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V Keim

Publications and source records attributed to V Keim.

At least 19 recordsLinked to original sources
PubMed2002

[Pitfalls in diagnosis of non-Hodgkin-lymphoma of the pancreas].

A 74 year-old woman was admitted because of upper abdominal pain radiating to the back. The patient was in good health prior to onset of symptoms. Both ultrasound and endoscopic ultrasound revealed a lesion of low echogenicity in the pancreatic head without indication of hepatic lesions, enlarged lymph nodes or vascular infiltration. An computed tomography (CT) did not show the lesion in the pancreas. Explorative laparotomy was performed. The biopsy specimen revealed a diffuse large cell Non-Hodgkin-Lymphoma. This case report illustrates, how simple ultrasound studies can detect lesions not seen in more expensive, complex, and time consuming imaging techniques like CT. The patient underwent a postoperative chemotherapy and is currently well.

Aged↗
PubMed2002

Relevance of variants in serum antiproteinases for the course of chronic pancreatitis.

BACKGROUND: Mutations of the pancreatic serine protease inhibitor, Kazal type 1 (SPINK1), the cationic trypsinogen (PRSS1) and the cystic fibrosis transmembrane conductance regulator (CFTR) were reported to be genetic risk factors of chronic pancreatitis (CP). The aim of this study was to determine the role of genetic variants of the main serum antiproteinases alpha-1-antitrypsin (AAT) and alpha-2-macroglobulin (A2M) for the course of chronic pancreatitis. METHODS: 124 patients with non-alcoholic chronic pancreatitis (with PRSS1 or SPINK1 mutations or idiopathic pancreatitis) and 64 healthy controls were investigated for the AAT mutations PiS and PiZ, and the PiM determining variants R101H, V213A, E376D. In 101 subjects, the 'bait region' of A2M was sequenced. A pentanucleotide deletion in the bait region of A2M was analysed in 147 chronic pancreatitis (CP) patients and 87 controls. RESULTS: The lowest prevalences of V213A and E376D were found in PRSS1 patients, whereas an increased rate of these mutations was present in the SPINK1 group, and the highest prevalence was found in patients with idiopathic pancreatitis. The prevalence of PiM variants was higher in patients with early onset CP than in late onset (P < 0.05 for E376D). The coding region of the bait region of A2M was of wild type in all investigated subjects. The A2M pentanucleotide deletion showed a homogenous distribution in patients and controls. CONCLUSIONS: Our study suggests a moderating, but not predominant, role of AAT variants in the course of chronic non-alcoholic pancreatitis.

Adolescent↗
PubMed2001

Clinical characterization of patients with hereditary pancreatitis and mutations in the cationic trypsinogen gene.

PURPOSE: We determined the clinical manifestations of hereditary pancreatitis in nearly 30 families. PATIENTS AND METHODS: The two trypsinogen mutations N29I and R122H were identified in a group of 550 patients with chronic pancreatitis of unclear origin. The following criteria were used to characterize the severity of chronic pancreatitis (one point each): calcifications, cysts, dilation of the pancreatic duct, diabetes, hospital treatment, and operation. Stages were defined as stage 0 (no points), stage 1 (one to two points), stage 2 (three to four points), and stage 3 (more than four points). Smoking and drinking habits were also recorded. RESULTS: Six families with the N29I mutation (25 subjects with the mutation) and 21 families with the R122H mutation (76 subjects with the mutation) were identified. The median ages for the onset of disease were 11 years in N29I and 10 years in R122H patients. The severity of chronic pancreatitis and symptoms were similar for both mutations. About 26% (n = 26) of the 101 subjects carrying a mutation were asymptomatic, and 42% (n = 42) had mild disease (stage 1). Twenty-nine percent (n = 29) had moderate disease (stage 2), and only 4% (n = 4) had severe disease (stage 3). CONCLUSIONS: Symptoms of patients with the N29I or R122H trypsinogen mutation were generally similar. The majority of subjects with trypsinogen mutations had mild disease or was asymptomatic.

Adolescent↗
PubMed2001

[Pneumatosis cystoides intestinalis, a rare complication of mixed connective tissue disease].

