Biomedical subjects
Publications and source records attributed to A Kulkarni.
Human cysticercosis and tuberculosis are endemic diseases in developing countries. Both these diseases have certain common factors of origin. We would like to present the co-existence of these infections in a 20-year-old female. She was a known case of pulmonary and ocular tuberculosis and she acquired cysticercosis of the eye and brain.
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AIMS AND OBJECTIVES: To review menstrual problems in women with congenital FVII deficiency and to study their effect on the quality of life during menstruation in women with congenital FVII deficiency. METHOD: 14 women with congenital factor VII deficiency registered with the Haemophilia Centre at the Royal Free Hospital were interviewed and their case notes reviewed. All women completed Pictorial Blood assessment Chart (PBAC) for assessment of menstrual blood loss and a quality of life questionnaire during menstruation. Similar questionnaire and PBAC was completed by an age matched healthy control group of 23 women. RESULTS: Median age of study group was 35 yrs and of control group 34 yrs. Median FVII level of the study group was 31.5 IU/dL Two women had severe FVII deficiency (FVII level < 10 IU/dL) and 12 women had mild-moderate FVII deficiency. 57% women (8/14) from study group had menorrhagia (PBAC score > 100) compared with 17% (4/23) women from the control group. Six women (43%) from the study group were diagnosed with anaemia due to heavy periods, compared to two (9%) in the control group. The quality of life scores during menstruation were significantly worse in the women with FVII deficiency, compared to controls. CONCLUSION: Women with factor VII deficiency exhibit a spectrum of bleeding symptoms, menorrhagia being one of the commonest symptoms. This has adverse effect on their quality of life.
OBJECTIVE: To determine the risk of ventriculoperitoneal (VP) shunt infections after percutaneous retrograde gastrostomy feeding tube (GT) placement in children with brain tumors. PATIENTS AND METHODS: All children (age 0-18 years) with primary brain tumors diagnosed and treated at the Hospital for Sick Children, Toronto, Canada, were subjected to a retrospective analysis. Two groups were identified: the study group included children with a VP shunt and a GT; the control group included children with VP shunts only. Each study patient was matched with 2 controls to compare the rate of infections (cohort comparative study). RESULTS: There were 1,167 children diagnosed and treated with primary brain tumors during the study period (1988-2003); 174 (15%) had a VP shunt and 23 (2%) children had both, a VP shunt and a GT. In the study group (n=17), GTs were inserted at a median time of 80 days (range 6-204 days) after VP shunts. VP shunt infection rate was 23.5% (4/17) compared to 8.8% (3/34) in the control group (OR 3.18; 95% CI 0.622-16.54, p=0.16). Three (75%) of the infection episodes in the study group presented with an ascending VP shunt infection directly related to the GT insertion or manipulation in the first 6 weeks. These GTs were inserted at 13, 47 and 49 days after VP shunt insertion. CONCLUSION: Placement of percutaneous retrograde GTs, in the acute phase, in children with brain tumors and VP shunts may increase the risk of ascending meningitis especially if there are early GT-related complications.
Our objective was to study the teeth of a mutant mice fro/fro that display severe forms of osteogenesis imperfecta. One day and 8 week-old fro/fro and +/fro heterozygote mice (wild type, WT) were processed for light and scanning electron microscopy. The genetic defect, shown to be located on chromosome 8, induced alveolar bone and teeth hypomineralisation. Due to defective cell proliferation in the fro/fro, the distal growth of the mandibular incisors was impaired. Immunolabelling revealed an increase of chondroitin/dermatan sulphate, whereas no difference was detected in dental tissues for decorin and biglycan. Amelogenin expression was decreased in the incisor and enhanced in the molar. Dentin sialoprotein was below the level of detection in the fro/fro, whereas osteonectin and osteopontin were unchanged. The main target of the mutation was seen in the lingual part of the incisor near the apex where dentine formation was delayed. In the molars, bulbous roots with obliteration of the pulp chamber were seen. In the TGFbeta1 overexpressing mice, the lingual root-analogue part of the incisor was missing. In the molar, short roots, circumpulpal dentine of the osteodentine type and pulp obliteration were seen. It may be noted that, although the mutant and transgenic strains mutations are two different genetic alterations not related to the same defective gene, in both cases the expression of the dentin sialoprotein is altered. Altogether, the present data suggest that the lingual forming part of the incisor seems to be an anatomical entity bearing its own biological specificities.
