A stable prostacyclin analogue (iloprost) in the treatment of ischaemic ulcers of the lower limb. A Scandinavian-Polish placebo controlled, randomised multicenter study.

The clinical efficacy of the prostacyclin analogue iloprost was studied during a 2 week treatment and 6 month follow-up period in 103 patients with ischaemic ulcers who were randomised to receive active treatment or placebo. Responders were defined as those patients who achieved healing of at least one third of the ulcer area during the study period. The overall responder rate was 41.3%, compared with 25% for the control group (P = 0.086). Side effects including flushing and headache, were common. The study population had a mortality of 23% during the 6 month period, the amputation rate was 43.5% for iloprost and 50% for placebo treated patients. In this severely diseased population of patients a treatment period limited to 2 weeks did not sufficiently improve ulcer healing.

Factors influencing the outcome of E. coli peritonitis in rats.

Substances that may influence the course and outcome of intra-abdominal sepsis were investigated in an experimental model of Escherichia coli peritonitis in rats. All rats received an intraperitoneal injection of E. coli. In the first set of experiments, substances commonly contaminating the abdominal cavity after trauma were intraperitoneally injected, and the following mortality rates were found: saline solution (controls) 27%, hemoglobin solution 80% (p less than 0.01), whole blood 20% (p greater than 0.05), whole blood together with bile 93% (p less than 0.001) and bile 87% (p less than 0.01). In the second set of experiments, intravenous injection of commonly used solutions gave mortality rates of 20% (controls) for saline solution, 80% for dextran (p less than 0.01) and 47% for Intralipid (p greater than 0.05). E. coli peritonitis in rats thus was aggravated by intraperitoneal hemoglobin, bile or whole blood plus bile, and also by intravenous dextran.

Intra-operative digital angiography as a control of the in situ saphenous vein by-pass grafts.

Forty-two patients undergoing in situ saphenous vein by-pass grafting procedures, in two patients bilaterally, were examined intra-operatively with digital subtraction angiography. In 19 (43%) of the examinations the graft and the anastomoses appeared adequate. In 8 cases (18%) significant abnormalities were found, including stenoses (11%), deficient anastomoses (5%) and graft kinking (2%). Remaining arteriovenous fistulas were found in 17 patients (39%). In most cases immediate correction was possible avoiding later re-operation. At follow up 11 of the 44 grafts were occluded, 10 of these during the first five months and of these five during the first week.

Colocalization of calcitonin gene-related peptide and somatostatin in pancreatic islet cells and inhibition of insulin secretion by calcitonin gene-related peptide in the rat.

Calcitonin gene-related peptide (CGRP)- and somatostatin (SRIF)-containing cells were identified by immunocytochemical techniques in pancreatic islet cells of the rat. CGRP-containing cells were found primarily in the peripheral portion of the pancreatic islets. In addition, CGRP-containing cells also contained somatostatin, which identifies the islet CGRP-containing cells as D cells. In the present study, we also tested the effect of CGRP on gastrin-releasing peptide (GRP; 10(-9) M)- or cholecystokinin (CCK-8, 10(-9) M)-stimulated release of insulin from isolated rat islets in vitro. At concentrations of 10(-8)-10(-11) M, CGRP inhibited GRP- and CCK-8-stimulated release of insulin significantly when compared with GRP or CCK-8 alone. At the lowest concentration of CGRP (10(-11) M), the inhibitory effect of CGRP on CCK-8-stimulated release of insulin was statistically significant (p less than 0.05) and exceptionally potent (65-90% inhibition). We have also found that CGRP does not stimulate the release of SRIF from isolated islet cells. These findings suggest that CGRP may play a regulatory role in the release of insulin.

Serum proteins in liver cirrhosis: effects of shunt surgery.

