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Biomedical subjects

R Malhotra

Publications and source records attributed to R Malhotra.

At least 37 records · Page 2Linked to original sources
PubMed2003

A consideration of the time taken to do dacryo-cystorhinostomy (DCR) surgery.

PURPOSE: Comparison of surgical times for dacryocystorhinostomy (DCR) by three different approaches: (1) external, (2) endoscopic endonasal surgical (EES), and (3) endoscopic endonasal laser (EEL) using the holmium:YAG laser. The merits and limitations of each approach are considered and surgical throughput predicted. METHODS: Prospective study of adult patients undergoing primary DCR surgery for nasolacrimal duct obstruction. Surgical times were recorded. Subjective and objective outcomes were assessed at a minimum of 6 months. RESULTS: A total of 48 patients undergoing 51 DCR procedures were studied. The mean surgical time for primary external (n=20), EES-DCR (n=16), and EEL-DCR (n=15) was 41.1+/-10.3, 39.6+/-13.8, and 20.9+/-7.8 min, with symptomatic success achieved in 95, 88, and 60%, respectively. Follow-up was 6-36 months, mean 8 months. It was calculated that if six EEL-DCR, four EES-DCR, or three external DCRs are performed per list for 45 lists per annum, this equals a total of 270 EEL-DCR, 180 EES-DCR, and 135 external DCRs. Of these, 108 EEL-DCR, 22 EES-DCR, and seven external DCRs will fail. If 75% of these have redo surgery using the same technique, an extra 13.5 (EEL-DCR), four (EES-DCR), and two (external DCR) lists are needed. CONCLUSIONS: There was no significant difference between the time taken to do EES-DCR compared to external DCR, and their clinical outcomes. Only EEL-DCR was significantly faster (P<0.001). However, its lower success rate negates the apparent benefit from the greater surgical throughput.

Adolescent↗
PubMed2003

The effectiveness of screening for diabetic retinopathy by digital imaging photography and technician ophthalmoscopy.

AIMS: To evaluate the introduction of a community-based non-mydriatic and mydriatic digital photographic screening programme by measuring the sensitivity and specificity compared with a reference standard and assessing the added value of technician direct ophthalmoscopy. METHODS: Study patients had one-field, non-mydriatic, 45 degrees digital imaging photography prior to mydriatic two-field digital imaging photography followed by technician ophthalmoscopy. Of these patients, 1549 were then examined by an experienced ophthalmologist using slit lamp biomicroscopy as a reference standard. The setting was general practices in Gloucestershire. Patients were selected by randomizing groups of patients (from within individual general practices) and 3611 patients were included in the study. Patients for reference standard examination were recruited from groups of patients on days when the ophthalmologist was able to attend. The main outcome measure was detection of referable diabetic retinopathy (DR) as defined by the Gloucestershire adaptation of the European Working Party guidelines. RESULTS: For mydriatic digital photography, the sensitivity was 87.8%, specificity was 86.1% and technical failure rate was 3.7%. Technician ophthalmoscopy did not alter these figures. For non-mydriatic photography, the sensitivity was 86.0%, specificity was 76.7% and technical failure rate was 19.7%. CONCLUSIONS: Two-field mydriatic digital photography is an effective method of screening for referable diabetic retinopathy. Non-mydriatic digital photography has an unacceptable technical failure rate and low specificity.

Adolescent↗
PubMed2003

Comparison of two reference standards in validating two field mydriatic digital photography as a method of screening for diabetic retinopathy.

AIM: To compare two reference standards when evaluating a method of screening for referable diabetic retinopathy. METHOD: Clinics at Oxford and Norwich Hospitals were used in a two centre prospective study of 239 people with diabetes receiving an ophthalmologist's examination using slit lamp biomicroscopy, seven field 35 mm stereophotography and two field mydriatic digital photography. Patients were selected from those attending clinics when the ophthalmologist and ophthalmic photographer were able to attend. The main outcome measures were the detection of referable diabetic retinopathy as defined by the Gloucestershire adaptation of the European Working Party guidelines. RESULTS: In comparison with seven field stereophotography, the ophthalmologist's examination gave a sensitivity of 87.4% (confidence interval 83.5 to 91.5), a specificity of 94.9% (91.5 to 98.3), and a kappa statistic of 0.80. Two field mydriatic digital photography gave a sensitivity of 80.2% (75.2 to 85.2), specificity of 96.2% (93.2 to 99.2), and a kappa statistic of 0.73. In comparison with the ophthalmologist's examination, two field mydriatic digital photography gave a sensitivity of 82.8% (78.0 to 87.6), specificity of 92.9% (89.6 to 96.2), and a kappa statistic of 0.76. Seven field stereo gave a sensitivity of 96.4% (94.0 to 98.8), a specificity of 82.9% (77.4 to 88.4), and a kappa statistic of 0.80. 15.3% of seven field sets, 1.5% of the two field digital photographs, and none of the ophthalmologist's examinations were ungradeable. CONCLUSION: An ophthalmologist's examination compares favourably with seven field stereophotography, and two field digital photography performs well against both reference standards.

