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Biomedical subjects

R Parikh

Publications and source records attributed to R Parikh.

At least 19 recordsLinked to original sources

Comparison of alamar blue and MTT assays for high through-put screening.

The performance of alamar blue and 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) cell viability assays in a high through-put format were compared. A total of 117 drugs chosen for their wide range of therapeutic areas were screened at 10 microM using both assays in human hepatoma cell line HepG2. Except for terfenadine and astemizole, which performed consistently in both assays, the alamar blue assay was slightly more sensitive than the MTT assay for most compounds. The MTT assay was less sensitive detecting an effect for daunorubicin and trifluoperazine. Seven drugs, astemizole, daunorubicin, ellipticine, fluphenazine, terfenadine, thioridazine and trifluoperazine, had percent viability results of 55% or less in the alamar blue assay at the single point screen. These were re-tested in both assays for reconfirmation of cytotoxicity and determination of the EC50 values. Except for daunorubicin, the EC50 values were comparable in both assays. Based on these results and the Z'-factor assessment of assay quality, both assays provided useful information to identify in vitro cytotoxic drugs at early stages of drug candidate selection. However, careful interpretation of data is warranted due to the possibility of false positive or negative results caused by inducers and/or inhibitors of metabolic enzymes that are responsible for transformation of cell toxicity end points, as we demonstrated using dicumarol.

Carcinoma, Hepatocellular↗

Five year risk of progression of primary angle closure suspects to primary angle closure: a population based study.

AIM: To report progression of primary angle closure suspects (PACS) to primary angle closure (PAC) at the 5 year follow up of a population based sample. METHODS: 82 of 118 PACS who could be contacted and 110 randomly selected normals from a population based survey in 1995 were invited for a follow up examination in 2000. Progression to PAC was based on the development of raised IOP or synechiae in a PACS. RESULTS: 50 of the 82 PACS contacted were examined. 11 (22%; 95% CI 9.8 to 34.2) developed PAC (seven synechial and four appositional); all were bilateral PACS. Two of 50 people previously diagnosed as PACS were reclassified as normal. One person among the 110 normals progressed to PAC. The relative risk of progression among PACS was 24 (95% CI 3.2 to 182.4). There was no significant difference in axial length, anterior chamber depth, or lens thickness between those who progressed and those who did not. None of the patients developed optic disc or field damage attributable to angle closure. One angle closure suspect was diagnosed to have normotensive glaucoma. CONCLUSION: In this population based study of PACS the 5 year incidence of PAC was 22%; none developed functional damage. Bilateral PACS was a clinical risk factor for progression.

Adult↗

Frequency doubling perimetry in glaucoma.

PURPOSE: To evaluate the validity of frequency doubling perimetry (FDP) in the detection of glaucomatous field defects. METHODS: Group I consisted of 85 eyes of 85 patients with established field defects in automated perimetry, classified by severity of defect. Group II consisted of 48 eyes of 48 control subjects. Both groups underwent Swedish Interactive Testing Algorithm (SITA) standard tests as well as FDP screening strategies (C20-1 and C20-5 and full threshold test). Sensitivity and specificity measures for the FDP tests were calculated using one new and two previously published algorithms. RESULTS: A described scoring system provided the best sensitivity (85.9%) and specificity (95.1%). For moderate and severe cases, the sensitivity improved to 91%. Quantification of the defect did not improve detection. CONCLUSIONS: FDP is a valid screening test for glaucoma. The scoring system described by Patel et al. provided the best results.

Adult↗

The implication of compromised renal function at presentation in myeloma: similar outcome in patients who receive high-dose therapy: a single-center study of 251 previously untreated patients.