HISTORY AND ADMISSION FINDINGS: A 77-year-old woman presented with diarrhoea and increasing malaise. The patient reported a weight loss of 30 kilogram over the past 12 months due to recurrent episodes of diarrhoea. During previous hospitalisations the diagnosis of a mixed connective tissue disease had been established, and the patient was treated with azathioprine and prednisolone. Clinical findings at presentation included diffuse oedema of the hands, Raynaud's and Sicca syndrome, dysphagia and a distended abdomen and pain on palpation of the left lower abdomen. INVESTIGATIONS: A chest X-ray revealed pneumoperitoneum. Contrast medium radiography of gastro-intestinal passage and an abdominal CT with contrast medium confirmed the existence of pneumoperitoneum and showed, in addition, intramural gas in the wall of the dilated jejunum. No contrast medium leakage as an indicator of an open perforation was detectable. DIAGNOSIS, TREATMENT AND CLINICAL COURSE: Due to suspected encapsulated perforation a laparotomy was performed. In situ, multiple gas bubbles were found both in the bowel walls and in the mesentery. The small intestine was severely distended, atonic but without evidence for a stenosis. In the absence of an open perforation, the diagnosis of pneumatosis cystoides intestinalis (PCI) was established as the underlying cause of the pneumoperitoneum. Treatment with metronidazole was initiated and the diarrhoea resolved over the following 3 weeks. CONCLUSION: PCI is a rare condition, to be considered if pneumoperitoneum is present. One possible underlying cause is an intestinal manifestation of a mixed connective tissue disease.

Aged↗
PubMed2001

C282Y and H63D mutation of the hemochromatosis gene in German porphyria cutanea tarda patients.

BACKGROUND AND AIMS: Patients with porphyria cutanea tarda (PCT) have a susceptibility to reversible inactivation of hepatocyte uroporphyrinogen decarboxylase, which can be triggered by alcohol, hepatitis C virus, and other agents. Inherited factors that may predispose to PCT include the C282Y mutation in the hemochromatosis (HFE) gene. METHODS: We analyzed the hemochromatosis mutations C282Y and H63D in liver biopsies and serum samples of 190 German patients (mean age 48+/-12.5 years) with sporadic PCT. The hepatic iron concentration was determined within the liver tissue. Age-matched healthy blood donors (115 donors) served as controls. RESULTS: The C282Y and H63D mutations were found in 75 (39%) and 85 (45%) of 190 patients with PCT, respectively. Twenty-two patients (12%) were homozygous for the C282Y mutation, and eighteen patients (9%) were compound heterozygotes, displaying both the C282Y and the H63D mutation. Within the control group, 3 of 115 patients were heterozygous for C282Y (3%) and 12 for H63D (10%). Serum and hepatic iron, ferritin, transferrin saturation, or liver enzymes did not differ significantly between patients with or without HFE mutations. CONCLUSIONS: The high frequency of homo- and heterozygosity for the C282Y and H63D alleles strongly suggests that these mutations are important predisposing factors for PCT in German patients.

DNA↗
PubMed2001

Role of prostaglandins in regulation of pancreatic enzyme secretion by various diets.

We have demonstrated by the use of isolated rat pancreatic acini that exogenous prostaglandins of the E type inhibit secretagogue-stimulated amylase secretion. We here studied whether the pancreas is a source of prostaglandin synthesis and whether prostaglandins mediate regulation of pancreatic enzyme secretion by various diets. Prostaglandin E2 was measured by enzyme immunoassay in pancreatic acini from either normal animals or after 10 days of feeding with different diets. Acini were prepared by collagenase digestion. Amylase secretion was measured after stimulation with cholecystokinin in the presence or absence of indomethacin, an inhibitor of prostaglandin synthesis. Prostaglandin E2 concentration in pancreatic acini was comparable to other organs such as kidney and liver. Feeding a diet enriched in proteins caused an increase of cholecystokinin-stimulated maximal amylase secretion and a decrease of prostaglandin E2 concentration. Incubation of acini with indomethacin caused a decrease in prostaglandin E2 concentration and an increase in cholecystokinin stimulated amylase secretion. We conclude that regulation of pancreatic enzyme secretion by diets may be mediated by prostaglandins.

Amylases↗
PubMed2001

Value of combinations of pancreatic function tests to predict mild or moderate chronic pancreatitis.

