Tolerability and pharmacokinetic profile of a novel benzene-poly-carboxylic acids complex with cis-diammineplatinum (II) dichloride in dogs with malignant mammary tumours.

The pharmacokinetic profile, tolerability and efficacy of benzene-poly-carboxylic acids complex with cis-diammineplatinum (II) dichloride (BP-C1) were studied in dogs with mammary cancer. A three-level response surface pathway designed trial was performed on seven dogs. At each level BP-C1 was administered subcutaneously daily for 7 days followed by a 7-day rest period in a dose escalating manner. Adverse events according to VCOG-CTCAE, performance status and tumour progression were recorded. The pharmacokinetic profile followed a two-compartment model with rapid absorption, short distribution, and a slow elimination phase. The overall elimination half-life was 125 h. The maximum tolerated dose of BP-C1 was estimated to be above 0.46 mg kg-1 . A significant reduction in VCOG-CTCAE toxicity which correlated negatively with increasing dose was found. The dogs' general performance status remained unchanged. No decrease in total tumour burden was found, although temporary tumour reduction was seen in some target tumours.

Autotransplantation of splenic tissue in an isolated segment of small intestine.

The ability of splenic tissue to regenerate when implanted in an isolated segment of small intestine with intact circulation was studied in six pigs. After total splenectomy, 10 per cent of the weight of the spleen was implanted in a 10-15-cm long isolated segment of small intestine with an intact vascular supply. Bowel continuity was established by end-to-end anastomosis. Before implantation, the mucosal layer was completely removed from the isolated segment of the small intestine. The animals were killed 6 months later and the isolated segment of small bowel containing the splenic tissue identified. Most of the implanted splenic tissue was recovered in the isolated segment of small intestine; the weight ranged from 43 to 120 (mean 80) per cent of that of the implanted tissue. An isolated segment of small intestine with an intact circulation produces a higher index of regeneration than other previously reported sites.

Carbohydrate and lipid metabolism of skeletal muscle in type 2 diabetic patients.

Peripheral hyperinsulinaemia is the cause of metabolic changes that might contribute to the high incidence of macrovascular disease in patients with diabetes mellitus. In order to test this hypothesis muscle biopsies from 12 Type 2 diabetic patients and 14 age and sex matched non-diabetic patients, undergoing minor surgery, were obtained. The diabetic patients had significantly elevated fasting serum insulin (0.29 +/- 0.05 vs 0.06 +/- 0.03 nmol-1) and glucose (8.3 +/- 1.5 vs 4.6 +/- 0.5 mmol-1) and HbA1 levels (8.4 +/- 0.4 vs 5.0 +/- 0.2 per cent). The fasting and 2-h postprandial C-peptide levels were 0.99 +/- 0.25 vs 0.39 +/- 0.12 and 3.12 +/- 0.75 vs 1.09 +/- 0.34 nmol/l, respectively. The diabetic patients showed a marked elevation of triglyceride in the striated muscle biopsies compared to the non-diabetic controls (290 +/- 52 vs 48 +/- 6 mumol/g wet weight, p less than 0.001). Moreover, the activities of glucose-6-phosphate dehydrogenase (0.25 +/- 0.03 vs 0.13 +/- 0.01 U/g wet weight) and malic enzyme (0.15 +/- 0.01 vs 0.05 +/- 0.01 U/g wet weight), necessary for lipid synthesis, were significantly increased (both p less than 0.001) in the diabetic patients while the glycolytic enzymes, hexokinase (0.65 +/- 0.09 vs 1.82 +/- 0.11 U/g wet weight), pyruvate kinase (7.3 +/- 0.9 vs 13.2 +/- 0.9 U/g wet weight), phosphofructokinase (1.3 +/- 0.2 vs 2.6 +/- 0.2 U/g wet weight), and alpha-glycerophosphate dehydrogenase (7.3 +/- 0.5 vs 12.5 +/- 0.7 U/g wet weight) were decreased (all p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Gastric inhibitory polypeptide (GIP) and insulin release after small-bowel resection in man.

