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Biomedical subjects

R Manchanda

Publications and source records attributed to R Manchanda.

At least 19 recordsLinked to original sources
PubMed2006

Post- and prejunctional consequences of ecto-ATPase inhibition: electrical and contractile studies in guinea-pig vas deferens.

At sites of purinergic neurotransmission, synaptic ecto-ATPase is believed to limit the actions of ATP following its neural release. However, details of the modulation by this enzyme of the ATP-mediated conductance change and the possible mechanisms mediating this modulation remain unelucidated. We have addressed these issues by studying the effect of ARL 67156, a selective ecto-ATPase inhibitor, on ATP-mediated electrical and contractile activity in the sympathetically innervated guinea-pig vas deferens. ARL 67156 at 100 mum significantly potentiated the amplitude of spontaneous excitatory junction potentials (SEJPs) by 81.1% (P < 0.01) and prolonged their time courses (rise time by 49.7%, decay time constant by 38.2%; P < 0.01). Moreover, the frequency of occurrence of SEJPs was strikingly increased (from 0.28 +/- 0.13 to 0.90 +/- 0.26 Hz; P < 0.01), indicating an additional, primarily presynaptic, effect of ecto-ATPase inhibition. The frequency of occurrence of discrete events (DEs), which represent nerve stimulation-evoked quantal release of neurotransmitter, was also increased ( approximately 6-fold; P < 0.01), along with the appearance of DEs at previously 'silent' latencies. Purinergic contractions of the vas deferens were potentiated significantly (P < 0.01) by ARL 67156; these potentiated contractions were suppressed by the A1 agonist adenosine (P < 0.01) but left unaffected by the A1 antagonist 8-phenyltheophylline (8-PT). Our results indicate (i) that ecto-ATPase activity, in addition to modulating the ATP-mediated postjunctional conductance change, may regulate transmitter release prejunctionally under physiological conditions, and (ii) that the prejunctional regulation may be mediated primarily via presynaptic P2X, rather than A1, receptors.

Action Potentials↗
PubMed2006

Effects of heptanol on neurogenic contractions of vas deferens: A comparative study of stimulation frequency in guinea pig and rat.

This study examines the role of gap junctional communication in smooth muscle in relation to the frequency of stimulation and the innervation density of the tissue in the generation of neurogenic contractions. Toward this end the effects of heptanol, a gap junctional blocker, on the neurogenic contractions of guinea pig and rat vas deferens at different frequencies of stimulation (single pulse, 5, 10, 20, 40, 60, and 80 Hz) were studied. In both the prostatic and epididymal halves of these tissues, heptanol abolished the neurogenic contractions at the lower frequencies of stimulation. At higher frequencies, contractions were resistant to heptanol action. The effect of heptanol on the neurogenic contractions was found to decrease with increasing stimulation frequency. The neurogenic contractions of rat vas deferens were more resistant to heptanol than those of guinea pig vas deferens. Our data indicate that gap junctional communication is significant in the generation of neurogenic contractions in both guinea pig and rat vas deferens in a frequency-dependent manner, and we discuss the mechanisms underlying these findings.

Animals↗
PubMed2005

Discovery of the short gamma-ray burst GRB 050709.

Gamma-ray bursts (GRBs) fall into two classes: short-hard and long-soft bursts. The latter are now known to have X-ray and optical afterglows, to occur at cosmological distances in star-forming galaxies, and to be associated with the explosion of massive stars. In contrast, the distance scale, the energy scale and the progenitors of the short bursts have remained a mystery. Here we report the discovery of a short-hard burst whose accurate localization has led to follow-up observations that have identified the X-ray afterglow and (for the first time) the optical afterglow of a short-hard burst; this in turn led to the identification of the host galaxy of the burst as a late-type galaxy at z = 0.16 (ref. 10). These results show that at least some short-hard bursts occur at cosmological distances in the outskirts of galaxies, and are likely to be caused by the merging of compact binaries.

Journal Article↗
PubMed2005

EEG abnormalities and two year outcome in first episode psychosis.

