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Biomedical subjects

S Sharma

Publications and source records attributed to S Sharma.

At least 577 records · Page 32Linked to original sources

Patient perceptions of quality-of-life associated with bilateral visual loss.

PURPOSE: To ascertain whether patients with unilateral visual loss to a specific level are able to approximate the degree of impairment of quality-of-life experienced by patients with bilateral visual loss to the same level. METHODS: One hundred thirty-three study group patients with (1) visual loss to 20/40 or worse in at least one eye, and (2) a marked difference between the visual acuities in their two eyes, were polled using the time tradeoff method of utility value measurement. All patients were asked to assume that the visual acuity in both of their eyes was as poor as the visual acuity in their worst seeing eye. These utility values were then compared to those obtained from a control group of 173 patients with known utility values who had similar bilateral visual loss. Both the study and control groups were stratified into 4 levels of visual loss (20/40 to 20/50, 20/60 to 20/100, 20/200 to 20/400, and counting fingers to light perception). RESULTS: Mean utility values for the study group ranged from 0.47 to 0.71. Patients with unilateral visual loss, given the assumption of bilateral visual loss to the same degree, routinely demonstrated no significant difference in utility preferences as compared to patients with true bilateral visual loss to the same level. CONCLUSIONS: Patients with unilateral visual loss can very accurately estimate the degree of impairment of quality-of-life that would result if visual loss to a similar degree occurred in the remaining eye with better vision.

Activities of Daily Living↗

Ca2+/calmodulin dependent protein kinase from Mycobacterium smegmatis ATCC 607.

A soluble Ca2+/calmodulin dependent protein kinase has been partially purified (approximately 400 fold) from Mycobacterium smegmatis ATCC 607 using several purification steps like ammonium sulphate precipitation (30-60%), Sepharose CL-6B gel filtration, DEAE-cellulose and finally calmodulin-agarose affinity chromatography. On SDS-PAGE, this enzyme preparation showed a major protein band of molecular mass 35 kD and its activity was dependent on calcium, calmodulin and ATP when measured under saturating histone IIs (exogenous substrate) concentration. Phosphorylation of histone IIs was inhibited by W-7 (calmodulin inhibitor) and KN-62 (CaM-kinase inhibitor) with IC50 of 1.5 and 0.25 microm respectively, but was not affected by inhibitors of PKA (Sigma P5015) and PKC (H-7). All these results confirm that purified enzyme is Ca2+/calmodulin dependent protein kinase of M. smegmatis. The protein kinase of M. smegmatis demonstrated a narrow substrate specificity for both exogenous as well as endogenous substrates. These results suggest that purified CaM-kinase must be involved in regulating specific function(s) in this organism.

Adenosine Triphosphate↗

Psychological well-being among cancer patients receiving radiotherapy--a prospective study.

The impact of cancer on the psychological well-being of newly diagnosed cancer patients before and during the course of radiotherapy was assessed in 70 consecutive cancer patients. Most of the patients were over 40 years of age, women, illiterate and from a lower socioeconomic group. During the course of treatment there was a decrease in the well-being scores on some dimensions such as perceived family and primary group support. Improvements were seen in the dimensions of positive feelings, coping, social support other than the family and spiritual well-being. There were no changes in the dimensions of negative feelings and perceived ill-health. The results give a profile on well-being and the changes observed during radiotherapy.

Adaptation, Psychological↗

Crystal structure of GyrA intein from Mycobacterium xenopi reveals structural basis of protein splicing.

Several genes from prokaryotes and lower eukaryotes have been found to contain an in-frame open reading frame, which encodes for an internal protein (intein). Post-translationally, the internal polypeptide auto-splices and ligates the external sequences to yield a functional external protein (extein) and an intein. Most, but not all inteins, contain, apart from a splicing domain, a separate endonucleolytic domain that enables them to maintain their presence by a homing mechanism. We report here the crystal structure of an intein found in the gyrase A subunit from Mycobacterium xenopi at 2.2 A resolution. The structure contains an unusual beta-fold with the catalytic splice junctions at the ends of two adjacent antiparallel beta-strands. The arrangement of the active site residues Ser 1, Thr 72, His 75, His 197, and Asn 198 is consistent with a four-step mechanism for the cleavage-ligation reaction. Using site-directed mutagenesis, the N-terminal cysteine, proposed as the nucleophile in the first step of the splicing reaction, was changed to a Ser 1 and Ala 0, thus capturing the intein in a pre-spliced state.

