Mutation in the SPINK1 trypsin inhibitor gene, alcohol use, and chronic pancreatitis.
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Alcoholism↗
Biomedical subjects
A Kingsnorth
Publications and source records attributed to A Kingsnorth.
Evidence that insulin is imprinted in the human yolk sac.
Allelic variation in the size of the insulin (INS) variable number tandem repeat (VNTR) correlates with the expression of both INS in the pancreas and thymus and IGF2 (the gene downstream of INS) in the placenta. In addition, the shorter, class I alleles are associated with type 1 diabetes, whereas the longer, class III alleles are associated with type 2 diabetes, polycystic ovary syndrome (PCOS), and size at birth. Parent-of-origin effects have been reported for type 2 diabetes and PCOS, thus implicating a role for genomic imprinting in these phenotypes. In mice, Ins2 is imprinted and paternally expressed in the yolk sac. In humans, evidence for the imprinting of INS is circumstantial, with occasional monoallelic expression in the thymus. In the present study, we found evidence for the imprinted paternal expression of INS in the human yolk sac. Two other imprinted genes from the same cluster are also expressed monoallelically in the human yolk sac. IGF2 was expressed solely from the paternal allele, and H19 was expressed solely from the maternal allele. These data suggest not only further functional roles for the human yolk sac in early fetal growth, but also evidence for a potential causal link between the control of insulin expression during development and insulin/growth-related diseases in later life.
Alleles↗
Chemokines MCP-1 and RANTES in isolated rat pancreatic acinar cells treated with CCK and ethanol in vitro.
The role of cholecystokinin (CCK) and ethanol on the expression and secretion of monocyte chemoattractant protein-1 (MCP-1) and regulated on activation, normal T-cell expressed and secreted (RANTES) chemokines from isolated rat pancreatic acinar cells was investigated. CCK at concentrations of 1 nM and 100 nM and ethanol at concentrations of 75, 200, 400, and 600 mM were used to stimulate isolated acini. The levels of MCP-1 and RANTES in the incubation medium were determined by enzyme-linked immunoabsorbent assay (ELISA). In the control groups, MCP-1 and RANTES were secreted into the incubation medium, and both increased with time. MCP-1 increased from baseline 17.6 pg/ml to 74.1 pg/ml, whereas RANTES increased from 255.5 to 318.3 pg/ml at 390 min. CCK at 100 nM caused a sustained increase in MCP-1 levels to 89.6 pg/ml at 390 min in the incubation medium, whereas the levels of RANTES gradually decreased after 180 min and reached its lowest level at 390 min. Ethanol at a concentration of 600 mM increased the levels of RANTES in the incubation medium, but inhibited the levels of MCP-1 at all concentrations (75, 200, 400, and 600 mM). In summary, rat pancreatic acinar cells secrete MCP-1 and RANTES, and the stimulation of these chemokines by CCK and ethanol suggests that they may be involved in the pathogenesis of acute pancreatitis.
Animals↗
Training for surgeons using digital satellite television and videoconferencing.
The TETRASUR project (TELematics TRAining for SURgeons) has investigated the effectiveness of distance-learning technologies in the delivery of training for doctors who are studying for membership of the Royal College of Surgeons. Digital satellite television receivers and ISDN videoconferencing equipment have been installed in hospitals to deliver the course modules, including a series of live television programmes transmitted by satellite. ISDN videoconferencing was integrated, live, into the satellite broadcasts to bring in guest lecturers and for interactive discussions with the trainee doctors. Videoconferencing was also used for seminars and discussion groups. These methods proved to be effective and popular with the doctors, although there was some dissatisfaction with the visual quality of the ISDN videoconferencing at 128 kbit/s. Efforts are now being made to improve the quality of the video feed from remote sites using ISDN at 384 kbit/s.
Education, Distance↗
Diagnosing acute pancreatitis: room for improvement?
Improving the diagnosis of acute pancreatitis is a crucial step in reducing its mortality. At present, up to 40% of cases may remain undetected until autopsy. Early diagnosis could have resulted in different management in about half of these patients, perhaps saving lives with modern interventions. This article reviews the obstacles to early diagnosis, and considers the steps that will improve the record.
