASH) -- may lead to progressive liver disease. Moreover, NAFLD sensitizes the liver to injury and increases the risk of developing acute-on-chronic liver failure following a "third hit". We here present one patient with NASH, as probably induced by long-standing Crohn's disease in the absence of ethanol consumption or abuse. The patient acquired an acute HBV infection and died from complications. As based on the clinical and histological findings, Crohn's disease appears to be a risk factor for developing NAFLD and thus to contribute to the progression into NASH. In conclusion, we suggest that Crohn's disease-related NAFLD may increase the vulnerability of the liver, which indicates that patients with a known history of CIBD merit special attention.

Crohn Disease↗
PubMed2006

Successful sealing of benign esophageal leaks after temporary placement of a self-expanding plastic stent without fluoroscopic guidance.

INTRODUCTION: We report on our experience with the temporary use of a self-expanding plastic stent (SEPS) in the treatment of non-malignant esophageal leaks. MATERIAL AND METHODS: Between November 2001 and May 2005 ten patients with iatrogenic esophageal perforations (n = 4), post-surgical leaks (n = 5) and esophago-mediastinal fistulas after caustic injury (n = 1) were treated by temporary SEPS placement. In eight out of ten patients SEPS placement was done without fluoroscopy due to the emergency setting. Stent removal was performed with a rat-toothed forceps. RESULTS: Leaks were located in the proximal (n = 1), middle (n = 6) and distal (n = 3) parts of the esophagus. The mean leakage size was 2 cm. Stent placement without fluoroscopy was always successful. The median duration of stent therapy was 55.5 days (range 15,438). In 7/10 cases the SEPS was readily removed, showing complete healing of the former leak. Four patients died during the follow-up. However, their deaths were not related to the stent therapy. DISCUSSION: The temporary use of the SEPS represents a safe method for sealing benign esophageal leaks. In the emergency-setting SEPS placement without fluoroscopy is feasible and the stent can be easily removed. In contained perforations without severe mediastinitis of the mid esophagus the SEPS should be discussed as a gentle first-line therapy.

Esophageal Perforation↗
PubMed2006

Dark lumen MR colonography: can high spatial resolution VIBE imaging improve the detection of colorectal masses?

PURPOSE: To assess whether the detection of colorectal lesions can be improved using high spatial resolution VIBE imaging. MATERIALS AND METHODS: 48 patients underwent same-day dark lumen MR colonography (MRC) and conventional colonoscopy (CC) as the standard for the detection of colorectal masses. MRC was performed using contrast-enhanced standard and high spatial resolution T1-weighted 3D VIBE sequences. The findings and the image quality of the standard and high spatial resolution VIBE sequences were compared qualitatively and quantitatively. The findings of both sequences regarding colorectal lesions were compared to those of a subsequently performed colonoscopy. RESULTS: The high spatial resolution VIBE sequence significantly improved the quantitative image quality (CNR 54.0 vs. 36.8). However, high spatial resolution VIBE imaging did not detect more colorectal lesions than the standard VIBE sequence. In addition, none of the sequences employed was able to detect lesions with a diameter of less than 5 mm (CC 40 lesions). However, 13 colorectal lesions with a diameter of greater than 5 mm were detected by both sequences (CC 15). CONCLUSION: High spatial resolution VIBE imaging did not improve the detection of colorectal masses and MRC fails to detect colorectal lesions with a diameter of less than 5 mm.

Adult↗
PubMed2006

Safety and efficacy of lamivudine in patients with severe acute or fulminant hepatitis B, a multicenter experience.

