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Biomedical subjects

V Sharma

Publications and source records attributed to V Sharma.

At least 163 records · Page 9Linked to original sources

Age-related changes in the association between serotonergic function and aggression in boys with ADHD.

The results of several studies have indicated an inverse relationship between central serotonergic (5-HT) mechanisms and aggression in animals and adults, but studies in children have yielded conflicting results. This study assessed 5-HT function, using a fenfluramine (FEN) challenge procedure, in an attempt to replicate a previously reported enhancement of the prolactin (PRL) response to FEN in aggressive relative to nonaggressive ADHD boys. The study failed to replicate the previous finding. Samples from both studies were then examined to reconcile the discrepant findings. The samples differed significantly in age. The entire group (n = 50) was then divided into older and younger subgroups and reanalyzed using a two-way (age-group x aggression) analysis of covariance (ANCOVA) controlling for plasma medication level. The ANCOVA generated a significant age-group x aggression interaction. Young aggressive boys had a significantly greater PRL response to FEN than young nonaggressive boys, but no such difference existed in the older age-group. These findings raise the possibility of different developmental trajectories in 5-HT function between aggressive and nonaggressive boys.

Aggression↗

Probing the chloroquine resistance locus of Plasmodium falciparum with a novel class of multidentate metal(III) coordination complexes.

The malaria organism Plasmodium falciparum detoxifies heme released during degradation of host erythrocyte hemoglobin by sequestering it within the parasite digestive vacuole as a polymer called hemozoin. Antimalarial agents such as chloroquine appear to work by interrupting the heme polymerization process, but their efficacy has been impaired by the emergence of drug-resistant organisms. We report here the identification of a new class of antimalarial compounds, hexadentate ethylenediamine-N, N'-bis[propyl(2-hydroxy-(R)-benzylimino)]metal(III) complexes [(R)-ENBPI-M(III)] and a corresponding ((R)-benzylamino)] analog [(R)-ENBPA-M(III)], a group of lipophilic monocationic leads amenable to metallopharmaceutical development. Racemic mixtures of Al(III), Fe(III), or Ga(III) but not In(III) (R)-ENBPI metallo-complexes killed intraerythrocytic malaria parasites in a stage-specific manner, the R = 4,6-dimethoxy-substituted ENBPI Fe(III) complex being most potent (IC50 approximately 1 microM). Inhibiting both chloroquine-sensitive and -resistant parasites, potency of these imino complexes correlated in a free metal-independent manner with their ability to inhibit heme polymerization in vitro. In contrast, the reduced (amino) 3-MeO-ENBPA Ga(III) complex (MR045) was found to be selectively toxic to chloroquine-resistant parasites in a verapamil-insensitive manner. In 21 independent recombinant progeny of a genetic cross, susceptibility to this agent mapped in perfect linkage with the chloroquine resistance phenotype suggesting that a locus for 3-MeO-ENBPA Ga(III) susceptibility was located on the same 36-kilobase segment of chromosome 7 as the chloroquine resistance determinant. These compounds may be useful as novel probes of chloroquine resistance mechanisms and for antimalarial drug development.

ATP-Binding Cassette Transporters↗

Changes in plasma prolactin and catecholamine metabolite levels following acute needle stick in children.

Changes in plasma levels of prolactin (PRL), homovanillic acid (HVA), and 3-methoxy-4-hydroxyphenylglycol (MHPG) following insertion of an indwelling catheter into a forearm vein were assessed in 11 boys with attention-deficit hyperactivity disorder. Results indicated decreases in plasma PRL and HVA, but not MHPG, from the time of needle stick until 105 min post-insertion. These data indicate a significant increase in plasma PRL and HVA in children following needle stick which gradually decreases over a 1.5-2-h period. These stress-induced changes indicate that values obtained immediately after needle insertion cannot be assumed to accurately reflect baseline levels.

Attention Deficit Disorder with Hyperactivity↗

Clofibrate feeding to Sprague-Dawley rats increases endogenous biosynthesis of oxalate and causes hyperoxaluria.

The effects of clofibrate feeding (5 g/kg diet) on oxalate metabolism were investigated in male and female rats. Following clofibrate feeding, 24-hour urinary excretion of oxalate increased until 4 days and then reached a plateau. Whereas the contribution of dietary oxalate (1.4 g/kg diet, as potassium salt) to urinary oxalate was less than 5% in both control and clofibrate-treated male rats, the contribution of dietary glycolate (1.0 g/kg diet, as sodium salt) to urinary oxalate was six times higher in clofibrate-treated male rats compared with controls, indicating that the clofibrate-induced hyperoxaluria is due to increased endogenous biosynthesis of oxalate. This was supported by the increased lactate dehydrogenase (LDH) activity observed in liver supernatants of clofibrate-treated rats compared with controls, and the increased rate of conversion of glycolate and glyoxylate to oxalate by clofibrate-treated male rat liver supernatants. Female rats had lower excretion of urinary oxalate and lower levels of liver glycolic acid oxidase (GAO) as compared with males. Clofibrate-treated female rat liver supernatants had higher LDH levels and produced more oxalate from glyoxylate. Thus, it can be concluded that the increase in LDH activity may be the cause of the increased endogenous biosynthesis of oxalate leading to increased urinary excretion of oxalate in male and female rats treated with clofibrate.