The purpose of the study was to determine the role of sequential therapy (ST) in new patients with myeloma presenting with renal dysfunction (RD): serum creatinine >140 micromol/L (1.6 mg/dL). Between April 1985 and June 1998, 251 patients, 59 (23%) with RD were entered into a ST program comprised of infusional chemotherapy (IC) with VAMP/C-VAMP (vincristine, doxorubicin, and methylprednisolone with/without cyclophosphamide) followed by autologous transplantation and interferon maintenance. The median overall survival (OS) of 251 patients from the start of IC was 4.2 yr with the RD group faring significantly poorer (median 2.5 yr) than those with no renal dysfunction (NRD; median 4.6 yr; p = 0.0025). Mortality during the first 100 d of IC was significantly higher in patients with RD (11/59; p = 0.01) compared to patients with NRD. In patients consolidated with high-dose therapy, the OS and event-free survival (EFS) were not significantly different between the two groups. Cox analysis of the variables at presentation failed to show RD as a factor influencing outcome, but it showed that patients with beta-2-microglobulin (beta2M) > or = 3.7 (p < 0.0001), age > or = 52.5 yr (p = 0.002), performance status (PS) > or = 2 (p = 0.005) and patients with light-chain myeloma (p = 0.03) had a significantly shorter OS, beta2M > or = 3.7, PS > or = 2, and light-chain myeloma were predictive of shorter EFS. The study shows that with modern intensive schedules of treatment, renal disease at presentation in isolation does not compromise outcome.

Adult↗

Anticalculus effect of two zinc citrate/essential oil-containing dentifrices.

PURPOSE: To assess the feasibility of incorporating zinc citrate, a known anticalculus ingredient, into a dentifrice formulation containing a fixed combination of essential oils, a known antiplaque/antigingivitis agent. MATERIALS AND METHODS: This randomized, parallel, double-blind study evaluated the potential of two essential oil dentifrice formulations containing different levels of zinc citrate (1.0% and 2.0% ZCT) to reduce supragingival calculus formation compared to a marketed control dentifrice, Crest Regular. Following a 3-month pre-test phase, subjects received a dental prophylaxis, were stratified into three balanced groups on the basis of Volpe-Manhold calculus scores and brushed twice daily with their assigned dentifrice for 3 months. RESULTS: One hundred ninety-six evaluable subjects completed all phases of the study. ANCOVA revealed that the 1.0% ZCT and 2.0% ZCT essential oil dentifrice formulations provided significant reductions in calculus formation of 26.4% and 29.0% (P< 0.001), respectively, compared to the control dentifrice, Crest Regular. The magnitude of calculus reductions is similar to those levels obtained by other zinc salt formulations.

Adolescent↗

Stain removal efficacy of two new fluoride dentifrices containing essential oils.

PURPOSE: To assess in vitro the stain removal efficacy of two new antiplaque/antigingivitis dentifrices utilizing a modification of a previously validated Stookey method. MATERIALS AND METHODS: The modifications to the original Stookey method are the following: (1) study design; three 5 x 5 Latin Squares were employed to minimize bias stemming from position or test run in the study. (2) statistical success criteria; a test formulation was judged to be effective if the lower one-sided 95% confidence limit was "equal to or higher than" 50 since a minimum PCR (pellicle cleaning ratio) score of 50 is needed for a dentifrice to show clinical efficacy. The two test dentifrice formulations contained a fluoride source, a silica abrasive system, and four essential oils. The ADA reference abrasive material (calcium pyrophosphate) and placebo toothpaste were included as positive and negative controls, respectively. RESULTS: Compared to the negative control, the positive control exhibited a statistically higher PCR score; therefore, the validity of this modified Stookey method was confirmed. Additionally, the lower limits of the one-sided 95% confidence interval for the two dentifrice formulations were above the threshold PCR of 50; therefore, this modified Stookey method should predict that both essential oil-containing dentifrices possess acceptable stain removal power.

Analysis of Variance↗

Essential oils in an antiplaque and antigingivitis dentifrice: a 6-month study.