Space flight is known to induce microgravity-associated immune dysfunction in humans, non-human primates and rodents. To understand the mechanism underlying these defects, several studies in rodents have been conducted in a ground-based antiorthostatic suspension (AOS) model that would mimic the effects of microgravity. In all these in vivo studies that showed the effects on cytokine profiles actually investigated the ex vivo production from culturing the cells isolated from whole organism that was exposed to space flight and/or microgravity. So, the purpose of the study was to examine the in vivo expression of cytokines in mice in immunologically important tissue environments of mice that were subjected to AOS. Cytokines such as Interleukin-1beta, (IL-1beta), IL-2, IL-3, IL-6, Interferon-gamma (IFN-gamma) and Tumor Necrosis Factor-alpha (TNF-alpha) were measured by Enzyme Linked Immunosorbent Assay (ELISA) in the homogenates of spleen tissue, lymph nodes and also in serum of AOS mice and compared with that of control mice. AOS induced no change in the IL-3 levels, but IL-1beta was increased significantly whereas IL-2 levels decreased in spleen, lymph nodes and serum. IL-6 levels did not differ in spleen but were significantly increased in lymph nodes and serum of AOS mice. IFN-gamma levels in spleen did not change but showed nonsignificant reduction in lymph nodes and significant reduction in serum in response to AOS. TNF-alpha levels in spleen and serum were unchanged and increased in lymph nodes. This in vivo cytokine study confirms the earlier findings that microgravity-simulated conditions induce tissue-specific immune response.
Tracheal extubation can evoke an equally strong haemodyamic stress response as tracheal intubation. We present a patient with myocardial infarction who repeatedly failed tracheal extubation. He developed acute pulmonary oedema following each attempt at tracheal extubation due to sympathetic overactivity. A change of approach with extubation under propofol sedation followed by continued sympatholysis with dexmedetomidine infusion allowed successful extubation.
A retrospective analysis of 100 out of 108 cases has been audited for suitability of bilateral knee arthroscopy as a day-case procedure. Fifty-three female and 47 male patients with age range of 15-78 years underwent bilateral knee arthroscopy. All patients had general anaesthetic and were ASA grade 1 or 2. Eight patients had more than one diagnosis and procedures. Post-operatively 68% could walk without walking aids, 1% had 1 stick and 31% needed 2 sticks and were given elbow crutches. One patient stayed overnight due to poor pain control and 1 attended A&E due to effusion. There were 5 (2.5%) major and 62 (31%) minor complications in 200 knees. Mild post-operative pain was the commonest minor complication in 52 (26%) out of 62 knees and was attributed to high number of bilateral arthritis cases in this study. Complication rate of bilateral arthroscopy is similar to unilateral arthroscopy. It is concluded that bilateral arthroscopy is safe as a day-case procedure.
Ten patients underwent endoprosthetic replacement of the distal humerus for bone tumours over a period of 30 years. There were eight primary and two secondary tumours in four men and six women with a mean age of 47.5 years (15 to 76). The mean follow-up was eight years (9 months to 31 years). Four patients required further surgery, three having revision for aseptic loosening; two of these and one other later needing a rebushing. There were no cases of postoperative nerve palsy, infection, local recurrence or mechanical failure of the implant. Four patients died from their disease, all with the prosthesis functioning satisfactorily. At follow-up the mean flexion deformity of the elbow was 15 degrees (0 to 35) and the mean range of lexion was 115 degrees (110 to 135). The functional results showed a mean Toronto extremity salvage score of 73% of normal. Endoprosthetic replacement of the distal humerus and elbow is a satisfactory method of treating these rare tumours.
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Sulfur mustard (bis(2-chloroethyl)sulfide, SM) is a highly reactive bifunctional alkylating agent that forms sulfonium ions in the body. SM alkylates DNA, leading to DNA strand breaks and cell death in a variety of cell types and tissues. Although several approaches have been proposed to challenge the toxic action(s) of SM, no satisfactory treatment regimen has evolved. The synthetic aminothiol amifostine, earlier known as WR-2721 (S-2-(3-aminopropylamino)ethyl phosphorothioate), has been extensively used as a chemical radioprotector for the normal tissues in cancer radiotherapy and chemotherapy. SM is known as a radiomimetic agent and this prompted us to evaluate the protective efficacy of amifostine (2.5 mM) and three of its analogues, DRDE-06 (S-2 (3-aminopropylamino) ethyl phenyl sulfide), DRDE-07 (S-2 (2-aminoethylamino) ethyl phenyl sulfide), and DRDE-08 (S-2 (4-aminobutylamino) ethyl phenyl sulfide), against SM toxicity in rat liver slices. Of the four agents tested, a 30-min pretreatment of amifostine and DRDE-07 enhanced the LC50 (a concentration producing 50% leakage of lactate dehydrogenase (LDH) or alanine aminotransferase (ALT)) of SM by 5.9- and 3.3-fold for LDH and 10.2- and 5.5-fold for ALT, respectively. Except DNA fragmentation, both these agents significantly attenuated the loss of intracellular K(+) and mitochondrial integrity (MTT assay), depletion of GSH levels, and histopathology produced by a toxic concentration (80 microM) of SM. However, when amifostine and DRDE-07 were introduced 2 h after SM, no significant protection was observed. SM (77.5 or 155 mg/kg) was also applied dermally on female albino mice and challenged by 0.20 LD50 (po) of amifostine, DRDE-06, DRDE-07, or DRDE-08 at -30 min, 0 min, or +6 h. Protection was observed only when the agents were administered at -30 min or 0 min; posttreatment (+6 h) did not offer any protection. The magnitude of in vivo protection was in the following order: DRDE-07 >or= amifostine > DRDE-08 > DRDE-06. Gas chromatographic analysis showed that there was no direct chemical interaction between SM and the antidotes. The po LD50s of amifostine, DRDE-06, DRDE-07, and DRDE-08 were 1049, 1345, 1248, and 951 mg/kg, respectively. Both in vitro and in vivo data indicate promising roles of amifostine and DRDE-07 as prophylactic agents against SM poisoning.
