Recurrent venous thrombosis following free flap surgery: The role of heparin-induced thrombocytopenia

Complications following free tissue transfer have been well established in the literature. Common and rare causes of free flap failure must be addressed by the treating surgeon when microvascular patency is threatened. With the evolution and prevalence of microsurgery, ‘rare’ causes of free flap failure will become increasingly frequent. A high index of suspicion must be established in patients with multiple failed operative interventions. A case of recurrent free flap failure secondary to heparin-induced thrombocytopenia is presented in a patient with a history of squamous cell carcinoma of the floor of the mouth, and a long-standing history of alcohol and tobacco consumption.     

Enterobacteriaceae isolated in nine general hospitals of the Ile-de-France in 1988 and 1989: susceptibility to beta-lactam antibiotics according to the length of hospitalisation

Susceptibility to beta-lactam antibiotics of strains of Enterobacteriaceae consecutively isolated in nine general hospitals during a period of 2 months (march and april) has been studied by the disk-agar diffusion method. The separation between susceptible and resistant strains was based on the measure of the inhibition zones centered by 2 disks: cephalothin and ticarcillin. Enterobacteriaceae were divided in 2 groups: strains isolated during the first 48 h of hospitalisation or isolated after. Fifty one per cent of the strains were isolated during the first 48 h: they did not belong to the residential flora of these hospitals. Klebsiella, Proteus indole positive, Providencia, Enterobacter, Serratia were more frequently isolated after 48 h of hospitalisation. Susceptible strains of Klebsiella, Proteus indole positive, Providencia, Serratia were more rarely isolated after 48 h of hospitalisation. E. coli whatever the duration of hospitalisation, is the less frequent susceptible bacterium.     

A 94-kDa protein, identified as neutral endopeptidase-24.11, can inactivate atrial natriuretic peptide in the vascular endothelium.

Neutral endopeptidase 24.11 (EC 3.4.24.11) inactivates atrial natriuretic peptide by cleaving the hormone between Cys7 and Phe8, and inhibitors of the enzyme have consequent natriuretic and diuretic properties. The in vivo sites of degradation of this peptide by the zinc-metallopeptidase, however, remain to be established. Because an endopeptidase-24.11-like activity has recently been reported in the rat mesenteric artery, we have further investigated the degradation of atrial natriuretic peptide in vascular tissue. Endopeptidase-24.11 activity was detected in solubilized membrane preparations from rat and rabbit vascular tissue, using [3H]D-Ala2-leucine enkephalin as substrate, and both rabbit and rat aorta preparations were also found to cleave atrial natriuretic peptide between Cys7 and Phe8. In both cases, hydrolysis was inhibited by neutral endopeptidase inhibitors, with Ki values close to their Ki values for the pure enzyme. In preparations of rabbit aorta denuded of endothelium by saponin treatment, the hydrolysis of the Gly3-Phe4 bond of [3H]D-Ala2-leucine enkephalin and the Cys7-Phe8 bond of atrial natriuretic peptide was reduced by greater than 90%. The high performance liquid chromatography method used to follow the degradation of atrial natriuretic peptide differed from previously published procedures, in that samples to be injected were first treated with excess dithiothreitol to reduce the Cys7-Cys23 disulfide bridge. This facilitated the separation of the intact peptide and its metabolites. The presence of the 94-kDa neutral endopeptidase in rabbit aortic tissue was definitively established using a new potent 125I-labeled inhibitor, [125I]RB104 [2-[(3-[125I]iodo-4-hydroxy)phenylmethyl]-4-N-[3- hydroxyamino-3-oxo-1-phenylmethyl propyl]amino-4-oxobutanoic acid] (Ki, 30 pM), which selectively labeled the enzyme after sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the membrane preparations. Therefore, despite its low concentrations in the vasculature, the presence of endopeptidase-24.11 almost exclusively in endothelial tissue suggests that the enzyme is ideally localized to inactivate circulating atrial natriuretic peptide.     

Salmonella typhimurium andSalmonella enteritidis: Changing epidemiology from 1973 until 1992

A retrospective analysis, covering a period of 20 years, of 2049 primo-isolates ofSalmonella typhimurium and 343 primo-isolates ofSalmonella enteritidis was performed at our laboratory. In 1991,S. enteritidis (43.8%) outnumberedS. typhimurium (32.1%) as the most frequently isolated Salmonella. The age group distribution ofS. enteritidis yielded peaks in the under-five and above-60 year age groups, whereasS. typhimurium only peaked in the under-five age group.S. enteritidis appeared to be twice as invasive asS. typhimurium. Both serotypes were more invasive in middle and older age groups than in under-fives.     

The interaction of parafluorohexahydrosiladiphenidol at muscarinic receptors in vitro

1. The antagonistic actions of parafluorohexahydrosiladiphenidol (pFHHSiD) at muscarinic receptors has been studied in cardiac muscle, smooth muscle and cell culture preparations. In this paper, the classification scheme of Doods et al. (1987) is employed. This scheme is based upon differential affinities of muscarinic antagonists. pFHHSiD exhibited high pA2 values at M3 receptors mediating contractions of guinea-pig ileum and oesophageal muscularis mucosae (7.8 and 8.2 respectively) whereas low values were determined at M2 receptors mediating negative inotropic responses in guinea-pig atria (6.0). Intermediate pA2 values were determined at M1 receptors mediating contractions of the canine femoral and saphenous veins. 2. The pA2 values of pFHHSiD at receptors mediating endothelial-dependent relaxation of rat aortic rings, rabbit jugular vein and canine femoral artery (7.6-7.9) were similar to those determined on the ileum. However, the pA2 values of pFHHSiD at receptors mediating contractions of the guinea-pig trachea (7.1), which has been previously shown to possess M3 receptors, were different from those determined in the ileum. 3. The similarity in pA2 values of pFHHSiD between the M3 receptors in guinea-pig ileum and the receptors mediating endothelial-dependent relaxations provide further evidence for the role of M3 receptors in this vascular response. Taken together, pA2 values for pFHHSiD range from 7.1 to 8.2, depending upon the M3 preparation used. The selectivity of the compound therefore for the M3 versus the M2 muscarinic receptor ranged from 13 to 163 fold.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparison of microsurgical vasovasostomy techniques in the rat

