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Biomedical subjects

Johann Ockenga

Publications and source records attributed to Johann Ockenga.

18 recordsLinked to original sources
PubMed2006

Rapid development of secondary sclerosing cholangitis due to vancomycin-resistant enterococci.

Secondary sclerosing cholangitis is a rare complication of acute bacterial cholangitis. The natural course of the disease is a slow progression over years. Here we report about a patient in whom sclerosing cholangitis evolved much faster as a consequence of a persistent biliary infection with vancomycin-resistant enterococci. The infection could be treated successfully with prolonged therapy with linezolid and teicoplanin. This is the first report of sclerosing cholangitis caused by vancomycin-resistant enterococci. It illustrates the rapidity with which this disease can evolve as a fulminant and ultimately fatal complication of acute bacterial cholangitis.

Aged, 80 and over↗
PubMed2006

Keratin 8 sequence variants in patients with pancreatitis and pancreatic cancer.

Keratin 8 (KRT8) is one of the major intermediate filament proteins expressed in single-layered epithelia of the gastrointestinal tract. Transgenic mice over-expressing human KRT8 display pancreatic mononuclear infiltration, interstitial fibrosis and dysplasia of acinar cells resulting in exocrine pancreatic insufficiency. These experimental data are in accordance with a recent report describing an association between KRT8 variations and chronic pancreatitis. This prompted us to investigate KRT8 polymorphisms in patients with pancreatic disorders. The KRT8 Y54H and G62C polymorphisms were assessed in a cohort of patients with acute and chronic pancreatitis of various aetiologies or pancreatic cancer originating from Austria (n=16), the Czech Republic (n=90), Germany (n=1698), Great Britain (n=36), India (n=60), Italy (n=143), the Netherlands (n=128), Romania (n=3), Spain (n=133), and Switzerland (n=129). We also studied 4,234 control subjects from these countries and 1,492 control subjects originating from Benin, Cameroon, Ethiopia, Ecuador, and Turkey. Polymorphisms were analysed by melting curve analysis with fluorescence resonance energy transfer probes. The frequency of G62C did not differ between patients with acute or chronic pancreatitis, pancreatic adenocarcinoma and control individuals. The frequency of G62C varied in European populations from 0.4 to 3.8%, showing a northwest to southeast decline. The Y54H alteration was not detected in any of the 2,436 patients. Only 3/4,580 (0.07%) European, Turkish and Indian control subjects were heterozygous for Y54H in contrast to 34/951 (3.6%) control subjects of African descent. Our data suggest that the KRT8 alterations, Y54H and G62C, do not predispose patients to the development of pancreatitis or pancreatic cancer.

Acute Disease↗
PubMed2006

A degradation-sensitive anionic trypsinogen (PRSS2) variant protects against chronic pancreatitis.

Chronic pancreatitis is a common inflammatory disease of the pancreas. Mutations in the genes encoding cationic trypsinogen (PRSS1) and the pancreatic secretory trypsin inhibitor (SPINK1) are associated with chronic pancreatitis. Because increased proteolytic activity owing to mutated PRSS1 enhances the risk for chronic pancreatitis, mutations in the gene encoding anionic trypsinogen (PRSS2) may also predispose to disease. Here we analyzed PRSS2 in individuals with chronic pancreatitis and controls and found, to our surprise, that a variant of codon 191 (G191R) is overrepresented in control subjects: G191R was present in 220/6,459 (3.4%) controls but in only 32/2,466 (1.3%) affected individuals (odds ratio 0.37; P = 1.1 x 10(-8)). Upon activation by enterokinase or trypsin, purified recombinant G191R protein showed a complete loss of trypsin activity owing to the introduction of a new tryptic cleavage site that renders the enzyme hypersensitive to autocatalytic proteolysis. In conclusion, the G191R variant of PRSS2 mitigates intrapancreatic trypsin activity and thereby protects against chronic pancreatitis.

Base Sequence↗
PubMed2006

Leptin and insulin response to long-term total parenteral nutrition depends on body fat mass.

BACKGROUND & AIMS: Circulating leptin and insulin concentrations are physiologically representing energy homeostasis. However, the artificial situation of long-term total parenteral nutrition (TPN) and its effects on serum leptin and insulin is not fully understood. METHODS: We studied 42 gastroenterological patients who received TPN for 19+/-11 days. Serum leptin and insulin levels as well as body composition assessed by bioelectrical impedance analysis were evaluated on days 0, 7 and 14. Insulin sensitivity was estimated by calculating the QUICKI. RESULTS: Before the start of TPN, leptin correlated positively with female gender (P<0.03), BMI (P<0.02), fat mass (P<0.02), insulin levels (P<0.001) and QUICKI (P<0.001). Within the first week of TPN, an increase of leptin levels was found only in patients with a body fat mass of >30% (P<0.02). As these were predominantly women, their leptin levels increased likewise (P<0.003). In regression analysis, fat mass (P<0.001), female gender (P<0.04), insulin levels (P<0.03), and i.v. glucose supply rates (P<0.05) were independently associated to leptin levels. CONCLUSIONS: TPN-especially glucose-induces a neurohumoral response as shown here for leptin and insulin that is mainly depending on the fat mass. Better understanding of this regulatory mechanism during artificial nutrition could offer a new approach to improve its therapeutic effects.

