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Biomedical subjects

R Mehta

Publications and source records attributed to R Mehta.

At least 73 records · Page 4Linked to original sources
PubMed1996

The effects of L-deprenyl on spatial short term memory in young and aged dogs.

1. Young and aged dogs were tested on a spatial memory task using a delayed non matching to sample technique. Dogs were tested with 20, 70 and 110 second delay intervals. Animals were pretrained to a stable level of performance prior to treatment. 2. During treatment periods, dogs were orally administered a placebo or I-deprenyl in doses of 0.5 and 1.0 mg/kg in a repeated measures design. 3. Young dogs did not show any significant effects of I-deprenyl, however the sample size was limited. 4. L-deprenyl administration improved spatial memory in aged dogs. 5. The optimal dose or length of treatment time of I-deprenyl varied among individual dogs.

Aging↗
PubMed1996

Extensor indicis opposition transfer in the ulnar and median palsied thumb in leprosy.

Twenty seven opponensplasties for ulnar and median paralysis in 25 leprosy patients were performed using extensor indicis proprius. An additional transfer of the radial half of flexor pollicis longus to extensor pollicis longus was done to stabilize the metacarpophalangeal joint of the thumb. The biomechanical aspects of extensor indicis proprius tendon transfer were studied and results evaluated using various anatomical and functional parameters. Extensor indicis proprius provides adequate strength to position the thumb. However, sometimes it does not reach its new insertion. There is no significant deficit at the donor site but in a few cases the index finger may lose its capability for independent extension and sometimes a proximal interphalangeal joint contracture may develop.

Adolescent↗
PubMed1996

Evaluation of the results of opponensplasty.

A comprehensive evaluation system for opponensplasties has been described taking into consideration several variables. Each variable has been assigned a score depending upon its significance in the normal hand. The total score of the hand is used for grading the results as good, fair and poor.

Hand Strength↗
PubMed1996

Single tendon--two insertion versus two tendon transfers for reablement of ulnar-median palsied thumb in leprosy.

Twenty-three opponensplasties for ulnar median paralysis in 20 leprosy patients were performed by two different procedures i.e. extensor indicis proprius and flexor digitorum superficialis transfers using standard techniques. The results were evaluated using various objective and subjective, anatomical and functional parameters. Two tendon transfers appeared to be superior to single tendon two insertion transfers. It was concluded that if situation permits, two tendon transfers should be performed for combined ulnar median paralysis.

Adolescent↗
PubMed1995

The potential for the use of cell proliferation and oncogene expression as intermediate markers during liver carcinogenesis.

Intense research using animal models has indicated that chemically-induced rat liver cancer proceeds through multiple, distinct stages that can be characterised morphologically and biochemically. Primary human liver cancer, with hepatitis B and other environmental factors such as poor nutrition and food contaminating mycotoxins as contributing etiological factors, is one of the major causes of cancer deaths in African, Asian and some Western countries. Recent advances in surgical and diagnostic techniques have also allowed the identification of potential morphological precursors of primary human liver cancer, and suggested a model consistent with the concepts of initiation--promotion--progression as in the rat. The expression of proliferating cell nuclear antigen (PCNA), silver-staining nucleolar organiser regions (AgNOR), oncogenes and the tumor suppressor gene p53 in preneoplastic and neoplastic lesions of rat and human livers is presently reviewed. This undertaking is an attempt to evaluate whether the current knowledge regarding molecular mechanisms of carcinogenesis is sufficient to permit the use of these molecular parameters as 'intermediate' markers in studies of risk assessment and cancer prevention, without having to resort to tumor appearance as an end-point.

Animals↗
PubMed1995

Flavonoids as DNA topoisomerase antagonists and poisons: structure-activity relationships.

Selected flavonoids were tested for their ability to inhibit the catalytic activity of DNA topoisomerase (topo) I and II. Myricetin, quercetin, fisetin, and morin were found to inhibit both enzymes, while phloretin, kaempferol, and 4',6,7-trihydroxyisoflavone inhibited topo II without inhibiting topo I. Flavonoids demonstrating potent topo I and II inhibition required hydroxyl group substitution at the C-3, C-7, C-3', and C-4' positions and also required a keto group at C-4. Additional B-ring hydroxylation enhanced flavonoid topo I inhibitory action. A C-2, C-3 double bond was also required, but when the A ring is opened, the requirement for the double bond was eliminated. Genistein has been previously reported to stabilize the covalent topo II-DNA cleavage complex and thus function as a topo II poison. All flavonoids were tested for their ability to stabilize the cleavage complex between topo I or topo II and DNA. None of the agents stabilized the topo I-DNA cleavage complex, but prunetin, quercetin, kaempferol, and apigenin stabilized the topo II DNA-complex. Competition experiments have shown that genistein-induced topo II-mediated DNA cleavage can be inhibited by myricetin, suggesting that both types of inhibitors (antagonists and poisons) interact with the same functional domain of their target enzyme. These results are of use for the selection of flavonoids that can inhibit specific topoisomerases at specific stages of the topoisomerization reaction.

