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Biomedical subjects

R Dhawan

Publications and source records attributed to R Dhawan.

At least 19 recordsLinked to original sources

An alternative strategy for universal infant hearing screening in tertiary hospitals with a high delivery rate, within a developing country, using transient evoked oto-acoustic emissions and brainstem evoked response audiometry.

OBJECTIVE: To formulate an alternative strategy for universal infants hearing screening in an Indian tertiary referral hospital with a high delivery rate, which could be extended to similar situations in other developing countries. The system should be able to diagnose, in a timely fashion, all infants with severe and profound hearing losses. METHODS: One thousand newborn were randomly selected. All underwent testing with transient evoked oto-acoustic emissions (TEOAE) in the first 48 hours of life. All TEOAE failures were followed up and repeat tests were performed at three weeks, three months and six months of age. Infants with acceptable TEOAE results at any of the four ages were discharged from the study. Infants with unacceptable TEOAE results at all the four ages underwent brainstem evoked response audiometry and oto-endoscopy. The 'pass rate' for TEOAE testing was calculated for all four ages. The time taken to perform TEOAE and brainstem evoked response audiometry was recorded for all subjects. These recordings were statistically analysed to find the most suitable strategy for universal hearing screening in our hospital. RESULTS: The pass rate for TEOAE was 79.0 per cent at < or =48 hours, 85.0 per cent at three weeks, 97.0 per cent at three months and 98.0 per cent at six months. The average time taken to perform the test was 12 minutes for TEOAE and 27 minutes for brainstem evoked response audiometry. Obstructed and collapsed external auditory canals were the two factors that significantly affected the specificity of TEOAE in infants < or =48 hours old. CONCLUSION: The concept of screening all neonates within the first 48 hours of life is impractical because the specificity of TEOAE is lowest at that age. Many false positive results are generated, such that a larger number must undergo brainstem evoked response audiometry, wasting time and resources. This can easily be avoided by delaying TEOAE screening until three months of age, when it has a substantially lower false positive outcome. We expect that implementation of this alternative strategy in our hospital will maximise the benefits of such a programme.

Audiometry↗

Persistency and treatment failure in newly diagnosed open angle glaucoma patients in the United Kingdom.

AIM: To determine utilisation patterns and calculate treatment failure and discontinuation rates in patients with open angle glaucoma treated in the United Kingdom with any of six groups of intraocular pressure (IOP) lowering agents. METHODS: The UK General Practice Research Database was used to identify newly diagnosed (after 1 January 1997) open angle glaucoma patients who were naive to therapy with any of six index drug groups: carbonic anhydrase inhibitors, latanoprost, miotics, sympathomimetics, timolol, and other (non-timolol) beta blockers. Analyses included drug treatment data for 1 year following diagnosis. Outcomes were (1) time to therapy failure, defined as either change in index drug (replacement or addition of therapy) or patient referral for surgery, and (2) time to therapy discontinuation, defined as either therapy failure or no refill of the index drug in a period twice that covered by the first prescription fill. Cox proportional hazard regression and Kaplan-Meier and life table methods were used to compare groups. RESULTS: Among the 2001 eligible patients, a beta blocker other than timolol was the most widely prescribed (42%), followed by timolol (32%), carbonic anhydrase inhibitors (10%), and latanoprost (7%). Compared to latanoprost, those treated with any alternative agent were significantly more likely to fail (p < or = 0.005 for each comparison) and to discontinue (p < or = 0.05 for each comparison) therapy. Failure rates ranged from 13% (latanoprost) to 45% (sympathomimetics), and discontinuation rates ranged from 30% (latanoprost) to 63% (miotics). CONCLUSION: Latanoprost treated patients demonstrated lower rates of therapy failure and therapy discontinuation compared with patients treated with other widely used IOP lowering medications, including beta blockers.

Adrenergic beta-Antagonists↗

The prevalence of nocturia and its effect on health-related quality of life and sleep in a community sample in the USA.