PURPOSE: To determine if a dentifrice formulated with the fixed combination of essential oils possessed antiplaque and antigingivitis properties. MATERIALS AND METHODS: This study was a blinded, randomized, controlled clinical trial. The 6-month study had clinical examinations at baseline, 3 and 6 months. The examinations consisted of three indices; a plaque index, the Modified Gingival Index and a bleeding index. RESULTS: At 6 months, the essential oil-containing dentifrice group had statistically significantly (P < 0.001) lower whole-mouth and interproximal mean plaque index scores exhibiting mean reductions of 18.3% and 18.1% relative to the vehicle control. At 6 months, the essential oil-containing dentifrice group had statistically significantly (P < 0.001) lower whole-mouth and interproximal mean gingival index scores compared to the vehicle control with reductions of 16.2% and 15.5%, respectively. Finally, for the gingival bleeding index, the essential oil-containing dentifrice group had statistically significantly (P < 0.001) lower whole-mouth and interproximal mean bleeding index scores and reductions of 40.5% and 46.9% at 6 months compared to the vehicle control.

Adolescent↗

Coping mechanisms in patients presenting for in-vitro-fertilization.

OBJECTIVES: The purpose of this study was to assess the coping mechanisms in patients presenting for in-vitro fertilization (IVF). METHODS: We evaluated thirty consecutive couples presenting for in-vitro-fertilization. All couples were interviewed individually at first, and then together, using a semi-structured interview technique. Psychiatric diagnoses were made using the Diagnostic and Statistical Manual-IV (DSM-IV) criteria. Coping mechanisms used by the individuals were assessed using the Mechanisms of Coping Scale (MOCS). Other instruments used were Hamilton Depression Rating Scale (HAM-D-17), Hamilton Anxiety Rating Scale (HAM-A), Brief Psychiatric Rating Scale (BPRS), Self-Rating Symptom Scale (SRSS), and Eysenck Personality Inventory (EPI). RESULTS: The mean age of the sixty patients was 32.3 +/- 5.2 years. Fatalism was the commonest factor on the mechanisms of coping scale. Analysis of variance (ANOVA) across all factors of the MOCS for demographic factors showed that men used problem-solving mechanisms significantly more often than women (F = 3.0, df = 1, 58, p < 0.05). ANOVA across coping factors on stressors with post-hoc tests of significance revealed that individuals facing social stress used fatalism significantly more often than other coping mechanisms, while those facing career stress used problem-solving significantly more often than other coping mechanisms (F = 5.6, df = 1, 58, p < 0.05 and F = 3.04, df = 1, 58, p < 0.01 respectively). ANOVA across coping factors on HAM-D-17 scores revealed that individuals who used fatalism had significantly higher HAM-D-17 scores compared to those who did not (F = 4.4, df = 1, 58, p < 0.05). ANOVA across coping factors on HAM-A scores revealed that individuals who used escape-avoidance had significantly lower HAM-A scores than those who did not (F = 4.3, df = 1, 58, p < 0.05). ANOVA across coping factors on SRSS scores revealed that individuals who used passivity or fatalistic coping mechanisms had significantly higher scores on SRSS than who did not (F = 4.6, df = 1, 58, p < 0.05 and F = 3.5, df = 1, 58, p < 0.05). CONCLUSIONS: Differential patterns of coping were found among the sixty individuals presenting for IVF and were associated with a variety of factors including gender, education, stressors, and levels of depression, anxiety, and overall psychopathology. Efforts to recognize and recruit the coping mechanisms of infertile individuals are likely to enhance their ability to participate effectively in treatment.

Adaptation, Psychological↗

Topical morphine in a canine model: a pilot study.