We compared three different microsurgical vasovasostomy techniques on the rat vas deferens using absorbable and non-absorbable sutures and a fibrin adhesive technique. The best method was an extramucosal technique over a splint using vicryl. The worst results were seen using adhesive.     

Inhibition of Human Mammary Cell Line Proliferation by Membrane Lectin-Mediated Uptake of Ha-ras Antisense Oligodeoxynucleotide

The Ha-ras oncogene promotes cell proliferation. Antisense oligonucleotides complementary to the ras gene sequence encompassing a mutated codon 12 selectively induce a cell proliferation inhibition. However, the concentration required to reach an effective inhibition is high due to the low efficiency of the oligonucleotide crossing through cell membranes, leading to a low concentration in the cytosol and/or the nucleoplasm. In the present paper, we show that anti-ras oligonucleotides linked to a glycosylated carrier, serum albumin bearing mannose 6-phosphate residues, are more efficient than free oligonucleotides or oligonucleotides bound to an unglycosylated carrier at inhibiting proliferation of a human tumor mammary cell line expressing the mutated Ha-ras. Using fluorescein-labeled neoglycoproteins and fluorescein-labeled oligonucleotides bound to neoglycoproteins, flow cytometry and confocal microscopy revealed that (i) these tumor cells express a membrane lectin specific for mannose 6-phosphate-bearing proteins, (ii) the membrane lectin actively mediates the uptake of macromolecules substituted with mannose 6-phosphate, and (iii) the fluorescein-labeled oligonucleotides bound to the neoglycoprotein accumulate in intracellular vesicles. Furthermore, with antisense oligonucleotides carried by the neoglycoproteins, the concentration required to inhibit cell proliferation is lower than that of the carrier-free antisense oligonucleotides.     

Laparoscopic hysterectomy

Summary Thirty-three patients were selected for laparoscopic hysterectomy and operated on in the Department of Obstetrics, Gynecology and Reproductive Medicine of Clermont-Ferrand University Hospital. Surgical techniques included blunt dissection with scissors and bipolar coagulation to achieve hemostasis. A case was considered successful when all the uterine vessels were treated by laparoscopy. Twenty-four cases were completed laparoscopically (72.7%). None of these patients had postoperative bleeding; 22 had an uneventful postoperative recovery. Nine procedures were converted to laparotomy (27.3%), five because of a difficult or unsatisfactory hemostasis. We conclude that in selected cases, a total hysterectomy can be performed safely by experienced laparoscopists. Further technological progress is necessary to make this procedure more acceptable. Its value as compared to the others will have to be demonstrated.     

Nonadrenergic [3H]idazoxan binding sites are physically distinct from alpha 2-adrenergic receptors

We have recently demonstrated that the alpha 2-adrenergic radioligand [3H]idazoxan also labels additional sites that do not recognize catecholamines but bind with high affinity several chemically distinct drugs previously assumed to be highly selective for alpha 2-adrenergic receptors [Mol. Pharmacol. 35:324-330 (1989)]. We now have used three approaches to distinguish the nonadrenergic [3H]idazoxan sites from alpha 2-adrenergic receptors. (a) No nonadrenergic [3H]idazoxan binding sites were found in COS-7 cells transfected with the genes for the two known alpha 2-adrenergic receptor subtypes. (b) The ratio of alpha 2-adrenergic and nonadrenergic [3H]idazoxan sites in human platelet membranes varied considerably between various donors. (c) Highly purified platelet plasma membranes were enriched for alpha 2-adrenergic receptors but did not contain any nonadrenergic [3H]idazoxan binding sites. We conclude that the nonadrenergic [3H]idazoxan binding sites are not co-expressed with alpha 2-adrenergic receptors and at least in human platelets may be located in an intracellular compartment.     

Pharmacokinetics of prednisolone in children with the nephrotic syndrome

The aim of this study was to establish whether the criteria for the clinical effectiveness of steroids are correlated with the pharmacokinetics of prednisolone in children treated with prednisone during an attack of idiopathic nephrotic syndrome (INS). Thirteen patients with nephrosis were included. Prednisolone, prednisone and cortisol levels were measured using a specific high-performance liquid chromatography assay after an oral dose of 1 mg/kg body weight of prednisone taken at the onset of the disease. All the pharmacokinetic parameters, including the conversion of prednisone to prednisolone were similar to the data already published in children with INS. No correlation was found between the values of pharmacokinetic parameters and criteria of clinical effectiveness. Hypo-albuminaemia was significantly correlated with the area under the plasma-concentration curve but not with the elimination half-life of prednisolone. Moreover, the prednisolone elimination half-life correlated with the urinary exretion of 17-hydroxycorticosteroids achieved in the first 6h. The present study suggests that routine measurements of prednisolone kinetics do not help when assessing the treatment of children with INS.