Acute hepatitis B progresses to liver failure with the need of liver transplantation in about 1% of cases. We treated patients with severe acute or fulminant hepatitis B with lamivudine in an attempt to prevent hepatitis B virus (HBV) reinfection after potential liver transplantation. Since September 2000, 17 patients with severe acute or fulminant HBV infection were treated with 100 or 150 mg lamivudine daily once we had evidence for a severe course as indicated by an INR >2.0. These were compared to a historic control from our unit and to external patients. Fourteen of the 17 patients (82.4%) survived with full recovery without liver transplantation. All these 14 individuals cleared HBsAg on lamivudine within less than 6 months. Twelve patients recovered quickly as indicated by a normalized prothrombin time within 1 week while two patients had a more prolonged course. None of the patients showed an adverse event. Three patients requiring transplantation despite lamivudine therapy had more advanced disease on admission, of whom one had additionally ingested paracetamol (acetaminophen) while the second was already HBV-DNA negative by polymerase chain reaction on admission. The lamivudine treated patients had significant higher frequency of survival without liver transplantation 82.4 vs 20% (4/20) in the historic control (P < 0.001). Similar data were derived from external centres using lamivudine (15/20, 75%). Lamivudine is safe in patients with severe acute or fulminant hepatitis B, leading to fast recovery with the potential to prevent liver failure and liver transplantation when administered early enough.

Adult↗
PubMed2006

Prevalence of unexplained upper abdominal symptoms in patients with migraine.

Patients with functional gastrointestinal disorders frequently report migraine. We aimed to determine the prevalence of idiopathic upper abdominal symptoms in patients with migraine and compare it with a control population of healthy blood donors. We assessed abdominal symptoms using the Bowel Disease Questionnaire in a series of 488 consecutive blood donors without migraine and 99 patients with migraine. Upper abdominal symptoms were reported by 38%[95% confidence interval (CI) 32, 44] of blood donors compared with 81% (67, 91, P<0.001) of migraine patients. Of the blood donors, 23% (18, 28) reported frequent dyspepsia compared with 60% (44, 74, P<0.001) of the migraine patients. Migraine was associated with frequent upper abdominal symptoms (odds ratio 2.7, 95% CI 1.2, 6.1) after adjusting for age, gender, smoking and consumption of analgesics and alcohol. Upper abdominal symptoms are significantly more frequent in patients with migraine compared with healthy controls. The association between migraine and idiopathic upper abdominal symptoms may suggest common pathophysiological mechanisms.

Adult↗
PubMed2005

The safety of pegylated interferon alpha-2b in the treatment of chronic hepatitis B: predictive factors for dose reduction and treatment discontinuation.

BACKGROUND: Treatment with interferon-alpha has been shown to be effective in one-third of hepatitis B e antigen-positive chronic hepatitis B patients, but is clinically associated with relevant adverse events. AIM: To investigate the safety of pegylated interferon alpha-2b in 300 hepatitis B e antigen-positive patients with compensated liver disease. METHODS: Patients were treated with pegylated interferon alpha-2b for 52 weeks combined with either lamivudine 100 mg/day or placebo. Pegylated interferon alpha-2b was administered for 100 microg once a week for 32 weeks; thereafter, the dose was reduced to 50 microg once a week. Adverse events and their effect on study medication were reported at monthly visits in a standardized way. RESULTS: The most frequently reported side-effects were flu-like syndrome (68%), headache (40%), fatigue (39%), myalgia (29%) and local reaction at the injection site (29%). These symptoms typically occurred within the first month of therapy and subsided during the course of therapy. Neutropenia and thrombocytopenia induced by pegylated interferon alpha-2b increased the risk of infections and bleeding complications, but these complications were rare and mild. The frequency of all side-effects was not different between patients treated with pegylated interferon alpha-2b combined with lamivudine or placebo. In 69 (22%) patients the dose of pegylated interferon alpha-2b was reduced prematurely. Of these dose reductions, 36 (52%) were because of neutropenia. Therapy was discontinued in 28 (8%) patients. The most frequent reasons for early discontinuation were psychiatric side-effects (depression, psychosis) and flu-like symptoms. Multivariate Cox regression analysis showed that low neutrophil count at baseline and cirrhosis were independent predictors of dose reduction or therapy discontinuation. CONCLUSION: We conclude that in patients with chronic hepatitis B and compensated liver disease prolonged pegylated interferon alpha-2b therapy is safe, and that pre-existent cirrhosis and neutropenia are the most important predictors of dose reduction or early treatment discontinuation.