OBJECTIVE: To determine if topical morphine can enter the synovial cavity and the effect of ultrasound on this process. DESIGN: A randomized control trial to investigate which body fluids morphine enters after topical application. SETTING: A university animal laboratory. SUBJECTS: Ten mongrel dogs raised by the Comparative Medicine Department. All animals were certified to be free of disease, all had received standard scheduled immunizations, and none had been used for any other research. INTERVENTION: Topical morphine and ultrasound or topical morphine and sham ultrasound was applied to the knees of the dogs. Samples were obtained afterward from synovial fluid, serum, and urine, and were analyzed for the presence of morphine. MAIN OUTCOME MEASURES: Blood samples were collected every 60 minutes for 240 minutes, urine samples were collected at 120 minutes and 240 minutes, and synovial joint fluid was collected at 120 minutes and 240 minutes. The process of collection and analysis was the same for dogs treated with topical morphine and ultrasound and those treated with topical morphine and sham ultrasound. Fisher's exact test was used to test for an association between the use of ultrasound and the presence of morphine in the synovial fluid, serum, or urine. Two-sample t tests were used to test for group differences in mean body weight. RESULTS: All samples (synovial fluid, serum, and urine) were negative at time zero. All of the subsequent serum samples were negative for morphine. Two or three of the dogs in each group of five (ultrasound or sham ultrasound) had positive urine and synovial fluid samples at 120 and 240 minutes. Ultrasound did not affect the results. Body weight of the dogs influenced the results, with lighter animals having a significantly larger percentage (p=.03) of synovial fluid samples positive for morphine. CONCLUSION: Ultrasound did not affect the absorption of topical morphine in this canine model. Body weight may have influenced the results. Dogs that tested positive for morphine in synovial fluid had a lower mean body weight than dogs that did not test positive (p=.03).

Administration, Topical↗

Metabolic and orexigenic effects of intracerebroventricular neuropeptide Y are attenuated by food deprivation.

Administration of neuropeptide Y (NPY) into the hypothalamus or cerebral ventricles has been shown to increase food intake, the secretion of hormones such as insulin, glucagon and corticosterone and to alter the metabolism of carbohydrate and lipids. It has been suggested that metabolic effects of hypothalamic NPY may contribute to fat accretion in some types of obesity and to the metabolic and behavioural adaptation to food deprivation. However, it is currently unknown if different nutritional states alter the responses to hypothalamic NPY. Consequently, we have compared the effects of NPY injected into the third ventricle (ICV) in the fed and overnight-fasted state on ingestive behaviour, on insulin, glucagon and corticosterone secretion before, and following, an IV glucose bolus (IVGTT) and on blood glucose following an intra-arterial insulin bolus (ITT). Studies were performed on conscious, unrestrained adult female rats. In the fed state, 2 and 6 micrograms ICV NPY produced a potent orexigenic and dypsogenic effect. In the fasted state, the 2 micrograms dose had a dypsogenic effect, while only the 6 micrograms dose had a significant orexigenic effect. In the fed but not fasted state, 3 micrograms ICV NPY increased plasma glucagon and corticosterone levels and attenuated the decline in blood glucose during the ITT. By contrast, in both fed and fasted groups, 3 micrograms ICV NPY potentiated the insulin secretory responses during the IVGTT. We conclude that, apart from stimulating insulin secretion, the acute metabolic and orexigenic responses to ICV NPY in this study were substantially reduced or abolished by overnight fasting. Therefore, behavioural and metabolic responses to endogenous hypothalamic NPY may also be more significant in the fed than the fasted state.

Animals↗

Effect of chemical sympathectomy on serum levels of thyroid hormones and the biochemical profile of domestic pigeons.