Amino Acid Sequence↗

Secretory acetylcholinesterase of Setaria cervi microfilariae and its antigenic cross-reactivity with Wuchereria bancrofti.

Setaria cervi, a bovine filarial parasite, secretes acetylcholinesterase during in vitro cultivation. A significant amount of enzyme activity was detected both in culture media and somatic extracts of different developmental stages of the parasite. The microfilarial stage showed a higher level of AChE activity than adult worms, with females being considerably more active than males. The secretory enzyme from microfilariae preferentially utilized acetylthiocholine iodide as substrate and showed two electrophoretically distinct isoforms in native PAGE. Secretory enzyme was purified from the excretory/secretory products of microfilariae using edrophonium chloride linked to epoxy-activated sepharose. Analysis of purified acetylcholinesterase by SDS-PAGE revealed the existence of two proteins of 75kD and 45kD under nonreducing conditions. These secretory enzymes are antigenic and cross-reactive with Wuchereria bancrofti-infected asymptomatic microfilaraemic human sera when tested by enzyme linked immunosorbent assay and immunoblotting. The secretory AChE(s) from S. cervi microfilariae may be utilized for diagnosis of early filarial infections.

Acetylcholinesterase↗

A Hindi version of the Diagnostic Interview for Genetic Studies.

The validity of a Hindi version of the Diagnostic Interview for Genetic Studies (DIGS) was investigated. The original English version was initially translated into Hindi. The Hindi version was then back-translated and compared with the original. Next, a group of psychiatric inpatients and outpatients were interviewed using the Hindi version. The resultant diagnoses were compared with those obtained for the same patients using a Hindi version of the Present State Examination (PSE), and the clinical diagnoses given by the treating psychiatrists. The DIGS diagnoses were significantly correlated with both the PSE diagnoses (Cohen's kappa = 0.80) and the clinical diagnoses (kappa = 0.56). Interrater reliability between three interviewers for diagnoses obtained using the Hindi version of the DIGS varied (kappa = 0.45-1.00). Possible causes for this variability are discussed. The Hindi version of the DIGS fulfills the need for a current comprehensive interview schedule not only for psychiatric genetic research in India, but also for nongenetic research.

Adult↗

Antiproliferative effects of recombinant human bone morphogenetic protein-2 on human tumor colony-forming units.

Bone morphogenetic protein-2 (BMP-2) is a differentiation factor for normal osteoblasts. BMP-2 is structurally related to transforming growth factor-beta which inhibits cell proliferation and enhances apoptosis. A recent study has shown the presence of BMP-2 receptors on several cancer cell lines. In this study, we attempted to determine if recombinant human BMP-2 (rhBMP-2) can modulate the proliferation of human tumor colony-forming units taken from 113 patients. Tumor cells were cultured in soft agar and continuously exposed to three concentrations of rhBMP-2 (10, 100 and 1000 ng/ml) for 14 days in the capillary cloning system. There were 65 evaluable specimens, including 17 breast cancers, 15 ovarian cancers, 14 non-small cell lung cancers and five prostate cancers. Importantly, rhBMP-2 did not stimulate the tumor cell proliferation. A significant inhibition (50% or less survival of tumor colony-forming units) was seen in 16 of 65 specimens (24.6%) at 1000 ng/ml, including five of 14 non-small cell lung cancers, five of 17 breast tumors and two of 15 ovarian tumors. A concentration-response relationship was observed (p<0.001 by Mantel-extension test). The results of this study encourage further evaluation of the antiproliferative effects of rhBMP-2 against human cancers.

Bone Morphogenetic Protein 2↗

Clinicomicrobiological review of Nocardia keratitis.