DNA Damage↗
PubMed1995

Spatial learning and memory as a function of age in the dog.

Spatial learning and memory were studied in dogs of varying ages and sources. Compared to young dogs, a significantly higher proportion of aged dogs could not acquire a spatial delayed nonmatching-to-sample task. A regression analysis revealed a significant age effect during acquisition. Spatial memory was studied by comparing performance at delay interval of 20, 70, and 110 s. At short delays aged and young dogs were similar; at longer delays, errors increased to a greater extent in old than in young dogs; however this was not statistically significant. It was possible to identify 2 groups of aged animals, age-impaired and age-unimpaired. Several of the dogs were also tested on an object recognition memory task, which was more difficult to learn than the spatial task. The possibility that these findings are confounded by breed differences is considered. Overall, the present results provide further evidence of the value of a canine model of aging.

Aging↗
PubMed1995

The dietary anticancer agent ellagic acid is a potent inhibitor of DNA topoisomerases in vitro.

Ellagic acid and 12 related agents have been tested for their ability to inhibit the activities of human DNA topoisomerase (topo) I and II. Using specific in vitro assays, we found ellagic acid and flavellagic acid to be potent inhibitors of the catalytic activities of the two topoisomerases. The minimum concentration required to inhibit > or = 50% of catalytic activity (IC50) of ellagic acid was determined at 0.6 and 0.7 micrograms/ml for topo I and topo II, respectively. Flavellagic acid's IC50 was determined at 3.0 and 3.6 micrograms/ml for topo I and topo II, respectively. Unlike topoisomerase poisons, these two plant phenols did not trap the enzyme-DNA reaction intermediate, known as the cleavable complex. In contrast, ellagic acid prevented other topo I and topo II poisons from stabilizing the cleavable complex, suggesting that the mode of its action is that of an antagonist. Structure-activity studies identified the 3,3'-hydroxyl groups and the lactone groups as the most essential elements for the topoisomerase inhibitory actions of plant phenols. On the basis of these findings and other properties of ellagic acid, a mechanistic model for the documented anticarcinogenic effects of the agent is proposed.

Anticarcinogenic Agents↗
PubMed1995

The effect of butylated hydroxytoluene on the growth of enzyme-altered foci in male Fischer 344 rat liver tissue.

Butylated hydroxytoluene (BHT) is a synthetic, food-use, phenolic antioxidant. It has previously been demonstrated to be operationally non-genotoxic and, in addition, failed to induce biologically significant increases in cellular proliferation in the liver, urinary bladder and thyroid gland on feeding to young adult Wistar rats. Nevertheless, it has been reported to enhance the yield of liver tumors when fed to rats or mice that developed an appreciable background incidence of these tumors without treatment. In order to resolve this situation, cell proliferation in response to BHT treatment was studied in enzyme-altered foci (EAF) induced in male Fischer 344 rats using the Solt-Farber procedure. It was demonstrated that feeding 0.5% dietary BHT for 30 days after the induction of EAF led to a 20- to 30-fold increase in the gamma-glutamyltranspeptidase-positive areas in both DEN- and saline-initiated rat livers, but to no major effects in glutathione S-transferase placental form (GSTP)-positive foci. Cell proliferation rates within EAF and surrounding normal liver were measured using different histological techniques. Nuclear labeling with [3H]thymidine and proliferating cell nuclear antigen (PCNA) over the total hepatocyte population indicated that BHT approximately doubled nuclear labeling in rats initiated with DEN. PCNA labeling in GSTP-positive foci was not affected by BHT. In GSTP-positive foci, evaluation of nucleolar organizer regions (AgNOR), which reflect cell proliferative in addition to transcriptional activity of ribosomal RNA, was achieved using a novel double staining technique. BHT diet did not affect the number of AgNOR per nucleus or the percentage AgNOR area/nucleus. Nevertheless, both PCNA labeling and the AgNOR area per nucleus were significantly greater in GSTP-positive foci compared with non-focal regions in rats fed either BHT or control diets. These results are discussed in the light of further experimental work required to determine the relevance of these data to possible human risk assessment for BHT.

