B-B10 (anti-CD25)-saporin immunotoxin--a possible tool in graft-versus-host disease treatment.

An immunotoxin containing the B-B10 MoAb, directed against the CD25 determinant, and the ribosome-inactivating protein saporin, inhibits 3H-TdR incorporation in phytohemagglutin, allogeneic-stimulated lymphocytes (primary and secondary mixed-lymphocyte reaction), and in an alloreactive T cell clone. A lower degree of inhibition was obtained with the B-B10 MoAb, which is known to inhibit IL-2 activity, as well as with the unconjugated compounds. These results suggest that the in vivo administration of the conjugate might be a more effective tool in the treatment of patients affected by graft-versus-host disease than B-B10 alone, by inducing an efficient killing of allogeneic-reacting T lymphocytes.     

Ruptured aneurysm of the sinus of Valsalva. Presentation of 4 cases and review of the literature

We studied four patients with ruptured aneurysms of the sinus of Valsalva. All were men with a mean age of 33 years. The presenting illness was insidious in three and of abrupt onset in one. Physical examination showed a continuous murmur in all. Chest X ray film showed moderate cardiomegaly. Electrocardiogram disclosed left ventricular hypertrophy. Echocardiogram revealed the site of the rupture which was corroborated by aortography. Two aneurysms ruptured to the right ventricle and two to the right atrium. All were corrected by surgery. All patients became asymptomatic.     

Onychopathy in a Patient with Fetal Hydantoin Syndrome

Abstract: Hydantoin is an anticonvulsant drug with several side effects. A teralogenic potential has been suggested. The fetal hydantoin syndrome is an entity that consists of a broad range of morphologic and developmental disorders in children born of epileptic mothers exposed to hydantoin during pregnancy. We treated a girl in whom onychopathy was a monosymptomatic or mild form of this syndrome.     

Prevention of hyperglycemia improves the long-term result of islet transplantation in streptozotocin-diabetic rats.

We examined the hypothesis that prevention of hyperglycemia during the critical period immediately following islet transplantation will improve the outcome of the transplantation in streptozotocin-diabetic rats. Two days after intravenous injection of streptozotocin (70 mg/kg), 400 or 1,000 islets were transplanted into the left kidney subcapsular space. A group of rats transplanted with 400 islets was treated with insulin from 1 day before transplantation and for 7 days. Intravenous glucose infusion was performed at 10 days and 3 months after transplantation. In addition, at 3 months, the grafts were examined by light and electron microscopy. We found that rats transplanted with 400 islets without any concomitant insulin administration remained diabetic throughout the 3-month period and no plasma insulin response was induced by glucose infusion in these rats. In contrast, diabetic rats transplanted with 400 islets and treated with insulin for 7 days remained normoglycemic throughout the 3-month period, as did rats transplanted with 1,000 islets. Furthermore, these rats had normal glucose-stimulated insulin secretion both at 10 days and at 3 months after transplantation. Moreover, islet grafts from rats transplanted with 400 islets and administered insulin as well as from rats transplanted with 1,000 islets were morphologically normal, and following removal of the graft, hyperglycemia developed rapidly. In contrast, the islet grafts from rats transplanted with 400 islets without concomitant insulin administration had only few insulin cells. Thus, by preventing hyperglycemia at the time of islet transplantation, the long-term result of islet transplantation was improved. Therefore, the ambient glucose level initially following islet transplantation is critical for the long-term result.     

Effects of beta-blockade on energy metabolism following burns

The purpose of this study was to compare the effects of propranolol administered either by i.v. infusion or by prolonged oral administration (4 days) during the first 3 weeks following burns. The resting metabolic rate (RMR) of 10 non-infected fasting burned patients (TBSA: 28 per cent, range 18-37 per cent) was determined four times consecutively by indirect calorimetry (open circuit hood system) following: (1) i.v. physiological saline; (2) i.v. propranolol infusion (2 micrograms/kg/min following a bolus of 80 micrograms/kg); (3) oral propranolol (40 mg q.i.d. during 4 +/- 1 days); and (4) in control patients. All patients showed large increases in both RMR (144 +/- 2 per cent of reference values) and in urinary catecholamine excretion (three to four times as compared to control values). The infusion of propranolol induced a significant decrease in RMR to 135 +/- 2 per cent and oral propranolol to 129 +/- 3 per cent of reference values. A decrease in lipid oxidation but no change in carbohydrate and protein oxidation were observed during propranolol administration. It is concluded that the decrease in RMR induced by propranolol was not influenced by the route of administration. The magnitude of the decrease in energy expenditure suggests that beta-adrenergic hyperactivity represents only one of the mediators of the hypermetabolic response to burn injury.     

