Biomedical subjects
Publications and source records attributed to V Agarwal.
Sarcoidosis is a chronic granulomatous disorder characterized by multisystem involvement, however, symptomatic thrombocytopenia as a presenting manifestation is rare. Here we are reporting a case of sarcoidosis presenting with splenomegaly and severe immune thrombocytopenia as a presenting manifestation.
Thrombotic thrombocytopenic purpura (TTP) is a rare disease. A high index of suspicion is required for early diagnosis and treatment. It can present in acute as well as chronic forms. Cyclophosphamide has been reported to be beneficial in relapsing TTP. Herein a case of acute TTP evolving into relapsing phase of the disease is presented. Cyclophosphamide in our case achieved partial remission without the need for plasma exchange therapy. The rationale of cyclophosphamide in management of relapsing TTP is discussed.
The purpose of this investigation was to (a) evaluate the coprecipitation technique for preparing microparticulates of insulin, (b) study the effect of variables such as addition of salts in the precipitating medium and ratio of polymeric solution to volume of precipitating medium on the dissolution and encapsulation efficiency of insulin microparticulates, and (c) evaluate the in-vitro enzymatic dissolution stability of insulin microparticulates in the presence of chicken ovomucoid (CkOVM) and duck ovomucoid (DkOVM) as inhibitors. Insulin dissolved in 0.01 N HCl was mixed with alcohol USP to get a final concentration of 32% v/v. Eudragit L100, a representative polymethyacrylate polymer, was then dissolved in this solution which was transferred to a beaker containing cold water with homogenization to obtain microparticulates. Dissolution studies were carried out in pH 6.8 phosphate buffer using a 100-ml conversion kit in a standard dissolution assembly. Dissolution stability of microparticulates was evaluated in the presence of 0.5 microM trypsin and 0.l microM chymotrypsin at various ratios of CkOVM and DkOVM. The results indicated that insulin microparticulates could be prepared using the coprecipitation technique with high encapsulation efficiency by proper selection of experimental conditions and amount of polymer. Presence of salts in the precipitating medium decreased the dissolution of insulin from the microparticulates. As the ratio of precipitating medium with respect to the polymeric solution was increased, the encapsulation efficiency increased. In dissolution stability experiments, insulin was not detected in the presence of enzymes alone. When CkOVM and DkOVM were incorporated, the stability of insulin increased significantly in a concentration dependent fashion.
Neurocysticercosis is a common neuroparasitosis. Presentation with psychiatric symptoms is uncommon in neurocysticercosis. The present paper describes a patient who presented with mutism, neglect of personal care and incontinence in a psychiatric setting and investigations revealed diagnosis of neurocysticercosis. The case report highlights the possible misdiagnoses of a case of neurocysticercosis as psychiatric illness and mutism as an uncommon presentation of neurocysticercosis.
A 9-year-old girl with a 5-6-month history of abdominal distension and fever was found to have massive splenomegaly with features of hypersplenism. Apart from a strongly positive Mantoux test, all investigations for massive splenomegaly proved negative. Splenectomy was carried out and histopathological examination of the spleen revealed granulomatous lesions suggestive of tuberculosis. The child improved after splenectomy and anti-tuberculous therapy and is doing well on follow-up. Splenic tuberculosis should be considered as an unusual cause of massive splenomegaly and hypersplenism.
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OBJECTIVE: To assess the prevalence of bacterial vaginosis (BV) in asymptomatic pregnant women and its association with preterm birth (PTB) and premature rupture of membranes (PROM). METHODS: In a cohort study 1,006 pregnant women between 16-28 weeks' gestation were screened for BV (Nugent's criteria) and for lower genital tract infection. Women were followed to confirm pregnancy outcome. Data were analyzed using STATA software. Univariate and multivariate methods were used to investigate the association between bacterial vaginosis and adverse pregnancy outcome. RESULTS: Prevalence of BV was 11.53%. Baseline characteristics were similar for both groups, 6.8% women were lost to follow-up. Incidence of PTB was higher in BV positive women compared to BV negative women (p = 0.001). On multiple logistic regression (MLR), BV was associated with an increased risk of PTB (p = 0.001) and PROM (p = 0.001), other correlates being previous PTB (p = 0.003) and the presence of enteropharyangeal organisms in vagina (p = 0.03). BV accounted for 82.53% of the attributable risk for PTB. CONCLUSION: Presence of BV in early pregnancy is associated with an increased risk of PTB and PROM. Multicentric interventional study is recommended.