2-Acetylaminofluorene↗
PubMed1995

The pharmacokinetics of alfentanil after normothermic and hypothermic cardiopulmonary bypass.

The pharmacokinetics of alfentanil were studied after two different methods of cardiopulmonary bypass (CPB) which used either a normothermic technique or a hypothermic technique with body temperatures below 30 degrees C. A group of surgical patients who did not undergo CPB were also studied. All patients (n = 36) received alfentanil 50 micrograms/kg as a rapid infusion over 10 min and plasma levels were measured for the following 8 h. The volume of distribution in steady state (Vdss) and the volume of central compartment (Vc) were significantly greater in the CPB groups (P = 0.009 and P = 0.04), compared to the nonbypass group. However, the elimination half-life of alfentanil (t1/2 beta) (mean, 95% confidence interval) did not differ significantly between the normothermic (134 min, range 104-172), hypothermic (143 min, range 111-184), and nonbypass (111 min, range 86-142) groups. Between the normothermic and hypothermic CPB groups no significant differences in Vdss, rate of clearance (Cl), or t1/2 beta were found. The pharmacokinetics of alfentanil showed fewer changes after CPB in this study than have been reported previously. Furthermore, different temperature management protocols during CPB did not influence alfentanil elimination.

Aged↗
PubMed1995

The effects of race on diagnosis and disposition from a psychiatric emergency service.

BACKGROUND: Previous studies have reported that racial differences exist in patterns of clinical psychiatric diagnoses as well as the distribution of mental health services resources. The psychiatric emergency service serves as an entry point into the mental health system, so it plays a potentially important role in addressing racial disparities in diagnosis and disposition. To address this disparity, the authors studied two specific questions: (1) are there racial differences in diagnosis and (2) are there racial differences in disposition of patients visiting a psychiatric emergency service? METHOD: Demographic and clinical data were obtained by retrospective chart review of 490 patients randomly selected from 9500 visits to a large psychiatric emergency service during a 1-year period. All clinical information had been recorded by the primary treaters who had no knowledge of this study. RESULTS: Black patients were significantly more likely to be diagnosed with schizophrenia and substance abuse than similar white patients, although less likely to be diagnosed with a personality disorder. Black patients were significantly more likely to be hospitalized, particularly at a public hospital, although there were no significant differences in insurance coverage or measures of suicidal or homicidal ideation. CONCLUSION: Despite the availability of DSM-III-R criteria, black patients continue to be disproportionately diagnosed with schizophrenia. In this sample, this diagnosis may have been given in lieu of a personality disorder or affective illness diagnosis. Black patients are also more likely to be hospitalized. These observations suggest that further research is needed to clarify the effects of race on the decision-making process in diagnosis and disposition from the psychiatric emergency service.

Adult↗
PubMed1995

Acute renal replacement in the intensive care unit: now and tomorrow.

Although acute renal failure (ARF) requiring dialysis affects only approximately 4% to 7% of patients admitted to the ICU, such individuals tend to be the sickest and most challenging patients in the ICU. The presence of ARF dramatically complicates their care and mandates the use of extracorporeal renal replacement therapy (RRT). The use of such therapy, with its technical and physiological demands, further complicates treatment. Not surprisingly, therefore, several controversies surround the management of these patients: the techniques of RRT, the indications and timing for their application, the intensity of their use, the selection of suitable patients, the nature of appropriate monitoring and physiologic targets for their application, the type of specialist best suited for the daily management of such patients, the cost-effectiveness of RRT, and the expansion of its use to treat patients without ARF. In many ways, the response to these controversies has diverged between Europe, Australia, and New Zealand on the one hand, and the United States on the other. In this article, we illustrate these sometimes quite different philosophies by presenting two perspectives (from Australia and the United States) on a number of important issues pertaining to RRT.

Acute Kidney Injury↗
PubMed1994

Glutathione S-transferases and P-glycoprotein in normal rat hepatocytes and hepatoma cells: analysis using flow cytometry.