OBJECTIVE: To evaluate the prevalence of nocturia and its effects, with and without concomitant overactive bladder (OAB, i.e. urgency, frequency, urge incontinence and nocturia), on health-related quality of life (HRQoL) and sleep. SUBJECTS AND METHODS: A national survey was conducted in the USA to assess the prevalence of OAB and nocturia. A nested case-control study was conducted among respondents with OAB symptoms and age- and gender-matched controls, with participants completing a series of questionnaires on HRQoL (OAB-q, Short Form-36, and Medical Outcomes Study (MOS) sleep scale). Descriptive analyses, t-tests, analysis of variance with post hoc comparisons and multivariate regressions were used to analyse the data. RESULTS: In all, 5204 people participated in the survey, with 919 in the nested case-control study. The sample population had a mean age of 45.8 years, was 52.6% female and 80% Caucasian. In the community sample, 31% reported > 1 void/night and 14.2% reported > 2 voids/night. The prevalence of nocturia increased with age, with no gender differences. For OAB cases, 66.8% reported > 1 void/night and 42.2% reported > 2. In the case-control cohort there were significant HRQoL differences (P < 0.01), with increasing episodes of nocturia in all OAB-q subscales except social interaction. The amount of sleep per night was significantly correlated with the sleep, concern and social interaction OABq subscale scores. The number of nocturia episodes/night was also significantly (P = 0.02) associated with the number of hours of sleep/night. CONCLUSION: Nocturia is widely prevalent and increases with age, affecting men and women equally. Incremental increases in the number of voids/night have further negative effects on sleep, symptom bother, and HRQoL.

Age Distribution↗

Persistency and clinical outcomes associated with latanoprost and beta-blocker monotherapy: evidence from a European retrospective cohort study.

PURPOSE: To evaluate persistency (time on initial therapy) and the clinical impact of latanoprost versus beta-blocker monotherapy in treating glaucoma. METHODS: This observational, multicenter, retrospective medical chart review study conducted in four European countries included patients with primary open-angle glaucoma or ocular hypertension who began their first glaucoma treatment with latanoprost or a beta-blocker between November 1996 and November 1998. Persistency and glaucoma-related clinical outcomes data were abstracted for the 2 years following treatment initiation. RESULTS: In all, 260 patient charts were analyzed (94 latanoprost, 166 beta-blocker). Patients in the latanoprost group stayed on therapy twice as long as those who received a beta-blocker (p < 0.0001). After adjusting for baseline characteristics, patients receiving a beta-blocker as initial therapy were 3.8 times more likely to change therapy than those initially treated with latanoprost (p < 0.0001). Patients in the latanoprost group also experienced greater mean decreases in intraocular pressure (IOP) than those receiving a beta-blocker (7.4 mmHg versus 4.6 mmHg, respectively; p < 0.0001), and fewer had worsened optic nerve head excavation (1.7% versus 14.2%, respectively; p < 0.05) by the time of their first therapy change or last study visit, whichever came first. CONCLUSIONS: Over a 2-year period, latanoprost was associated with significantly greater persistency and better clinical IOP outcomes compared with beta-blocker therapy.

Adrenergic beta-Antagonists↗

Clinical and economic impacts of latanoprost 0.005% in first-line treatment of open-angle glaucoma and ocular hypertension in France.

PURPOSE: To assess the cost-effectiveness of treatment strategies that utilize first-line latanoprost compared to those based on initial beta-blocker therapy in patients with open-angle glaucoma (OAG) or ocular hypertension (OH) in France. METHODS: The study was based on a decision-analytic model that was populated with data from a retrospective chart review. A hypothetical cohort of patients newly diagnosed with OAG and/or OH was assessed over a period of 2 and 3 years. For each treatment strategy 10,000 patients were assumed. RESULTS: First-line latanoprost therapy was significantly more effective than initial treatment with a beta-blocker, providing more days of intraocular pressure (IOP) control primarily due to its longer time until initial treatment failure. Latanoprost's higher acquisition cost was largely offset by reductions in costs associated with surgical procedures. The additional cost for latanoprost was estimated at approximately 41 Euro and 27 Euro over 2 and 3 years, respectively. The incremental cost per day of IOP control when latanoprost was used as first-line strategy compared to the first-line beta-blocker strategy was 0.82 Euro and 0.36 Euro over 2 and 3 years, respectively. CONCLUSIONS: These results provide compelling evidence that first-line latanoprost therapy can provide superior clinical outcomes at a small additional cost in actual clinical practice.