The serum protein patterns of 38 patients with alcoholic liver cirrhosis were studied and compared with those of 15 patients with cryptogenic cirrhosis and of 18 normal volunteers. Serum prealbumin and albumin were significantly lowered in alcoholic liver cirrhosis in comparison with the normals. In liver cirrhosis, the four acute phase reactants, alpha 1-antiproteinase, orosomucoid, and haptoglobin and caeruloplasmin, showed a pattern in serum, in which alpha 1-antiproteinase was increased, orosomucoid and haptoglobin were decreased, and caeruloplasmin was normal. Immunoglobulins G, A and M were significantly elevated. IgA was significantly more elevated in patients with alcoholic disease than in patients with cryptogenic cirrhosis. The construction of a surgical portal-systemic shunt resulted in a significant decrease in serum concentrations of the acute phase reactants, while prealbumin, albumin and immunoglobulins were unaffected.

Digital subtraction angiography with bandpass filtration during by-pass operation.

Experience is reported on a simple, inexpensive video processor for angiographic control during operation. In 6 patients with graft complications instant operative corrections could be performed.

Phentolamine reverses NPY-induced inhibition of insulin secretion in isolated rat islets.

It has been shown that the rodent pancreas is innervated by neuropeptide Y (NPY) nerves, some of which are adrenergic, and that NPY inhibits glucose-induced insulin secretion in vivo in the mouse and that from isolated rat islets in vitro. We now investigated whether the alpha-adrenoceptor antagonist phentolamine affects the inhibitory action of NPY on insulin secretion from isolated rat islets. It was found that NPY dose dependently inhibited insulin secretion stimulated by glucose (11.1 mM). At a concentration of 10(-7) M, NPY totally abolished the insulin secretory response to glucose. It was also found that incubation with the alpha-adrenoceptor antagonist phentolamine (10(-6) M) itself enhanced the insulin secretion at 3.3 mM but not at 16.7 mM glucose. Moreover, phentolamine counteracted the inhibitory action of NPY. Thus, at 10(-8) M, NPY could no longer inhibit insulin secretion when phentolamine (10(-6) M) was present, whether 3.3 mM or 11.1 mM glucose was present. In contrast, somatostatin (10(-7) M) could inhibit insulin secretion, both in the presence and absence of phentolamine (10(-6) M); this showed that phentolamine does not reverse all types of inhibition. However, when the dose of phentolamine was decreased to 10(-7) M, the inhibitory action of NPY on glucose-induced insulin secretion was retained indicating that the reversal of the NPY effect by phentolamine is a competitive effect. It is concluded that NPY inhibits glucose-induced insulin secretion by a direct action on the islets, and that phentolamine reverses this inhibitory action of NPY in a competitive manner.

Insulin and glucagon production in experimental cirrhosis.

The release of insulin and glucagon in cirrhotic rats was examined. Rats were made cirrhotic by a combination treatment of carbon tetrachloride (CCl4) and phenobarbitone. Liver cirrhosis was verified by histologic findings. Both basal and stimulated release of insulin from isolated pancreatic islets, in vitro, were decreased significantly in cirrhotic rats, as compared with control rats. Basal, but not stimulated, levels of glucagon, in vitro, were reduced significantly in cirrhotic rats. Circulating levels of plasma insulin, glucagon, glucose, bilirubin, and amylase levels were unaffected in cirrhotic rats when compared with control rats. There were no signs of pancreatitis. The results indicated that the release of insulin and glucagon is depressed in cirrhotic rats and in rats treated with phenobarbitone and CCl4. Clearance of circulating insulin and glucagon by the liver was apparently reduced, since circulating levels of insulin and glucagon were unaltered in all treated rats.

Influence of dextran on pneumococcal septicemia in splenic artery-ligated or splenectomized rats.

Splenic artery ligation is one of several methods in splenic preservation. In this experimental work the susceptibility of splenectomized rats and rats treated with splenic artery ligation to pneumococcal infection and the influence of the plasma expander dextran in the same groups were studied. The mortality among splenectomized rats was 100% vs nil after sham operation. Animals treated with splenic artery ligation and saline had a 23% mortality in pneumococcal septicemia, significantly different (P less than 0.05) from the 59% mortality after splenic artery ligation and dextran. A significant increase (P less than 0.05) in number of abscesses was also seen among rats given dextran.

Nonoperative treatment of blunt trauma to liver and spleen.

