Chronic pancreatitis (CP) is a continuing or relapsing inflammatory disease of the pancreas. In approximately one-third of all cases, no aetiological factor can be found, and these patients are classified as having idiopathic disease. Pathophysiologically, autodigestion and inflammation may be caused by either increased proteolytic activity or decreased protease inhibition. Several studies have demonstrated mutations in the cationic trypsinogen gene (PRSS1) in patients with hereditary or idiopathic CP. It is thought that these mutations result in increased trypsin activity within the pancreatic parenchyma. Most patients with idiopathic or hereditary CP, however, do not have mutations in PRSS1 (ref. 4). Here we analysed 96 unrelated children and adolescents with CP for mutations in the gene encoding the serine protease inhibitor, Kazal type 1 (SPINK1), a pancreatic trypsin inhibitor. We found mutations in 23% of the patients. In 18 patients, 6 of whom were homozygous, we detected a missense mutation of codon 34 (N34S). We also found four other sequence variants. Our results indicate that mutations in SPINK1 are associated with chronic pancreatitis.

M ultiple epiphyseal dysplasia (MED) is a generalised skeletal dysplasia that although relatively mild is associated with significant morbidity. Joint pain, joint deformity, waddling gait, and short stature are the main clinical signs and symptoms. In the past, the disorder was subdivided into the milder Ribbing type, usually with flattened epiphyses, 1 and the more severe Fairbank type with round epiphyses, 2 but many cases were not classifiable as clearly either type.3 MED can be caused by mutations in at least six separate genes: COMP, 4-7 collagen IX (COL9A1, COL9A2, and COL9A3), [8][9][10][11][12][13] matrilin 3 (MATN3), 15 and the sulphate transporter, DTDST (DTDST/SLC26A2). We have previously reported an adult with a recessively inherited form of MED (rMED) characterised by club feet, double layered patellae, and normal stature, who was homozygous for the mutation 862c>t/ R279W in the DTDST gene, previously associated with the achondrogenesis 1B-atelosteogenesis 2-diastrophic dysplasia spectrum. We now report on a group of 18 subjects who are homozygous for this point mutation, allowing a comprehensive assessment of this particular MED phenotype. Distinction of rMED is important because of its recessive inheritance (unlike other MED types) and genetic counselling implications. The frequency of the R279W mutation and the number of subjects with molecularly proven rMED identified since its description suggest that rMED may be more common than hitherto assumed. MATERIAL AND METHODSBlood or genomic DNA was sent to the Zurich centre for DTDST mutation analysis because of clinical and radiographic signs similar to the reported case of rMED, 20 or because of a clinical diagnosis of MED and negative mutation analysis of COMP or collagen IX genes. Genomic DNA was extracted from blood leucocytes using standard protocols and was subjected to DTDST mutation analysis. The fragment of interest, that is, the 5′ part of exon 3, was amplified according to the procedure previously described.18 20 The PCR fragment was digested with the restriction endonuclease StyI. Results were visualised on agarose gels in the presence of positive and negative controls. As the nucleotide change 862c>t (leading to amino acid substitution R279W) creates a new restriction site for StyI, heterozygous and homozygous patients can be distinguished from wild type homozygous subjects. In all subjects with a positive StyI digestion, the genotype was confirmed by direct sequencing of the fragment amplified in a second PCR. The ABI Prism Big Dye Terminator Ready Reaction Kit and protocol were used for sequencing in an ABI Prism 310 Genetic Analyzer. In all subjects who were not homozygous for R279W, a complete DTDST mutation screening was performed 19 to test for the presence of other mutations.When R279W homozygosity was identified, the referring physician was asked to participate in this study by sending photographs and radiographs, as well as by completing a questionnaire about family and personal history, symptoms leading to diagnosis, clinical c...

Undesired side effects and complications of gastrointestinal endoscopy and premedication are rare events. However, this is true only of endoscopic units with experienced investigators, modern equipment and monitoring. The complication rate of upper gastrointestinal endoscopy is about 0.1% with cardiopulmonary events predominating. The typical complication of colonoscopy is perforation, seen in 0.2%. The relevant ERCP specific complication is acute pancreatitis in about 1%, followed by acute cholangitis. The most serious complications of laparoscopy are hemorrhage from the liver biopsy site, bleeding from abdominal wall varices, and perforation of the colon. The cardiopulmonary mortality is low for upper gastrointestinal endoscopy as well as for colonoscopy (1 death/20,000 procedures). Premedication, chronic obstructive pulmonary disease, coronary heart disease, valvular heart disease and, last but not least, advanced age, must be considered risk factors for the development of complications of gastrointestinal endoscopy. Balanced indication, particularly in the elderly patient, should be the consequence. If possible, endoscopy should be performed without sedatives. If premedication is necessary, it should be used sparingly. Not only patients at high risk for the development of cardiopulmonary complications, but all patients undergoing endoscopy must be carefully monitored after premedication, during and after endoscopy. The non-invasive procedure of pulse-oximetry is appropriate for continuous monitoring of arterial oxygen saturation in patients with cardiopulmonary diseases, irrespective of their premedication status. Antibiotic prophylaxis is recommended in patients with valvular heart disease or prosthetic valves. Standardized cleaning and disinfection of the instruments is of great importance to avoid hepatitis B or HIV transfer.(ABSTRACT TRUNCATED AT 250 WORDS)

Preoperative cholangiography and subsequent removal of bile duct stones may increase the efficacy of laparoscopic cholecystectomy and reduce the rate of conversion to open cholecystectomy. Since there is little data on the incidence of choledocholithiasis in this group of patients, we undertook a prospective study on the routine performance of ERC in 288 patients selected for laparoscopic cholecystectomy. ERC succeeded in 264 of the 288 patients (91.7%) and showed a normal bile duct system in 227 (86.0%). Atypical bile duct anatomy was seen in eight patients. Open cholecystectomy was performed in seven of them but was judged to be absolutely necessary in only two cases (one patient each with Caroli syndrome and Mirizzi syndrome). ERC also revealed bile duct stones in 29 of 264 patients (11.0%) which had not been suspected on the basis of clinical, laboratory and ultrasonographic findings in nine cases (3.4%). EPT succeeded in all of the 29 patients with choledocholithiasis but open cholecystectomy was subsequently performed in four patients due to incomplete bile duct clearance (n = 3) or temporary bleeding after EPT (n = 1). The rate of ERC/EPT-related morbidity was 2.8%. It is concluded from a risk-benefit analysis in these patients that ERC should be restricted to patients with suspected bile duct stones. Following this strategy, small ductal concrements and bile duct abnormalities will be missed in 6.4% of cases but the clinical relevance of these findings is still unclear. In patients with combined gallbladder and common bile duct stones, preoperative EPT plus subsequent laparoscopic cholecystectomy appears to be an effective and time-saving therapeutic regimen which should be compared with open cholecystectomy plus common bile duct exploration in future studies.

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