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Biomedical subjects

R Chopra

Publications and source records attributed to R Chopra.

At least 37 records · Page 2Linked to original sources
PubMed2001

Mycotic infections of brain.

Six cases of mycotic infectation of the brain are presented. All the patients were in the age group ranging from 18 years to 38 years. the duration of clinical symptoms varied from 6 days to 7 months. Computerized tomographic visualization of brain revealed a mass lesion in all. Operative findings were suggestive of tumour in 3 cases. All the patients were non-immunocompromised. There was history of previous ear infection and sinusitis in one case. Histopathological examination of biopsy tissue showed dichotomously branching septate fungal hyphae highlighted by special stains like methanamin silver and PAS in all cases.

Adolescent↗
PubMed2000

In vivo CAMPATH-1H prevents graft-versus-host disease following nonmyeloablative stem cell transplantation.

A novel nonmyeloablative conditioning regimen was investigated in 44 patients with hematologic malignancies. The median patient age was 41 years. Many of the patients had high-risk features, including 19 patients with a previous failed transplant. Recipient conditioning consisted of CAMPATH-1H, 20 mg/day on days -8 to -4; fludarabine, 30 mg/m(2) on days -7 to -3; and melphalan, 140 mg/m(2) on day -2. Thirty-six recipients received unmanipulated granculocyte colony-stimulating factor-mobilized peripheral blood stem cells from HLA-identical siblings, and 8 received unmanipulated marrow from matched unrelated donors. GVHD prophylaxis was with cyclosporine A alone for 38 patients and cyclosporine A plus methotrexate for 6 sibling recipients. Forty-two of the 43 evaluable patients had sustained engraftment. Results of chimerism analysis using microsatellite polymerase chain reaction indicate that 18 of 31 patients studied were full-donor chimeras while the other patients were mixed chimeras in one or more lineages. At a median follow-up of 9 months (range 3 to 29 months), 33 patients remain alive in complete remission or with no evidence of disease progression. Seven patients relapsed or progressed post-transplantation, and 4 of them subsequently died. Four patients died of regimen-related complications. There were no cases of grades III-IV acute GVHD. Only 2 patients developed grade II acute GVHD, and only 1 had chronic GVHD. The estimated probability of nonrelapse mortality was 11%. Although longer follow-up is needed to establish the long-term remission rates, this study demonstrates that this nonmyeloablative preparative regimen is associated with durable engraftment, minimal toxicity, and low incidence of GVHD.

Adolescent↗
PubMed2000

Blood stem cells compared with bone marrow as a source of hematopoietic cells for allogeneic transplantation. IBMTR Histocompatibility and Stem Cell Sources Working Committee and the European Group for Blood and Marrow Transplantation (EBMT).

Peripheral blood cells are increasingly used in place of bone marrow as a source of hematopoietic stem cells for allogeneic transplantation. The relative efficacy of these 2 approaches is unknown. This retrospective multivariate analysis compared results of 288 HLA-identical sibling blood stem cell transplantations with results of 536 HLA-identical sibling bone marrow transplantations. No transplants were T-cell depleted. Median follow-up was 12 months, and analyses focused on 1-year outcomes. Recipients of blood stem cell transplants had more rapid recovery of neutrophils to at least 0.5 x 10(9)/L (median time to recovery, 14 days, compared with 19 days for marrow transplants; P <.001) and of platelets to at least 20 x 10(9)/L (median time, 18 days, compared with 25 days for marrow transplants; P <.001). There was no significant difference in the incidence of grades II to IV acute graft versus host disease (GVHD). The incidence of chronic GVHD was significantly higher after blood stem cell transplantation (1-year probability [95% confidence interval], 65% [56%-72%] compared with 53% [47%-59%]; P =.02) Relapse incidence in the 2 transplant groups did not differ significantly. Treatment-related mortality rates were lower and leukemia-free survival rates were higher with blood stem cell transplants in patients with advanced leukemia (acute leukemia in second remission or chronic myelogenous leukemia in accelerated phase) but not in early leukemia (acute leukemia in first remission or chronic myelogenous leukemia in chronic phase). The median time from transplantation to hospital discharge was 23 days after blood stem cell transplantation and 28 days after bone marrow transplantation (P =.003). Further study with longer follow-up is necessary to definitively establish the role of blood stem cells for allogeneic transplantation, especially in patients with good-risk disease. (Blood. 2000;95:3702-3709)

Acute Disease↗
PubMed2000

The structure of an HIV-1 specific cell entry inhibitor in complex with the HIV-1 gp41 trimeric core.