Adipose Tissue↗
PubMed2006

Elevated resistin levels in cirrhosis are associated with the proinflammatory state and altered hepatic glucose metabolism but not with insulin resistance.

The adipokine resistin has been implicated in obesity and insulin resistance. Liver cirrhosis is associated with decreased body fat mass and insulin resistance. We determined plasma resistin levels in 57 patients with cirrhosis, 13 after liver transplantation, and 30 controls and correlated these with hemodynamic as well as hepatic and systemic metabolic parameters. Patients with cirrhosis had, dependent on the clinical stage, an overall 86% increase in resistin levels (P < 0.001) with hepatic venous resistin being higher than arterial levels (P < 0.001). Circulating resistin was significantly correlated with plasma TNF-alpha levels (r = 0.62, P < 0.001). No correlation was observed between resistin and hepatic hemodynamics, body fat mass, systemic energy metabolism, and the degree of insulin resistance. However, plasma resistin in cirrhosis was negatively associated with hepatic glucose production (r = -0.47, P < 0.01) and positively with circulating free fatty acids (FFA; r = 0.40, P < 0.01) and ketone bodies (r = 0.48, P < 0.001) as well as hepatic ketone body production (r = 0.40, P < 0.01). After liver transplantation, plasma resistin levels remained unchanged, whereas insulin resistance was significantly improved (P < 0.01). These data provide novel insights into the role of resistin in the pathophysiological background of a catabolic disease in humans and also indicate that resistin inhibition may not represent a suitable therapeutic strategy for the treatment of insulin resistance and diabetes in patients with liver cirrhosis.

Biomarkers↗
PubMed2006

Respiratory-triggered MRCP applying parallel acquisition techniques.

PURPOSE: To evaluate the influence of parallel imaging on the image quality of respiratory triggered magnetic resonance cholangiopancreatography (MRCP). MATERIALS AND METHODS: A total of 30 consecutive patients underwent MRCP applying a respiratory triggered T2-weighted (T2w) turbo spin-echo (TSE) sequence without and with parallel imaging (acceleration factor of 2). Acquisition times of both sequences were recorded. Quantitative evaluation included measurement of a contour sharpness index of two segments of the pancreaticobiliary tree as well as calculation of the relative contrast between ductal structures and organ parenchyma at four different segments. The qualitative evaluation was performed by two independent radiologists who graded overall image quality, depiction of eight segments of the pancreaticobiliary tree, and the frequency of artifacts. RESULTS: The application of parallel imaging significantly (P<0.05) reduced the acquisition time of the respiratory triggered MRCP sequence by 37.7% (six minutes and two seconds+/-one minute and 26 seconds vs. three minutes and 46 seconds+/-58 seconds). The quantitative and qualitative evaluation revealed no statistically significant differences between the two sequences (P>0.05). The frequency of artifacts was at the same level for both sequences as well. CONCLUSION: The application of parallel imaging for respiratory triggered MRCP significantly reduces the acquisition time without relevant influence on image quality.

Adult↗
PubMed2005

Introducing genetic testing for adult-type hypolactasia.

BACKGROUND AND AIMS: To evaluate genotyping for two DNA variants (c.1993+327C>T and c.1438+117G>A), recently found to be associated with adult-type hypolactasia, in the diagnosis of lactose intolerance. METHODS: In total, 166 consecutive patients with gastrointestinal symptoms mimicking hypolactasia admitted to the clinic between March 2002 and December 2002 were included. Genotyping for the two DNA variants (c.1993+327C>T and c.1438+117G>A) and standard H2 breath test was performed. RESULTS: Among 116 patients with positive H2 breath test, the c.1993+327C variant was detectable in 106 (91.4%) patients. Among 50 patients with negative H2 breath test, the c.1993+327C variant was seen in 2 patients. Sensitivity, specificity, positive and negative predictive values for the c.1993+327C variant were 91.4, 96.0, 98.1 and 82.8%, respectively. Genotyping for the c.1438+117G variant did not bring any additional information. Among 4 of the 10 patients with positive H2 breath test but negative for the c.1993+327C and the c.1438+117G variant,further evaluation revealed other diseases known to cause secondary hypolactasia such as celiac disease and short bowel syndrome. CONCLUSION: In symptomatic patients, genotyping for the DNA variant c.1993+327C is a reliable test for adult-type hypolactasia with high sensitivity and specificity and thus provides a new tool in the diagnostic workup of hypolactasia.