Nonoperative management of 20 cases of liver injury in 1969-1984 and 13 of splenic injury in 1977-1984, all due to blunt abdominal trauma, is retrospectively reviewed. The total of blunt hepatic injuries treated in the same period was 63 and that of blunt splenic injuries 52. There were no major differences in etiology, age, sex distribution or need for blood transfusion between the liver and splenic trauma cases. After initial resuscitation and diagnostic work-up with angiography, computed tomography, ultrasonography and/or scintiscan, circulatorily stable patients were selected for nonoperative treatment. These patients showed evidence of mild trauma with few associated major injuries, few complications and no mortality. Following initial bedrest and observation, they were gradually mobilized and could leave the hospital after about 2 weeks.

Portal-systemic encephalopathy. Influence of shunt surgery and relations to serum amino acids.

Fifty patients with liver cirrhosis, portal hypertension, and a history of bleeding oesophageal varices underwent 15 different cognitive psychometric tests to evaluate the presence of subclinical portal-systemic encephalopathy. None of the patients were clinically encephalopathic. The patients were compared with 50 healthy control subjects. Twenty-three patients showed definite signs of encephalopathy in the psychometric tests, 17 were normal, and 10 were borderline cases. The most pronounced abnormalities were seen in tests reflecting logic inductive capacity, visual spatial performance, cognitive flexibility, perceptual speed, spatial perceptive ability, and psychomotor performance. Tests reflecting word memory were less affected. Serum liver function tests did not differ between patients with deranged and normal brain functions. The serum isoleucine concentration was, however, significantly lower in the encephalopathic patients. The psychometric test results did not differ between patients with alcoholic and nonalcoholic liver cirrhosis, and no change was noted 2 years after shunt surgery.

Outcome of pneumococcal challenge in rats after splenic artery ligation or splenectomy.

Reports of postsplenectomy septicemia led to development of various methods for splenic salvage, including ligation of the splenic artery. For study of susceptibility to pneumococci after splenectomy or splenic artery ligation, 35 Sprague-Dawley rats, in three groups, underwent splenectomy or central ligation of the splenic artery, or sham operation with omental resection. Blood cell counts prior to injection of pneumococci (3 X 10(3) intravenously in each rat) showed no intergroup differences. All the splenectomized rats died, but only 20% of those with splenic artery ligation (p = 0.000047). None of the rats with sham operation died, but this was not significantly different from the mortality in the group with splenic artery ligation (p = 0.22).

Hypersplenism--effect on haemostasis. An experimental study in the rat.

Hypersplenism induced by methylcellulose given to rats i.p. was characterized by splenomegaly, anaemia, leucocytopenia and thrombocytopenia. Hb, Hct and WBC count were normalized, and platelet count rose to supernormal values by splenectomy. At a standardized liver resection, the hypersplenic rats had an increased blood loss and prolonged bleeding time in comparison with control rats. Removal of the large spleen normalized these abnormalities. Hypersplenism also shortened APT time and impaired ADP and collagen-induced platelet aggregation, findings not normalized by splenectomy.

Calcitonin inhibition of insulin release from isolated rat pancreatic islets.

Calcitonin is known to inhibit secretion of gastrin and insulin in vivo. The objective of this study was to determine whether calcitonin can act directly on pancreatic islets in vitro to inhibit insulin release. Isolated islets were obtained from collagenase-treated rat pancreas, and three peptides (gastrin-releasing peptide, cholecystokinin-8, bombesin) and glucose were used to stimulate insulin release. All agents caused a significant increase in insulin secretion and calcitonin inhibited these responses, but had no consistent effect on basal release. This study provides evidence that calcitonin is an effective inhibitor of insulin secretion and acts directly on islet tissue.

The value of 5-hydroxyindolacetic acid analysis in urine. A clinical and cost-benefit study.