Antihypertensive Agents↗

Acute renal infarction secondary to left ventricular thrombus, masquerading as a renal calculus--a case report and brief review of literature.

Acute embolic renal infarction is an entity that is often misdiagnosed as a renal calculus because of similar presenting symptoms. This leads to delay in the initiation of treatment and to increased morbidity. Few case reports exist relating cardiac emboli to acute renal infarction. The authors present a patient with a renal embolism secondary to left ventricular thrombus. A brief review of the literature highlighting the importance of clinical suspicion in making an accurate diagnosis, the utility of various diagnostic studies, and comparison of various treatment options is presented.

Aged↗

Glibenclamide vs gliclazide in reducing oxidative stress in patients of noninsulin dependent diabetes mellitus--a double blind randomized study.

OBJECTIVE: Parameters of oxidative stress were quantitated in 50 patients with type 2 diabetes mellitus in uncontrolled state and after control using oral glibenclamide or gliclazide. The estimates were further compared between the two groups irrespective of drug used to evaluate the difference, if any. METHODS: The study was a double blind, uncontrolled, noncrossover and randomized trial. Fifty patients of uncontrolled type 2 diabetes were divided in to two groups. Group I (25 patients) received capsule A (glibenclamide) while Group II (25 patients) received capsule B (gliclazide). The parameters studied were Superoxide dismutase (SOD), malonyl-dialdehyde (MDA) and reduced glutathione (GSH). They were done at (a) uncontrolled stage (FBS--165 +/- 16.7 mg/dl, PP--240 +/- 30.1 mg/dl and HbA1--10.5 +/- 0.9% in group I and FBS--150 +/- 15.8 mg/dl, PP--246 +/- 29.1 mg/dl HbA1 10.6 +/- 0.8% in group II) and during controlled stage at 12 weeks (FBS--120 +/- 18.5 mg/dl, PP--180 +/- 19.1 mg/dl and HbA1--8.4 +/- 0.29% in group I and FBS--118 +/- 17.6 mg/dl, PP--176 +/- 20.1 mg/dl and HbA1--8.5 +/- 0.39% in group II patients). RESULTS: The significantly raised levels of MDA and SOD, and decreased levels of reduced glutathione (GSH) during uncontrolled stage of diabetes indicated free radical stress induced lipid peroxidation. The significant fall of MDA and SOD and increased levels of GSH in blood in both groups after control revealed beneficial effects of glycemic control on oxidative stress. The levels were not normalized and stayed higher than those in controls. On intergroup comparison; the control of diabetes with gliclazide (group II) showed improvement in oxidative stress (MDA, GSH) better (p < 0.001) than glibenclamide (group I). CONCLUSION: Oxidative stress in uncontrolled diabetes is decreased with glycemic control. The control of diabetes with gliclazide reduced oxidative stress more than glibenclamide, indicating higher antioxidant properties of gliclazide. Normalization of oxidative stress was not achieved. Further studies are required to see long-term effect of drug therapy in combating oxidative stress after achieving acceptable control of diabetes.

Diabetes Mellitus, Type 2↗

Assessing health utilities in schizophrenia. A feasibility study.

