Relaparotomy in abdominal gunshot wounds]

Clinical signs of postoperative complications were studied in 642 patients with abdominal wounds, including 102 (15.9%) cases with relaparotomy features. The article makes a comparison between the frequency of various complications on the one hand, and the character of internal lesions, size of the first surgical intervention and the time of the secondary surgical care on the other hand. The authors determine the basic trends of complex intensive therapy taking into account metabolic disorders in patients with gunshot abdominal injuries.     

Tannic acid-induced nucleolar changes in hepatocytes transplanted into syngeneic or xenogeneic host and in hepatocytes maintained in primary culture

In this study we have investigated the effect of a single dose of tannic acid, administered s.c., on the nucleolar ultrastructure of hepatocytes transplanted into a syngeneic or xenogeneic host in order to evaluate the validity of our hepatocyte transplantation system as an in vivo alternative to the use of whole animals to test for species and strain differences to the effects of hepatotoxins. Within 4-6 h following tannic acid injection, rat hepatocytes transplanted into the anterior chamber of eye and inguinal fat pads of rat and athymic nude mouse, showed changes of nucleolar components, with separation of ribonucleoprotein containing granules into discrete dark zones. These dark areas were surrounded by light areas consisting of granular and fibrillar components of the nucleolus. These changes were identical to tannic acid-induced nucleolar alterations in the homotopic liver. Hamster and rat hepatocytes xenotransplanted into athymic nude mice also displayed prominent nucleolar alterations in response to tannic acid. The similarity and extent of nucleolar alterations observed in transplanted hepatocytes and the in situ homotopic liver cells attest to the usefulness of the hepatocyte transplantation system for the evaluation of species differences in biological response to toxic/carcinogenic effects of xenobiotics.     

Pharmacogenetics of antipsychotic adverse effects: Case studies and a literature review for clinicians

There is a growing body of literature supporting the contribution of genetic variability to the mechanisms responsible for the adverse effects of antipsychotic medications particularly movement disorders and weight gain. Despite the current gap between research studies and the practical tools available to the clinician to identify such risks, it is hoped that in the foreseeable future, pharmacogenetics will become a critical aid to guide the development of personalized therapeutic regimes with fewer adverse effects. We provide a summary of two cases that are examples of using cytochrome P450 pharmacogenetics in an attempt to guide treatment in the context of recent literature concerning the role of pharmacogenetics in the manifestation of adverse effects of antipsychotic therapies. These examples and the review of recent literature on pharmacogenetics of antipsychotic adverse effects illustrate the potential for applying the principles of predictive, preventive, and personalized medicine to the therapy of psychotic disorders.     

Transjugular intrahepatic cavoportal shunt for Budd–Chiari syndrome

Budd–Chiari syndrome (BCS) is characterized by obstruction of the hepatic venous outflow tract. Therapeutic options for BCS are limited. We report a case of a 21-year-old woman with protein S and C deficiency with gross ascites. Treatment with transjugular intrahepatic portosystemic shunt (TIPS) was attempted, which revealed occluded hepatic veins, so transcaval TIPS was performed. No serious procedure-related complication occurred. After successful shunt creation, the patient's symptoms subsided and she was discharged and followed up for 6 months.     

Magnetic Resonance Imaging of Corticobasal Degeneration

Corticobasal degeneration (CBD) is an adult–onset, progressive parkinsonian syndrome with strikingly asymmetrical features, and signs and symptoms referable to both cerebral cortex and basal ganglia. Although once considered rare, it is now recognized with increasing frequency during life. Eight patients with clinically diagnosed CBD and 8 age– and sex–matched patients with Parkinson's disease underwent high–field–strength magnetic resonance imaging (MRI) of the brain. MRIs were graded by a blinded neuroradiologist using a semiquantitative (0–3) scale. MRI of patients with CBD revealed significantly greater T2–weighted signal hypointensity in the putamena and globi pallidi, and ventricular enlargement. When specifically sought, asymmetrical cortical atrophy was identified in 5 of 8 CBD patients. Increased T2–weighted lenticular signal hypointensity, ventricular enlargement, and asymmetrical cortical atrophy are supportive MRI findings of CBD.     