The clinical value and the cost-benefit of 5-hydroxyindolacetic acid in urine (5-HIAA/u) measurements in diagnosing carcinoid tumours were analysed. During a 5-month period a total of 1397 analyses yielded 62 patients with elevated 5-HIAA/u levels, of which 28 patients had previously been operated on for a carcinoid tumour. Only one carcinoid tumour was found to have been diagnosed on the evidence of elevated 5-HIAA/u levels. In patients previously operated on for carcinoid tumour, elevated leves of 5-HIAA/u did not influence their treatment. Several border-line values were probably due to a temporary decline in hepatic function or to substances interfering with the analytical methods used. It is concluded that 5-HIAA/u measurements are of limited clinical value.

Standardized intraabdominal abscess formation with generalized sepsis: pathophysiology in the rat.

Gelatine capsules containing Escherichia coli and Bacteroides fragilis in a standardized mixture with rat colonic content and barium sulfate were implanted intraabdominally into rats. Capsules of 0.75 g gave approximately 50% mortality whereas 0.35 and 1.10 g caused no or 100% mortality, respectively. In subsequent experiments, using the 0.75 g capsule, all animals became ill with signs of tachypnea, piloerection, low physical activity and hypersecretion of saliva 6-8 h after the implantation. The animals reduced their water and food intake substantially and the body weight decreased. A significant reduction in blood pressure, glucose and leukocyte and platelet counts was found 12 h after challenge. Blood cultures obtained at 12, 24, 48 and 60 h all grew E. coli but none B. fragilis. Succumbed animals revealed diffuse peritonitis with growth of E. coli and B. fragilis at autopsy, whereas surviving animals showed abscess formation at investigation on day 8 after challenge. It was concluded that the model closely resembled intraabdominal abscess formation with sepsis in man.

Splenic artery ligation for traumatic rupture of the spleen. A case report.

Reports on postsplenectomy septicemia have led to a more conservative attitude to treatment of splenic trauma. A case of traumatic rupture of the spleen treated with splenic artery ligation is presented. In the 5-year follow-up the investigations included repeated scintigraphy. Alternative management of traumatized spleen is discussed.

Administration route and splenectomy effects on resistance to pneumococci in rats.

Normal and splenectomized rats were challenged with Streptococcus pneumoniae type 1 via different administration routes. In experiment I, previously splenectomized or sham-operated rats received 4 X 10(3) colony-forming units (CFU) of pneumococci via (i) a peripheral vein, (ii) subcutaneously, or (iii) intraperitoneally. The results indicated an increased susceptibility of the splenectomized animal to pneumococci administered via all three routes. However, subcutaneously administered pneumococci gave a lower mortality than pneumococci given intravenously or intraperitoneally. In experiment II 40 splenectomized rats received 4 X 10(3) CFU of pneumococci via (i) peripheral, (ii) portal, or (iii) caval veins or the aorta. No differences in mortality were found. In experiment III, non-operated animals received 4 X 10(5) CFU of pneumococci either intravenously or intraperitoneally, resulting in mortality rates of 0/20 and 17/20, respectively. After 2 weeks the rats surviving intravenous challenge received 4 X 10(5) CFU of pneumococci intraperitoneally; all survived. The data indicate the the spleen and the subcutis have a greater capacity to protect against pneumococci in the absence of specific antibody than the peritoneum or the circulation outside the spleen.

Pattern of serum amino acids in patients with liver cirrhosis. Influence of shunt surgery and transesophageal sclerotherapy.

The serum amino acid pattern was studied in 30 patients with alcoholic liver cirrhosis, in 15 patients with non-alcoholic cirrhosis, and in nine healthy controls. Patients with alcoholic liver cirrhosis had significantly increased serum levels of aspartic acid, proline, methionine, tyrosine, phenylalanine, and tryptophan compared with controls. Valine was significantly decreased. Patients with non-alcoholic liver cirrhosis differed from patients with alcoholic liver cirrhosis only in having significantly greater serum levels of glycine. The serum amino acid pattern of nine cirrhotic patients who underwent mesocaval interposition shunt surgery because of bleeding esophageal varices was prospectively compared with that of nine matched patients treated with transesophageal sclerotherapy. A further significant increase in methionine and tyrosine serum levels was noted after shunt surgery. It is concluded that sclerotherapy influences serum amino acids less, which might be an advantage in relation to the development of hepatic encephalopathy.