OBJECTIVE: This study examines the relationship of EEG to 2 year symptomatic outcome, duration of illness and untreated psychosis and gender. METHOD: A total of 122 patients presenting for treatment of first episode psychosis had their baseline EEG classified by modified Mayo Clinic system criteria as normal, essentially normal or dysrhythmia. Positive and negative symptoms of psychoses were rated on entry and after 2 years of treatment. The socio-demographic variables and duration of illness and of untreated psychosis were also recorded. RESULTS: Patients with a normal EEG showed significantly more reduction in both positive and negative symptoms of psychoses over 2 years and were more likely to be in 'remission' as compared with the essentially normal or dysrhythmia group. The dysrhythmic group had significantly higher duration of illness than either the normal or essentially normal groups. There were no gender differences in the distribution of EEGs. CONCLUSION: An abnormal EEG in patients with first episode psychosis is associated with a poorer prognosis and a longer duration of untreated illness.

Adolescent↗
PubMed2005

Premorbid adjustment in first episode schizophrenia and schizoaffective disorders: a comparison of social and academic domains.

OBJECTIVE: Recent evidence suggests that premorbid adjustment in schizophrenia and related disorders can be separated into social and academic domains. In this paper, we examine the correlates of and prognostic significance of social and academic premorbid adjustment in a sample of 113 patients. METHOD: Premorbid adjustment, symptoms and cognitive functioning were assessed at presentation for treatment and symptoms were re-assessed after a year of treatment. RESULTS: Females and those with a diagnosis of schizoaffective disorder were found to have better premorbid adjustment in the academic domain, but not in the social domain. Neurocognitive functioning was more consistently related to academic than social adjustment. Better social and academic premorbid adjustment was correlated with lower negative symptoms after 1 year of treatment, but neither was a significant predictor of positive symptoms. CONCLUSION: Social and academic premorbid adjustments show different relations to gender, specific diagnosis and neurocognitive functioning in schizophrenia and related disorders.

Achievement↗
PubMed2003

Simulation framework for electrophysiological networks: effect of syncytial properties on smooth-muscle synaptic potentials.

A building block-based software framework was developed to simulate electrophysiological networks. The synaptic potentials generated during neurotransmission were simulated in an existing discrete bidomain model of smooth muscle, using cubic, three-dimensional grids of varying sizes. The model is automatically derived and numerically solved, and the results of the simulation agree with previous results obtained analytically. An enhanced model was also proposed, incorporating an additional (junctional) capacitance in the network. The correctness of the model was verified, and the effect of the extra capacitance on the synaptic potentials was explored. It was found that, with a junctional capacitance C(i) of 1.4 x 10(-10) F incorporated, the peak amplitude of the spontaneous excitatory junction potential V(peak) declined by approximately 13% at node 0 and by approximately 37% at node 3x for a system size of 9(3). Similar results were obtained for different system sizes. V(peak) also declined as the junctional capacitance Ci was increased. In a system of size 11(30, a 200-fold increase in C(i) induced a 55% reduction at node 0. It is suggested that the type of modular simulation framework developed here may find general applicability for simulations of other physiological systems.

Electrophysiology↗
PubMed2002

Symptoms, cognition, treatment adherence and functional outcome in first-episode psychosis.

BACKGROUND: The differential strength of correlation between symptoms, cognition and other patient characteristics with community functioning in first-episode psychosis has not been fully investigated. METHOD: In a sample of 66 first-episode psychosis patients demographic variables, ratings of pre-morbid adjustment, positive and negative symptoms, duration of untreated psychosis (DUP) and assessment of cognitive functions at baseline, and symptoms, cognitive functions and adherence to medication 1 year, were correlated with scores on social relations and activities of daily living (ADL) (outcome) at 1 year. Hierarchical regression analysis was used to confirm the independent contribution of baseline and concurrent variables to functional outcome at 1 year. RESULTS: Scores on functioning related to social relations and ADL were both significantly correlated with pre-morbid adjustment, all dimensions of residual positive and negative symptoms and adherence to medication at 1 year. Scores on social relations were also modestly correlated with DUP and several cognitive measures at baseline and 1 year (verbal IQ, attention, visual memory, word fluency and working memory). Hierarchical regression confirmed independent contribution of pre-morbid adjustment, total residual symptoms and adherence to medication at 1 year for both dimensions of outcome, and psychomotor poverty and working memory for social relations. CONCLUSIONS: In addition to pre-morbid adjustment potentially malleable variables such as level of residual (but not acute) symptoms, adherence to medication and cognitive deficits are likely to influence outcome on aspects of community functioning in individuals treated for first episode of psychosis.