The three-dimensional structure of the complex between an HIV-1 cell-entry inhibitor selected from screening a combinatorial library of non-natural building blocks and the central, trimeric, coiled-coil core of HIV-1 gp41 has been determined by X-ray crystallography. The biased combinatorial library was designed to identify ligands binding in nonpolar pockets on the surface of the coiled-coil core of gp41. The crystal structure shows that the non-peptide moiety of the inhibitor binds to the targeted cavity in two different binding modes. This result suggests a strategy for increasing inhibitor potency by use of a second-generation combinatorial library designed to give simultaneous occupancy of both binding sites.

Anti-HIV Agents↗
PubMed2000

Clonal patterns of X-chromosome inactivation in female patients with aplastic anaemia studies using a novel reverse transcription polymerase chain reaction method.

Conflicting results have been published on the frequency of clonal patterns of X-chromosome inactivation in female patients with aplastic anaemia. Previous studies have used DNA methylation to measure X-inactivation, but aberrant methylation is known to occur in some situations. We have developed a non-radioactive reverse transcription polymerase chain reaction (RT-PCR) method to study expression of the polymorphism at nt. 1311 of the G6PD gene at the RNA level. Using this, and a similar method for the iduronate-2-sulfatase (IDS) gene, we have re-evaluated X-inactivation in AA patients. 32/35 normal individuals showed polyclonal haemopoiesis. Patients with presumed clonal diseases showed both monoclonal and polyclonal patterns, consistent with previous reports. Overall, clonal patterns were observed in granulocytes of 10/26 AA patients (38%), a significantly higher proportion than in controls (p<0.01). Two cases showed discordance between lymphocytes and granulocytes, indicating clonality arising within the myeloid lineage. Eight cases showed clonal patterns in both myeloid and lymphoid cells, indicating the involvement of a pluripotent stem cell. Clonal patterns did not correlate with age, but there appeared to be an association with duration of disease. In PNH patients, CD59-negative cells showed clonal patterns of X-inactivation. In two cases, however, clonal patterns were also detected in CD59-positive cells.

Alleles↗
PubMed2000

Detection of hTERT protein by flow cytometry.

Telomerase is a telomere-specific DNA polymerase consisting of protein and RNA components, which is activated in germline cells and the majority of cancers and serves to counter the consequences of telomere shortening. The protein component, hTERT, is believed to be the catalytic subunit of human telomerase and its expression at the mRNA level correlates well with telomerase activity in vitro. Current techniques for assaying telomerase activity detect only the mean activity in a sample and are unable to isolate specific cell sub-populations. This report describes the development and validation of a cellular, immunofluorescence-based flow cytometry assay that allows detection of intranuclear hTERT while maintaining identifiable cell population characteristics. The assay was shown to be both sensitive to changes in telomerase expression and was semi-quantitative. In both cell line differentiation experiments and in primary cells, a good correlation existed between hTERT expression measured by flow cytometry and telomerase activity detected by the telomeric repeat amplification protocol (TRAP). The method developed offers a quick, simple and reproducible cellular-based assay for hTERT expression. This assay will provide a useful, new tool for future investigations, facilitating the analysis of hTERT expression in mixed cell populations.

Cell Differentiation↗
PubMed2000

Dynamics of telomere shortening in neutrophils and T lymphocytes during ageing and the relationship to skewed X chromosome inactivation patterns.

Human haemopoiesis undergoes profound changes throughout life, resulting in compromised regenerative capacity of haemopoietic stem cells. It has been suggested that telomere shortening results in senescence of haemopoietic stem cell subsets and may influence the balance between stem cell renewal and proliferation. Telomere length and telomerase activity was measured in whole blood leucocytes, neutrophils and T cells from cord blood and individuals aged from 1 year to 96 years. Rapid telomere shortening [700 base pairs (bp)] was demonstrated in the first year of life, followed by a gradual decline of 31 bp/year. T cells were shown to have longer telomeres than neutrophils (mean difference 372 bp, P = < 0.001) but demonstrated similar rates of shortening (20 +/- 0.3 bp/year vs. 22 +/- 0.3 bp/year). Telomerase was detectable in T cells but not in neutrophils, suggesting that telomerase is not the rate-limiting step for regulation of telomere length in haemopoietic cells. Stem cell utilization as measured by X chromosome inactivation patterns was found to be independent of telomere length. This supports the concept that age-dependent skewed haemopoiesis is the result of random stem cell loss or X-allelic exclusion rather than telomeric senescence. These studies provide insight into the ageing process and a reference point for evaluating replicative stress in individuals of different age groups.

