Urological injuries during obstetric and gynaecological surgical procedures

Urological injuries during obstetric and gynaecological operations carried out between Jan. '88 to Dec. '88, at a hospital involved in resident teaching programmes were analysed retrospectively. Each case was reviewed for predisposing factors, location and type of injury, time and method of recognition and management. Fifteen injuries were documented in 892 gynaecological procedures and 296 obstetric procedures. Twelve injuries occurred during gynaecological operations whereas 3 occurred during obstetric operations. Thirteen were bladder injuries and two were ureteric injuries. Infiltrating carcinoma of cervix, pelvic adhesions, adhesions because of previous operations and distorted anatomy, were the important risk factors.     

Emergence of a unique O3:K6 clone of Vibrio parahaemolyticus in Calcutta, India, and isolation of strains from the same clonal group from Southeast Asian travelers arriving in Japan.

Active surveillance of Vibrio parahaemolyticus infection among hospitalized patients in Calcutta, India, was initiated in January 1994. The incidence of cases of V. parahaemolyticus infection suddenly increased in February 1996 and has remained high since then. One hundred thirty-four strains of V. parahaemolyticus isolated from January 1994 to August 1996 were examined for serovar, the presence of the thermostable direct hemolysin gene (tdh) and tdh-related hemolysin genes (trh1 and trh2), production of urease, and antibiogram. Strains of the O3:K6 serovar appeared for the first time in February 1996. The O3:K6 serovar strains accounted for 50 to 80% of the strains isolated during the high-incidence period (February to August 1996). All of the serovar O3:K6 strains carried the tdh gene but not the trh genes and did not produce urease. All of the isolates except two were sensitive to all of the antibiotics tested. These and the results of analysis by an arbitrarily primed PCR method indicated that the O3:K6 serovar strains belong to a unique clone. When the O3:K6 serovar strains, isolated from travelers arriving in Japan from Southeast Asian countries, were compared by the arbitrarily primed PCR method, the strains isolated between 1982 and 1993 were distinct from Calcutta O3:K6 while the strains isolated in 1995 and 1996 were indistinguishable from the Calcutta O3:K6 strains. The results suggest that this unique O3:K6 clone may have become prevalent not only in Calcutta but also in Southeast Asian countries very recently. Not only the O3:K6 strains but also the non-O3:K6, tdh-bearing strains isolated in 1996 produced thermostable direct hemolysin at high levels, and thus the level of hemolysin produced does not appear to have influenced the high incidence of serovar O3:K6 strains.     

Long-range temporal correlations in the spontaneous spiking of neurons in the hippocampal-amygdala complex of humans

The spontaneous or background discharge patterns of in vivo single neuron is mostly considered as neuronal noise, which is assumed to be devoid of any correlation between successive inter-spike-intervals (ISI). Such random fluctuations are modeled only statistically by stochastic point process, lacking any temporal correlation. In this study, we have investigated the nature of spontaneous irregular fluctuations of single neurons from human hippocampus-amygdala complex by three different methods: (i) detrended fluctuation analysis (DFA), (ii) multiscale entropy (MSE), (iii) rate estimate convergence. Both the DFA and MSE analysis showed the presence of long-range power-law correlation over time in the ISI sequences. Moreover, we observed that the individual spike trains presented non-random structure on longer time-scales and showed slow convergence of rate estimates with increasing counting time. This power-law correlation and the slow convergence of statistical moments were eliminated by randomly shuffling the ISIs even though the distributions of ISIs were preserved. Thus the power-law relationship arose from long-term correlations among ISIs that were destroyed by shuffling the data. Further, we found that neurons which showed long-range correlations also showed statistically significant correlated firing as measured by correlation coefficient or mutual information function. The presence of long-range correlations indicates the history-effect or memory in the firing pattern by the associative formation of a neuronal assembly.     

High tidal volume ventilation induces proinflammatory signaling in rat lung endothelium

Alveolar overdistension during mechanical ventilation causes leukocyte sequestration, leading to lung injury. However, underlying endothelial cell (EC) mechanisms are undefined. In a new approach, we exposed isolated blood-perfused rat lungs to high tidal volume ventilation (HV) for 2 h, then obtained fresh lung endothelial cells (FLEC) by immunosorting at 4 degrees C. Immunoblotting experiments indicated that as compared with FLEC derived from lungs ventilated at low volume (LV), HV markedly enhanced tyrosine phosphorylation (TyrP). The tyrosine kinase blocker, genistein, inhibited this response. HV also induced focal adhesion (FA) formation in FLEC, as detected by immunofluorescent aggregates of the alpha(v)beta(3) integrin that co-localized with aggregations of focal adhesion kinase (FAK). Immunoprecipitation and blotting experiments revealed that HV increased TyrP of the FA protein, paxillin. In addition, HV induced a paxillin-associated P-selectin expression on FLEC that was also inhibited by genistein. However, HV did not increase lung water. These results indicate that in HV, EC signaling in situ causes FA formation and induces TyrP-dependent P-selectin expression. These signaling mechanisms may promote leukocyte-mediated responses in HV.     