Activities of Daily Living↗
PubMed2001

Laparoscopic ovarian drilling in clomiphene citrate-resistant women with polycystic ovary syndrome.

STUDY OBJECTIVE: To analyze the efficacy of laparoscopic ovarian drilling using monopolar diathermy in women with anovulatory infertility with clomiphene-resistant polycystic ovary syndrome (PCOS), and to determine factors influencing pregnancy rate and pregnancy outcomes. DESIGN: Prospective study (Canadian Task Force classification II-2). SETTING: Infertility clinic in a tertiary referral teaching hospital. PATIENTS: Seventy women with clomiphene-resistant PCOS. INTERVENTION: Laparoscopic ovarian drilling, with follow-up for 4.5 years. MEASUREMENTS AND MAIN RESULTS: Follow-up data, which were available for 66 patients, showed a spontaneous ovulation rate of 81.8%, cumulative ovulation rate of 93.9%, and pregnancy rate of 54.5%. Successful pregnancies were commonly complicated by gestational diabetes mellitus and pregnancy-induced hypertension. Pregnancy rates (23.5%) were low in women with tuboperitoneal disease and those whose partners had subfertile male factors. Statistical evaluation using a proportion test (Z test) and multivariable logistical regression analysis showed that elevated luteinizing hormone levels (>10 IU/L), short duration of infertility (<3 yrs), and absence of preexisting tubal disease were associated with better outcomes. CONCLUSION: Laparoscopic ovarian drilling is an effective surgical procedure in women with clomiphene-resistant PCOS.

Adult↗
PubMed2001

Methotrimeprazine in the treatment of agitation in acquired brain injury patients.

Medical management of the agitation associated with acquired brain injury (ABI) has been proble matic. At least 12 distinct drugs are currently recommended in the medical literature. In recent years, on the ABI in-patient rehabilitation unit, methotrimeprazine (MTZ) has come to be the preferred drug and is used routinely for effective treatment of agitation. The objective of this paper is to describe the use and safety of MTZ in the rehabilitation of ABI patients. A retrospective chart review of all patients discharged from the ABI unit over a course of 2 years was conducted. In addition to demographics such a aetiology of ABI, sex, age, length of stay, Glasgow Coma Scale, length of posttraumatic amnesia and others, a detailed analysis was made of the multidisciplinary progress notes to determine the daily agitation status and the daily use of psychotropic medication. All notes on side effects and adverse reactions were carefully documeneted. 120 first admission recent ABI patients were discharged in the 2 year study period. Of these, 69 (57%) had some level of agitation and 56 (48%) were treated with MTZ, in doses of 2-50 mg up to four times daily. Agitation was controlled in most cases. In only two cases were significant side effects noted. While MTZ has been used as a safe and effective neuroleptic in psychiatry for over 40 years, this is the first report of its use in treating agitation in ABI.

Adolescent↗
PubMed2001

Depot medroxy progesterone acetate: a poor preparatory agent for endometrial resection.

