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Biomedical subjects

R Sharma

Publications and source records attributed to R Sharma.

At least 217 records · Page 12Linked to original sources

Association of ureaplasma urealyticum with abnormal reactive oxygen species levels and absence of leukocytospermia.

PURPOSE: Ureaplasma urealyticum is a commensal of the lower genitourinary tract of many sexually active adults. The organism is more common in partners of infertile than fertile marriages. We conducted a prospective study at our tertiary care center to confirm a possible association between U. urealyticum and abnormal sperm function parameters. MATERIALS AND METHODS: A total of 50 consecutive male patients seeking general urology consultation for lower urinary tract symptoms characteristic of chronic prostatitis were evaluated. Urine and semen localization cultures were performed with additional semen cultures for U. urealyticum, Chlamydia trachomatis and Mycoplasma hominis. Specimens from 21 healthy men were used as controls. Specimens were analyzed by a computer assisted semen analyzer, and verified manually for concentration, percent motility and morphology. Leukocytospermia was measured by the Endtz test. Semen specimens were also analyzed for reactive oxygen species (ROS), acrosome reaction and mannose binding assay. RESULTS: Of the patients 17 had positive U. urealyticum cultures and the other cultures were negative. Patients with U. urealyticum had significantly higher ROS levels (log [ROS + 1] = 2.52 +/- 0.25) than those without U. urealyticum (1.49 +/- 0.20, p = 0.002) or controls (1.31 +/- 0.19, p = 0.002). Leukocytospermia was detected in only 1 of the 17 (6%) positive specimens and 4 (12%) negative specimens. CONCLUSIONS: Seminal ROS levels are elevated among patients with U. urealyticum. ROS induces lipid peroxidation, which reduces membrane fluidity and sperm fertilization capability, and may be the mechanism by which U. urealyticum impairs sperm function. Absence of leukocytospermia does not exclude U. urealyticum.

Adult↗

Clinical spectrum of HIV infection.

OBJECTIVE: To study the modes of transmission of pediatric HIV infection, to categorize clinical manifestations and to compare clinical spectrum of perinatal with transfusion acquired HIV infection. DESIGN: Case series study. SETTING: Hospital based pediatric HIV clinic. METHODS: Children confirmed to have HIV infection were evaluated and relevant details recorded. RESULTS: 55 children were enrolled of whom 41 (74.5%) had perinatal transmission of HIV, 12 (21.8%) were infected through blood transfusions and 2 (3.6%) through other routes. Thirty-seven (90.2%) of the 41 perinatally infected children were symptomatic. Tuberculosis was seen in 25 (67.5%) of these children and failure to thrive in 18 (48.6%). Nonspecific features such as recurrent bacterial infection, oral candidiasis and chronic diarrhea were other manifestations. Eight (26.3%) of the 30 children available for follow up for a median period of 9 months died at the median age of 8.5 months. Amongst the transfusion acquired HIV infection, 11 (91.6%) of the 12 were asymptomatic at presentation. Six (50%) of these children died at the median age of 3 years and the remaining 6 had no major symptoms at a median follow up of 3.5 years. CONCLUSION: Perinatal route is the major route of HIV transmission in children and clinical manifestations are different from those of adults.

Adolescent↗

Imaging in epilepsy.

Epilepsy is a common problem in the paediatric age group. Imaging plays a vital role in identifying the seizure focus. Cross-sectional imaging modalities like CT and MRI have had a major impact on the management of seizure disorders. MRI, because of its high contrast resolution and multiplanar capability is the ideal imaging modality but its use is restricted due to high cost. Computed tomography is cheaper and is the first, and often, the only modality used, especially in the underprivileged areas of the world. In the tropical countries inflammatory granuloma are a common cause of epilepsy and CT is adequate to detect these lesions. Other causes include congenital abnormalities, neoplastic and vascular causes.

Astrocytoma↗

Surgical therapy for the univentricular heart.