Blood Glucose↗
PubMed2005

The presence of the proteolysis-inducing factor in urine does not predict the malignancy of a pancreatic tumour.

BACKGROUND: The proteolysis-inducing factor (PIF) was identified as a tumour product in various gastrointestinal cancers. A previous study in pancreatic cancer patients suggested PIF expression as a tumour marker, which is not related to tumour size. We hypothesized that PIF could be a useful marker to exclude benign pancreatic tumors, as chronic pancreatitis with a pancreatic mass. METHODS: Urine of patients with a pancreatic mass of uncertain malignancy was investigated for PIF expression by Western blot. Sufficient urine protein for analysis was available in 59 patients. The diagnosis was established by histology in 54 patients and by follow up in five patients with chronic pancreatitis. In addition, serum CA19-9 was measured. RESULTS: The sensitivity (specifity) for the detection of a malignant pancreatic tumour was 90% (75%) and 54% (71%) for CA19-9 and PIF, respectively. The sensitivity (specifity) for the distinction of pancreatic cancer from chronic pancreatitis was 89% (80%) and 57% (63%) for CA19-9 and PIF, respectively. CONCLUSION: Evaluation of PIF in urine is of no diagnostic value in patients with a pancreatic mass of unknown malignancy.

Adult↗
PubMed2004

Treatment of refractory chronic lymphocytic leukemia with Campath-1H in combination with lamivudine in chronic hepatitis B infection.

Campath-1H, a monoclonal antibody against human CD52, is used for the therapy of refractory or relapsed chronic lymphocytic leukemia (CLL). Treatment with campath is associated with an increased incidence of infections and also fatal reactivation of viral infections. Reactivation of hepatitis B virus (HBV) in HBsAg-positive patients is a well-documented complication of cytotoxic or immunosuppressive therapy and has also been observed after treatment with rituximab. To date, there are no reports on campath treatment in HBsAg carriers. Here, we present the case of a patient with heavily pretreated CLL who was HBsAg-positive with a high virus load (>2 billion copies/mL). He required treatment because of progressive CLL with massive bone marrow infiltration, severe anemia and thrombocytopenia. Campath was initiated and lamivudine, an inhibitor of reverse transcriptase, was simultaneously given to prevent HBV proliferation. During the treatment, no deterioration of liver parameters was observed, and the virus load decreased. After therapy with campath, hemoglobin and platelet counts increased markedly. This report shows that lamivudine is highly effective in inhibiting HBV proliferation and can be used to prevent HBV flare-up during campath treatment in patients tested positive for HBs antigen.

Aged↗
PubMed2004

Overlap syndrome of autoimmune pancreatitis and cholangitis associated with secondary Sjögren's syndrome.

In approximately 25% of patients with acute or chronic pancreatitis the cause remains unclear. Despite progress in understanding so-called idiopathic pancreatitis, more diagnostic criteria are needed. We report on a patient who presented with jaundice, but without pain or fever. Under the assumption of pancreatic cancer the patient underwent hemipancreatoduodenectomy. Histological examination showed chronic sclerosing inflammation of the pancreas and bile ducts without any signs of malignancy. Ten weeks later he developed bilateral parotid swelling and recurrent bouts of fever. Again liver enzymes were elevated and unsuccessfully treated with antibiotics for bacterial cholangitis. Further biopsies from submandibular gland, lymph nodes and liver again showed chronic sclerosing inflammation with lymphoplasmacytic infiltration. For sicca symptoms the diagnosis of a primary Sjogren's syndrome was proposed. However, with corticosteroid treatment the patient improved remarkably but after tapering he relapsed. On the basis of established criteria, we diagnosed autoimmune pancreatitis with (1) diffuse swelling of the pancreas, (2) irregularities of the pancreatic duct, (3) lymphoplasmacytic infiltration, (4) response to corticosteroids, (5) hypergammaglobulinaemia, and (6) disproportionately raised IgG4. In addition, the patient fulfilled the criteria for secondary Sjogren's syndrome. Autoimmune pancreatitis may present as an isolated or syndromic disease. It is an autoimmune disorder of unknown cause and should be included in the differential diagnosis of pancreatic disorders.

Acute Disease↗
PubMed2003

UDP glucuronosyltransferase (UGT1A7) gene polymorphisms increase the risk of chronic pancreatitis and pancreatic cancer.

