Effects of cardiopulmonary bypass and circulatory arrest on endothelium-dependent vasodilation in the lung

Endothelial injury with failure of pulmonary endothelium-dependent vasodilatation has been proposed as a possible cause for the increased pulmonary vascular resistance observed after cardiopulmonary bypass, but the mechanisms underlying this response are not understood. An in vivo piglet model was used to investigate the role of endothelium-dependent vasodilatation in postbypass pulmonary hypertension. The pulmonary vascular responses to acetylcholine, a receptor-mediated endothelium-dependent vasodilator, and nitric oxide, an endothelium-independent vasodilator, were studied in one group of animals after preconstriction with the thromboxane A2 analog U46619 (n = 6); a second group was studied after bypass with 30 minutes of deep hypothermic circulatory arrest (n = 6). After preconstriction with U46619, both acetylcholine and nitric oxide caused significant decreases in pulmonary vascular resistance (34% +/- 6% decrease, p = 0.007, and 39% +/- 4% decrease, p = 0.001). After cardiopulmonary bypass with circulatory arrest, acetylcholine did not significantly change pulmonary vascular resistance (0% +/- 8% decrease, p = 1.0), whereas nitric oxide produced a 32% +/- 4% decrease in pulmonary vascular resistance (p = 0.007). These results demonstrate a loss of receptor-mediated endothelium-dependent vasodilatation with normal vascular smooth muscle function after circulatory arrest. Administration of the nitric oxide synthase blocker Ngamma-nitro-L-arginine-methyl-ester after circulatory arrest significantly increased pulmonary vascular resistance; thus, although endothelial cell production of nitric oxide may be diminished, it continues to be a major contributor to pulmonary vasomotor tone after cardiopulmonary bypass with deep hypothermic circulatory arrest. In summary, cardiopulmonary bypass with deep hypothermic circulatory arrest results in selective pulmonary endothelial cell dysfunction with loss of receptor-mediated endothelium-dependent vasodilatation despite preserved ability of the endothelium to produce nitric oxide and intact vascular smooth muscle function.     

Intramuscular injection as a provoking factor for paralysis in acute poliomyelitis. A case control study

In order to identify the role of intramuscular injection (IM) as a provoking factor for poliomyelitis, a case control study as done at the Institute of Child Health, Madras from May 1988 to May 1989. The case was defined as acute poliomyelitis if he had acute asymmetric flaccid paralysis of lower motor neurone type without objective sensory disturbance following a short episode of fever. Controls were taken from children attending outpatient department for fever. Two controls matched for aged and sex were recruited for each case. Recruitment, data collection and clinical examination were done by a single pediatrician. IM injection received within 30 days prior to onset of paralysis or illness was considered to be the risk factor. The total number of cases and controls recruited were 257 and 515, respectively. Among cases, 172 (66.9%) out of 257 and among controls 252 (48.9%) out of 515, received IM injection within one month earlier to onset of paralysis or illness. The overall risk of paralysis, estimated for IM injection, was increased [odds ratio (OR) 2.1 (95% CI, 1.5-3.0)]. The maximum risk for paralysis was observed to be 2 weeks preceding the illness; the ORs for < 7 days was 2.2 (95% CI, 1.6-3.2) and for 7-13 days 3.2 (95% CI, 1.8 to 5.8). The risk of paralysis associated with IM injection was similar for unimmunized and immunized cases (OR 2.4 and 2.2). Multiple injections were not associated with a higher risk of developing paralysis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Sequential invasions of pancreatic pseudocysts in pancreatic tail, hepatic left lobe, caudate lobe, and spleen

A 66-year-old male patient without a history of risk factors for pancreatitis suffered from pancreatitis and developed pseudocyst. During the course of treatment and follow-up, the pseudocyst was found to have migrated through the pancreatic tail, left hepatic lobe, caudate lobe, and spleen on abdominal sonography and computed tomography scan. Finally, emergent laparotomy was done for splenic abscess and removal of infected pseudocyst in the spleen and lesser sac of the abdomen. The patient made a full recovery after operation.     