BACKGROUND: Utility, a concept derived from economics, is the desirability or preference that individuals exhibit for a certain health state. Utility measurement could be viewed as an alternative means of appraising the quality of life of individuals affected by a chronic illness such as schizophrenia. Traditional techniques of utility measurement involve 2 steps: (i) identifying the different health states experienced by individuals during the course of an illness; and (ii) assigning them numerical values known as utilities. AIM: The study examined the feasibility issues and psychometric aspects of obtaining accurate health state descriptions and their utilities from symptomatically stable patients with schizophrenia. METHODS: The study used a cross-sectional, case-controlled design, with a study group consisting of 120 clinically stabilised patients with schizophrenia and a control group of 32 treated and recovered patients with major depression. Patients were asked to provide detailed descriptions of 3 distinct health states associated with their illness: current state, worst state experienced since the onset of illness and a perfect state desired in the future. Further, patients were asked to assign utilities to these health states with the aid of a purpose-built evaluation protocol comprising Magnitude Estimation (ME), Rating Scale (RS), Standard Gamble (SG), Time Trade-Off (TTO) and Willingness-to-Pay (WTP) techniques. The battery was repeated after a 1-week interval. Independent raters assessed symptom severity, insight and quality of life, and nurse-clinicians involved in their care were asked to provide the utility ratings of their clients' mental health state. Patients' opinions about the acceptability of utility measurement techniques, and the respondent burden were also ascertained. RESULTS: Compared with control patients with treated depression, patients with schizophrenia were able to distinguish and describe the specified health states with an equal degree of ease and accuracy. RS, TTO and WTP techniques emerged as the favoured methods of utility evaluation. The test-retest reliability of utility ratings (r = 0.87 to 0.97; p < 0.001) was high, and concurrent validity with the quality of life measures was acceptable. Reliability and validity of patients' appraisals were unaffected by symptoms severity and insight. The accuracy of nurse-clinicians' appraisals were dependent on their close familiarity with the patients and their illness. CONCLUSION: Clinically stabilised patients with schizophrenia can provide accurate health state descriptions and assign them utilities with a fair degree of reliability and validity. Utility evaluations based on patients' self-appraisals can be seen as potential tools in outcome studies and clinical trials involving patients with schizophrenia, but the methodology requires further refinement to accommodate the limitations imposed by the patients' disturbed mental status.

Adult↗

Comparison of lethality, reproduction, and behavior as toxicological endpoints in the nematode Caenorhabditis elegans.

This study describes a new approach for assessing behavioral changes following toxicant exposure and compares the method to other common endpoints used in environmental toxicology. The nematode Caenorhabditis elegans was exposed to a range of ethanol concentrations to determine its effect on survival, reproduction and behavior. Each endpoint was evaluated for its sensitivity by comparing LC50, RC50 (concentration at which there is a 50% reduction in number of offspring as compared to controls), and BC50 (concentration at which there is a 50% reduction in movement as compared to controls) values for ethanol exposure. Worms showed 24-h lethality at concentrations of ethanol in the range of 83 g/L to 99 g/L. Reproduction in C. elegans was estimated by counting the number of off-spring after 3 d of exposure, which decreased with the increase in ethanol concentration from 8 g/L to 71 g/L. Behavior was quantified by using a new computer tracking method, which can simultaneously assess hundreds of nematodes and provides several behavioral parameters in real time. Worms showed some hyperactivity (increased movement) at very low ethanol concentrations (0.8 g/L and 2.4 g/L) and a decrease in movement at higher ethanol concentrations (4 g/L to 40 g/L). A comparison for sensitivity between the three endpoints was performed. Behavior and reproduction responses were found to be similar and, as expected, both are much more sensitive indicators of toxicity than lethality. The advantages and disadvantages of the computer tracking system are discussed.

Animals↗

Endosulfan poisoning in Northern India: a report of 18 cases.

Eighteen cases of endosulfan poisoning by accidental overexposure during spray, admitted between October 1995 to September 1997, were observed and analyzed. These accounted for approximately one third of the total number of poisoning cases admitted in our unit during this period. Nausea, vomiting abdominal discomfort, tonic and clonic convulsions, confusion, disorientation, and muscular twitchings were cardinal manifestations. None of the patients succumbed to their illness. Analysis of various incriminating factors revealed that accidental overexposure was due to failure to adhere to the instructions for spray either due to ignorance or due to illiteracy. All the patients avoided preventive measures and developed toxicity both due to inhalation and absorption through skin. Endosulfan (a chlordiene derivative) poisoning is gaining up momentum in this part of world and has become an important matter for public health in India.

Accidents↗

Hepatitis B virus infection in pregnant women and its transmission to infants.