BACKGROUND: A wide range of professionals including psychiatrists, psychologists, general physicians, faith-healers and religious healers cater to the needs of mentally ill patients. Psychiatric facilities are available at general hospitals, office based practice and mental hospitals. Psychiatrists are preferred the least due to stigma. The present work reports on treatment options used by a group of psychiatric patients before visiting a mental hospital. AIM: To study the help seeking behaviour of patients visiting a mental hospital. METHOD: Patients attending psychiatric outpatient service at a mental hospital were asked specifically about various treatment facilities utilized by them before coming to the hospital and the reasons thereof. RESULTS: A wide range of services was used by the subjects varying from professional care to faith healers. Trust, easy availability and accessibility, recommendations by the significant others and belief in supernatural causation of illness were the important reasons for choosing a particular facility. Thus sociocultural factors appeared to influence the help seeking behaviour. CONCLUSION: A substantial number of patients suffering from severe mental disorders seek non-professional care. There is a need of studies in community to assess the help seeking behaviour of psychiatric patients and factors associated with it.
The pharmacokinetic interactions between BAY 12-9566 and two nonsteroidal anti-inflammatory drugs (NSAIDs), naproxen and ibuprofen, were investigated in osteoarthritis (OA) patients. The study comprised six groups: two NSAID groups with three levels of treatment (BAY 12-9566 400 mg, BAY 12-9566 100 mg, and placebo). Plasma pharmacokinetic parameters (AUC(0-tau), Cmax, and tmax) were determined for each treatment group following 5 days of NSAID administration, 14 days of BAY 12-9566 administration, and 14 days of concurrent NSAID and BAY 12-9566 administration. For most conditions, the total plasma drug concentrations of both NSAID and BAY 12-9566 were diminished by coadministration; total plasma BAY 12-9566 was not affected by ibuprofen treatment. Importantly, the free drug concentrations were largely unaffected by coadministration. Most side effects were mild or moderate in intensity, and all events, with the exception of headache, were reported in both NSAID groups and in both placebo and BAY 12-9566 groups.
Our aim was to evaluate the transport of insulin across rat jejunum in the presence of ovomucoids and to assess the effect of ovomucoids on intestinal tissue by studying the permeation of a lipophilic and a hydrophilic marker. Rat jejunal segments were mounted in a side-by-side diffusion chamber filled with Krebs bicarbonate buffer, bubbled with 95% O2/5% CO2 at a fixed flow rate and maintained at 37 degrees C. The permeation of insulin, a lipophilic marker ([7- 3H] testosterone) and a hydrophilic marker (D-[1- 14C] mannitol) was evaluated in the presence of 0.5-1.5 microM duck ovomucoid (DkOVM) or chicken ovomucoid (CkOVM). For stability and permeation of insulin in the presence of alpha-chymotrypsin, an enzyme-to-inhibitor ratio of 1:1 and 1:2 was used. In the absence of alpha-chymotrypsin, the permeability coefficient (Papp) of insulin at pH 7.4 was 0.922+/- 0.168 x 10(-7) cm s(-1), which decreased with increasing concentrations of DkOVM or CkOVM. Conversely, the permeation of the hydrophilic and lipophilic marker increased with increasing concentrations of CkOVM and DkOVM. In stability studies, the percentage of drug remaining was found to be 2-fold higher at the 1:2 ratio than with the 1:1 ratio of enzyme to inhibitor. This was in agreement with the 2-fold increase in flux values of insulin in the presence of alpha-chymotrypsin and DkOVM at the 1:2 ratio of enzyme to inhibitor. The decrease in permeation of insulin in ovomucoids was unexpected. Marker transport studies indicated that ovomucoids have the potential to modulate transcellular and paracellular permeability. The flux enhancement of insulin in the presence of alpha-chymotrypsin and DkOVM is encouraging. The use of ovomucoids offers potential to enhance oral delivery of insulin and warrants further investigation.