Alcohol Oxidoreductases↗

Endometrial carcinoma in a young patient with polycystic ovarian syndrome: first suspected at time of embryo transfer.

Adenocarcinoma of the endometrium is a rare condition in women under 40 years of age. However, patients with anovulatory polycystic ovarian syndrome are at risk of developing endometrial carcinoma due to the unopposed and prolonged effect of oestrogen on the endometrium. This case report discusses the dilemma of various treatment options for early disease in such patients.

Adenocarcinoma↗

The application of neural networks in predicting the outcome of in-vitro fertilization.

Infertility affects one in six couples at some time in their lives, with 48% of these couples requiring assisted conception techniques in order to achieve a pregnancy. Whilst the overall clinical pregnancy rate per embryo transfer is 23%, this varies widely between clinics. The Human Fertilisation and Embryology Authority has attempted to analyse the results of all units, with weighting of different factors affecting assisted conception, and the published data have invariably led to comparisons between units. However, statistical models need to be developed to eliminate bias for valid comparisons. Neural networks offer a novel approach to pattern recognition. In some instances neural networks can identify a wider range of associations than other statistical techniques due in part to their ability to recognize highly non-linear associations. It was hoped that a neural network approach may be able to predict success for individual couples about to undergo in-vitro fertilization (IVF) treatment. A neural network was constructed using the variables of age, number of eggs recovered, number of embryos transferred and whether there was embryo freezing. Overall the network managed to achieve an accuracy of 59%.

Adult↗

Plasma cortisol and aggression in boys with ADHD.

OBJECTIVE: The results of several studies suggest an inverse relationship between cortisol secretion and aggressive behavior. This study examined basal plasma cortisol levels in aggressive and nonaggressive boys with attention-deficit hyperactivity disorder (ADHD). METHOD: The subjects were 23 aggressive and 27 nonaggressive boys with ADHD, aged 7 to 11 years. After 3 days of a low monoamine diet and an overnight fast, an indwelling catheter was inserted into a forearm vein. Samples for plasma cortisol levels were obtained 105 and 115 minutes after insertion of the catheter. RESULTS: A one-way analysis of covariance (ANCOVA) controlling for body mass revealed no significant difference in plasma cortisol between the aggressive and nonaggressive boys. Furthermore, when the children were alternatively divided on the basis of the presence or absence of a DSM-III-R diagnosis of conduct disorder, a one-way ANCOVA again revealed no significant difference in cortisol levels. CONCLUSIONS: The hypothesized inverse relationship between cortisol secretion and aggressive behavior in boys with ADHD was not found. These findings are consistent with a large body of literature indicating that the biological substrate of aggression is complex and that the identification of biological laboratory markers of aggressive behavior is not a clinically useful strategy at this time.

Aggression↗

Serotonin, aggression, and parental psychopathology in children with attention-deficit hyperactivity disorder.

OBJECTIVE: To explore the relationship between central serotonergic (5-HT) function and history of parental aggression in aggressive and nonaggressive boys with attention-deficit hyperactivity disorder (ADHD). METHOD: History of psychiatric symptoms was assessed in the biological parents of 41 boys with ADHD. The relationship between 5-HT function in aggressive and nonaggressive probands, as assessed via the prolactin response to fenfluramine (FEN) challenge, and parental history of aggression was examined. RESULTS: Aggressive boys with a parental history of aggressive behavior had a significantly lower prolactin response to FEN challenge than aggressive boys without a parental history of aggression. Nonaggressive boys had a prolactin response midway between those of the two aggressive subgroups, and their prolactin response did not vary as a function of parental aggression. Children subdivided on the basis of parental history of other psychiatric symptoms did not differ in their response to the FEN challenge. CONCLUSIONS: These data indicate an association between parent aggressive behavior and lower 5-HT function in aggressive boys with ADHD but do not indicate the extent to which this association is environmentally and/or genetically transmitted. There may be different neurochemical mechanisms in familial and nonfamilial aggressive children, which have clinical implications for pharmacological interventions.

Adult↗

Adolescent boys in Gujarat, India: their sexual behavior and their knowledge of acquired immunodeficiency syndrome and other sexually transmitted diseases.

We assessed the sexual behavior patterns of 368 unmarried, sexually active adolescent boys (294 rural, 74 urban) and their knowledge of sexually transmitted diseases (STDs) and correct use of condoms. The mean knowledge score for STDs was low and significantly associated with educational level (p < .0001). The mean awareness score for correct use of condoms was 0.42 on a scale of 10 and significantly associated with employment status and age at first coitus (p < .001). There was a negative correlation (-0.17) between literacy and knowledge of correct use of condoms. Selection of the first sexual partner, usually a prostitute, was influenced by employment status, age at first coitus, and literacy level. These data suggest that sexually active adolescent boys in Gujarat, India are inadequately prepared to protect themselves against STDs and, therefore, that it is imperative to impart to them some knowledge of safe sex.