Recent studies have stressed the importance of the cholinergic system on avian metabolism. However, the role of the sympathetic nervous system (SNS) remains unclear. The present study was, therefore, aimed to probe the mechanisms for modulation of avian metabolism by the sympathetic nervous system after inhibition of the adrenergic responses. Activities of serum thyroid hormones (tri-iodothyronine, T3, and thyroxine, T4), body weight, hepatic weight, as well as total lipid and water content in the liver and body temperature were some of the parameters examined after chemical sympathectomy with 6-hydroxydopamine (6-OHDA) and reserpine treatment in 24-h starved pigeons. In addition, glucose was administered to the pigeons to identify the regulatory role played by glucose after disruption of the SNS. A reduction in body weight of the pigeons and an enhancement in the lipogenic machinery along with a corresponding increase in water content were some of the obvious effects in 6-OHDA+reserpine treated, as well as glucose-loaded sympathectomized birds. The cloacal temperature (Tc) and both the thyroid hormones showed a drastic decrease while the T3/T4 ratio was augmented as a result of sympathectomy. However, serum T3 and T4 levels were restored to control values when glucose load was given, indicating that glucose might be reversing some of the detrimental effects of 6-OHDA treatment by activating intrinsic autoregulatory mechanisms of thyroid gland, thereby reviving the levels of thyroid hormones. Thus, the influence of SNS appears to be crucial in the maintenance of serum thyroid hormones and body temperature, as well as metabolic activities of hepatic cells.

Animals↗

Ranitidine bismuth citrate and ranitidine do not affect gastric emptying of a radio-labelled liquid meal.

Ranitidine bismuth citrate, a new chemical entity which is a salt complex of ranitidine and bismuth citrate, is being developed for the treatment of relapse of benign gastric and duodenal ulcer and eradication of Helicobacter pylori. The aim of the present study was to establish whether ranitidine bismuth citrate (800 mg) or ranitidine hydrochloride (300 mg) have any effect on gastric emptying of a liquid meal using gamma scintigraphy. On three separate occasions, each of twelve subjects received a single oral tablet of 800 mg ranitidine bismuth citrate, 300 mg ranitidine hydrochloride or placebo in random order. Thirty minutes after dosing each subject was given 375 ml of 99mTc-DTPA (diethylene triaminepentaacetic acid) labelled Clinifeed-ISO. The primary endpoint was the time to 50% gastric emptying (t50%). The proportion of the meal remaining was summarised by weighted mean proportion of the meal remaining in the stomach over 0-60 min and 0-180 min, separately. No differences were observed for t50%, weighted mean 0-60 min, and weighted mean 0-180 min between any two treatments. In man, we have detected no significant effect of single oral doses of ranitidine bismuth citrate 800 mg or ranitidine hydrochloride 300 mg on the rate of gastric emptying of a liquid meal when compared with placebo.

Adult↗

PET imaging of cortical S2 serotonin receptors after stroke: lateralized changes and relationship to depression.

Patients with right-hemisphere strokes (N = 9) more than 1 year after injury had greater cortical binding of (3-N-[11C]methyl)spiperone than a similar group of patients with left-hemisphere strokes (N = 8) or normal control subjects (N = 17). The higher S2 serotonin receptor binding occurred in uninjured regions of the right parietal and temporal cortex. The ratio of binding in the ipsilateral to contralateral cortex showed a significant negative correlation with severity of depression scores in the left temporal cortex. These findings suggest that the biochemical response of the brain may be different depending on which hemisphere is injured and that some depressions may be a consequence of the failure to upregulate serotonin receptors after stroke.

Adult↗

Application of transpubic approach in the management of lower urinary tract pathology in 110 patients. A critical review.

The male lower urinary tract, which comprises the bladder neck, prostate and membranous urethra, is well hidden behind the pubic symphysis. Historically, surgeons have attempted to expose this part of the anatomy by removing the pubic symphysis, in part or in total, during the surgical procedure. In 1923, for the first time, Walker from Australia attempted to obtain better access to the prostate to treat prostatic cancer. Since the surgeons have utilized transpubic approach in a variety of surgical pathologies. We present our experience in managing 110 patients of both sexes ranging in age from 6 to 70 years. They presented with different lower genitourinary tract pathologies, with prostatomembranous strictures comprising 77% of the cases. Clinical indications for transpubic approach, crucial surgical principles, complications of the procedure, and, more importantly, long term evaluation of patients for 10 years or more, is presented. Transpubic approach has an ongoing role in the surgical and urological management both in children and adult patients of both sexes. Transpubic approach is a safe technique with minimal long-term complications and no post-operative orthopedic sequelae.

Adolescent↗