Adult↗
PubMed2005

[Evaluation of non-invasive scores in the follow-up of chronic hepatitis].

To differentiate biliary diseases the biopsy of liver tissue for histological examination is still the method of choice (golden standard). By histology the exact grading (inflammatory activity) and staging (of fibrosis) is possible. Hereby, the severity of liver disease and the progress of fibrosis can be determined. None of the various fibrosis marker like hyaluronate or collagen III peptid are able to replace the histology, neither alone nor as score. These biochemical marker and clinical parameter are suitable to follow up the progress of the detected fibrosis using the so-called noninvasive staging and to reduce the number of follow up biopsies. In fast progression of liver fibrosis the follow up by biopsy is almost more affirmative. For non-invasive follow ups the particular parameter hyaluronate is qualified best, according to the actual literature. Scores must keep on being evaluated on its value.

Algorithms↗
PubMed2005

Staging laparoscopy in gastric cancer.

BACKGROUND: As patients with gastric cancer are offered choices between surgical resection, neoadjuvant or palliative chemotherapy, or symptomatic relief alone, the need for accurate preoperative staging becomes apparent. Laparoscopy has been suggested as an appropriate staging modality in a variety of upper gastrointestinal malignancies. METHODOLOGY: Staging laparoscopy was performed in 45 patients with potentially resectable gastric cancer as determined by physical examination, gastroscopy, endosonography, transcutaneous ultrasonography and current generation computed tomography. Conventional clinic staging and laparoscopic staging according to the Tumor-Node-Metastases classification of the International Union against Cancer were registered separately on a database. Results were then compared to evaluate the agreement of both staging procedures. RESULTS: Compared to conventional staging, laparoscopy resulted in up staging of 23 patients (51.1%). In 10 patients of them peritoneal seeding was first found during laparoscopy, whereas additional liver metastases were detected in 3 patients and Krukenberg's tumor in one. As a consequence, the therapy planning was changed and laparotomy was avoided in 14 of these patients as the first operative procedure. Sensitivity of clinical staging was especially poor for stage IV tumors (5.3%) and for the majority of stage IIIB tumors (42.9%). Cytologic examination of peritoneal fluid had no additional information in our series. CONCLUSIONS: The value of laparoscopy in staging patients with gastric carcinoma could be demonstrated in this study. It is a safe and effective staging modality, helping to avoid unnecessary laparotomies and providing new means of directing appropriate treatment strategy.

Adult↗
PubMed2005

The relationship between apoptosis and non-alcoholic fatty liver disease: an evolutionary cornerstone turned pathogenic.

The data currently available favor a model for the pathogenesis of non-alcoholic fatty liver disease that is based on an apparent sequential relationship of intrahepatic apoptosis, inflammation and fibrogenesis. Based on both hepatic and peripheral insulin resistance, the hepatocellular accumulation of triglycerides, termed steatosis, initially leads to an altered metabolism of glucose and free fatty acids in the liver. In response, increased expression of death receptors in simple steatosis enhances the hepatocytes' susceptibility for pro-apoptotic stimuli, thus eliciting excessive hepatocyte apoptosis and inflammation. Evidence indicates that these processes, if prolonged, activate both hepatic stellate and Kupffer cells, thus leading to a vicious circle in which apoptosis, inflammation, cellular activation, and collagen deposition are upregulated even further.

Animals↗
PubMed2005

Magnetic resonance colonography for the detection of inflammatory diseases of the large bowel: quantifying the inflammatory activity.