A 12-week, double-blind, randomized, placebo-controlled trial of oral clonidine in three fixed doses (4, 6, and 8 mcg/kg/day) using a crossover design was conducted with 10 children who had hyperkinetic disorder (mean age 7.6 years +/-.54). All had comorbid mental retardation. Both parents' ratings on the Parent Symptom Questionnaire and clinicians' ratings on the Hillside Behaviour Rating Scale showed a marked dose-related response to clonidine in hyperactivity, impulsivity, and inattention. Drowsiness was a common side effect of clonidine. It wore off by the 2nd to 4th week in most cases. Thus, clonidine is a safe and effective medication in young hyperkinetic children with comorbid mental retardation.
OBJECTIVE: To investigate the effects of concomitant food intake on the pharmacokinetics of a single oral dose of moxifloxacin 400mg. DESIGN: This was a randomised 2-way nonblinded crossover study in healthy volunteers. PARTICIPANTS: 18 young, healthy, male volunteers were enrolled in the study, of whom 16 were considered evaluable for the pharmacokinetic analysis. METHODS: Moxifloxacin was given under 2 conditions separated by a 1-week washout period: fasted and fed (immediately after a standardised high fat breakfast). Concentrations of moxifloxacin in serum were determined by a validated high performance liquid chromatography procedure with fluorescence detection. OUTCOME MEASURES: Pharmacokinetic parameters such as maximum concentration (Cmax), time to reach Cmax (tmax), area under the concentration-time curve from zero to 48 hours (AUC48h), AUC from zero extrapolated to infinity (AUCinfinity) and elimination half-life (t1/2z) were estimated using noncompartmental methods. The natural logarithms of AUC and Cmax were analysed using analysis of variance. Bioequivalence of the 2 treatments was determined at the 5% significance level with the two 1-sided tests procedure and limits of 80% and 125% for AUC and 70 to 143% for Cmax. RESULTS: The mean serum concentration versus time profiles were similar between the 2 treatments. The geometric mean AUCinfinity values under fed and fasted conditions were almost identical, 37.7 versus 38.5 mg/L x h, respectively [90% confidence interval (CI) of the ratio of fed versus fasted based on geometric least-square means was 0.95, 1.00]. Geometric mean Cmax values were slightly reduced by food, 2.5 versus 2.8 mg/L, respectively (90% CI of fed versus fasted based on geometric least-square means was 0.78, 0.98). The absorption of moxifloxacin seems to be mildly delayed because of the effect of food; the median tmax values were 1.0 and 2.5 hours for fasted and fed conditions, respectively. The single oral dose of moxifloxacin 400mg was well tolerated when taken with and without food.
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AIMS AND METHODS: Sarcoidosis is systemic granulomatous disorder. Articular manifestations have received little attention in the literature. Case records of patients with sarcoidosis, presenting with articular symptoms between 1990-1999, were retrospectively analysed. RESULTS: Twenty nine patients, 15 males and 14 females, median age 44 years (range 15-67 years) and median duration of articular symptoms of eight months diagnosed clinically (n=9) and on biopsy (n=20) were studied. Twenty five patients had arthritis as the presenting manifestation. Fifteen patients had chronic arthritis (> six months). Lofgren's syndrome was seen in 7% of the patients. Acute arthritis was episodic (n=4), more common in males (M:F = 9:5), predominantly affected lower limb joints and mimicked reactive arthritis. Chronic arthritis was more frequently observed in females (M:F = 1:2) and presented with involvement of bilateral symmetric hand joints, mimicking rheumatoid arthritis. Extra-articular manifestations like neuropathy and constitutional symptoms were observed in acute arthritis. Skin plaque, splenomegaly and interstitial lung disease were seen with chronic arthritis. At a median follow up of 12 months, 10/14 and 5/15 achieved complete remission whereas 2/14 and 9/15 achieved partial remission of the articular symptoms in the acute and chronic groups, respectively. CONCLUSION: Arthritis in sarcoidosis is an early manifestation of disease and may mimic reactive or rheumatoid arthritis. Unsatisfactory response in chronic arthritis highlights the need for immunosuppressive drugs in addition to steroids.