PURPOSE: To present the clinical profile, laboratory results, and outcome of treatment in 16 patients with Nocardia keratitis. METHODS: A retrospective review of 16 culture-proven cases of Nocardia keratitis was done. Clinical and microbiologic data were analyzed. RESULTS: Nocardia constituted 1.7% of laboratory-confirmed bacterial keratitis and was seen predominantly in male subjects (13 of 16) with a mean age of 39.1 years. Although the predisposing factor was unknown in the majority, a definite history of trauma was present in four (25%) cases. Patchy stromal infiltrates were seen in 12 patients. Wreath pattern of infiltrates (six of 16) and hypopyon (nine of 16) were notable features. Nocardia was detectable in corneal scrapings of 10 patients with Gram stain and all patients with 1% acid-fast preparation (six of six). Nocardia asteroides was the causative agent in all except one (N. caviae). All isolates were sensitive to gentamicin; however, topical 30% sulfacetamide was the preferred drug for treatment. Favorable outcome (healed scar) was achieved in 11. CONCLUSION: Although Nocardia keratitis is a rare condition, a high index of clinical suspicion should be kept in agricultural workers or in patients with trauma who have patchy stromal infiltrates. Sulfonamides are the initial drug of choice, and gentamicin could be an effective alternative. If recognized early, Nocardia keratitis responds to medical treatment with good visual recovery.

Administration, Topical↗

Role of in vivo proton magnetic resonance spectroscopy in the diagnosis and management of brain abscesses.

OBJECTIVE: In vivo proton magnetic resonance spectroscopy was performed for 24 patients with pyogenic brain abscesses, to examine the consistency of the spectral patterns and to observe the changes in metabolites with treatment. METHODS: Localized proton spectra were obtained from 4- to 8-ml volumes in the abscesses, using stimulated echo acquisition mode and spin echo sequences. Twenty-two patients were treated with combined surgical and medical therapy, and two patients were treated conservatively. High-resolution magnetic resonance spectroscopy was performed for 15 samples of abscesses obtained from these patients, to confirm the assignments of resonances seen in vivo. Postaspiration studies were performed for 12 patients treated with combined medical and surgical therapy and 2 patients treated medically. RESULTS: Lactate and amino acids were seen in spectra for all patients, irrespective of the time of spectroscopy after the onset of combined medical and surgical therapy. Acetate and pyruvate disappeared after 1 week of combined treatment. CONCLUSION: It was concluded that spectral patterns for brain abscesses are consistent and specific and can assist in the noninvasive diagnosis of abscesses. Responses to combined treatment could be monitored by showing the changes in metabolite patterns in serial spectroscopic studies.

Adolescent↗

Mycosis fungoides metastasizing to the brain parenchyma: case report.

OBJECTIVE AND IMPORTANCE: Mycosis fungoides is a rare T-cell lymphoma of the skin that can, in one-half to three-quarters of patients suffering from this disease, involve the viscera in late stages of the disease. Although autopsy series performed more than 2 decades ago showed that the incidence of metastatic mycosis fungoides to the central nervous system is approximately one of seven, a total of only several dozen cases have been reported to date. As compared to meningeal involvement, intraparenchymal metastases are even rarer. We describe a biopsy-proven case of intraparenchymal central nervous system mycosis fungoides in a patient with nonprogressive skin involvement and no detectable visceral involvement, and we present a review of the relevant literature. CLINICAL PRESENTATION: A 68-year-old man, 3 years after the diagnosis of his skin disease, developed fatigue, confusion, and frontal lobe signs without the presence of cerebriform cells in the peripheral blood or any other clinical evidence of visceral involvement. Magnetic resonance imaging revealed a diffuse area of increased T2-weighted signal involving the white matter of both cerebral hemispheres as well as a focal area of T2 abnormality along the body of the corpus callosum. The radiological differential diagnosis was either leukodystrophy caused by chemotherapy, progressive multifocal leukoencephalopathy, or glioma with associated white matter changes. INTERVENTION: A stereotactic serial brain biopsy revealed diffuse perivascular infiltrates of atypical lymphocytes, as well as several large cells with cerebriform nuclei consistent with mycosis fungoides. The cells were immunoreactive for LCA, MT1, UCHL1, and CD3. CONCLUSION: We stress the importance of including mycosis fungoides as part of the differential diagnosis for a brain lesion in patients with cutaneous T-cell lymphoma, because treatments do exist, and we conclude that a serial stereotactic biopsy may be necessary to provide a definitive diagnosis.

Aged↗

Seroprevalence of Helicobacter pylori infection in Nepal: low prevalence in an isolated rural village.