HBsAg was screened by Reverse Passive Haemagglutination Test (RPHA) and was confirmed by ELISA test in 157 pregnant females and their newborns. Anti-HBc and IgM anti-HBc was done in these cases by enzyme immuno-assay. The overall prevalence of HBsAg in mothers was 16 out of 157 (10 per cent) and in cord blood of newborns 5 per cent. The transplacental transmission was found in eight of 16 (50 per cent) HBsAg positive mothers. Anti-HBc was present in 12 out of 16 (75 per cent) HBsAg positive mothers and, of these, seven (58 per cent) neonates acquired HBsAg infection. IgM anti-HBc was present in seven out of eight (88 per cent) HBsAg positive neonates, suggesting active in utero infection. Fourteen out of 16 (88 per cent) neonates born to HBsAg positive mothers were alive and healthy, one was stillborn and one had a congenital anomaly.

Adult↗

Identification and characterization of receptor for dengue virus-induced macrophage cytotoxin.

The present study was undertaken to identify the receptor for dengue virus type 2 (DV) induced macrophage cytotoxin (CF2) on mouse peritoneal macrophages (MPhi). The binding of 125I-labelled CF2 to MPhi was saturable (15 nM), reversible, temperature, pH- and time-dependent. The saturation concentration was similar to that causing cell death. Scatchard analysis showed the presence of intermediate type of affinity receptor and the number of receptor sites was 1.1 x 10(6) per cell with dissociation constant of 14.28 nM.

Animals↗

Dengue virus-induced human cytotoxic factor: production by peripheral blood leucocytes in vitro.

During dengue type 2 virus (DV) infection of mice a unique cytokine, the cytotoxic factor (CF), is produced which reproduces the pathological lesions seen in patients of dengue haemorrhagic fever (DHF). Recently we have observed a CF-like protein in the sera of DHF cases. The present study was undertaken to investigate whether DV can stimulate human peripheral blood mononuclear cells (PBMC) in vitro to produce human CF (hCF). Cultures prepared from PBMC or its enriched subpopulations were inoculated with 1000 LD50 of DV and controls with normal mouse brain suspension (NMB). Aliquots of cultures were harvested daily from 24 h to 96 h and their supernatant (CS) and cells were separated. CS were screened for viral titres and for the presence of hCF by cytotoxicity assay, inhibition ELISA, dot blot and Western blot tests using anti-mouse-CF antibodies. The RNA from the cells was screened in Northern blot and dot blot tests for the presence of mRNA for CF. It was observed that hCF appeared in the CS of DV-infected culture of PBMC and T-enriched cells at 48 h and was present until 96 h; no CF was detected in CS of B cells or monocyte cultures. The production of hCF was abrogated by pretreatment of the T cells with anti-CD4 antibodies but not with anti-CD8 antibodies, indicating that hCF was produced by CD4+ T cells. The Northern blot analysis using oligonucleotide probes prepared on the basis of amino-terminal sequence of mouse CF, showed presence of mRNA for hCF in PBMC and T cell cultures. DV replicated in PBMC cultures with peak titres at 48 h. The findings of the present study demonstrate that DV-induced hCF is produced by human T cells.

Animals↗

Differential temporal and spatial expression of insulin-like growth factor binding protein-2 in developing chick ocular tissues.