INTRODUCTION: The purpose of this study was to assess the diagnostic accuracy of magnetic resonance colonography (MRC) for its ability to detect and quantify inflammatory bowel disease (IBD) affecting the colon. Endoscopically obtained histopathology specimens were used as the standard of reference. MATERIALS AND METHODS: Fifteen normal subjects and 23 patients with suspected IBD of the large bowel underwent MRC. Three dimensional T1 weighted data sets were collected following rectal administration of water prior to and 75 seconds after intravenous administration of paramagnetic contrast (gadolinium-BOPTA). The presence of inflammatory changes in patients was documented based on bowel wall contrast enhancement, bowel wall thickness, presence of perifocal lymph nodes, and loss of haustral folds. All four criteria were quantified relative to data obtained from normal subjects and summarised in a single score. This MRC based score was compared with histopathological data based on conventional endoscopic findings. RESULTS: MRC correctly identified 68 of 73 segments found to reveal IBD changes by histopathology. All severely inflamed segments were correctly identified as such and there were no false positive findings. Based on the proposed composite score, MRC detected and characterised clinically relevant IBD of the large bowel with sensitivity and specificity values of 87% and 100%, respectively, for all investigated colonic segments. CONCLUSION: MRC may be considered a promising alternative to endoscopic biopsy in monitoring IBD activity or assessing therapeutic effectiveness.

Adult↗
PubMed2004

Cardiovascular risk factors and probability for cardiovascular events in HIV-infected patients - part III: age differences.

OBJECTIVE: In recent years, concerns have been growing about an elevated rate of cardiovascular diseases in HIV-infected patients due to side effects of antiretroviral therapy. The present study analyses the cardiovascular risk profile and the probability of cardiovascular events with regard to the age of HIV-infected patients. METHODS: Cardiovascular risk factors of 309 HIV-infected adults were analysed. Patients were divided into four groups: 18-30 years (group 1), 31-40 years (group 2), 41-50 years (group 3), > 50 years (group 4). Overall 10-years probability for cardiovascular events was evaluated by the Framingham algorithm. RESULTS: Differences between the groups were detected in cardiovascular risk factors including changes in lipid- and glucose metabolism. Lipid values increased with elevated age, such as total cholesterol concentration (Mean +/- SEM in group 1 vs. group 4: 4.71 +/- 0.20 to 6.36 +/- 0.21 mmol/L, p < 0.05), LDL-cholesterol concentration (2.86 +/- 0.17 vs. 4.17 +/- 0.21 mmol/L, p < 0.05) and triglyceride concentration (1.56 +/- 0.14 vs. 3.48 +/- 0.40 mmol/L, p < 0.05). HDL-cholesterol concentration did not show a significant difference (1.15 +/- 0.03 mmol/L). Glucose concentration increased with elevated age in HIV-infected patients (5.28 +/- 0.19 vs. 6.46 +/- 0.24 mmHg, p < 0.05), but there was no significant difference in HbA1c - concentration, blood pressure and smoking rate between the groups. The overall 10-years probability for cardiovascular events was higher in group 1 (median: 1.9%) than in group 4 (20.5%; p < 0.01). CONCLUSIONS: The risk of cardiovascular events is related to the age in HIV-infected patients. Therefore, an increased duration of life due to a more effective antiretroviral therapy will have a significant impact on the rate of cardiovascular events in this patient population. In the future, further increase of cardiovascular events in HIV-infected patients may be expected.

Adolescent↗
PubMed2004

Cardiovascular risk factors and probability for cardiovascular events in HIV-infected patients. Part II: gender differences.

OBJECTIVE: Due to the side effects of antiretroviral therapy and long term survival there is an increasing concern of an elevated rate of cardiovascular diseases in HIV-infected patients. The present study analysed the cardiovascular risk profile and the probability of cardiovascular events in HIV-infected patients, due to differences of gender. METHODS: Cardiovascular risk factors of 309 HIV-infected adults, including 240 males were analysed. Overall 10-years probability for cardiovascular events was evaluated by the Framingham algorithm. RESULTS: Gender differences were detected in cardiovascular risk factors such as lipid values, blood pressure and the rate of smoking. Tobacco use was much more common in HIV-infected males compared with HIV-infected females (67.5% vs. 49.3%; p<0.001). Although no significant difference was noticed in total cholesterol (5.49 +/- 0.09 vs. 5.53 +/- 0.19 mmol/L, p = 0.84), the HDL-cholesterol concentration was significantly lower (1.09 +/- 0.03 vs. 1.36 +/- 0.06 mmol/L, p < 0.001) and the triglyceride concentration higher (3.01 +/- 0.21 vs. 2.06 +/- 0.26 mmol/L, p = 0.02) in HIV-infected males compared to HIV-infected females. Additionally, systolic blood pressure was higher in HIV-infected males compared with HIV-infected females (123.1 +/- 1.1 vs. 115.4 +/- 2.1 mmHg, p < 0.01). No significant differences were detected in HbA1c concentrations between both groups (5.15 +/- 0.07 vs. 5.31 +/- 0.11, p = 0.26). The overall 10-years probability for cardiovascular events was 8.7% (median) in HIV-infected males and 1.7% in HIV-infected females (p < 0.0001). CONCLUSIONS: In the present study, we observed gender differences in the cardiovascular risk profile of HIV-infected individuals. The risk of premature atherosclerosis and associated cardiovascular events was significantly higher in HIV-infected males.

