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Biomedical subjects

V Keim

Publications and source records attributed to V Keim.

At least 19 recordsLinked to original sources
PubMed2006

ESPEN Guidelines on Enteral Nutrition: Pancreas.

The two major forms of inflammatory pancreatic diseases, acute and chronic pancreatitis, require different approaches in nutritional management, which are presented in the present guideline. This clinical practice guideline gives evidence-based recommendations for the use of ONS and TF in these patients. It was developed by an interdisciplinary expert group in accordance with officially accepted standards and is based on all relevant publications since 1985. The guideline was discussed and accepted in a consensus conference. In mild acute pancreatitis enteral nutrition (EN) has no positive impact on the course of disease and is only recommended in patients who cannot consume normal food after 5-7 days. In severe necrotising pancreatitis EN is indicated and should be supplemented by parenteral nutrition if needed. In the majority of patients continuous TF with peptide-based formulae is possible. The jejunal route is recommended if gastric feeding is not tolerated. In chronic pancreatitis more than 80% of patients can be treated adequately with normal food supplemented by pancreatic enzymes. 10-15% of all patients require nutritional supplements, and in approximately 5% tube feeding is indicated.

Acute Disease↗
PubMed2005

[Chronic pancreatitis--pancreas cancer: influence of genetic factors].

Chronic pancreatitis: Only recently mutations in several genes were found in patients with chronic pancreatitis. In those with a familial chronic pancreatitis mutations of the cationic trypsinogen were identified and the variants N29I and R122H lead to an autosomal dominant disease. In this group of patients the mutation N34S of the trypsin inhibitor SPINK1 was detected. In so-called idiopathic pancreatitis both variants of the SPINK1 and of the CFTR (cystic fibrosis transmembrane conductance regular) were identified. Alterations in both genes were also found in patients with alcoholic chronic pancreatitis. The strongest risk factor for chronic pancreatitis were trypsinogen mutations N29I and R122H mutations. However, both SPINK1 and CFTR increased the risk for chronic pancreatitis to a higher level than alcohol consumption. A genetic investigation should be performed in familial disease and younger age, but also in patients without family history and higher age a mutation could be found. Pancreas cancer: In 10% of the patients with pancreas cancer other members of the family were affected from the disease. Some of them belong to well characterized familial syndroms like HNPCC or Peutz-Jeghers-syndrom. In a minority of the others a genetic factor may be found, too. In sporadic disease the development of the tumor is characterized by continued acquirement of genetic alterations described by the PanIN model (pancreatic intraepithelial neoplesia). This means that the evolution of the neoplasia progresses from normal tissue via epithelial hyperplasy (PanIN 1A), papillary hyperplasy without (PanIN 1B) and with dysplasy (PanIN 2) and carcinoma in situ (PanIN 3) to invasive pancreas cancer. The progression is associated with genetic alterations of the cells (mutations of ki-ras, p16, p53 etc.). This results in deterioration of control of the cell cycle and the apoptosis and explains the malignancy of the disease. These findings may be used in the future to develop newer therapeutic principles in order to improve the dismal prognosis of this disease.

Carrier Proteins↗
PubMed2005

[Clinical implications of genetic risk factors of chronic pancreatitis].

The identification of a specific mutation in the human cationic trypsinogen gene in large kindreds with hereditary pancreatitis was the key to understand the genetic background of chronic pancreatitis. Rapidly, other variants within the same gene were identified-even in small families with a minority of patients. Later, mutations of the most important intrapancreatic trypsin inhibitor SPINK1 were found with high prevalence in patients with idiopathic, tropical and alcoholic chronic pancreatitis. We summarize interesting genetic and biochemical findings, point to clinical features and review recommendations for genetic analysis, follow-up and cancer prevention.

Carrier Proteins↗
PubMed2005

[Diagnosis and treatment of acute pancreatitis].