Comparison of the antithrombotic effects of heparin, enoxaparin and prostacycline in continuous hemofiltration

Continuous anticoagulation is required during haemofiltration to prevent the deposition of fibrin and the formation of thrombus which would lead to early clotting of the haemofilter. This study aimed to compare the efficiencies of 3 different anticoagulation protocol: 150 IU.kg-1.day-1 heparin (group HEP), 1.2 mg.kg-1.day-1 enoxaparin (group ENX), and a combination of 0.8 mg.kg-1.day-1 enoxaparin with 5 ng.kg-1.min-1 prostaglandin I2 (group ENX and PGI2). A flat ANS69S (Hospal) haemofilter was used for continuous venovenous haemofiltration. Antithrombotic efficiency was assessed with a haemofilter permeability index (HPI) including the transmembraneous pressure gradient and the rate of production of ultrafiltrate. The time required for HPI to decrease to 1/3 of its initial value (HPI1/3) was used to compare the 3 protocols. Treatment tolerance was judged by monitoring the usual haemodynamic and haemostatic parameters. No adverse effects (bleeding, thrombosis, hypotension) were observed. HPI1/3 was 15.1 +/- 2.4 h, 18.3 +/- 3.1 h and 28.2 +/- 4.2 h in groups HEP, ENX and ENX and PGI2 respectively. High dose enoxaparin reached antithrombotic efficiency without increasing the risk of haemorrhage. The use of low doses of prostaglandin I2 greatly increased HPI1/3, without any deleterious haemodynamic effects. However, the high cost of prostaglandin I2 needs to be put in the balance with the increase in duration of haemofilter life. Therefore, further investigations are required to evaluate the possible synergy between heparin and prostaglandin I2, as well as the biological parameters which need to be monitored.     

Reduced pancreatic content of the inhibitory neurotransmitter galanin in genetically obese, hyperinsulinemic mice.

Because abnormalities of the autonomic nervous system have been described in several animal models of obesity, and because galanin has been proposed to be a sympathetic neurotransmitter in the endocrine pancreas, we hypothesized that the hyperinsulinemia observed in genetically obese (ob/ob) mice may result either from defective ability of galanin to inhibit insulin release or from a reduced degree of pancreatic galaninergic innervation. To address these possibilities, we examined the effect of exogenous galanin on immunoreactive insulin (IRI) levels in ob/ob mice and compared the pancreatic content of galaninlike immunoreactivity (GLIR) in ob/ob mice with that in lean littermates. Intravenous administration of synthetic porcine galanin significantly reduced basal IRI levels in ob/ob mice, suggesting that a defect in galanin action is unlikely to account for the hyperinsulinemia in this model. In contrast, reduced pancreatic galaninergic innervation was supported by findings that pancreatic content of GLIR in ob/ob mice was less than 10% of that in age- and sex-matched lean littermates. The reduction of pancreatic GLIR in ob/ob mice appeared organ specific; no such reduction was observed in adrenal GLIR content when comparing obese and lean mice. In addition, the relationship between pancreatic GLIR content and plasma IRI levels was examined in groups of obese and lean mice. It was found in young females, young males, and older mice of mixed sex that there was a significant negative correlation between pancreatic GLIR and plasma IRI in lean mice, whereas no such correlation was observed in obese mice.(ABSTRACT TRUNCATED AT 250 WORDS)     

Folate status during pregnancy: relationship with alcohol consumption, other maternal risk factors and pregnancy outcome.

This study was designed to identify the factors affecting folate status in pregnant women and to explore the relationship between folate status and alcohol consumption during pregnancy. For this purpose, 347 French women were recruited during 1985-1986 on their first visit to the antenatal clinic at Roubaix Hospital (northern France). Alcohol consumption was ascertained by a standardized interview. Folate status assessment was available for 246 pregnant women who were not given folate supplementation. Average folate levels during pregnancy were lower among young women and smokers. Serum folate values diminished with the educational level, and red cell folate values increased with high parity. Unexpectedly, high red cell folate values were strongly related with high alcohol consumption after adjustment for the maternal risk factors associated with alcohol consumption and folate status. This was probably because in the Roubaix region where the study was conducted women consume mostly beer, which contains folates. Pregnancy outcome was not related to folate levels; birthweight was negatively associated with alcohol consumption during the first trimester of pregnancy.     

Surgical treatment of Budd-Chiari syndrome and veno-occlusive disease]

We operated 5 patients with the Budd-Chiari syndrome or veno-occlusive disease between 1984 and 1989 (2 porto-caval shunts, one Warren distal spleno-renal shunt, one meso-atrial shunt and one Le Veen peritoneo-jugular shunt). As liver transplantation is now part of the therapeutic armamentarium for these conditions, this paper reviews retrospectively the indications for surgery in these 5 patients.     

Electromagnetic location of central venous catheters]

A new technique, the Cath Finder (Pharmacia Deltec) system, for locating central venous catheters is described. It was initially designed to facilitate the insertion of the PAS Port (Pharmacia Deltec), a long central venous catheter with an implantable chamber. It is based on a low intensity high frequency electromagnetic field generated by a locator wand. A preconnected sensor guide wire is introduced into the catheter so as to make the catheter tip detectable by the electromagnetic field. The wand is placed over an appropriate landmark on the anterior chest wall (third right rib, parasternally). When the centre of the field has been passed over by the sensor tip in the catheter-sensor assembly, a light signal is set off. This technique is simple and easily mastered. It is far less cumbersome than the usual techniques, like fluoroscopy and chest X-rays. The Cath Finder provides reliable continuous information on the position of the catheter tip during its insertion. It seems to provide an acceptable alternative to peroperative fluoroscopy. The accuracy of this system was assessed in ten patients. All had malignancies and required long term central venous access. In 6 cases, catheterisation and locating of the catheter were uneventful. In 2 cases, the catheter entered a wrong vein. The diagnosis having been made with the Cath Finder system, the false route was amended and the catheter placed accurately. In one case, the sensor in the catheter broke.(ABSTRACT TRUNCATED AT 250 WORDS)