PURPOSE: To determine the developmental expression and localization of mRNA for insulin-like growth factor binding protein-2 (IGFBP-2), a major binding protein of IGF-I and IGF-II, in ocular tissues of the embryonic and early posthatched chick. METHODS: In situ hybridization and northern blot analysis were used to analyze the cellular origin and relative expression of IGFBP-2 mRNA in ocular tissues. RESULTS: Wholemount in situ hybridization reveals that, as early as 3.5 days of embryonic development (E3.5), IGFBP-2 mRNA is already expressed in many areas of the embryo, including surface ectoderm, certain regions of the brain, pharyngeal clefts, somites, and limb buds. In the eye, IGFBP-2 mRNA is expressed only in the presumptive corneal epithelium at this time. By E6, IGFBP-2 mRNA expression is present in both the corneal epithelium and endothelium. By E12, IGFBP-2 mRNA is detected clearly in the corneal stroma as well as in several other ocular structures, such as the sclera, eyelid, and ciliary body. In the neural retina, a low, diffuse expression of IGFBP-2 mRNA is found at E6, which becomes more localized to the nuclear layers by E12. Northern blot analysis confirms that a high level of IGFBP-2 expression is present in the cornea and sclera by E8 to E12. A high level of IGFBP-2 mRNA expression, however, is not observed in the retina until E18. At posthatch day 2 (P2), northern blot analyses of ocular tissues reveal that the cornea contains the highest ocular level of IGFBP-2 mRNA expression, a value equal to that of brain and liver. CONCLUSIONS: The early appearance, along with differential temporal and spatial expression of IGFBP-2 mRNA in developing ocular tissues, suggests a role for IGFBP-2 in the regulation of growth and differentiation of several ocular tissues, including the cornea, sclera, and retina.

Aging↗

Role of calcium in induction of dengue virus-specific helper T cells.

Dengue type 2 virus (DV) induces the generation of T helper cells (TH) in the mouse spleen. These TH on adoptive transfer to DV primed syngeneic mice enhance the clonal expansion of antigen-specific antibody plaque forming cells. The present study was undertaken to investigate the role of M phi and Ca2+ in the induction of DV-specific TH. The results show that M phi are obligatory for the induction of DV-specific TH. It was observed that DV antigen stimulate the influx of calcium ion (Ca2+) into T cells as shown by radiolabelled (45Ca) and the influx of Ca2+ increases with time of incubation, reaching a maximum level after 1 hr of incubation. The proliferation of T cells was found to be dependent on presence of Ca2+ as it was inhibited by Ca channel blocking drugs and in the absence of Ca in the medium. Thus showing that Ca2+ plays an important role in the induction of DV-specific TH cells.

Animals↗

Flow cytometric analysis of T4:T8 splenic cell during dengue virus infection of mice.

The present study was undertaken to investigate the effect of dengue type 2 virus (DV) and DV-induced cytokines (CF and CF2) on T lymphocyte subpopulations of spleen by flow cytometry. Following DV-ic inoculation in mice the percent number of CD4+ and CD8+ lymphocytes in the spleen was reduced, the peak reduction in both was observed on the 6th day post-inoculation (p.i.). Intravenous inoculation of CF or CF2 in mice also decreased the percent number of CD4+ as well as CD8+ T lymphocytes subpopulation in the spleen, the maximum reduction being observed at 1 and 2 hr, respectively. The reduction in T lymphocyte subpopulation by CF and CF2 was found to be dose dependent. Thus, the alterations of T lymphocyte subpopulations during DV infection are mediated via cytokines.

Animals↗

Active immunization by a dengue virus-induced cytokine.

Dengue type 2 virus (DV)-induced cytotoxic factor (CF) is capable of reproducing various pathological lesions in mice that are seen in human dengue. The present study was undertaken to investigate the protective effect of active immunization of mice with CF. Mice were immunized with 5 microgram of CF and prevention of CF-induced increase in capillary permeability and damage to the blood-brain barrier were studied at weekly intervals, up to 48 weeks, by challenging with 3 microgram of CF. Maximum protection against increase in capillary permeability and damage to the blood-brain barrier was observed in week 4 after immunization. A breakthrough in the protection occurred with higher doses of CF in a dose-dependent manner. Challenge with a lethal intracerebral (i.c.) dose of DV showed significantly prolonged mean survival time and delayed onset of symptoms of sickness in the immunized mice compared with the normal mice, but the titre of the virus in the brain was similar in the two groups. On i.p. challenge with the virus the protection against damage to the blood-brain barrier was 86 +/- 7% at week 4 and 17 +/- 4% at week 26 after immunization. Sera obtained from the immunized mice showed the presence of CF-specific antibodies by ELISA, Western blot, and by neutralization of the cytotoxic activity of CF in vitro. The present study describes successful prevention of a cytokine-induced pathology by specific active immunization.

Animals↗