Adult↗
PubMed2004

Combination therapy with peginterferon alpha-2B and ribavirin in liver transplant recipients with recurrent HCV infection: preliminary results of an open prospective study.

Allograft reinfection with hepatitis C virus (HCV) in transplant recipients occurs commonly and represents a major concern in the transplant setting. Suppression of viral replication in HCV transplant patients should prevent or delay progression to cirrhosis and graft failure. In this ongoing study, we present preliminary data from a prospective trial of standard interferon (IFN) alpha-2b (2 million units daily) for 3 months and subsequent peginterferon (PEG IFN) alpha-2b (1.5 microg/kg/week) for 9 months. IFN therapy was combined with ribavirin (10 to 12 mg/kg). So far, HCV has become undetectable by qualitative PCR in 33% of patients while 25% had a reduction of HCV RNA to undetectable by the bDNA assay and 42% had no virological response after 6 months of therapy. A biochemical response was detected in 42% of patients. Improvement of inflammatory activity was observed in 42% of patients after 6 months. In three patients anemia necessitated administration of erythropoietin and three patients received granulocyte-colony stimulating factor (G-CSF) due to leucopenia [corrected] In conclusion, we observed that daily IFN alpha-2b and subsequent PEG IFN alpha-2b therapy in combination with ribavirin provides biochemical and virological benefits in transplant recipients with established recurrent HCV infection.

Adult↗
PubMed2004

Impact of combined mycophenolate mofetil and low-dose calcineurin inhibitor therapy on renal function, cardiovascular risk factors, and graft function in liver transplant patients: preliminary results of an open prospective study.

As liver transplantation (LT) is now being performed with excellent 1-year graft survival rates of 85% to 90%, attention has been shifted to reducing long-term complications of calcineurin inhibitors (CNI). We randomized LT patients (2:1) who displayed renal dysfunction under CNI treatment to either mycophenolate mofetil (MMF) (1000 mg twice a day) followed by stepwise reduction of CNI (n = 21; Tac trough levels <4 ng/mL, CsA trough levels <50 ng/mL); or continue their current CNI dose (n = 11; control group). Three months after study entry, we observed significantly decreased mean values in the CNI reduction group of serum creatinine (1.88 +/- 0.36 versus 1.58 +/- 0.33 mg/dL, P < .001) and BUN (39.2 +/- 11.8 versus 29.9 +/- 9.59 mg/dL, P < .001) with a significantly increased GFR (51.4 +/- 10.8 versus 61.6 +/- 14.1 mL/min, P < .001). Improved renal function in these long-term LT recipients (5.6 +/- 3.6 years posttransplant; range, 2 to 13 years) suggests at least a partial reversibility of CNI-induced renal damage. Furthermore, we found an improved lipid profile as well as a significantly decreased mean systolic (140 +/- 19 versus 130 +/- 14 mm Hg, P < .01) and diastolic (82 +/- 9 to 74 +/- 8 mm Hg, P < .001) blood pressure 3 months after introduction of MMF therapy. Additionally, transaminases significantly improved in the CNI reduction group within this time period (ALT 37.9 +/- 25.9 versus 25.2 +/- 13.2, P < .05). MMF and CNI-reduced immunosuppressive regimens may improve long-term patient survival, suggesting a broad application within the liver transplant setting.

Aged↗