Adult↗
PubMed2002

Psychiatric morbidity in vitiligo: prevalence and correlates in India.

BACKGROUND: Vitiligo, a common pigmentary disorder, is recognized to be associated with a high psychiatric morbidity, yet compared to other dermatological disorders like leprosy, psoriasis, etc., it has not been subjected to detailed evaluation of its psychological consequences. The data from the developing countries on this aspect in particular is meager. METHODS: One hundred and thirteen cases with vitiligo were evaluated along with 55 healthy controls comparable for sociodemographic profile and matched on attitude to appearance scale. Clinical details, impact of illness, associated dysfunction and psychological morbidity were additionally assessed. RESULTS: Twenty-eight patients with vitiligo were found to have psychiatric morbidity, a clinic prevalence rate of 25% (95% confidence interval 20.3-29.3%). The majority of the cases had a diagnosis of adjustment disorder. Psychiatric morbidity was significantly correlated with dysfunction arising out of illness. CONCLUSIONS: Vitiligo is associated with high psychiatric morbidity. There is a need to develop cross-cultural database on psychosocial aspects and psychiatric morbidity associated with vitiligo.

Adjustment Disorders↗
PubMed2002

Health care seeking pattern of tuberculosis patients attending an urban TB clinic in Delhi.

The study of pattern of health care seeking of tuberculosis patients is important for identification of factors which might influence delayed reporting of tuberculosis cases, especially the open pulmonary cases. Consecutive 301 pulmonary TB patients, belonging to any of the categories under RNTCP, diagnosed at New Delhi Tuberculosis Centre or its sub-centres over a six-month period were assessed for health care seeking pattern. "Delay" was defined as the time over 3 weeks that a case took to report to the area TB facility. 43.2% patients reported to the TB health facility on their own and others were referred by government hospitals (34.9%) and general practitioners (21.9%). Median delay over 3 weeks was 2.69 weeks for all three categories combined, with a significantly higher delay (3.41 weeks) for retreatment cases as compared to new cases (2.13 weeks). No significant differences were observed in health seeking delay in relation to sex, income, literacy status and source of referral and sputum status. Extensive health education activities can reduce this period of delay in health seeking and result in reduction of transmission of tuberculosis to healthy members of the family and community.

Adult↗
PubMed2001

Chaos and stability of the solar system.

Over the last two decades, there has come about a recognition that chaotic dynamics is pervasive in the solar system. We now understand that the orbits of small members of the solar system-asteroids, comets, and interplanetary dust-are chaotic and undergo large changes on geological time scales. Are the major planets' orbits also chaotic? The answer is not straightforward, and the subtleties have prompted new questions.

Journal Article↗
PubMed2001

Mammalian plasma membrane ecto-nucleoside triphosphate diphosphohydrolase 1, CD39, is not active intracellularly. The N-glycosylation state of CD39 correlates with surface activity and localization.

CD39 is a member of the membrane-bound ecto-nucleoside triphosphate diphosphohydrolase family. The active site for native CD39 is located on the outer surface of the cellular plasma membrane; however, it is not yet known at what stage this enzyme becomes active along the secretory pathway to the plasma membrane. In this study, sucrose density fractionations performed on CD39-transfected COS-7 cell membranes suggest that CD39 activity resides primarily in the plasma membrane. Furthermore, we have created recombinant, soluble versions of CD39, one that is secreted and others that are retained in the endoplasmic reticulum, to demonstrate that CD39 is not active until it reaches the plasma membrane both in yeast and COS-7 cells. Moreover, the secreted active soluble CD39 in COS-7 cells is found to receive a higher degree of N-glycan addition than the inactive form retained intracellularly. When COS-7 cells were treated with tunicamycin to prevent N-glycosylation, soluble CD39 was not detected in the extracellular medium and remained inactive intracellularly. Surface biotinylation analysis also revealed that surface-expressed wild type CD39 receives a higher degree of N-glycosylation than intracellular forms and that inhibition of N-glycosylation prevents its plasma membrane localization. In addition, both intact and digitonin-permeablized COS-7 cells transfected with CD39 possess similar ecto-ATPase activities, further supporting the conclusion that only surface-expressed CD39 is enzymatically active. All of these data suggest that intracellular CD39 is inactive and that only a fully glycosylated CD39 has apyrase activity and is localized at the cell surface.

