Genotype-phenotype and genotype-origin correlations in children with mediterranean fever in Germany - an AID-net study.

Familial Mediterranean fever (FMF) is the most inherited common autoinflammatory disease (AID) with mutations in the MEFV (MEditerraneanFeVer) gene.The Mor- and Pras-Score modified for children and C-reactive protein (CRP) were used to assess FMF disease severity in Germany. We evaluate the applicability of the 2 severity scores and the correlations between ethnic origin, phenotype, and genotype.Among 242 children (median 5 age at diagnosis), we detected 431 pyrin mutations and 22 different sequence variants, including one new mutation (p.Gly488Asp). The 5 most -frequent alterations were p.Met694Val (55.2%), p.Met680lle (11.8%), p.Val726Ala (10%), p.Glu148Gln (7.9%) and p.Met694IIe (2.3%). The prevailing ancestries of 223 cases were Turkish (82.5%) and Lebanese (8.1%). Homozygous p.Met694Val substitution (30.2%) was associated with a more severe disease activity by Mor-Score, as well as with a higher mean CRP (74 mg/l) compared to patients with other mutations. Indeed, Mor- and Pras-Score were inconsistent with each other. A typical distribution of mutations in different ethnic populations was obvious, but not statistically verifiable due to the low number of cases.The homozygous p.Met694Val substitution was associated with a more severe disease activity in our German cohort. The common severity scores were inconsistent in -children.

Exocrine pancreatic function in patients with end-stage renal disease.

AIM: malnutrition is a common problem in patients with end-stage renal disease (ESRD). Several studies showed 30 years ago that more than half of patients with ESRD suffered from exocrine pancreatic insufficiency. However, the studies never investigated whether the functional impairments led to morphological changes of the pancreas or to steatorrhea and thus indicating the need for lifelong pancreatic enzyme substitution. Our goal was therefore not only to establish the frequency but also the severity of exocrine pancreatic insufficiency in hemodialysis patients. METHODS: the study included 50 hemodialysis patients with no history of acute or chronic pancreatitis or upper abdominal symptoms of uncertain origin. All patients with hyperthyroidism, status post-gastrectomy or (partial) small bowel resection, or chronic inflammatory bowel disease were excluded. In all 50 patients, fecal elastase-1 was determined using two different methods (Bioserv Diagnostics and ScheBo Biotech) and fecal fat content and fecal weight were measured. RESULTS: mild to moderate exocrine pancreatic insufficiency (elastase-1 100 - 200 microg/g stool) was found in 10% of patients. It was not correlated with age, sex, and underlying renal disease, duration of hemodialysis, or diarrhea and steatorrhea. In no patient was the enzyme content < 100 microg/g stool, i.e., it never sank to a level at which pancreatic enzyme substitution would have been recommended. Nine patients (18%) had mild diarrhea (200 - 300 g stool/ day), and 10 (20%) had mild steatorrhea (7 - 15 g fat/day in the stool). Five patients had both diarrhea and steatorrhea. CONCLUSIONS: mild to moderate but not severe exocrine pancreatic insufficiency is not infrequent in patients on hemodialysis but unlikely to be responsible for malnutrition in ESRD. Non-pancreas-related steatorrhea is also not uncommon. This finding requires further analysis because steatorrhea might influence nutrition, thus potentially opening the way to new therapeutic approaches.

Alcohol consumption in patients with acute or chronic pancreatitis.

Understanding of the relation between the alcoholic consumption and the development of pancreatitis should help in defining the alcoholic etiology of pancreatitis. Although the association between alcohol consumption and pancreatitis has been recognized for over 100 years, it remains still unclear why some alcoholics develop pancreatitis and some do not. Surprisingly little data are available about alcohol amounts, drinking patterns, type of alcohol consumed and other habits such as dietary habits or smoking in respect to pancreatitis preceding the attack of acute pancreatitis or the time of the diagnosis of chronic pancreatitis. This review summarizes the current knowledge. Epidemiological studies clearly show connection between the alcohol consumption in population and the development of acute and chronic pancreatitis. In the individual level the risk to develop either acute or chronic pancreatitis increases along with the alcohol consumption. Moreover, the risk for recurrent acute pancreatitis after the first acute pancreatitis episode seems also to be highly dependent on the level of alcohol consumption. Abstaining from alcohol may prohibit recurrent acute pancreatitis and reduce pain in chronic pancreatitis. Therefore, all the attempts to decrease alcohol consumption after acute pancreatitis and even after the diagnosis of chronic pancreatitis should be encouraged. Smoking seems to be a remarkable co-factor together with alcohol in the development of chronic pancreatitis, whereas no hard data are available for this association in acute pancreatitis. Setting the limits for accepting the alcohol as the etiology cannot currently be based on published data, but rather on the 'political' agreement.

Serum cystatin C is a suitable marker for routine monitoring of renal function in pediatric cancer patients, especially of very young age.