UNLABELLED: Pancreatic function tests share an insufficient accuracy concerning the detection of mild or moderate forms of chronic pancreatitis. It was evaluated here whether by combination of different assays the prediction or exclusion of chronic pancreatitis could be improved. METHODS: 62 patients with chronic abdominal pain and suspected chronic pancreatitis underwent an endoscopic retrograde pancreaticography. The duct alterations were classified according to the Cambridge criteria. In all individuals the pancreolauryl test in serum (PLT-S) and urine (PLT-U) was performed and elastase 1-immunoreactivity (E) as well as chymotrypsin (Chy) activity in stool were measured. Sensitivities, specificities, receiver-operator-curves as well as cut-off points at optimal accuracies were calculated for each single assay and all test combinations. Cut offs were optimized by a mathematical model to achieve highest accuracies. RESULTS: In 30 patients the pancreatic duct was normal and in 32 patients alterations of the duct system were found. These were classified as mild in 10 patients, as moderate in 8 patients and as severe in 14 patients. In those with mild and moderate disease all pancreatic function tests showed sensitivities/specificities of 60-65% and 65-70%, respectively. Only in severe chronic pancreatitis elastase was superior to the other tests. Combinations of function tests did not lead to improved accuracy. After mathematical optimization the accuracy (sensitivity 80%, specificity 80%) was best for the combination of PLT-S (cut off 4.7 micrograms/ml) and E (cut off 500 micrograms/g). Both parameters had to be below these newly defined cut offs to diagnose chronic pancreatitis. CONCLUSIONS: The accuracy of pancreatic function tests may be improved by use of altered cut offs and a combination of serum pancreolauryl test and elastase. These newly defined cut offs will have to be evaluated in a much larger study.

Adult↗
PubMed2001

Ofloxacin and ursodeoxycholic acid versus ursodeoxycholic acid alone to prevent occlusion of biliary stents: a prospective, randomized trial.

BACKGROUND AND STUDY AIMS: Biliary plastic stents are highly effective in the treatment of malignant biliary obstruction, but may become occluded over time, leading to jaundice and cholangitis. Stent occlusion is thought to be caused by bacterial adhesion and formation of biofilm. This study was carried out to assess whether treatment with ofloxacin in combination with ursodeoxycholic acid is superior to ursodeoxycholic acid alone in preventing stent occlusion. PATIENTS AND METHODS: Patients with obstructive jaundice due to inoperable malignant disease underwent placement of a straight 11.5-Fr polyethylene stent. After stent insertion, the patients were randomly assigned to receive either ofloxacin (200 mg b.i.d.) with ursodeoxycholic acid (250 mg t.i.d.) or ursodeoxycholic acid alone. The end points of the study were the frequency of stent occlusions, the time to stent occlusion, and the safety of the two regimens. RESULTS: Fifty-two patients were enrolled, of whom 26 were assigned to the combined therapy group and 26 to the control group. Thirty patients were suffering from pancreatic cancer, 13 from gallbladder or bile duct cancer, and nine had metastases from other malignant tumors. Eight stent occlusions (31%) occurred in the ofloxacin group and six (23 %) in the control group (P = 0.76). The mean times to stent occlusion were 95 +/- 9 days and 101 +/- 9 days, respectively (P = 0.91). No significant differences regarding survival time or safety were observed between the two groups. CONCLUSIONS: Ofloxacin in combination with ursodeoxycholic acid is not superior to ursodeoxycholic acid alone in preventing stent occlusion in patients with malignant obstructive jaundice.

Aged↗
PubMed2001

[Pathogenetic concepts of chronic pancreatitis].

Summary. The understanding of the pathogenesis of chronic pancreatitis is limited. Several theories (i. e. obstruction hypothesis) were suggested in the past but could not be confirmed by experimental data. As a formal description of the course of the disease, the necrosis-fibrosis concept seems to be very attractive. According to this theory, there is no significant difference in the pathogenesis of acute and chronic pancreatitis. A major step was the identification of mutations of the cationic trypsinogen, the secretory trypsin inhibitor (SPINK 1) and the cystic-fibrosis protein (CFTR) in some patients. Investigation of these mutations may significantly contribute to a better understanding of the pathogenesis of chronic pancreatitis.

Adult↗
PubMed2000

Chronic pancreatitis associated with an activation peptide mutation that facilitates trypsin activation.