Acquired Immunodeficiency Syndrome↗

Treatment of bipolar depression: a survey of Canadian psychiatrists.

OBJECTIVE: This study was conducted to examine how Canadian psychiatrists manage bipolar depression. METHOD: A questionnaire specific to the treatment of bipolar depression was mailed to 1639 active members of the Canadian Psychiatric Association. RESULTS: Seven hundred and sixty-six completed questionnaires were returned (46.7%). Most psychiatrists indicated that a combination of psychotherapy and somatic therapy was their preferred approach. For bipolar disorder, depressed, lithium carbonate and selective serotonin reuptake inhibitors (SSRIs) were the preferred treatment strategies. For substitution, tricyclic antidepressants (TCAs) were the favoured choice. Lithium carbonate was the preferred choice for augmentation and, addition. CONCLUSION: These findings indicate that a combination of psychotherapy and somatic therapy is the preferred treatment approach for bipolar depression. Lithium carbonate and SSRIs are the favoured somatic therapies.

Adult↗

Role of psychiatric disorders in self-inflicted periodontal injury: a case report.

Self-inflicted or factitious injuries (FI) are not uncommon in psychiatric patients. In general, this kind of behavior is linked to secondary gain. However, the role of underlying psychiatric illness should not be overlooked. Usually, the diagnosis of factitious injury can be confirmed by a careful medical-dental history, clinical appearance of the lesion, laboratory investigations, and response to established treatment protocol. A case is presented in which repetitive injurious behavior resulted in rapid periodontal attachment loss. The lesion responded well to conservative periodontal treatment. The role of underlying psychiatric morbidity leading to repetitive self-injurious behavior is discussed.

Adolescent↗

The foundations of effective management of bipolar disorder.

OBJECTIVES: To understand the epidemiology and course of bipolar disorder; to outline the importance of accurate and reliable diagnosis of bipolar disorder both on a cross-sectional and longitudinal basis; and to emphasize the value of a collaborative therapeutic relationship, psychoeducation, and psychotherapy. METHODS: A brief review of relevant literature to deal with the issues of diagnosis and laying the foundations for effective treatment. RESULTS: Bipolar disorder may well be a heterogeneous group of conditions with varying forms of biphasic mood dysregulation and a changing course across a lifetime. A collaborative therapeutic relationship, psychoeducation, and psychotherapy can be the basis for effective management. CONCLUSIONS: As the concept of bipolar disorder has broadened, the condition is being identified with increasing frequency in many clinical settings. It is a relapsing and recurring condition. It is now recognized that in addition to rational pharmacotherapy, there is a need to encourage a high level of treatment adherence while providing a holistic package of interventions.

Bipolar Disorder↗

Psychosocial interventions as an adjunct to pharmacotherapy in bipolar disorder.

OBJECTIVE: To summarize the evidence and make treatment recommendations regarding the use of psychosocial interventions as an adjunct to pharmacotherapy for bipolar disorder. METHODS: We reviewed published outcome studies since 1975 identified in MEDLINE and PsychLIT searches. RESULTS: Available studies are initial and of highly variable methodological rigour. Evidence is most robust for the efficacy of psychoeducation and family therapy, and these received the highest level of recommendation as interventions. Group therapy, cognitive-behavioural therapy, and behavioural family management therapy are supported by weaker evidence and received a lower-level treatment recommendation. Availability of only a single interpersonal and social rhythms therapy trial limited the confidence of the recommendation for this intervention. CONCLUSIONS: Controlled trials are needed to replicate early outcome studies and guide treatment recommendations. Accumulated evidence of favourable psychosocial intervention outcomes supports, with variable confidence, their use as adjuncts to pharmacotherapy in the treatment of bipolar disorder.

Bipolar Disorder↗

Treatment of mania, mixed state, and rapid cycling.

OBJECTIVES: To summarize the quality of evidence for the efficacy of different biological treatments in mania, mixed state, and rapid cycling and to propose guidelines for treatment of these conditions. METHOD: Articles published on treatment of acute mania, mixed states, and rapid cycling were reviewed and rated for quality of evidence using Periodic Health Examination guidelines. RESULTS: Lithium and divalproex sodium are effective in classical pure mania, whereas divalproex sodium and carbamazepine are likely more effective in mixed states. Divalproex sodium is likely more efficacious than carbamazepine and lithium when the mania is part of a rapid-cycling course. Typical neuroleptics are efficacious in acute mania, particularly in the presence of marked psychotic symptoms. Atypical neuroleptics can be useful in refractory mania. Some benzodiazepines do have antimanic effects, but they are increasingly being shown to have usefulness as adjuncts to mood stabilizers or neuroleptics rather than as primary antimanic agents. Electroconvulsive therapy (ECT) is an efficacious and broad-spectrum treatment. CONCLUSIONS: Mania can present with or without mood-congruent or mood-incongruent psychotic features and as part of a rapid-cycling or nonrapid-cycling course. Mixed state is a common presentation in an acutely manic patient. The accurate assessment of these issues can serve as a guide in determining treatment options and choices.

Bipolar Disorder↗