Acid Anhydride Hydrolases↗
PubMed2001

Characterization of sodium channel alpha- and beta-subunits in rat and mouse cardiac myocytes.

BACKGROUND: Sodium channels isolated from mammalian brain are composed of alpha-, beta(1)-, and beta(2)-subunits. The composition of sodium channels in cardiac muscle, however, has not been defined, and disagreement exists over which beta-subunits are expressed in the myocytes. Some investigators have demonstrated beta(1) expression in heart. Others have not detected any auxiliary subunits. On the basis of Northern blot analysis of total RNA, beta(2) expression has been thought to be exclusive to neurons and absent from cardiac muscle. METHODS AND RESULTS: The goal of this study was to define the subunit composition of cardiac sodium channels in myocytes. We show that cardiac sodium channels are composed of alpha-, beta(1)-, and beta(2)-subunits. Nav1.5 and Nav1.1 are expressed in myocytes and are associated with beta(1)- and beta(2)-subunits. Immunocytochemical localization of Nav1.1, beta(1), and beta(2) in adult heart sections showed that these subunits are expressed at the Z lines, as shown previously for Nav1.5. Coexpression of Nav1.5 with beta(2) in transfected cells resulted in no detectable changes in sodium current. CONCLUSIONS: Cardiac sodium channels are composed of alpha- (Nav1.1 or Nav1.5), beta(1)-, and beta(2)-subunits. Although beta(1)-subunits modulate cardiac sodium channel current, beta(2)-subunit function in heart may be limited to cell adhesion.

Animals↗
PubMed2001

Centrosome defects can account for cellular and genetic changes that characterize prostate cancer progression.

Factors that determine the biological and clinical behavior of prostate cancer are largely unknown. Prostate tumor progression is characterized by changes in cellular architecture, glandular organization, and genomic composition. These features are reflected in the Gleason grade of the tumor and in the development of aneuploidy. Cellular architecture and genomic stability are controlled in part by centrosomes, organelles that organize microtubule arrays including mitotic spindles. Here we demonstrate that centrosomes are structurally and numerically abnormal in the majority of prostate carcinomas. Centrosome abnormalities increase with increasing Gleason grade and with increasing levels of genomic instability. Selective induction of centrosome abnormalities by elevating levels of the centrosome protein pericentrin in prostate epithelial cell lines reproduces many of the phenotypic characteristics of high-grade prostate carcinoma. Cells that transiently or permanently express pericentrin exhibit severe centrosome and spindle defects, cellular disorganization, genomic instability, and enhanced growth in soft agar. On the basis of these observations, we propose a model in which centrosome dysfunction contributes to the progressive loss of cellular and glandular architecture and increasing genomic instability that accompany prostate cancer progression, dissemination, and lethality.

Antigens↗
PubMed2001

A monoclonal antibody cytolytic to androgen independent DU145 and PC3 human prostatic carcinoma cells.