The natural history of the univentricular physiology is determined primarily by the presence (severity) or absence of obstruction to pulmonary blood flow and secondarily by the single ventricular cardiomyopathy that develops in response to chronic volume overload. Important obstruction to pulmonary blood flow will affect survival because of severe hypoxia and may necessitate surgical treatment (systemic to pulmonary artery shunt or cavopulmonary shunt depending on the age of the patient and a host of other factors). In the absence of significant obstruction to pulmonary blood flow, the symptomatology is one of congestive heart failure with later development of irreversible pulmonary vascular disease. In this situation, a pulmonary artery band is indicated to limit pulmonary blood flow and reduce pulmonary artery pressures to acceptable levels. Even in the presence of significant limitation of pulmonary blood flow, the single ventricle is a volume-loaded ventricle as it receives both pulmonary and systemic venous return. Chronic volume overload and persistent hypoxia is detrimental to ventricular function and gradually lead to the development of atrioventricular valve incompetence. Complete separation of oxygenated and deoxygenated blood may be obtained by ventricular septation in suitable cases (beyond the scope of this presentation) or by systemic venous diversion to the pulmonary (the Fontan circulation) arteries thus achieving complete oxygenation simultaneous with abolition of any recirculation.

Cardiac Surgical Procedures↗

Diagnostic dilemma: aspergillosis.

Two cases of varied forms of Aspergillosis are reported who were being diagnosed and treated on different lines. One case, who was treated on lines of allergic bronchitis, had very high total eosinophil count and, fleeting pulmonary infiltrates over a period of 5 years along with history of cough, fever and weight loss. Aspergillus fumigatus was grown on sputum culture. On the background of a long standing history of bronchial asthma with evidence of peripheral as well as central eosinophilia, fleeting pulmonary infiltrates and A. fumigatus grown on sputum culture, we kept the diagnosis of Allergic Bronchopulmonary aspergillosis (ABPA) and put the patient on steroids and Itraconazole. Patient showed good response to therapy. Another case, a 50 year old male, presented to us with clinical picture of subacute myelitis. Being a known case of ABPA and on steroid therapy for long duration, we kept the diagnosis of invasive aspergillosis. Growth of Aspergillus fumigatus on sputum culture on three occasions and MR imaging of spine further supported our view. Aspergillosis of the lung do not have characteristic clinico-radiological features of permit the diagnosis and should be considered in the differential diagnosis of tuberculosis, pneumonia, bronchiectasis, lung abscess and bronchial asthma.

Aspergillosis↗

Efficacy of noninvasive nasal mechanical ventilation in acute respiratory failure: monitored by breathing patterns.

OBJECTIVES: Till a decade back, the mainstay delivery of mechanical ventilation to patients with acute respiratory failure was through the endotracheal tube. To obviate the various complications of endotracheal intubation, noninvasive mechanical ventilation (NIMV) techniques were devised which could be used outside the confines of an ICU setting, and have been employed by several workers to achieve a high success rate. METHODS: Twenty patients of acute respiratory failure (ARF) were treated with NIMV. The latter was delivered by assist control mode of ventilator and nasal CPAP mask. Improvement of the illness was monitored by serial ABG analysis and breathing pattern parameters over one week. RESULTS: The application of NIMV was successful in reversing the illness in 17 patients (85%) and the other three patients had to be intubated. The pH rose from 7.267 +/- 0.087 at presentation to 7.411 +/- 0.032 (p < 0.00005), the PaCO2 dropped from 85.17 +/- 13.48 mmHg to 46.27 +/- 3.79 mmHg (p < 0.00005). The PaO2 improved from 52.36 +/- 11.14 mmHg to 63.60 +/- 7.55 mmHg (p < 0.005) on the seventh day. The respiratory rate (RR) decreased from 30.07 +/- 6.10 breaths/min to 22.05 +/- 4.05 breaths/min (p < 0.00005), the %RC (percent rib cage) also showed a significant reduction in rib cage contraction from 61.7 +/- 10.17 to 42.76 +/- 10.66 (p < 0.00005). A marked improvement during the initial four hours of application of NIMV was observed in all the 17 patients. CONCLUSIONS: It was concluded that NIMV resulted in marked improvement in both the breathing pattern and blood gas parameters in patients of ARF; and PaCO2, pH, RR, %RC served as the best indicators of improvement. NIMV was observed to be most useful in those patients who had CO2 retention.

Blood Gas Analysis↗

Transport of glutathione-conjugates in human erythrocytes.