Functional characterization of missense mutations at codon 838 in retinal guanylate cyclase correlates with disease severity in patients with autosomal dominant cone-rod dystrophy

Three different mutations in codon 838 of GUCY2D, the gene for retinal guanylate cyclase 1, have been linked to autosomal dominant cone-rod dystrophy at the CORD6 locus. To examine the relationship between enzyme activity and disease severity, the three disease-causing substitutions (R838C, R838H and R838S) and four artificial mutations (R838A, R838E, R838L and R838K) were generated. Assay of GCAP1-stimulated cyclase activity in vitro shows that, compared with wild-type, R838E, R838L and R838K possess only low activity, whereas R838A, R838C, R838H and R838S have activity equal or superior to wild-type at low Ca(2+) concentrations. These four latter mutants showed a higher apparent affinity for GCAP1 than did wild-type. The Ca(2+) sensitivity of the GCAP1 activation was also altered with marked residual activity at high Ca(2+), the effect increasing: wild-type < R838C < R838H < R838A < R838S. Within the photoreceptor, this would result in a failure to inactivate cyclase activity at high physiological Ca(2+ )concentrations. Amongst the three disease-associated mutations, the effect correlates directly with disease severity. The wild-type and R838H mutant displayed a difference in pH sensitivity, with the mutant showing a higher specific activity with pH > 6.0. Site 838 is in the dimerization domain that forms a coiled-coil in the active protein. A computer-aided structure prediction of this region indicates that R838 in the wild-type breaks the structure at four helical turns, and there is an increasing tendency for the structure to continue for further turns in the order R838C < R838H,S,K < R838E < R838A < R838L.     

Evaluation of beta-tethymustine, a new anticancer compound, in murine tumour models

beta-Tethymustine, 1-[2- {bis(2'-chloroethyl)amino}ethyl]spiro[imidazolidine-4,2'-(1'H),3',4'-dihydronaphthalene]-2,5-dione, has been synthesised and LD50 value determined in Swiss male mice, which was found to be 100.00 mg/kg by single i.p. injection. The following three criteria, namely ascites cell count, ascites fluid measurement and increase in median survival times (MST) of drug-treated (T) over untreated control (C) mice, were studied for evaluation of its antitumour efficacy in vivo in three murine ascites tumours, namely Ehrlich ascites carcinoma (EAC), sarcoma-180 (S-180) and Dalton's lymphoma (DL). At the optimum dose range of 8.0 mg/kg (higher) to 4.0 mg/kg (lower) for 1-7 days treatment following tumour transplantation on day 0, it exhibited a very high percentage of inhibition of both the ascites cell and fluid in these models and displayed excellent ILS(max) value of 80 in EAC, 224 in S-180 and 240 in DL, respectively, showing 'curative' effect (2-3/6 mice having 90 days survival rate). It also demonstrated a high ILS value of 150 with one cure/six mice bearing S-180 for 6 days prior to drug therapy. Screening results were compared with two clinical drugs, cyclophosphamide and 5-fluorouracil, serving as positive controls. Its chemical alkylating activity was compared with nor-HN2 (NSC 10873) and spiromustine (NSC 172112). The results indicate that it possesses greater alkylating activity than nor-HN2 and comparable activity with spiromustine.     

Possible role of dopamine in central effects of cocaine as measured by apomorphine gnawing test in mice

Apomorphine (10 mg/kg, s.c.) does not induce in mice a compulsion to gnaw, but pretreatment with cocaine (10–40 mg/kg, i.p.) caused gnawing activity. This effect of cocaine was inhibited by pretreatment with -methyl-p-tyrosine, haloperidol, and physostigmine, but not with FLA-63, phenoxybenzamine and tetrabenazine. These findings would suggest that dopaminergic mechanism plays a significant role in the potentiation of apomorphine gnawing activity by cocaine and also support the view that inhibition of dopamine uptake is responsible for the stimulatory action of cocaine.