Using indirect immunofluorescence with fluorescein isothiocyanate-conjugated antibodies, in combination with flow cytometry (FCM), we have developed a technique to detect the alpha, mu and pi isozymes of GST in cell suspensions from normal rat liver, and in H4IIE cells, a rat hepatoma cell line. Cell suspensions fixed in 1% paraformaldehyde were observed to require cell membrane permeation with lysolecithin to allow access and binding of antibodies to immunoreactive proteins within the cytoplasm. FCM analysis indicated normal rat hepatocytes to be positive for GST alpha and mu, but not GST pi, and the H4IIE cells to be positive for all three GST isozymes. Further analysis by FCM for the expression of P-glycoprotein (mdr), a membrane-associated protein product of the multidrug resistance gene, showed an association between the presence of GST pi and mdr in the two cell types. Thus, mdr was detected in significant amounts in H4IIE cells, but not in rat hepatocytes. The method described here has potential applications in screening, sorting and further characterisation for GST pi-positive hepatocytes for mechanistic studies during sequential rat liver carcinogenesis, as well as for characterisation of human tumors for the expression of different GST isozymes and P-glycoprotein during therapeutic management.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1994

Repeated treatment with chimeric anti-CD4 antibody in multiple sclerosis.

We treated 21 multiple sclerosis patients with two to four doses of cM-T412, a chimeric monoclonal antibody against the CD4 antigen found on helper/inducer T lymphocytes. The mean number (+/- standard error) of circulating CD4 lymphocytes decreased from 888 (+/- 81) cells/mm3 at baseline to 246 (+/- 18) after treatment. At 1 year after the last treatment, the CD4 count had recovered to only 335 (+/- 32). The antibody had no effect on CD8 lymphocytes, B lymphocytes, or other leukocytes. Side effects were minimal. Despite the prolonged depletion of CD4 lymphocytes, no opportunistic infections occurred. Only 1 patient had a possible allergic reaction. Most patients were clinically stable, but a few progressed. We conclude that repeated treatment with cM-T412 is effective in reducing the number of circulating CD4 lymphocytes and has no limiting side effects.

Adult↗
PubMed1994

International Commission for Protection Against Environmental Mutagens and Carcinogens. Oxidative DNA damage--the effects of certain genotoxic and operationally non-genotoxic carcinogens.

A wide variety of oxidative DNA lesions are commonly present in untreated human and animal DNA. One of these lesions, 8-hydroxydeoxyguanosine, has been shown to lead to base mispairing (mutation) on DNA replication. Other lesions remain to be investigated in this respect. Oxidative DNA lesions on cell replication may, in appropriate circumstances, lead to proto-oncogene activation. Oxidative DNA damage, on fixation, may also lead to cytotoxicity followed by regenerative proliferation. The probable or possible importance of oxidative DNA damage is reviewed for various classes of carcinogens and natural processes, including metal ions, high-energy radiation, miscellaneous chemicals, tumor-promoting agents, polyhydroxyphenols/quinones, lipid metabolism, peroxisome proliferators and thyroid function. It is concluded that although the evidence needs considerable strengthening in many of these examples, the available information indicates the potential importance of oxidative DNA damage in the induction of tumors by these agents. It is also possible that non-cancerous degenerative diseases associated with aging are the result of the accumulation of lesions resulting from unrepaired oxidative DNA damage.

Animals↗
PubMed1994

Fitness to drive in patients with cirrhosis and portal-systemic shunting: a pilot study evaluating driving performance.

It has been suggested that some patients with cirrhosis are unfit to operate a motor vehicle. However, performance while driving a motor vehicle has not been evaluated in such patients. In this pilot study, we assessed the fitness to drive of stable individuals with cirrhosis and clinical evidence of portal hypertension, portal-systemic shunting and no prior history of hepatic encephalopathy. We examined 15 ambulatory patients with cirrhosis together with 15 age-, educational level- and driving experience-matched healthy controls. Neuropsychological testing was performed with the Reitan trail test, block design and digit symbol tests as well as visual reaction time. A driving test in the laboratory used a film to measure complex visual reaction time (reaction to road symbols) and threat recognition (accident avoidance). Driving on the road was assessed by a licensed Illinois state driving evaluator. Penalty points were given according to 11 standardized driving categories. As a group, patients with cirrhosis had no significant differences in their performance on a simulator or during actual driving conditions when compared to matched controls. Sixty-six percent of the subjects with cirrhosis had two or more abnormal neuropsychological tests, a criterion used to define the presence of subclinical encephalopathy. No deficiencies in simulated or real driving performance was seen when compared to patients with cirrhosis with normal neuropsychological tests. In this study, stable subjects with cirrhosis and evidence of portal hypertension, portal-systemic shunting, abnormal neuropsychological tests and no prior history of overt encephalopathy did not exhibit a major impairment in their fitness to drive.

Adult↗