APACHE↗
Unusual appearance of viable liver on Tc-99m mebrofenin hepatobiliary imaging.
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Aniline Compounds↗
Role of cytokines and their inhibitors in acute pancreatitis.
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Acute Disease↗
Phase I study of methylacetylenic putrescine, an inhibitor of polyamine biosynthesis.
In a phase I clinical trial, nine patients with advanced malignancies not amenable to alternative therapy received alpha-methyl-delta-acetylenic putrescine (MAP), an enzyme-activated, irreversible inhibitor of ornithine decarboxylase (ODC). MAP was given orally in increasing doses to successive groups of three patients as follows: 375 mg, 750 mg and 1500 mg/day, given as three equally divided doses for 4 weeks. Doses of 375 and 750 mg/day were well tolerated, with no detectable toxicity. Of three patients receiving 1500 mg/day, two experienced moderate to severe myelosuppression; one of these also became anuric, requiring the discontinuation of therapy after 9 days. Both effects were reversible after treatment was stopped. No objective responses were observed, with five patients having stable disease and four, progressive disease during the study period. In the seven patients in whom it could be calculated, the plasma elimination half-life t1/2 of MAP measured on the last day of treatment was between 3.9 and 9.2 h in six patients (mean, 5.6 h) and 26.1 h in the seventh. Mean steady-state trough concentrations of MAP were 2.3 mumol after the 375 mg/day dose, 7.1 mumol after 750 mg/day and 16.6 mumol after dosing with 1500 mg/day for 4 weeks, the levels after each treatment schedule being sufficient to inhibit ODC as demonstrated by increases in the urinary excretion of decarboxylated S-adenosylmethionine (dc-SAM). MAP treatment was associated with mean maximal increases in the urinary excretion of dc-SAM of 2.6-, 9.3- and 17.9-fold after 375, 750 and 1500 mg/day for 4 weeks, respectively, but no consistent changes in the urinary excretion of the polyamines, putrescine, spermidine or spermine were observed. Thus, the 24-h urinary excretion of dc-SAM may be used as a conveniently accessible marker of ODC inhibition in cancer patients.
Adult↗
Glutamate metabolism in malnutrition and sepsis in man.
The metabolism of intravenous glutamate has been studied for its usefulness as a nutrient in intravenous feeding regimens. Intravenously infused monosodium L-glutamate was rapidly removed from the blood with a half-life of 10.7 and 9.1 min in healthy control and malnourished septic patients, respectively. Under the same conditions, alanine was metabolized much more slowly, with a half-life of 35 min (1). After the infusion of glutamate, blood lactate fell and glucose was increased in the control patients but not in the sick patients. Blood pyruvate, ketone bodies, glutamine, aspartate and alanine levels did not change after the infusion of glutamate in either group of patients. Increased urinary excretion of aspartate was observed in the control patients following the infusion of glutamate, but in the sick patients there was an increased excretion of glutamine. Insulin concentration in the blood rose after the infusion of glutamate in the control patients but not in the sick patients. Although the glutamate half-life life was similar in the two groups of patients, glutamate was metabolized differently in the sick. Deamination predominates over transamination. We conclude that glutamate, in the amounts provided in intravenous feeding, is safe, although its effectiveness may be less than previously thought.
Adult↗
Antibiotics in appendicectomy.
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Appendicitis↗
Treatment of chronic oesophageal perforations with special reference to an endoscopic method.
The endoscopic treatment of chronic oesophageal perforations (more than 18--24 h old) by the application of sodium hydroxide 20 per cent to the edges of the perforation is described. The importance of pleural and mediastinal toilet and the accurate siting of drainage tubes and full expansion of the lung, together with measures for diminishing oral, gastric and bilary secretions from the perforation, are stressed. Five patients who have been treated by this conservative method are presented and the method compared with the more radical surgery advocated by the majority of other surgeons.
Aged↗