Role of Periductal and Ductular Epithelial Cells of the Adult Rat Pancreas in Pancreatic Hepatocyte Lineage: A Change in the Differentiation Commitment

Development of pancreatic hepatocytes in adult rats maintained on copper deficient diet containing 0.6% trien (CuDT) has been reported recently. To elucidate the histogenesis of hepatocytes a sequential study was undertaken using morphologic, histochemical, immunochemical, in situ hybridization, and Northern blot analysis. Male F-344 rats weighing 80 to 90 g were fed CuDT for 8 weeks and returned to normal rat chow. Beginning from 4 weeks of copper depletion, there was a progressive loss of acinar cells and by 8 weeks more than 90% of the acinar tissue was lost. During this period, there was an increase in the number of adipocytes in the interstitium, and in the number of interstitial and ductular cells. Morphologic observations were confirmed by immunoblot and Northern blot analysis, in which the amount of pancreatic proteins and their mRNAs decreased between 5 and 8 weeks. During this period, a progressive increase in the level of albumin mRNA was observed. In situ hybridization, performed at 7 weeks of copper deficiency, showed localization of albumin mRNA over interstitial and ductular cells. Pancreatic hepatocytes were identified immediately after the rats were returned to a normal diet and gradually increased in number. The hepatocytes occupied almost 60% of the pancreatic volume by 8 weeks. During the early recovery phase, hepatocytes were identified in ductules as well as in the interstitium. Based on these studies, it is concluded that both the ductular cells and interstitial cells, which resemble oval cells of liver, are capable of transforming into pancreatic hepatocytes and these cells may be considered stem-cell equivalent.     

Analysis of genomic downsizing on the basis of region-of-difference polymorphism profiling of Mycobacterium tuberculosis patient isolates reveals geographic partitioning

Mycobacterium tuberculosis, the etiological agent of tuberculosis, has lost many coding and noncoding regions in its genome during the course of evolution. We performed region-of-difference (RD) analysis using PCR-based genotyping of 131 M. tuberculosis clinical isolates obtained from four different countries, namely, India, Peru, Libya, and Angola. Our studies revealed that RD patterns are often distinct for strains circulating in specific geographical regions and can be used to trace the descent and spread of an isolate from its original reservoir. We describe our findings, which show that no single isolate from the four countries (n = 131) had all the 15 RDs either deleted or retained. Tuberculosis-specific deletion 1 (TbD1) was found to be conserved in 23% of the Indian isolates, indicating their possible ancient origin. RD9 was the most conserved region, RD11 was predominantly deleted, and RD6 was the most variable among the isolates in our collection irrespective of their geographic region. In contrast to earlier reports, our results demonstrate that the deletion of RD1 does not correlate with a decrease in the virulence potential of M. tuberculosis, as Indian isolates (n = 30) examined by us were from diseased individuals and yet had lost the RD1 region. Our results further illustrated that the intactness of the RD5 region may be associated with increased virulence of the organism. This study highlights that the RDs in M. tuberculosis genomes are geographically distributed and specific and may possibly be associated with virulence spectrum.     

Profile of autoantibody to basement membrane zone proteins in patients with mucous membrane pemphigoid: long-term follow up and influence of therapy

Mucous membrane pemphigoid (MMP) is an autoimmune mucocutaneous blistering disease characterized by autoantibodies to components within the basement membrane zone. In this study, we report the titers of autoantibodies to antigens in the BMZ, in the sera of 13 patients, treated with intravenous immunoglobulin as monotherapy over a consecutive 18-month period. Using bovine gingiva lysate as substrate in an immunoblot assay, autoantibodies to human bullous pemphigoid antigens (BPAg1 and BPAg2), human beta4 integrin, and laminin 5 were measured. A statistically significant (P < 0.05) decline in the autoantibody titers to beta4-integrin was observed after 3.42 months of initiating the IVIg therapy. These titers were undetectable after 13 months of therapy. The titers of antibodies to BPAg1 and BPAg2 did not correlate with disease activity or response to therapy. Antibodies to laminins were not detected. In patients with MMP, autoantibody titers to beta4-integrin correlate with disease activity and response to therapy.     

Rescue of abasic hammerhead ribozymes by exogenous addition of specific bases.

We have synthesized 13 hammerhead ribozyme variants, each containing an abasic residue at a specific position of the catalytic core. The activity of each of the variants is significantly reduced. In four cases, however, activity can be rescued by exogenous addition of the missing base. For one variant, the rescue is 300-fold; for another, the rescue is to the wild-type level. This latter abasic variant (G10.1X) has been characterized in detail. Activation is specific for guanine, the base initially removed. In addition, the specificity for guanine versus adenine is substantially altered by replacing C with U in the opposite strand of the ribozyme. These results show that a binding site for a small, noncharged ligand can be created in a preexisting ribozyme structure. This has implications for structure-function analysis of RNA, and leads to speculations about evolution in an "RNA world" and about the potential therapeutic use of ribozymes.