BACKGROUND & AIMS: Chronic pancreatitis and pancreatic adenocarcinoma are associated with alcohol abuse, consumption of tobacco smoke, and environmental aromatic hydrocarbon exposure. The role of genetic factors is incompletely defined. Uridine 5'-diphosphate glucuronosyltransferases are phase II detoxifying enzymes capable of tobacco-borne toxicant inactivation and cellular protection. This study analyzes UGT1A7 gene polymorphisms in pancreatic diseases. METHODS: Genomic DNA from northern German white patients with pancreatic adenocarcinoma (n = 52) and chronic pancreatitis (n = 146), as well as healthy blood donors (n = 235) was analyzed by UGT1A7-specific PCR, sequencing analysis, and temperature gradient gel electrophoresis. Pancreatic expression of UGT1A genes was identified by duplex reverse-transcription PCR. RESULTS: Predominant expression of the UGT1A7 gene was identified in human pancreatic tissue. Pancreatic adenocarcinoma was associated with the low detoxification activity UGT1A7*3 allele, which combines the W208R, N129K, and R131K mutations (odds ratio [OR], 1.98; 95% confidence interval [CI ], 1.24-3.14; P = 0.003). The association of UGT1A7*3 was especially strong in smokers with pancreatic carcinoma who were younger than 55 years (OR, 4.7; 95% CI, 1.9-11.8; P = 0.0009). Chronic pancreatitis was also associated with UGT1A7*3 (OR, 1.76; 95% CI, 1.26-2.46; P = 0.0009). UGT1A7*3 was specifically associated with the subgroup of patients with alcoholic pancreatitis, of whom 89% were smokers (OR, 2.24; 95% CI, 1.46-3.43; P = 0.0001) but was not associated with the nonalcoholic pancreatitis subgroup. CONCLUSIONS: The UGT1A7 gene is predominantly expressed in human pancreas. The low detoxification activity UGT1A7*3 allele is identified as a novel risk factor of pancreatic diseases defining the interaction of genetic predisposition and environmentally induced oxidative injury.

Adenocarcinoma↗
PubMed2002

Effect of glutamine-enriched total parenteral nutrition in patients with acute pancreatitis.

BACKGROUND: The management of acute pancreatitis (AP) frequently includes parenteral nutrition, but conditionally essential amino acids such as glutamine are not included in conventional total parenteral nutrition (TPN). AIM: This study was conducted to determine whether the inclusion of glutamine has a beneficial effect in patients with AP receiving TPN. METHODS: In a randomized, controlled study 28 patients with AP received either a standard TPN with 1.5 g/kg body weight protein or an isonitrogen, isocaloric TPN which contains 0.3 g/kg L -alanine- L -glutamine. Patients were assessed for nutritional and inflammatory parameters, infectious complications, length of TPN, length of hospital stay (LOS) and cost of TPN. RESULTS: There were no side-effects related to glutamine substitution observed. Glutamine was associated with a significant increase of cholinesterase, albumin and lymphocyte count in AP as well a decrease of C-reactive protein compared to standard TPN at day 14. There was a reduced length of TPN (10 [6-16] vs 16 [10-18] days, P<0.05) and a trend of reduced LOS (21 [14-32] vs 25 [19-40] days) in AP patients receiving glutamine. The overall cost per patient for TPN did not differ (gln+: 929+/-586 vs gln-: 981+/-507 euro/patient). CONCLUSION: Our results suggest that glutamine substitution is beneficial and does not increase the overall cost of parenteral feeding in patients with acute pancreatitis.

Acute Disease↗
PubMed2002

Impaired glucose phosphorylation and transport in skeletal muscle cause insulin resistance in HIV-1-infected patients with lipodystrophy.

Insulin resistance is a frequently observed side effect of highly active antiretroviral therapy (HAART). Currently, very little is known about the mechanisms or specific tissues involved. We aimed to identify possible defects in skeletal muscle glucose uptake and metabolism in HIV patients receiving HAART. Whole-body glucose disposal and oxidation were determined by combination of the euglycemic-hyperinsulinemic clamp technique and indirect calorimetry. Muscle glucose uptake of the thighs was measured simultaneously by dynamic 2[(18)F]fluoro-2-deoxy-D-glucose positron emission tomography. Patients receiving HAART had signs of lipodystrophy as confirmed by dual energy x-ray absorptiometry. Whole-body glucose disposal was significantly reduced in these patients compared with untreated patients. Analysis of kinetic constants using a three-compartment model indicated reduced skeletal glucose uptake caused by significantly impaired glucose transport and phosphorylation. Skeletal muscle glucose uptake was reduced by 66% in treated patients and explained 46% and 43% of whole-body glucose disposal in patients on HAART and therapy-naive patients, respectively. Insulin-stimulated whole-body oxidative and nonoxidative glucose disposal was significantly lower in the treated group, as was suppressive insulin action on lipolysis. To our knowledge, this is the first report providing in vivo evidence that, in lipodystrophic HIV patients, impaired glucose transport and phosphorylation cause reduced insulin-mediated glucose uptake.

Acquired Immunodeficiency Syndrome↗