Adolescent↗
PubMed2000

Defibrotide for the treatment of hepatic veno-occlusive disease: results of the European compassionate-use study.

Severe hepatic veno-occlusive disease (VOD) is a recognized complication of autologous and allogeneic stem cell transplantation (SCT) that is often fatal. Defibrotide (DF) is a polydeoxyribonucleotide that has been found to have anti-thrombotic, anti-ischaemic and thrombolytic properties without causing significant anticoagulation. Preliminary studies have demonstrated activity for DF in the treatment of VOD, with minimal associated toxicity. In the present study, 40 patients who fulfilled established criteria for VOD were treated with DF on compassionate grounds in 19 European centres; 28 patients met risk criteria predicting progression of VOD and fatality or had evidence of multiorgan failure (MOF), and were defined as 'poor-risk'. DF was commenced intravenously at a median of 14 d (range, -2 d to 53 d) post SCT at doses ranging from 10 to 40 mg/kg. The median duration of therapy was 18 d (range, 2--71 d). Twenty-two patients showed a complete response (CR) (bilirubin < 34.2 micromol/l and resolution of signs/symptoms of VOD and end-organ dysfunction) [CR = 55%, confidence interval (CI) 40--70%] and 17 patients (43%) are alive beyond d +100. Ten poor-risk patients showed a complete response (CR = 36%, CI 21--51%). These results demonstrate that DF is an active treatment for VOD following SCT and a randomized trial is now underway in order to further evaluate its role.

Acute Disease↗
PubMed2000

Mesenchymal stem cells as vehicles for gene delivery.

Mesenchymal stem cells contribute to the regeneration of mesenchymal tissues such as bone, cartilage, muscle, ligament, tendon, adipose, and marrow stroma. Transduction of mesenchymal stem cells from species other than humans is required for the development of disease models in which mesenchymal stem cells-based gene delivery is evaluated. Attempts to transduce mesenchymal stem cells from some species with amphotropic retroviral vectors were unsuccessful, leading to comparative mesenchymal stem cells transductions with xenotropic and gibbon-ape leukemia virus envelope-pseudotyped retroviral vectors. Human, baboon, canine, and rat mesenchymal stem cells were transduced optimally with amphotropic vector supernatants. In contrast, sheep, goat, and pig mesenchymal stem cells showed highest transduction levels with xenotropic retroviral vector supernatant, and rabbit mesenchymal stem cells were transduced optimally with gibbon-ape-enveloped vectors. Using a myeloablative canine transplantation model and gene-marked canine mesenchymal stem cells, the biodistribution of infused and ex vivo expanded mesenchymal stem cells were examined. The majority of transduced canine mesenchymal stem cells were found in the bone marrow samples. The current study shows the use of mesenchymal stem cells as a delivery vehicle for gene transfer studies, and validates the feasibility of delivering mesenchymal stem cells to the marrow compartment for stromal regeneration after cancer-associated cytotoxic therapies.

Animals↗
PubMed2000

Feasibility of linear arrays for interstitial ultrasound thermal therapy.

The feasibility of linear array transducers for interstitial ultrasound thermal therapy was evaluated. Theoretical acoustic power distributions were used to calculate spatial heating patterns using the bioheat transfer equation. The spatial heating patterns of linear array and single element planar rectangular transducers were compared. Scanned heating with both transducer geometries produced asymmetric heating volumes; however, a more uniform radial temperature profile with a sharper margin was achieved with linear arrays. Single element transducers produced excessive heating near the probe surface. Homogeneous blood flow is predicted to reduce the mean temperature within the heated region, with little effect on the spatial pattern.

Biophysical Phenomena↗
PubMed2000

Epistaxis: a review.