Involvement of different cysteines in the inactivation of octopine dehydrogenase by p-chloromercuricphenyl sulfonic acid and o-phthalaldehyde

Inactivation of octopine dehydrogenase by p-chloromercuricphenyl sulfonic acid (PCMS) and o-phthalaldehyde have been investigated. The activity loss due to the PCMS was faster than o-phthalaldehyde. PCMS associated inhibition was reversed by dithiothreitol completely which was not observed with o-phthalaldehyde inactivated enzyme. Fluorescence spectra of o-phthalaldehyde modified enzyme showed the formation of isoindole derivative with characteristic emission maximum at 410 nm. This derivative formation essentially involves cross-linking of proximal cysteine and lysine residues. Protection and selective reversible reaction studies have established that NADH prevents the enzyme against PCMS inactivation and the essential cysteine present at the NADH binding site is not involved in the o-phthalaldehyde reaction.     

Stage I testicular tumours: the Tata Memorial Hospital experience

One hundred and fifty-six patients with stage I testicular germ cell tumours--81 seminomas and 75 nonseminomatous tumours--were treated at the Tata Memorial Hospital, Bombay over a 5 year period. Among the seminomas, 71 were treated with post-orchidectomy prophylactic radiation therapy to the retroperitoneum and/or mediastinum, while 10 patients refused radiation therapy and were put on surveillance. The disease-free and total survival in seminomas were 92.6% and 100%, respectively. Among the patients with nonseminomatous tumours, 58 had normal levels of serum biomarkers while 17 had raised biomarkers. In the normal marker group, 20 patients underwent retroperitoneal lymph node dissection (RPLND) with a nodal positivity of 30%, while the other 38 patients refused surgery and were either placed on unplanned surveillance (33 patients) or chemotherapy (5 patients). In this group, the patients undergoing RPLND had a survival rate of 100% as compared to 93.9% in those with surveillance. The overall disease-free and total survival rates in patients with normal markers were 86.2% and 96.6%, respectively. In the raised marker group, 6 patients underwent RPLND with a survival rate of 100% and 11 patients received chemotherapy with a survival of 90%, with the overall survival for patients with raised markers being 94.1%. The overall disease-free and total survival rates for all patients with stage I nonseminomatous tumours were 88% and 96%, respectively.     

Three-dimensional solution structure of Callinectes sapidus metallothionein-1 determined by homonuclear and heteronuclear magnetic resonance spectroscopy

Metallothionein is a cysteine-rich metal-binding protein whose biosynthesis is closely regulated by the level of exposure of an organism to zinc, copper, cadmium, and other metal salts. The metallothionein from Callinectes sapidus is known to bind six divalent metal ions in two separate metal-binding clusters. Heteronuclear 1H-113Cd and homonuclear 1H-1H NMR correlation experiments have been used to establish that the two clusters reside in two distinct protein domains. The three-dimensional solution structure of the metallothionein has been determined using the distance and angle constraints derived from these two-dimensional NMR data sets and a distance geometry/simulated annealing protocol. There are no interdomain short distance (< or = 4.5 A) constraints observed in this protein, enabling the calculation of structures for the N-terminal, beta domain and the C-terminal, alpha domain separately. A total of 18 structures were obtained for each domain. The structures are based on a total of 364 experimental NMR restraints consisting of 277 approximate interproton distance restraints, 12 chi 1 and 51 phi angular restraints, and 24 metal-to-cysteine connectivities obtained from 1H-113Cd correlation experiments. The only element of regular secondary structure in either of the two domains is a short segment of helix in the C-terminal alpha domain between Lys42 and Thr48. The folding of the polypeptide backbone chain in each domain, however, gives rise to several type I beta turns. There are no type II beta turns.