BACKGROUND: Monitoring renal function is crucial in children undergoing chemotherapy. To date, a combination of routine serum creatinine (SCR) monitoring with occasional determination of creatinine clearance ratio (CCR) is widely used as clinical standard for this purpose. Both methods have their limitations regarding diagnostic value (SCR) or practicability (CCR), especially in young children. Diagnostic alternatives, such as glomerular filtration rate (GFR) estimation formulas have not been proved to be superior. The aim of the study was to evaluate whether serum cystatin C (CysC) may have a diagnostic impact on pediatric patients. PROCEDURE: CysC, SCR, several GFR estimation formulas (Counahan-Barratt, Ghazali-Barratt, Schwartz, Shull, Traub), and CCR were studied in 80 pediatric cancer patients (age range: 0.17-17.9 years) during their chemotherapy. Special attention was given to children under the age of 3 in whom accurate urine collection for CCR is difficult. RESULTS: All parameters correlated similarly well with CCR. Total accuracy was 66% and 67% for CysC and SCR, respectively. In very young children (<3 years), correlation with CCR was for CysC r = -0.74 with an area under the curve (AUC) of 0.646, and for SCR r = -0.27 with AUC = 0.594. Total accuracy was 60% for CysC, 50% for SCR. CONCLUSIONS: CysC represents a suitable marker for monitoring renal function in pediatric cancer patients. In young children (<3 years), CysC may have a better diagnostic value than SCR. Future studies should show if CysC can improve renal monitoring by replacing SCR, especially in very young children.

[Diagnosis and treatment of acute pancreatitis: are the guidelines accepted?]. / Diagnose und Therapie der akuten Pankreatitis: Werden die Leitlinien akzeptiert?

BACKGROUND AND OBJECTIVE: Eight international guidelines exist for the diagnosis and treatment of acute pancreatitis, a disease that is often difficult to assess and treat, particularly when the necrotising variety of the disease is present. The knowledge of and compliance with these guidelines in Germany is unknown. METHOD: In order to assess the knowledge and compliance with acute pancreatitis guidelines, a structured questionnaire was sent out to the 190 members of the ALGK (Arbeitsgemeinschaft Leitender Gastroenterologischer Krankenhausärzte), a professional organisation of gastroenterology chairmen, who, in their respective institutions, are responsible for the diagnosis and treatment of acute pancreatitis. University hospitals were excluded to cover the entire severity spectrum of the disease and to avoid a referral bias. RESULTS: The questionnaire was responded by 182 (96 %) members. To a large extent (acceptance > 2/3 of the consultants), guideline recommendations were complied with. There was, nevertheless, disagreement regarding the prophylactic use of antibiotics (acceptance < 2/3 of the consultants), as to when a contrast-enhanced computed tomography was indicated, and the timing of cholecystectomy for biliary pancreatitis. The choice of pain therapy for patients with acute pancreatitis also remained equivocal. CONCLUSION: Based on the high response rate which excludes a non-responder bias, the results of our study reflect the current status of the diagnosis and therapy of acute pancreatitis in Germany and to what extent international guidelines are known and complied with. This study also highlights the need for additional clinical trials in areas of diagnostic or therapeutic uncertainty.

Cigarette smoking accelerates progression of alcoholic chronic pancreatitis.

BACKGROUND: Smoking is a recognised risk factor for pancreatic cancer and has been associated with chronic pancreatitis and also with type II diabetes. AIMS: The aim of this study was to investigate the effect of tobacco on the age of diagnosis of pancreatitis and progression of disease, as measured by the appearance of calcification and diabetes. PATIENTS: We used data from a retrospective cohort of 934 patients with chronic alcoholic pancreatitis where information on smoking was available, who were diagnosed and followed in clinical centres in five countries. METHODS: We compared age at diagnosis of pancreatitis in smokers versus non-smokers, and used the Cox proportional hazards model to evaluate the effects of tobacco on the development of calcification and diabetes, after adjustment for age, sex, centre, and alcohol consumption. RESULTS: The diagnosis of pancreatitis was made, on average, 4.7 years earlier in smokers than in non-smokers (p = 0.001). Tobacco smoking increased significantly the risk of pancreatic calcifications (hazard ratio (HR) 4.9 (95% confidence interval (CI) 2.3-10.5) for smokers v non-smokers) and to a lesser extent the risk of diabetes (HR 2.3 (95% CI 1.2-4.2)) during the course of pancreatitis. CONCLUSIONS: In this study, tobacco smoking was associated with earlier diagnosis of chronic alcoholic pancreatitis and with the appearance of calcifications and diabetes, independent of alcohol consumption.

[Diagnosis and therapy of chronic pancreatitis]. / Diagnostik und Therapie der chronischen Pankreatitis.

Chronic pancreatitis is characterized by recurrent or persisting pain. As the exocrine pancreatic insufficiency occurs early in the progression of the disease, the endocrine function may persist intact. Imaging procedures and pancreatic function tests are used to make a diagnosis. Therapy consists of pain reduction, which might require endoscopic or surgical intervention. Treatment of exocrine and endocrine pancreatic insufficiency is based on diet and substitution of pancreatic enzymes, minerals and vitamins, as well as insulin.

[Acute pancreatitis]. / Akute Pankreatitis.