Epistaxis, being the commonest ear, nose and throat (ENT) emergency requiring hospital admission, is clearly an important condition--not only to the specialist but also to any general practitioner. This short review looks at the aetiology, associated clinical considerations (especially those of hypertension and hypoxaemia) and evolution of its management. Herein is also suggested a methodical and systematic approach to treating the disorder, both at the level of the accident and emergency department and at that of in-patient care. The patient with epistaxis of a refractory nature is included, too--along with a selection of the options available for treatment.

Cautery↗
PubMed2000

'Glue ear' in perspective.

Contrary to common perception 'glue ear' is a vast and complex subject. It is the most common cause of hearing loss in children; its treatment is often questioned and involves utilisation of substantial health service resources. This article is aimed not only at placing the condition in perspective but also at establishing a short yet comprehensive understanding of its many aspects including aetiology and management. There is no intention, however, to dwell here excessively upon its intricacies and abstrusities.

Child↗
PubMed1999

Lithium prophylaxis of recurrent bipolar affective disorder: long-term outcome and its psychosocial correlates.

BACKGROUND: Discrepancy between efficacy of prophylactic lithium and its effectiveness in ordinary clinical practice necessitates long-term follow-up data from specialised lithium clinics. Also, role of psychosocial factors in influencing the outcome is unclear. METHODS: One hundred and eighteen patients of bipolar affective disorder attending a lithium clinic were followed-up for approximately 11 years (range 2-27 years). Demographic and clinical data, measures of social support and psychosocial stress were obtained at the intake in 1989-1990. Study design combined retrospective chart-review (till the time of intake) with prospective follow-up till July 1995. RESULTS: On lithium, the patients had a mean of 0.43 relapses per year (manic, 0.26; depressive, 0.17) which was significantly less (p < 0.01) than the pre-lithium episode frequency. The figure for entirely relapse-free patients was 24%, and 62% had relapses up to one episode per year (median = 0.3 per year). Fifty-eight (49%) patients were good responders to lithium (relapses < or = 0.30 per year). In comparison to good responders, partial/poor responders had a significantly greater number of pre-lithium depressive episodes, poor lithium compliance, more psychosocial stress and lower social support at intake. These variables correlated well with relapses and explained 32% of the variance of the data. CONCLUSIONS: Lithium had a definite prophylactic effect on long-term outcome. Social support and stressful life events are significant correlates of response to lithium. CLINICAL IMPLICATIONS: Lithium prophylaxis of bipolar affective disorders seems justified though psychosocial factors appear to modulate its effectiveness. LIMITATIONS: Other psychotropic medications were used during relapse and the assessment of psychosocial factors was cross-sectional.

Adolescent↗
PubMed1999

Elevated growth of Saccharomyces cerevisiae ATH1 null mutants on glucose is an artifact of nonmatching auxotrophies of mutant and reference strains.

Yeast strains disrupted for ATH1, which encodes vacuolar acid trehalase, have been reported to grow to higher cell densities than reference strains. We showed that the increase in cell density is due to the URA3 gene introduced as a part of the disruption and concluded that the misinterpretation is a result of not using a control strain with matching auxotrophic markers.

Culture Media↗
PubMed1999

Mixed germ cell tumour of the pineal region: a case report.

An intracranial mixed germ cell tumour with germinoma and teratoma components is reported. The patient presented with parinaud's syndrome and precocious puberty. The treatment involved partial surgical debulking followed by whole brain radiotherapy (4500 cGY in 25 fraction over 5 weeks) and chemotherapy (consisting of cisplatin and etoposide). Post treatment MRI showed no residual lesion. The controversies in the management are discussed.

Adolescent↗
PubMed1999

Locality commissioning: how much influence have general practitioners really had?

This paper investigates the various models of locality commissioning in relation to the participation of general practitioners (GPs), and explores the perceived successes of locality commissioning in the 15 health boards in Scotland and 13 health authorities in the Northern and Yorkshire Region of England. A postal questionnaire was sent to 190 individuals involved in commissioning, and semi-structured interviews with GPs (n = 31) and health authority managers (n = 41) were undertaken in each of the 28 health authorities. Seventy-five per cent of the health authorities had introduced some form of locality commissioning. Five types of locality commissioning organization were identified on the basis of the level of GP influence over decisions. All GP responders identified benefits resulting from their involvement in the process but only 27% of health authority responders did so. Most benefits related to improved professional relationships, not to service changes. On the whole, locality commissioning does not appear to have resulted in major changes to contracts or services.

England↗