OBJECTIVE: To determine the seroprevalence of Helicobacter pylori infection in Nepal. DESIGN: H. pylori infection was identified using a specific and sensitive enzyme-linked immunosorbent assay for anti-H. pylori immunoglobulin G. STUDY POPULATION: Serum samples were collected from 1142 inhabitants (age range 4-93 years) from two villages: Kotyang, a rural isolated village (250 men, 210 women) and Bhadrakali, a suburban village of Kathmandu (334 men, 348 women). RESULTS: The overall prevalence of H. pylori infection was 56.8%, while significantly higher prevalence was found in the suburban village (Bhadrakali; 67.2%) than in the rural village (Kotyang; 41.5%). This difference was generally reflected by the infection rate in the 10-14-year-old age-group (Bhadrakali, 60% compared with Kotyang, 22.2%). The prevalence of infection significantly increased with age, while no significant difference was found in the prevalence of infection by gender. There was no difference in H. pylori positivity between individuals with and without upper abdominal symptoms in both villages. CONCLUSION: There was a significant regional difference in the seroprevalence of H. pylori within Nepal, which showed lower prevalence in an isolated rural village. This difference was mainly caused by the different acquisition rate in teenagers, thus indicating that the teenage lifestyle of this particular environment seemed to be the major determinant in the acquisition of H. pylori infection in the population.

Adolescent↗

The systemic evaluation of acute retinal artery occlusion.

Acute retinal arterial occlusion is an ophthalmic condition that is associated with a high prevalence of systemic disease. Recent studies have demonstrated that significant numbers of patients with acute retinal arterial occlusion have both hemodynamically significant carotid artery stenosis and cardiac pathology that necessitates systemic therapy. Furthermore, emerging evidence show that coagulopathies and hyperhomo-cysteinemia may be responsible for acute retinal arterial occlusion. In this paper, we review recent scientific evidence that supports that adoption of specific guidelines for the systemic evaluation of acute retinal arterial occlusion.

Acute Disease↗

T wave complexity in patients with hypertrophic cardiomyopathy.

The complexity of the T wave assessed by principal component analysis (PCA) has been proposed to reflect abnormal repolarization, which may be arrhythmogenic. To determine whether PCA can differentiate patients with hypertrophic cardiomyopathy (HCM) from normal subjects and whether PCA is of prognostic importance in HCM, 112 patients with HCM (41 +/- 14 years, 64 males) and 72 healthy subjects (39 +/- 9 years, 41 males) were studied. Patients with sinus node dysfunction, AV conduction block, flat T waves, QRS > 140 ms, and those < 15 years were excluded from this study. Standard 12-lead ECGs were recorded digitally using the MAC-VU system (Marquette Medical Systems). PCA parameters were computed using the QT Guard software package by Marquette. PCA ratio was significantly greater in HCM patients than in normal controls (23.9% +/- 12.4% vs 16.1% +/- 7.6%, P < 0.0001) and was correlated with QT-end dispersion (r = 0.24, P = 0.01) and QT peak (Q point to T peak) dispersion (r = 0.35, P < 0.0001). HCM patients with syncope (n = 23) had increased PCA ratios compared with those without syncope (29.1% +/- 11.5% vs 22.5% +/- 12.3%, P = 0.01). PCA ratio was similar in patients with and without nonsustained ventricular tachycardia on Holter (25.9% +/- 11.4% vs 22.7% +/- 12.1%, P = 0.2), as well as in patients treated with amiodarone or sotalol versus those not on therapy. In conclusion, assessment of the complexity of the T wave by PCA differentiates HCM patients from normal subjects. PCA ratio correlated with QT dispersion and an increased PCA ratio was associated with a history of syncope in HCM.

Adult↗

Detection and confirmation of Mycoplasma pneumoniae in urogenital specimens by PCR.

Following the isolation of Mycoplasma pneumoniae from urogenital specimens (M. Goulet, R. Dular, J. G. Tully, G. Billows, and S. Kasatiya, J. Clin. Microbiol. 33:2823-2825, 1995), a study was undertaken to confirm the observations by PCR. Specific primers directed to the P1 adhesin gene of M. pneumoniae were used. A total of 300 genital specimens were tested for M. pneumoniae and Mycoplasma genitalium by culture and PCR. Of these, 15 were positive by culture and 17 were positive by PCR for M. pneumoniae. No M. genitalium was detected in any of the specimens by either method. The present study demonstrates that PCR is sensitive and rapid compared to cumbersome culture methods and can be used to detect M. pneumoniae in urogenital specimens in a routine diagnostic laboratory.