The requirement for processing glycolipid antigens in T cell recognition was examined with mouse CD1d-mediated responses to glycosphingolipids (GSLs). Although some disaccharide GSL antigens can be recognized without processing, the responses to three other antigens, including the disaccharide GSL Gal(alpha1-->2)GalCer (Gal, galactose; GalCer, galactosylceramide), required removal of the terminal sugars to permit interaction with the T cell receptor. A lysosomal enzyme, alpha-galactosidase A, was responsible for the processing of Gal(alpha1-->2)GalCer to generate the antigenic monosaccharide epitope. These data demonstrate a carbohydrate antigen processing system analogous to that used for peptides and an ability of T cells to recognize processed fragments of complex glycolipids.
Mycotic keratitis, being frequently refractive to most of the currently available antifungal therapy, continues to pose a therapeutic challenge to the clinician. In keratitis of infectious etiology stromal dissolution may be brought about by a combination of agent and host factors. An understanding of the source and nature of corneal tissue damage is essential for evolving more effective therapeutic modalities in the treatment of fungal keratitis. In the present study, we have characterized the extracellular proteases produced in vitro by corneal fungal pathogens namely the Aspergillus flavus and Fusarium solani when collagen was provided as the sole nitrogen source. In addition, fungal infected rabbit corneas were investigated for proteolytic activities and nature of inflammatory reaction. Gelatin zymography detected protease bands with molecular mass ranging from 100 to 200 kDa in the culture extracts of A. flavus, and a single major band of molecular mass approximately 200 kDa in the culture extracts of F. solani. A basal proteolytic activity of mass 65 kDa was visualized in all uninfected and infected rabbit corneal extracts. Infected corneas in addition revealed the presence of additional proteolytic species of mass 92 and 200 kDa. The enzyme inhibitory profile suggested that fungal cultures in vitro contained predominantly serine protease activity and to a lesser extent metalloprotease activity. However, fungal infected corneal homogenates showed the presence of metalloproteinase activity alone, the enzymatic activities entirely being sensitive to ethylene diamine tetra acetate (EDTA), a metalloprotease inhibitor. Interestingly, the serine proteolytic activity detected in fungal cultures in vitro was not present in the fungal infected corneas in vivo. However, the possible role of fungal serine proteases in the activation of corneal matrix metalloproteinases (MMPs) cannot be ruled out. Based on the criteria of molecular mass, proteolytic activity in the presence of calcium at neutral pH, and sensitivity to inhibition by a metalloprotease inhibitor, the 65 and 92 kDa gelatinases were identified as MMP 2 and MMP 9, respectively. The expression of 92 and 200 kDa gelatinases correlated positively with the amount of polymorphonuclear cells present in the infected tissues. Activated resident corneal cells or inflammatory cells may largely contribute to the increased proteolytic activities in fungal infected corneas resulting in tissue matrix degradation in fungal keratitis.
Improvement in survival rates of low birth-weight infants particularly in the neonatal intensive care units of India appears to be accompanied by frequent recognition of Necrotizing enterocolitis (NEC) among early survivors. As the philosophy and practice of advanced care for tiny infants becomes more acceptable and affordable in the country, a steady increase in survival of such infants is predictable. However there is growing concern in India that NEC could become a significant contributor to morbidity and mortality in the future. NEC is currently regarded as the most common acquired gastrointestinal emergency in the newborn period, and the outcome of this disease is universally poor. Improved understanding of the pathophysiology and pathogenesis of this condition is required for formulating optimal principles of prevention and management.