While interstitial acute pancreatitis usually takes a benign course, necrotizing acute pancreatitis takes a severe course, mainly because of severe local and systemic complications. After a quick diagnosis it is necessary to rapidly assess a degree of severity of the disease and thus the prognosis. The clinical picture and the result of imaging procedures do not always correspond. The management basically includes to treat pain as well as to administer fluid, electrolyte, protein and calories. In addition, systemic treatment of complications such as shock or respiratory and renal insufficiency--if occurring--is necessary. In case of pancreatic necrosis, prophylactic administration of pancreas-penetrable antibiotics is recommended to avoid infection. In the severely ill with infected pancreatic necrosis, surgery is the treatment of choice. In approximately 10% of all patients with alcohol-induced pancreatitis, there is a gradual transition to chronic pancreatitis.

The problem of diagnosing chronic pancreatitis.

High alcohol consumption in Europe makes it necessary to consider chronic pancreatitis when a patient with history of alcohol abuse presents with abdominal pain. Diagnosis should be made on the basis of imaging procedures and function tests. A scoring system for this, together with a short evaluation of the present diagnostic procedures, are presented.

Epidemiology of pancreatic diseases in Lüneburg County. A study in a defined german population.

BACKGROUND/AIMS: Worldwide, the incidence of pancreatic cancer is very well known, that of acute pancreatitis and chronic pancreatitis not. Our study sought to determine the incidence of all three pancreatic diseases in a well-defined population in Germany. METHODS: Records of all patients treated for acute (first attacks only) and chronic pancreatitis as well as pancreatic cancer from 1988 to 1995 and who resided in the county of Lüneburg were evaluated. RESULTS: The crude incidence rates for acute pancreatitis, chronic pancreatitis and pancreatic cancer per 100,000 inhabitants/year were 19.7, 6.4, and 7.8. In acute and chronic pancreatitis the male gender dominated, whereas in pancreatic carcinoma the gender ratio was almost even. Peak incidence for acute pancreatitis was in the age group of 35-44 years, for chronic pancreatitis 45-54, and for pancreatic cancer 65-75. Etiology of acute pancreatitis was biliary in 40%, alcohol abuse in 32%, unknown in 20%, and other in 8% of the patients. In chronic pancreatitis alcohol abuse was the etiology in 72% and unknown (idiopathic) in 28%. CONCLUSION: For the first time, epidemiological data obtained in a well-defined German population are being published relating to all three pancreatic diseases: acute pancreatitis (incidence rate, etiology and severity), chronic pancreatitis (incidence rate and etiology), and pancreatic carcinoma (incidence rate). A peak incidence of chronic pancreatitis occurring in an age group 10 years older than the peak age group for acute pancreatitis suggests that chronic pancreatitis develops during this time-frame following first attacks of acute pancreatitis.

Acute pancreatitis: does gender matter?

In a number of gastrointestinal and nongastrointestinal diseases, gender has been proven to be an independent risk factor for severity. To determine whether this holds true for severity in acute pancreatitis is the aim of our study. This paper derives from a prospective study on the epidemiology of acute pancreatitis, which included 274 patients (172 male and 102 female) with a first attack of the disease. Severity parameters were: Atlanta criteria (arterial Po2 < or = 60 mm Hg, and serum creatinine on admission >2 mg/dl after rehydration); Ranson's and Imrie's prognostic factors; APACHE II score; Balthazar-scored contrast-enhanced computed tomography (CT) results obtained within 72 hr of admission; days spent in the intensive care unit and total hospital stay; the necessity for artificial ventilation, dialysis, or surgery; and mortality. As already known, there is a significant association between gender and etiology of pancreatitis in general. Not surprisingly, the men in our study had alcohol-induced acute pancreatitis more frequently than women, whereas biliary pancreatitis predominated among the women. As for severity, there was no significant association between gender and any of the severity parameters with a few minor exceptions: longer hospital stays, higher Imrie scores and more pseudocysts for women, and more necroses in women with idiopathic pancreatitis. Thus, gender is no independent risk factor for the severity and outcome of acute pancreatitis.

Publication rates following pancreas meetings.

Publication rates and determinants of publication were studied based on abstracts presented at pancreatic meetings. All abstracts presented at the 1994 and 1995 annual meetings of the European Pancreatic Club (EPC) and the American Pancreatic Association (APA) were followed up by searching MEDLINE. Publication rates were compared using log-rank tests and multiple logistic regression. The prestige of the publishing journals was compared using Kruskal-Wallis tests on scientific impact factors (SIF). Overall, 340 abstracts were presented at the EPC, and 254 were presented at the APA. Of these, 203 (59.7%, EPC) and 138 (54.3%, APA) were later published in peer-reviewed journals. Publication rates did not differ by study type or country region of origin. In addition, median SIFs were similar by conference (APA vs. EPC) and research type (basic science vs. clinical studies) (overall, 1.7). However, North American and North/West European articles were published in higher impact journals as compared with those from other countries. Publication rates and median journal SIFs in pancreas research are similar to those reported from other medical specialty meetings. There is no difference by conference, type of research, or origin (North American vs. European).