Lung salvage by pulmonary arterioplasty after vascular injury during video-assisted thoracoscopic surgical right upper lobectomy.

Video Assisted Thoracoscopic Surgical (VATS) lobectomy is now considered feasible and safe. Nevertheless, thoracic surgeons need to be aware of dramatic complications that may occur during this procedure and how best to manage them. We report the case of a severe tear of the right pulmonary artery (PA) during elective VATS upper lobectomy, leading to emergency conversion to control the bleeding. Initial arterial repair was performed by end-to-end anastomosis. Early CT angiography showed thrombosis of the right PA due to anastomotic stenosis. We performed emergency pulmonary arterioplasty with a prosthetic patch to save the right lung. A CT scan days after surgical lung salvage confirmed the permeability of the PA and normal vascularization of the two remaining right lobes. We discuss herein this dramatic complication of VATS lobectomy, the viability of the lung after pulmonary arterial thrombosis, and advocate for early postoperative imaging after pulmonary arterioplasty.

Sigmoid Resection with Primary Anastomosis for Uncomplicated Giant Colonic Diverticulum : a Report of two Cases.

Giant colonic diverticulum (GCD) is a rare complication of colonic diverticulosis. A small number of cases has been reported in the literature. Patients with GCD have often few non-specific symptoms. Unfortunately, severe complications exist and may lead to surgical acute abdomen. Therefore, this complication of the diverticular disease must be known and properly treated. There is no gold standard diagnostic test, but an air-fluid or air-filled, rounded, pseudocystic image in relation with the colonic wall in a patient with colonic diverticula should suggest this diagnosis to the clinician. We report two cases of a 70-year-old male patient and a 44-year-old female patient having a giant sigmoid diverticulum. The treatment of choice of an uncomplicated GCD is an elective colonic resection, including the giant -diverticulum, with primary anastomosis ; while in case of complicated GCD (peritonitis, abscess or complex fistula), a two-stage resection should be considered.

Assessment of sperm quality parameters of six bulls showing different abilities to promote embryo development in vitro.

Experiments were conducted to investigate the possible origins of variation between six bulls showing various blastocyst rates after in vitro fertilisation. No significant difference was observed for the rates of cleavage and 5-8 cell stages, whereas blastocyst yields at Day 6, 7 and 8 post insemination were significantly different between bulls (P < 0.05). Fertilisation rates ranged from 59.5 to 79.3% (P < 0.05), with no difference in the incidence of polyspermy. The proportions of motile and progressive spermatozoa before and after Percoll separation were analysed. A positive effect of Percoll was noted on both parameters (P < 0.05), leading to the absence of difference between bulls after the separation process. Sperm viability and spontaneous acrosome reaction were assessed during 18 h incubation in fertilisation medium. A sharp decrease in sperm viability was observed for all bulls after 2 h incubation, with only 12.6-21.7% of spermatozoa still viable at 18 h. In contrast, the proportion of reacted acrosomes was low in five out of six bulls (<15% at 18 h). In conclusion, the fertilisation rate was the only parameter to show some correlation with blastocyst rate for all bulls.

Combinatorial peptide libraries: robotic synthesis and analysis by nuclear magnetic resonance, mass spectrometry, tandem mass spectrometry, and high-performance capillary electrophoresis techniques.

Combinatorial peptide libraries are a new source of compounds from which a large number of pharmacological leads will emerge in the next few years. A large body of literature shows that this approach is of considerable interest in many areas of biological sciences for the search of enzyme substrates and inhibitors, of receptor agonists or antagonists, or of antigen sequences. Nevertheless, the analytical investigation of such complex mixtures as libraries which contain up to millions of individual molecules is still poorly documented. In this work, we present analytical solutions for their characterization. NMR and tandem mass spectrometry (MS/MS) can provide an in deep description of any type of combinatorial libraries, while MS and high-performance capillary electrophoresis can bring a rapid and overall information at the routine level, sufficient to ensure a first assessment of their composition. MS in the fast atom bombardment mode was used to describe the libraries O1X2X3X4X5 or O1X2X3X4 (Oi and Xi are fixed and random residue in position i, respectively). Advantage was taken of the high proton affinity of arginine and of its induction of charge remote fragmentation to interpret the MS spectra of whole libraries and neutral losses (MS/MS) in the model sublibraries ArgGlyX3X4 and NipValX3X4 (Nip,4-nitrophenylalanine). Two-dimensional NMR allowed the incorporation of the individual residues during synthesis to be tested in 24 sublibraries O1X2X3X4. While from the pharmacological point of view, impressive discoveries made with combinatorial peptide libraries have already been reported, our results show that they should be complemented by appropriate analytical tools, crucial for the proper characterization and exploitation of these libraries.

Synthesis of 1,2-diacyl-3-nicotinoyl glycerol derivatives and evaluation of their acute effects on plasma lipids in the rat.

Nicotinic acid (CAS 59-67-6) is the only hypolipidemic agent whose activity has been shown both on atherosclerotic lesions and on long term mortality. Unfortunately, its use is hindered by the frequent occurrence ( > 70%) of adverse reactions (i.e. cutaneous rash, pruritus and, most significantly, flush). New prodrugs of nicotinic acid have been prepared by the use of diacylglycerol esters. In the rat, after acute oral administration of these products, a significant decrease of the free fatty acid plasma levels was obtained without the dramatic increase in nicotinic acid plasma levels observed after the oral administration of an equimolecular dose of nicotinic acid. The most interesting ester, S 16961 ((d,l)-1,2-dipalmitoyl-3-nicotinoyl glycerol, CAS 160555-46-4) is undergoing clinical trials.