BACKGROUND: While a range of therapeutic products is available for androgen-dependent prostatic cancer, no specific intervention modality exists for androgen-independent prostatic cancer. The objective of this research was to explore whether epitopes exist on androgen-independent prostatic DU145 cancer cells, which could be susceptible to cytotoxic action of specific antibodies. METHODS: Hybrid cell clones were developed by immunization of mice with DU145 cells and tested for immunoreactivity by solid phase EIA and cytotoxicity in vitro on DU145 in the presence of the complement, employing colorimetric quantitation by MTS (3- (4-, 5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-(4-sulfophenyl)-2H-tetrazolium). Binding and cytotoxicity studies were also carried out by flow-cytometry. RESULTS: Of 15 stabilized clones immunoreactive with DU145 cells, one monoclonal antibody (mAb 730) manifested cytotoxicity on DU145 cells. Approximately 80% of cells in the DU145 cell line were susceptible to lysis with this antibody at saturating levels. This figure corresponded quantitatively to the number of cells binding with this antibody as determined by Flow-cytometry. Staining with ethidium monoazide bromide (EMA) showed that the cell binding the antibody was also the one killed by the antibody in the presence of the complement. MAb 730 was also cytotoxic to PC3, another androgen-independent human prostatic cancer cell line. This antibody is devoid of classical autoantibody reactivities and does not react with normal human liver, thyroid, kidney, pancreas, and adrenal tissues, as determined by immunofluorescence. Also, it shows negative immuno-reactivity to benign glandular tissue but is observed to positively react with neoplastic prostate tissue. CONCLUSIONS: Epitopes exist on androgen-independent prostatic cancer cells that are susceptible to cytolysis by monoclonal antibodies and these could be investigated for potential immunotherapy.

Animals↗
PubMed2001

Elbow arthropathy in hemophilia.

Twenty-one affected elbows in 14 known hemophilic patients undergoing treatment at the Hemophilia Clinic of our institution between 1994 and 1997 were evaluated using the clinical evaluation score of the Orthopaedic Advisory Committee of the World Federation of Hemophilia and radiological examination using the Pettersson score. The mean age of patients was 16.2 years (range 10-25 years), and all patients except 1 had severe hemophilia with factor VIII levels less than 1% of normal. The mean duration of disease at the time of presentation was 12.8 years. The mean clinical score was 6, while the mean radiological score was 4.9. There was a positive correlation between the clinical and radiological scores (P < 0.0001). However, the clinical and radiological scores did not correlate with either duration of disease or joint bleeding score. Two new radiological signs of obliteration of the capitello-lateral epicondyle groove with rounding off of the lateral aspect of the distal humerus and lipping of the medial trochlear surface were also recognized in hemophilic arthropathy of the elbow.

Adolescent↗
PubMed2001

Role of PTCH and p53 genes in early-onset basal cell carcinoma.

Basal cell carcinoma (BCC) is the most common skin cancer in the Western world. Ultraviolet (UV) exposure, race, age, gender, and decreased DNA repair capacity are known risk factors for the development of BCC. Of these, UVB irradiation from sunlight is the most significant risk factor. The incidence of sporadic BCC increases in individuals older than age 55, with the greatest incidence reported in individuals who are older than 70, and is rare in individuals who are younger than 30. In this study, we analyzed 24 BCC samples from individuals who had BCC diagnosed by the age of 30. Fifteen single-stranded conformation polymorphism variants in the PTCH gene were identified in 13 BCC samples. Sequence analysis of these single-stranded conformation polymorphism variants revealed 13 single nucleotide changes, one AT insertion, and one 15-bp deletion. Most of these nucleotide changes (nine of 15) were predicted to result in truncated PTCH proteins. Fifteen p53 mutations were also found in 11 of the 24 BCC samples. Thirty-three percent (five of 15) and 60% (nine of 15) of the nucleotide changes in the PTCH and p53 genes, respectively, were UV-specific C-->T and CC-->TT nucleotide changes. Our data demonstrate that the p53 and PTCH genes are both implicated in the development of early-onset BCC. The identification of UV-specific nucleotide changes in both tumor suppressor genes suggests that UV exposure is an important risk factor in early onset of BCC.

Adolescent↗
PubMed2001

Testing the stress-vulnerability hypothesis in ICD-10-diagnosed acute and transient psychotic disorders.

OBJECTIVE: To examine if family-history-positive (FHP) vis-à-vis family-history-negative (FHN) probands with ICD-10-diagnosed acute and transient psychotic disorders (ATPD) differ significantly with respect to number of life events and cumulative stress score prior to the onset of ATPD. METHOD: Forty probands with ICD-10-based clinical diagnosis of acute and transient psychotic disorders were studied with respect to: (a) history of psychiatric disorders in first-degree relatives, and (b) antecedent life events and cumulative stress. The FHP and FHN probands were compared on the latter variables using Mann-Whitney U-test. RESULTS: FHP probands reported significantly less number of total life events compared to FHN probands (P = 0.006). Similarly, FHP probands had significantly less stress score than FHN probands (P = 0.002). There were no significant demographic or clinical differences between the two groups. CONCLUSION: The findings support the stress-vulnerability hypothesis in the aetiology of ATPD.

Acute Disease↗