BACKGROUND & AIMS: Mutations of the cationic trypsinogen have been described in hereditary pancreatitis. We report a new trypsinogen mutation in the activation peptide of the proenzyme in a family with chronic pancreatitis. METHODS: The coding region of the cationic trypsinogen gene was sequenced after polymerase chain reaction amplification. The following peptides homologous to the N-terminal end of cationic trypsinogen were synthesized (one-letter code, mutated amino acid underlined): wild-type peptide, APFDDDDKIVGG; pD22G, APFDDDGKIVGG; pK23R, APFDDDDRIVGG. The sequences of pD22G and pK23R correspond to the recently identified mutation K23R and to the mutation described here (D22G). To mimic trypsinogen activation, these peptides were digested with trypsin for 30 minutes at pH 5.0-8. 0, and the fragments were analyzed by high-performance liquid chromatography. RESULTS: In a family with clinical evidence of hereditary chronic pancreatitis, a missense mutation of codon 22 (GAC-->GGC) of the cationic trypsinogen was found. This mutation results in a substitution of aspartic acid by glycine; therefore, the mutation was called D22G. Chromatographic analysis of tryptic digests of the peptides pD22G and pK23R showed hydrolysis rates of 22% and 75%, respectively, whereas the wild-type peptide was hydrolyzed at only 6%. The cleavage rates were reduced at lower pH, and no hydrolysis occurred without trypsin. CONCLUSIONS: The activation peptides of the trypsinogen variants D22G and K23R could be released at a higher rate than in wild-type trypsinogen, resulting in increased amounts of trypsin in the pancreas, which could initiate pancreatitis.

Adult↗
PubMed2000

Decrease of CA 19-9 during chemotherapy with gemcitabine predicts survival time in patients with advanced pancreatic cancer.

Chemotherapy with gemcitabine has been shown to be an effective regimen in advanced or metastatic pancreatic cancer with improvement of both quality of life and survival time. The response of the tumour marker CA 19-9 to chemotherapy with gemcitabine was studied in order to find out whether it is related to survival time of patients. Forty-three consecutive patients (median age 61 years, range 39-76 years; 20 males, 23 females) suffering from histologically proven locally advanced or metastatic pancreatic adenocarcinoma and a baseline Karnofsky-index > or = 60 were treated with gemcitabine in a dose of 1,000 mg/m(-2) weekly x 7 followed by 1 week of rest during the first cycle and thereafter 1,000 mg/m(-2) weekly x 3 followed by 1 week of rest until progression. In 36 of 43 patients serial measurements of CA 19-9 could be performed. Patients with a decrease of > 20% of the baseline CA 19-9 level after 8 weeks of treatment (n = 25) had a significantly better median survival than patients with a rise or a decrease < or = 20% (n = 11) (268 vs 110 days; P < 0.001). The response of CA 19-9 was the strongest independent predictor of survival (P < 0.001) in the multivariate analysis. In conclusion, a decrease of CA 19-9 > 20% during the first weeks of chemotherapy with gemcitabine is associated with a better survival of patients with locally advanced or metastatic pancreatic cancer. Serial measurements of CA 19-9 are useful to decide whether further chemotherapy after the first weeks of treatment is indicated.

Adult↗
PubMed2000

Mutations of the cystic fibrosis gene, but not cationic trypsinogen gene, are associated with recurrent or chronic idiopathic pancreatitis.

OBJECTIVE: We investigated whether mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene and cationic trypsinogen gene are associated with recurrent acute, or chronic idiopathic pancreatitis. METHODS: Twenty patients with idiopathic pancreatitis (11 women, nine men; mean age, 30 yr) were studied for the presence of a CFTR mutation by screening the genomic DNA for more than 30 mutations and variants in the CFTR gene. Selected mutations of the cationic trypsinogen gene were screened by Afl III restriction digestion or by a mutation-specific polymerase chain reaction (PCR). In each patient exons 1, 2, and 3 of the cationic trypsinogen gene were sequenced. Patients with a CFTR mutation underwent evaluation of further functional electrophysiological test (intestinal current measurement). RESULTS: No mutation of the cationic trypsinogen gene was detected. A CFTR mutation was detected in 6/20 (30.0%) patients. Three patients (15.0%) had a cystic fibrosis (CF) mutation on one chromosome (deltaF508, I336K, Y1092X), which is known to cause phenotypical severe cystic fibrosis. One patient was heterozygous for the 5T allele. In addition, two possibly predisposing CFTR variants (R75Q, 1716G-->A) were detected on four patients, one of these being a compound heterozygous for the missense mutation I336K and R75Q. No other family member (maternal I336K; paternal R75Q; sister I1336K) developed pancreatitis. An intestinal current measurement in rectum samples of patients with a CFTR mutation revealed no CF-typical constellations. CONCLUSIONS: CFTR mutations are associated with recurrent acute, or chronic idiopathic pancreatitis, whereas mutations of the cationic trypsinogen mutation do not appear to be a frequent pathogenetic factor.

Adult↗