OBJECTIVE: To evaluate the efficacy of depot medroxy progesterone acetate (DMPA) as a preparatory agent for endometrial resection. STUDY DESIGN: Endometrial resection was performed on 50 women for excessive uterine bleeding. The patients were randomly divided into 2 equal groups, with the first group receiving DMPA and the second group not receiving any hormonal pre-medication. The resected tissue was sent for histopathology and all the patients were followed up regularly for a maximum period of 4 years. RESULTS: DMPA was found to increase the thickness of the endometrium, making it more fluffy and oedematous. The procedure in these patients was associated with a significantly greater fluid consumption and deficit. A power analysis showed the overall power of the study to be >90%. Forty-four percent of group 1 and 64% of group 2 patients achieved amenorrhoea or spotting. Three patients in all underwent a repeat procedure, and 1 a hysterectomy, following a dissatisfactory result. However, no statistically significant difference was found in the outcomes of the 2 groups. CONCLUSION: As a preparatory agent, DMPA, seems to have no added benefit. Larger studies are required to bring out differences in outcomes, if any.

Adult↗
PubMed2001

Laparoscopic management of Sertoli-Leydig cell tumors of the ovary. A report of two cases.

BACKGROUND: Sertoli-Leydig cell tumor is a rare ovarian tumor with an incidence of < .5% of all ovarian tumors. Laparotomy is the standard approach to these cases. CASES: Sertoli-Leydig cell tumors were diagnosed in two young, nulliparous, infertile women. Both presented with secondary amenorrhea. Virilization was found in one. Their testosterone levels were high, and sonography revealed a solid, echogenic mass in the fornix. Laparoscopic removal was performed. Both women achieved normal menstruation one month after the operation, and one became pregnant and gave birth to a healthy infant. CONCLUSION: There are very few case reports of laparoscopic removal of such tumors. Laparoscopic surgery, which is minimally invasive and cosmetically acceptable and has a speedy recovery, should be the approach of choice for these patients.

Adult↗
PubMed2001

Role of prostaglandins in the suppression of apoptosis in hen granulosa cells by transforming growth factor alpha.

Although transforming growth factor alpha (TGF-alpha) is known to be an important survival factor for granulosa cells, the cellular and molecular mechanisms involved are uncertain. The purpose of the present study was to investigate the possible involvement of prostaglandins in the anti-apoptotic action of TGF-alpha. Hen granulosa cells from healthy prehierarchical follicles (2-6 mm) cultured in serum-free medium underwent spontaneous apoptosis as demonstrated by DNA fragmentation and nuclear chromatin condensation. TGF-alpha (20 ng ml(-1)) stimulated maximum synthesis of prostaglandins (PGE and PGF) in granulosa cells and completely inhibited serum deprivation-induced apoptosis. The addition of an inhibitor of cyclooxygenase (COX; N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide (NS398) or ibuprofen) or phospholipase A(2) (PLA(2); aristolochic acid, 2-p-amylcinnamoyl amino-4-chlorobenzoic acid (ONO-RS-82) or arachidonyl triflouro methyl ketone (TFMK)), to the culture medium markedly suppressed the TGF-alpha-induced prostaglandin synthesis and significantly increased granulosa cell apoptosis. The apoptotic effect of NS398 and aristolochic acid was completely inhibited by exogenous prostaglandins (PGF(2 alpha), PGE(1), PGE(2)) and arachidonic acid, respectively. However, exogenous prostaglandins failed to inhibit the PLA(2) inhibitor-induced apoptotic DNA fragmentation, implying that in addition to prostaglandins, arachidonic acid or leukotrienes may be important in transducing the anti-apoptotic action of TGF-alpha. In the absence of exogenous TGF-alpha, prostaglandins had no significant influence on granulosa cell apoptosis induced by serum withdrawal. These findings indicate that prostaglandin synthesis is a necessary, but not sufficient, event in the suppression of granulosa cell apoptosis by TGF-alpha. Whether arachidonic acid or leukotrienes are important in the anti-apoptotic action of TGF-alpha in hen granulosa cells remains to be determined.

Alprostadil↗
PubMed2000

Influence of the size of syncytial units on synaptic potentials in smooth muscle.