S 16118 (p-guanidobenzoyl-[Hyp3,Thi5,D-Tic7,Oic8]bradykinin) is a potent and long-acting bradykinin B2 receptor antagonist, in vitro and in vivo.

The in vitro and in vivo effects of S 16118 [p-guanidobenzoyl-[Hyp3, Thi5,D-Tic7,Oic8]bradykinin (BK)], a new BK receptor antagonist, were studied. S 16118 inhibited the contraction produced by BK in the rabbit jugular vein, but was ineffective in the rabbit aorta, indicating the BK B2 receptor specificity of the compound. In isolated organs from various species including humans, S 16118 was a potent antagonist (Ki, pA2 or pKB value from 9.58-7.37). The effect of S 16118 was specific as it did not show any affinity for a number of other receptors or channels and did not possess residual agonistic properties in most of the tissues studied. Furthermore, S 16118 is a poor secretagogue agent either in the rat or human mast cells and is resistant to degradation with an in vitro half-life in blood from different species, including humans, of more than 24 hr. In vivo, in the rabbit, i.v. injection of S 16118 inhibited the hypotension induced by BK up to 4 hr after administration. In the guinea pig, it was also effective in inhibiting the bronchoconstriction induced by BK, although when administered i.v. it had a shorter duration than in the rabbit. However, in the same species, when aerosolized, S 16118 was effective and long-acting against BK-induced bronchoconstriction. Changes in permeability induced by BK injection in the guinea pig trachea and bronchus, and by BK superfusion in the hamster cheek pouch, were abolished by i.v. pretreatment with S 16118.(ABSTRACT TRUNCATED AT 250 WORDS)

Estimation of blood levels of endothelin and neurokinin receptor antagonists at the rat portal and jugular veins after oral administration as a tool in peptide drug design.

The blood concentration of three representative endothelin and four neurokinin receptor antagonists were monitored both at the portal and jugular vein of rats 30, 60 and 90 min after oral administration. Peptide-derived structures, in the size range tetra-pentapeptides, were shown to be absorbed in the reverse order of their log P values, to be weakly metabolized in the first hepatic transit and to maintain high blood levels during the observation time. These interesting results obtained by a simple and convenient UV assay, stress once again the importance of monitoring oral absorption early in the process of peptide drug design.

Reactivity of 42 disulfides with thiol group of human haemoglobin and human serum albumin.

The reactivities of disulfides of different compound families towards thiol groups of human haemoglobin and human serum albumin were determined at physiological pH 7.4 by anion-exchange liquid chromatography. The apparent second-order kinetic rate constants, K1, were calculated for the reaction of these disulfides with each protein. The results show that the studied heterocyclic disulfides are the most reactive compounds with both proteins. The lipophilic properties of these disulfides were evaluated by reversed-phase high performance liquid chromatography, using the percentage of acetonitrile (PAC) required for eluting each compound of the chromatographic column in a water-acetonitrile gradient. The structure-reactivity correlations between log K1 and log PAC are stated for each protein and compared. They fit a parabolic curve which permits one to define a lipophilic domain corresponding to a quantitative reaction of disulfides towards these proteins. The studied disulfides present a similar optimum of reactivity for both proteins.

Determination of the dissociation constant of oligomeric proteins by size-exclusion high-performance liquid chromatography: application to human haemoglobin.

The measurement of protein retention volumes on a size-exclusion chromatographic column offers the possibility of determining dissociation constants for oligomeric proteins, as changes in the retention volume, depending on the concentration of the protein, are due to a dissociation equilibrium. The retention volume may be calibrated in terms of dissociation constant by using either extreme concentration conditions or chemical modifications that shift the equilibrium towards a single species. When zonal chromatography is used, the dilution during elution modifies the equilibrium state. In contrast, the saturation method permits the concentrations of the different species to be kept constant. These two methods were compared and the elution factor that must be used in zonal chromatography on high-performance size-exclusion columns (LiChrospher Diol) was obtained. The tetramer-dimer dissociation constants of normal and modified haemoglobins were measured by this method, and the results are in accordance with flash photolysis measurements.

Pertussis in a rural area of Kenya: epidemiology and a preliminary report on a vaccine trial.

PIP: In the course of 2 years of surveillance of whooping cough by fortnightly home visits among a population of 24,000 in a rural area of Kenya, 918 cases were observed with a peak of 218 in December 1974-January 1975. The attack rate was highest (15.8%) during the 1st year of life; for those ages 0-6 it was 12.8%. 90% of the cases occurred in children age 6 or younger. The median age was 3.5 years, the age range 1 month-13 years. Girls were significantly more affected than boys. The overall case fatality rate was 1.3% but among infants, it was 2.5 times higher. In order to contribute to the improvement of immunization coverage in countries where health resources are limited, a schedule of child immunization requiring a minimum number of contacts with the children was introduced into the study area with the aim of evaluating its effectiveness in protecting children from clinical pertussis. In this trial, the effect of 2 and 3 diphtheria-pertussis-tetanus (DPT) vaccine doses was compared. Pertussis agglutinating antibody determinations showed an equally satisfactory response after 2 and 3 DPT vaccine doses. (author's)^ieng