Maintenance of constant drug levels in the body for those drugs that are used in management of hypertension is extremely beneficial. This can be successfully achieved by delivering the antihypertensives as osmotically-controlled drug-delivery system that essentially eliminates the influence of pH on the drug release. The main objective of this study was to evaluate the main effects of the formulation variables on the release of captopril from osmotically-controlled drug-delivery system coated with a custom-made cellulose acetate (CA) pseudolatex reported earlier. A secondary objective was to identify a suitable antioxidant for incorporating in the formulation as the drug undergoes metal-catalyzed oxidative degradation. The drug showed good stability (> or = 90% intact captopril) in solution in the presence of ascorbic acid for a period of 48 h. A seven-factor, 12-run Plackett-Burman screening design was employed to study the main effects of amounts of Polyox(R) N10 and N80, Carbopol(R) 934P and 974P, sodium chloride, orifice size, and % coating weight gain. The response variable was cumulative percent of drug released in 12 h, Y(3), with constraints on lag time Y(1) and time for 50% drug released Y(2)amount of sodium chloride (1.97).
The present study was conducted to determine the effects of ageing at exaggerated storage conditions on controlled release tablets prepared with indomethacin-Eudragit((R)) coprecipitates (CPs) and solid dispersions (SDs). CPs and SDs compressed as tablets were stored at -20, 4, 37, 45, 55, 37 degrees C/11% RH, 37 degrees C/51% RH and 37 degrees C/91% RH. The samples were analyzed over a period of six months for their dissolution, crystalline reversion and thermal changes. Samples stored at extremely low temperatures, higher temperatures and humidity conditions exhibited a significant decrease in dissolution rates. However, no significant change in the release rates was observed for samples stored at 4 degrees C. The degree of crystallinity increased over a period of time as confirmed by X-ray diffractometry. DSC data demonstrated that indomethacin exists in two polymorphic forms, Form I (mp 160-161 degrees C) and Form II (mp 153-154 degrees C). CPs showed an endotherm of Form I, whereas SDs showed a mixture of Form I and II.
BACKGROUND: 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) are metabolized by distinct pathways that may alter the extent of drug-drug interactions. Cerivastatin is metabolized by cytochrome P450 (CYP)3A4 and CYP2C8. Atorvastatin is metabolized solely by CYP3A4, and pravastatin metabolism is not well defined. Coadministration of higher doses of these statins with CYP3A4 inhibitors has the potential for eliciting adverse drug-drug interactions. OBJECTIVE: To determine the comparative effect of itraconazole, a potent CYP3A4 inhibitor, on the pharmacokinetics of cerivastatin, atorvastatin, and pravastatin. METHODS: In this single-site, randomized, three-way crossover, open-labeled study, healthy subjects (n = 18) received single doses of cerivastatin 0.8 mg, atorvastatin 20 mg, or pravastatin 40 mg without and with itraconazole 200 mg. Pharmacokinetic parameters [AUC(0-infinity), AUC(0-tn), peak concentration (Cmax), time to reach Cmax (tmax), and half-life (t1/2)] were determined for parent statins and major metabolites. RESULTS: Concomitant cerivastatin/itraconazole treatment produced small elevations in the cerivastatin AUC(0-infinity), Cmax, and t1/2 (27%, 25%, and 19%, respectively; P < .05 versus cerivastatin alone). Itraconazole coadministration produced similar changes in pravastatin pharmacokinetics [AUC elevated 51% (P < .05 versus pravastatin alone), 24% (Cmax), and 23% (t1/2), respectively]. However, itraconazole dramatically increased atorvastatin AUC (150%), Cmax (38%), and t1/2 (30%) (P < .05). The elevation in atorvastatin AUC was significantly greater than that of cerivastatin (P < .005) or pravastatin (P < .005). CONCLUSION: Itraconazole markedly elevated atorvastatin plasma levels (2.5-fold) after 20 mg dosing, suggesting that concomitant itraconazole/atorvastatin therapy be carefully considered. Itraconazole produced modest elevations in the plasma levels of cerivastatin 0.8 mg or pravastatin 40 mg (1.3-fold and 1.5-fold, respectively), indicating that combination treatment with itraconazole with cerivastatin or pravastatin may be preferable.