Fifteen patients in whom various parts of the small intestine had been resected because of Crohn's disease or mesenteric thrombosis and 10 healthy volunteers were studied. A 50-g oral glucose load (OGTT) and an intravenous glucose infusion giving the same plasma glucose profile as the OGTT were carried out to study (a) the relation between the plasma gastric inhibitory polypeptide (GIP) levels after oral glucose and the length and nature of the intestinal residues and (b) the importance of endogenous GIP as an incretin in man. The magnitude of the increase in plasma GIP after oral glucose load was positively correlated to the length of residual jejunum. The incretin effect was positively correlated to the length of residual intestine. Patients with preserved ileal residues had larger incretin effects than patients with less than 150 cm jejunal residues and no ileal residues, although the integrated increases in plasma GIP after oral glucose were equal. Compared with healthy volunteers, the patients with more than 150 cm residual jejunum had significantly higher increases in plasma GIP and normal incretin effects. The GIP release and the incretin effect in patients with preserved ileal residues were normal. The incretin effect of the patients with less than 150 cm jejunum was significantly subnormal in spite of a normal GIP release. These findings indicate that the upper intestine releases GIP after oral glucose and that other as yet unknown intestinal hormonal factors act as incretins in concert with GIP.

Gastric release in pigs during intestinal pouch stimulation with meat extract.

In six pigs the gastric concentrations in the pancreaticoduodenal vein were slightly, but significantly, higher than in the carotid artery (p < 0.05). After instillation of meat extract into the duodenal pouches the gastrin concentrations in the pancreaticoduodenal vein increased significantly (p < 0.05), whereas the corresponding arterial concentrations remained almost unchanged. In four pigs the gastrin concentrations remained unchanged in the regional veins and equalled those in the carotid arteries after meat extract installation into jejunal and ileal pouches. Instillation of meat extract into duodenal pouches (three pigs), jejunal pouches (three pigs), and jejunal + ileal pouches (two pigs) caused substantial increase of gastrin concentrations in the regional antral veins (right gastroepiploic veins), whereas no increase was detected after instillation of meat extract into ileal pouches (three pigs). It is concluded that the duodenum in anaesthetized pigs released gastrin, whereas neither the jejunum nor the ileum does. However, an antral release of gastrin may result from duodenal and jejunal protein meal stimulation. The mechanism of this duodeno- and jejuno-antral release is still unknown.

Elevated serum proinsulin in beta cell nesidioblastosis. Report of a case in a newborn.

A newborn infant with severe hypoglycaemia and nesidioblastosis was subjected to subtotal pancreatectomy without any sign of improvement. In spite of very low plasma levels of glucose (i.e. less than 1 mmol/l) plasma insulin concentrations were high (i.e. greater than 700 pmol/l). Plasma proinsulin was considerably enhanced comprising 43% of the total insulin immunoreactivity. Plasma glucagon concentrations were normal. Postoperatively normal to subnormal plasma glucose levels could only be maintained by treatment with frequent meals, diazoxide and intramuscular injections of a long-acting glucagon preparation. With time, signs of mental retardation became obvious.

Inhibition of salicylate and lithium absorption in the human intestine by copper sulfate.

Copper sulfate, given orally in an emetic dose, decreased the absorption of therapeutic doses of acetylsalicylic acid or lithium carbonate, more than was expected judging from the recovery of salicylic acid in the vomit. Ten volunteers participated.

Acute hemorrhagic gastritis--diagnosis and treatment.

Approximately 10-20% of patients admitted with acute gastrointestinal bleeding suffer from hemorrhagic erosive gastritis. A material of 36 patients is presented and the literature reviewed. The moderate bleeders stop bleeding within hours to a few days and the majority may safely be managed conservatively, i.e. with blood transfusions. The severe bleeders continue to bleed for a long time and surgery is often required. Different operative procedures have been suggested. The mortality in this group of patients is high--nearly 30%, and the frequency of postoperative rebleeding is also high. It is concluded that there is no absolute operative procedure of choice but vagotomy combined with subtotal gastrectomy offer the best protection against rebleeding. Treatment with selective application of vasoconstrictors is mentioned.

The effect of magnesium sulfate on the absorption of acetylsalicylic acid and lithium carbonate from the human intestine.

Magnesium sulfate given orally in a hypertonic or isotonic solution did not alter the absorption of therapeutic doses of acetylsalicylic acid or lithium carbonate, despite a purgative effect in 10 volunteers. The concentration of magnesium in serum remained unchanged during the experiments.