A tumour that secretes glucagon-like peptide-1 and somatostatin in a patient with reactive hypoglycaemia and diabetes

Glucagon-like peptide 1 (GLP-1), an insulinotropic hormone normally synthesised in the intestinal mucosa and released in response to a meal, is essential for normal glucose homoeostasis. There is much interest in the use of GLP-1 to treat diabetes, since the risk of hypoglycaemia is thought to be low. We report an instance of a 45-year-old woman with a GLP-1 and somatostatin secreting neuroendocrine tumour who presented with reactive hypoglycaemia and hyperglycaemia, but who was subsequently cured by surgery. This case, of a neuroendocrine tumour secreting GLP-1 and causing reactive hypoglycaemia, indicates a potential adverse effect of GLP-1 therapy for diabetes.     

Selective loss of chromosome 11 in pheochromocytomas associated with the VHL syndrome

By using comparative genomic hybridization (CGH), we characterized the genetic profiles of 36 VHL-related pheochromocytomas. We then compared the results with those of sporadic and MEN 2-related pheochromocytomas. In 36 VHL-related tumors, loss of chromosome 3 and chromosome 11 were found in 34 tumors (94%) and 31 tumors (86%), respectively. There was significant concordance of deletions in chromosomes 3 and 11 (Kappa=0.64, P=0.0095), suggesting that they are involved in two different but necessary and complementary genetic pathways. The loss of chromosome 11 appeared to be specific for VHL-related pheochromocytoma as it was not present in any of the 10 VHL-related CNS hemangioblastomas studied and was significantly less common when compared with (a) sporadic pheochromocytomas from previously published results (13%; P=<0.0001), and (b) MEN 2-related pheochromocytomas from this and previously published studies (30%; P=0.0012). In summary, this is the first report of a novel consistent genetic alteration that is selected and specific for VHL-related pheochromocytoma, besides the two hits of the VHL gene.     

Single-dose pharmacokinetics and dose proportionality of oral cibenzoline

The pharmacokinetics of cibenzoline were evaluated in four young healthy volunteers who received ascending oral doses of 65, 97.5, 130, 162.5, 195, 227.5, and 260 mg separated by one week. Cibenzoline plasma concentrations exhibited an apparent biexponential decline following oral absorption. Maximum plasma concentrations and area under the plasma concentration-time curve increased in proportion to the dose. The mean elimination half-life among subjects was independent of dose and ranged from 7.3 to 8.7 hours. Oral clearance ranged from 380 to 575 ml/min and was also independent of dose. A single pharmacokinetic equation was used to adequately describe the plasma concentration data over the entire range of doses for each subject, indicating dose-proportional and linear pharmacokinetics.     

The influence of nutritional factors on lead absorption

The nutritional factors which affect lead absorption have been studied. Synthetic diets of known composition were compounded to contain 0·075% Pb as PbCl₂ labelled with ²⁰³Pb. Rats were exposed to lead for periods of 48 hr. The dietary intake was then measured and the absorption of lead determined by means of a whole-body counter. Lead absorption was increased by high fat, low mineral, low protein and high protein diets but was decreased by high mineral diet. Low fat, low fibre, high fibre, low vitamin and high vitamin diets had no effects on lead absorption.     

Reactions in rabbit Fallopian tube after plastic reconstruction. I. Gross pathology, tubal patency, and pregnancy

Rabbit tubal repair surgery was aseptic with Nembutal and ether anesthesia. Both tubes were cut at the uterotubal junction, a .61 mm thick polyethylene splint was inserted, sutured to the myometrium, and the junction sutured. At 2, 6, 10, 16, and 24 weeks the splint was removed through an incision. After a dye test for patency, 1 tube was removed and the rabbit was mated 1 week later. Results were 30% distorted placement of tube, 30% fibrose tubes (especially after 16 weeks), 47% adhesion (particularly after 6 weeks), some infection, and 55% positive dye flow test. 3 out of 7 rabbits delivered, all in those of the 2-week group that had no adhesions. 2 of the pregnancies occurred in rabbits with no dye passage.     

Transplantation of neonatal porcine islets and sertoli cells into nonimmunosuppressed nonhuman primates

A Mexican group reported transplantation of cocultured neonatal porcine islets and Sertoli cells resulting in insulin independence in nonimmunosuppressed type 1 diabetes patients. We have transplanted similar islets alone (naked islets) or cocultured islets with sertoli cells (islet/sertoli cells) into an omental site and other locations of seven nondiabetic, nonimmunosuppressed, nonhuman primates. Porcine endogenous retrovirus was not detected in recipient blood 8 weeks after porcine islet grafts, and porcine C-peptide was detected at a very low level in all animals. Histology examination failed to demonstrate obviously recognizable islets, but in the animals transplanted with islet/Sertoli cells at the omentum site, there were some surviving glucagons, pan-cytokeratin, and inhibin stained cells at 8 weeks.