In patients with abdominal pain, an acute pancreatitis is likely when lipase is elevated more than 3-fold above normal. The diagnosis should be confirmed by an imaging technique (either sonography or CT). The determination of the severity is difficult as all methods (laboratory values, imaging systems, scores) exhibit a significant uncertainty. The regular clinical investigation of the patients is still needed. In contrast to a severe course, in mild or moderate disease the treatment of the patient in an intensive care unit is not obligatory. In biliary pancreatitis the extraction of biliary stones after papillotomy is indicated and in severe disease the procedure should be done without delay. Meanwhile enteral nutrition is standard treatment although the data are not completely convincing. Further measures are administration of pain killers, volume substitution and treatment of pulmonary and renal failure. Although data are not completely clear the prophylactic administration of antibiotics in necrotizing pancreatitis is routine. Puncture of the necrosis may be used to detect the responsible microorganisms. In patients with infected necrosis who deteriorate during conservative treatment, necrosectomy may be an option. There is a tendency to postpone the operation until the necrosis can be clearly separated from non-necrotic tissue. Although a specific pharmacological agent for the treatment of pancreatitis is still not available, the above procedure has led to a significant reduction of mortality in patients with severe acute pancreatitis.

Abdominal Pain↗
PubMed2005

Genetics of pancreatitis.

There was some recent progress in the understanding of genetic risk factors in chronic pancreatitis. Due to this progress some of the traditional views of the subject will change. Today, genetic risk factors are attributed a much more important role that in the past. The frequency and strength of mutations were higher than expected. Strong variants were the rare autosomal-dominant mutations N29I and R122H of PRSS1 (cationic trypsinogen) and homozygous N34S of SPINK1 (pancreatic secretory trypsin inhibitor). Other mutations (heterozygous N34S, CFTR) were of lower relevance but still mediate a higher risk than alcohol consumption. The course of genetically determined pancreatitis is rather mild. In the long term pancreas cancer was found in some patients but apart from non-smoking no adequate prophylactic strategy is available up to now.

Carrier Proteins↗
PubMed2003

[Therapy of acute pancreatitis].

Despite our increasing knowledge in the pathophysiology of acute pancreatitis therapeutic strategies based on this knowledge, such as inhibition of proteases, are not convincing. It is most likely that these strategies are initiated to late after the onset of pancreatitis. It is of utmost importance to clarify the severity of the disease for planning interdisciplinary approaches: therapy of pain, enteral nutrition via a jejunal tube, as well as treatment of extrapancreatic complications, such as respiratory insufficiency, coagulopathy, and renal insufficiency. A key role plays the exact balance of potential high fluid losses. Prophylactic application of antibiotics such as imipenem in cases of necrotizing pancreatitis to prevent infection is widely used. Infected necroses are an indication for surgery. In biliary pancreatitis one has to remove impacted bile duct stones via ERCP and papillotomy followed by elective cholecystectomy.

Acute Disease↗
PubMed2003

[Therapy of chronic pancreatitis].

Treatment of chronic pancreatitis is dependend on the stage of the disease and its complications. Pain therapy should be based on the knowledge of various causes of pain. In therapy of complications such as bile duct or pancreatic duct strictures interventional endoscopy is usually the first choice followed by surgery. Exocrine insufficiency is treated by porcine pancreatic extracts, endocrine insufficiency by insulin. One has to apply various imaging procedures such as sonography, MRCP, ERCP, endosonography, CT for exact diagnosis of complications and planning various therapeutic strategies. Pseudocysts may be drained via the transgastric, transduodenal, transpapillary or transcutaneous route. Distal prepapillary stenosis of the main pancreatic duct and bile duct stenoses can be drained by stents. Pancreatic duct stones can be desintegrated by shock waves and removed by endoscopy. Early diagnosis of pancreatic carcinoma as a potential complication of long standing inflammation of the pancreas remains an unsolved problem.

Analgesia↗
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↗