The last step of detoxification of both endogenous and environmental toxicants is typically a conjugation that produces a bulky hydrophilic molecule. The excretion of such conjugates out of cells is of sufficient biological importance to have led to the evolution of ATP-driven export pumps for this purpose. The substrate specificity of such transporters is broad, and in some cases it has been shown to include not only anionic conjugates but also neutral or weakly cationic drugs. In the present article, we review the molecular identity, functional and structural characteristics of these pumps, mainly on the example of human erythrocytes, and discuss their physiological role in detoxification and in the multidrug resistance phenotype of cancer cells.

Adenosine Triphosphatases↗

Foetal amygdalar transplantation facilitates recovery of retention deficit in CeA lesioned rats.

Neural tissue transplant has come off age as a valuable technique for studying normal development and regeneration. Bilateral lesions of the central nucleus of amygdala (CeA) produce complete retention and acquisition deficit in inhibitory avoidance paradigms. The present study reports recovery of retention deficit in active avoidance task (AA) after amygdalar tissue transplantation in CeA lesioned rats. In a group of adult wistar rats, bilateral lesions of the CeA were produced electrolytically. In a separate group of rats foetal amygdalar tissue was transplanted at the CeA lesioned site 2 days after producing lesion. All the rats were trained on AA task before and after 5 days of lesion. In bilaterally CeA lesioned rats, the percentage of avoidance (% avoidance) decreased significantly (P < 0.05) from 85 +/- 18% prelesion to 15.5 +/- 35% postlesion. However, no change in the % avoidance was observed after amygdalar tissue transplantation. The results indicate that the transplanted rats are capable of retaining the learnt information in contrast to the lesion alone group of rats.

Amygdala↗

Reliability of information obtained by illiterate health workers regarding risk pregnancy.

The present study aims at testing the reliability of information obtained by illiterate workers (IHW) on risk pregnancy. Eight maternal risk factors known to be related to low birth weight were utilised for the purpose. The reliability of information obtained by the IHWs were compared with that of the trainer. The reliability proportions (RP) for various parameters ranged from 0.78 to 0.96 with an average of 0.86. For the overall risk assessment, the RP was 0.73. The results of the present study suggest that the IHWs can recorded the risk indicators with fair degree of reliability and accuracy, which may be applied to the training of traditional birth attendants in field settings.

Adult↗

Characterization of anionic amino acid transport systems in mouse mammary gland.

L-glutamate was transported into mammary tissue via Na(+)-dependent system XAG- that strongly interacted with both D- and L-isomers of aspartate but only with L-isomer of glutamate. Replacement of Cl- by gluconate from the extracellular medium did not affect the uptake of L-glutamate. Although neutral amino acids weakly inhibited the uptake of L-glutamate, there was no evidence for the heterogeneity of anionic amino acid transport system. The XAG- system was inhibited by sulfhydryl group blocking reagent N-ethylmalemide. Low pH (6) partially inhibited the uptake by L-glutamate by mammary tissue. Prior loading of mammary tissue with L-glutamate slightly down regulated its uptake. Culturing pregnant mouse mammary tissue explants in vitro in the presence of lactogenic hormones (insulin plus cortisol plus prolactin) did not affect appreciably the uptake of L-glutamate.

Amino Acid Transport Systems↗

Use of locally isolated saprophytic Leptospira strain for serological testing of human leptospirosis.

A saprophytic Leptospira isolate recovered from tap water was utilized for serological testing. One hundred-twenty Serum samples comprising 55 cases from PUO/febrile jaundice and 65 samples from apparently healthy individuals were tested by MAT and HA using this environmental saprophytic strain and the results compared with that of Leptospira biflexa semaranga patoc, the standard saprophytic strain commonly employed for sero-diagnosis of leptospirosis. The MAT data showed 96.4 per cent correlation between the two strains. Similarly, the HA results were matching to the extent of 94.5 per cent. Results, therefore, suggest that local saprophytic Leptospira strain may serve as a substitute to serovar patoc for serodiagnosis of leptospirosis.

Antibodies, Bacterial↗

Effect of tonic pain on schedule specific feeding behaviour.

Food deprivation produces analgesia. This response is reversed i.e. pain sensitivity is lowered, when the food deprived rats are fed. In the present study the effect of chronic pain on the motivation to get food, in food deprived rats, was observed. In ten rats the effect of formalin and morphine plus formalin on the motivation to get food was studied. Injection of formalin significantly (P < 0.01) decreased the number of lever presses from 450 +/- 30 to 225 +/- 25. However, after injecting morphine the effect was reversed. The present study shows reduced internal drive to procure food by the food deprived animals, when they were under chronic pain. The effect was blocked by morphine, suggesting the role of opioids in modulating the motivation for getting food.