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Olfaction is influenced by a complex mix of environmental and genetic factors that modulate the production, migration, and maturation of cells in the olfactory bulbs. In this study we analyzed effects of sex, age, body weight, and brain weight on olfactory bulb size in sexually mature mice. We then used regression corrected values (residuals) to map quantitative trait loci (QTLs) that selectively modulate bulb weight. This biometric analysis has relied on an F2 intercross between C57BL/6J (B6) and DBA/2J (D2) inbred strains and a large sample of 35 BXD recombinant inbred (RI) strains. Bilateral bulb weight in adult mice ranges from 10 to 30 mg. Half of this remarkable variation can be predicted from differences in brain weight, sex, body weight, and age. A 100-mg difference in brain weight is associated with a 4.4-mg difference in bulb weight. Bulbs gain in weight by 0.2 mg/week--a 1% increase that continues until at least 300 days of age. Males tend to have slightly larger bulbs than females. By combining data from both related crosses (F2 and RI) we identified four QTLs with selective effects on bulb size (genomewide p < .05). Bulb4a is located on chromosome 4 (Chr 4) and Bulb6a is located on Chr 6. Alleles inherited from B6 at both of these loci increase bulb weight by 0.5-1.0 mg. Bulb11a is located on proximal Chr 11 and Bulb17a is located on the proximal part of Chr 17. In contrast to the first two QTLs, B6 alleles at these two loci decrease bulb weight by 0.5-1.0 mg. Collectively, the four loci account for 20% of the phenotypic variance in bulb weight.
OBJECTIVES: Molecular assays are now considered to be the "gold standard" for assessment of human cytomegalovirus (CMV) infection and disease in those at risk from severe associated clinical manifestations. There is, however little consistency in the methods used in different centres. This study was undertaken to compare different qualitative molecular-based approaches for assessment of CMV activation from latency in samples from immunosuppressed transplant recipients. METHODS: Nucleic acid amplification techniques based on the polymerase chain reaction (PCR) and nucleic acid sequence-based amplification (NASBA) were undertaken for the assessment of CMV replication and associated disease in immunosuppressed transplant recipients. Samples from 32 transplant recipients were tested during this study using three molecular-based strategies: (1) detection of CMV DNA in whole blood extracts (positive after a single round of PCR considered "high-level" positive, N = 55); (2) detection of cell-free CMV DNA in plasma (two methods, N = 55 for each); and (3) detection of late pp67 CMV mRNA after NASBA (N = 51). Results using a commercial pp65 antigenemia assay were available for comparison from 40 samples. RESULTS: Seven samples were positive for CMV by all methods and 36 were negative by all methods undertaken. The other 12 samples gave discordant results using different molecular methods. The correlation between whole blood "high-level" PCR, NASBA for pp67 mRNA and antigenemia results was generally good. Results presented show that plasma PCR results do not always correlate with methods utilizing whole blood as the substrate and that inhibitors in these samples could be problematic. Whole blood PCR gave more positive results than the other assays but use of a nested assay on whole blood or plasma led to detection of CMV in individuals who had no other indicators of virus replication and who did not develop associated disease (low specificity). Although the number of confirmed CMV disease episodes was low in this study, the problems of low positive predictive value for sensitive, qualitative PCR assays was clearly demonstrated. CONCLUSION: Assays based on qualitative detection of viral nucleic acid may provide information useful for management of CMV but caution is necessary when making comparisons between results using different molecular strategies. It remains to be proven in large, comparative clinical studies in which the approach and method give the best balance between sensitivity, specificity and clinical relevance for different patient groups.
Eye irritation potency of a compound or mixture has traditionally been evaluated using the Draize rabbit-eye test (Draize et al., 1944). In order to aid predictions of eye irritation and to explore possible corresponding mechanisms of eye irritation, a methodology termed "membrane-interaction QSAR analysis" (MI-QSAR) has been developed (Kulkarni and Hopfinger 1999). A set of Draize eye-irritation data established by the European Center for Ecotoxicology and Toxicology of Chemicals (ECETOC) (Bagley et al., 1992) was used as a structurally diverse training set in an MI-QSAR analysis. Significant QSAR models were constructed based primarily upon aqueous solvation-free energy of the solute and the strength of solute binding to a model phospholipid (DMPC) monolayer. The results demonstrate that inclusion of parameters to model membrane interactions of potentially irritating chemicals provides significantly better predictions of eye irritation for structurally diverse compounds than does modeling based solely on physiochemical properties of chemicals. The specific MI-QSAR models reported here are, in fact, close to the upper limit in both significance and robustness that can be expected for the variability inherent to the eye-irritation scores of the ECETOC training set. The MI-QSAR models can be used with high reliability to classify compounds of low- and high-predicted eye irritation scores. Thus, the models offer the opportunity to reduce animal testing for compounds predicted to fall into these two extreme eye-irritation score sets. The MI-QSAR paradigm may also be applicable to other toxicological endpoints, such as skin irritation, where interactions with cellular membranes are likely.