Adolescent↗

Accuracy of visible retinal emboli for the detection of cardioembolic lesions requiring anticoagulation or cardiac surgery. Retinal Emboli of Cardiac Origin Study Group.

AIM: To determine the accuracy of visible retinal emboli as a diagnostic "test" for the likelihood of receiving anticoagulation or cardiac surgery based on the results of transthoracic echocardiography, in the setting of acute retinal arterial occlusion. METHODS: A multicentre retrospective diagnostic study at Kingston Eye Centre, Queen's University, Kingston, Ontario; Wills Eye Hospital, Philadelphia; Ottawa Eye Institute, Ottawa, Ontario; and the Halifax Infirmary, Halifax, Nova Scotia of 104 patients with both embolic and nonembolic acute retinal arterial obstruction who underwent transthoracic echocardiography was performed, to determine the accuracy of visible retinal emboli as a diagnostic "test" for anticoagulation or cardiac surgery. Anticoagulation or surgical intervention on the basis of abnormalities was detected solely through the technology of transthoracic echocardiography. RESULTS: 41 patients had visible retinal emboli (calcific, cholesterol, or fibrin). The remaining 63 had no evidence of embolic disease. The sensitivity of emboli for the likelihood of a patient receiving anticoagulation or cardiac surgery was 50%. The specificity, positive predictive value, and negative predictive value were 62%, 15%, and 90%, respectively. The likelihood ratio (LR = 1.31) obtained given the presence of a visible retinal embolus was neither clinically nor statistically significant (LR+ve = 1.31; 95% CI (0.91, 3.16)). This likelihood ratio, when applied to a patient with a pretest probability of 50%, results in a post-test probability of 56.7%. CONCLUSIONS: These results demonstrate that the presence of a visible retinal embolus should not be the sole determinant of whether to order transthoracic echocardiography, as the likelihood ratio for a patient receiving anticoagulation or cardiac surgery, given the presence of a visible retinal embolus was only 1.31.

Anticoagulants↗

Cardiopulmonary responses to exercise in patients with hypertrophic cardiomyopathy.

OBJECTIVE: To examine the submaximal and maximal indices of the exercise response of patients with hypertrophic cardiomyopathy. DESIGN AND SETTING: Prospective examination of cardiopulmonary responses to ramp exercise test of a consecutive group of patients with hypertrophic cardiomyopathy attending a cardiomyopathy outpatient clinic. METHODS: 50 patients aged 12 to 76 years (mean (SD) 35 (14)) with diagnosis of hypertrophic cardiomyopathy performed incremental cycle ergometry; 22 sedentary volunteers (seven female, 15 male) aged 14 to 58 years (mean (SD) 31 (12)) served as controls. Respiratory gas was continuously sampled from the mouth-piece, and its concentration profile phase aligned to the respired air flow signals. Following analogue to digital conversion, gas exchange variables were computed breath by breath and the data were averaged every 30 seconds for graphic display. A 12 lead ECG was monitored continuously and recorded every three minutes during the exercise. RESULTS: Both the peak oxygen uptake attained on the test (VO2 peak) and anaerobic threshold were reduced in patients with hypertrophic cardiomyopathy compared with the control group (p < 0.0001). In 29 patients (59%) the VO2 peak was less than 60% and only two patients achieved a peak above 80% of their predicted values. The anaerobic threshold was below 60% of the predicted value in 31 patients and above 80% in only three patients. The slope of oxygen uptake/work rate relation (delta VO2/delta WR) was decreased in 16 patients (32%). The maximum oxygen pulse (VO2/HR) was reduced as a percentage of the predicted value, and became flat at high work rates in 32 patients. There was a significant correlation between anaerobic threshold and VO2 peak (p < 0.0001), work efficiency (p < 0.0001), and maximum oxygen pulse (p < 0.0001). The slope of change in ventilation against change in carbon dioxide output (delta VE/delta VCO2) for the subanaerobic threshold range was increased in 36 patients (72%) and was inversely correlated with anaerobic threshold (p < 0.0002). CONCLUSIONS: There were severe abnormalities in maximal and submaximal indices of pulmonary gas exchange in a cohort of hypertrophic cardiomyopathy patients attending a referral cardiovascular clinic. The pattern of the abnormalities suggests that a reduced stroke volume response, ventilation/perfusion mismatch, and abnormal peripheral oxygen utilisation are the possible mechanisms of exercise intolerance.

Adolescent↗