The effect of the size of syncytial bundles of cells on the passive synaptic potentials generated within them has been explored. Computer simulations have been performed of neuronally produced spontaneous excitatory junction potentials (SEJPs) generated in cubical 'bidomain' model of syncytial tissue. It is found that indical properties of SEJPs vary conspicuously in syncytium sizes smaller than about 15-17-cube, but change very little in syncytium sizes greater than this. At the centroid of the cube, the peak amplitude Vp of the SEJP declines from 14.32 mV to 11.70 mV as syncytium size increases from 7-cube to 15-cube, i.e. a decrease of approximately 18%, while between system sizes 15-cube (Vp = 11.70 mV) and 29-cube (Vp = 11.67 mV), the reduction is only approximately 0.3%. Similar trends are observed for the time to peak of SEJPs. These observations indicate a minimum bundle size in smooth muscle below which syncytial function is modified; the implications of this are discussed.

Computer Simulation↗
PubMed2000

Maternal smoking and fetal erythropoietin levels.

OBJECTIVE: To determine the influence of maternal smoking on fetal erythropoietin concentrations in health term pregnancies and test the correlation between cotinine, a biomarker of maternal smoking, and erythropoietin levels in fetuses. METHODS: We invited women with healthy term pregnancies to participate in the study, excluding those with conditions previously known to be associated with elevated fetal erythropoietin levels. We recorded demographic data, smoking status, and labor outcome prospectively for each patient. Umbilical venous samples were collected, and serum was stored at -70C to be analyzed later for erythropoietin and cotinine. Umbilical arterial samples were tested for pH and base excess determination. We compared fetal erythropoietin and cotinine between smokers and nonsmokers and examined correlations between erythropoietin and cotinine. Kruskal-Wallis test, t test, median test, and Spearman rank correlation test were used when appropriate. Statistical significance was P <.05. RESULTS: We recruited 35 nonsmokers and 26 smokers and analyzed their samples. The two groups were comparable in demographics and birth outcomes, except for birth weights, which were lower in smokers. Fetal erythropoietin concentrations increased significantly with increasing maternal cigarette consumption, ranging from none to more than 15 cigarettes per day (P =.03). There was positive correlation between fetal erythropoietin and cotinine concentrations (r =.41; P =.04), suggesting a dose-response relationship. CONCLUSION: Fetuses of smokers had increased erythropoietin concentrations that correlate positively with fetal cotinine levels; which suggests an increased risk of subacute hypoxia related to degree of maternal cigarette consumption.

Adult↗
PubMed2000

Psychiatric assessment of candidates for epilepsy surgery.

Patients with medically intractable epilepsy often present with comorbid psychiatric diseases. When referred to a program for the surgical treatment of the epilepsies, these patients benefit from a pre-admission psychiatric assessment with a view to lessen the chances of a psychiatric crisis during the pre- and postoperative investigations. This article proposes a practical approach to the psychiatric assessment and monitoring of adult candidates to the surgery of epilepsy. It emphasizes, in agreement with a world literature review, that definitive psychiatric contraindications to this elective surgery are few, and that adverse long-term psychiatric outcomes are less frequent when good seizure outcome is achieved.

Epilepsy↗
PubMed2000

Analysis of synaptic quantal depolarizations in smooth muscle using the wavelet transform.

The time-frequency characteristics of synaptic potentials contain valuable information about the process of neurotransmission between nerves and their target organs. For example, at the synapse between autonomic nerves and smooth muscle, two central issues of neurophysiology, i.e., 1) the probability of neurotransmitter release and 2) the quantal behavior of transmission can be deduced from analysis of the rising phases of evoked excitatory junction potentials (eEJP's) recorded from smooth muscle. eEJP rising phases are marked by prominent inflexions, which reflect these features of neuronal activity. Since these inflexions contain time-varying frequency information, we have applied recent techniques of time-frequency analysis based upon wavelet transforms to eEJP's recorded from the guinea-pig vas deferens in vitro. We find that these techniques allow accurate and convenient characterization of neuronal release sites, and that their probability of release falls between 0.001-0.004. We have also analyzed eEJP's recorded in the presence of the chemical 1-heptanol, which reveals quantal depolarizations. These results have helped clarify the nature of the quantal depolarizations that underly eEJP's. The present method offers significant advantages over those previously employed for these tasks, and holds promise as a novel approach to the analysis of synaptic potentials.

Animals↗