Animals↗

Mechanism of the aspirin-induced rise in blood alcohol levels.

Aspirin increases blood alcohol levels after post-prandial alcohol consumption in men. This was attributed to a decrease in first pass metabolism secondary to inhibition of gastric alcohol dehydrogenase. Since accelerated gastric emptying, decreased volume of distribution or delayed elimination could also result in higher blood alcohol levels, we investigated the effect of aspirin (1 g taken with a meal) on these parameters. Aspirin did not change the volume of ethanol distribution or the rate of its elimination. Moreover, it did not have a significant effect on gastric emptying. The half-time of 99Tc-DTPA loss was 65.5+/-5.4 minutes without and 71.3+/-6.5, with aspirin. Despite a trend for slower gastric emptying with aspirin, the alcohol bioavailability increased and was associated with a 39% decrease in the first pass metabolism of alcohol (from 106+/-4 to 65+/-19 mg/kg, p<0.05), consistent with the inhibition of gastric ADH activity. In keeping with this interpretation, the effect of aspirin was virtually absent in women, who have a much smaller first pass metabolism available for inhibition by aspirin.

Administration, Oral↗

A sequence-selective single-strand DNA-binding protein regulates basal transcription of the murine tissue inhibitor of metalloproteinases-1 (Timp-1) gene.

Tissue inhibitor of metalloproteinases-1 (TIMP-1) is important in maintaining the extracellular proteolytic balance during tissue remodeling processes. To allow homeostatic tissue turnover, the murine Timp-1 gene is expressed by most cells at a low basal level, and during acute remodeling its transcription is activated by a variety of stimuli. A non-consensus AP-1-binding site (5'-TGAGTAA-3') that is conserved in mammalian timp-1 genes is a critical element in basal and serum-stimulated transcription. We show here that each strand of this unusual AP-1 site binds a distinct single-stranded DNA-binding protein, although neither strand from a perfect consensus AP-1 site from the human collagenase gene shows similar binding. One of the single-strand binding factors, which we term ssT1, binds to a second upstream Timp-1 region between nucleotides -115 and -100. Deletion analysis demonstrated that this region is important in basal but not serum-inducible transcription. The ssT1 factor was 52-54 kDa by UV cross-linking of electrophoretic mobility shift assays and Southwestern blot analysis. Its binding to DNA shows sequence selectivity rather than specificity, with 5'-CT/ATTN((4-6))ATC-3' as a favored motif. Multiple ssT1-like activities were found in nuclear extracts from mouse fibroblasts and rat liver and testis, suggesting that these factors may regulate basal Timp-1 transcription in a tissue-specific fashion.

Animals↗

Ligands for the tyrosine kinase p56lck SH2 domain: discovery of potent dipeptide derivatives with monocharged, nonhydrolyzable phosphate replacements.

p56lck is a member of the src family of tyrosine kinases. Through modular binding units called SH2 domains, p56lck promotes phosphotyrosine-dependent protein-protein interactions and plays a critical role in signal transduction events that lead to T-cell activation. Starting from the phosphorylated dipeptide (2), a high-affinity ligand for the p56lck SH2 domain, we have designed novel dipeptides that contain monocharged, nonhydrolyzable phosphate group replacements and bind to the protein with KD's in the low micromolar range. Replacement of the phosphate group in phosphotyrosine-containing sequences by a (R/S)-hydroxyacetic (compound 8) or an oxamic acid (compound 10) moiety leads to hydrolytically stable, monocharged ligands, with 83- and 233-fold decreases in potency, respectively. This loss in binding affinity can be partially compensated for by incorporating large lipophilic groups at the inhibitor N-terminus. These groups provide up to 13-fold increases in potency depending on the nature of the phosphate replacement. The discovery of potent (2-3 microM), hydrolytically stable dipeptide derivatives, bearing only two charges at physiological pH, represents a significant step toward the discovery of compounds with cellular activity and the development of novel therapeutics for conditions associated with undesired T-cell proliferation.

Crystallography, X-Ray↗