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Biomedical subjects

S Verma

Publications and source records attributed to S Verma.

At least 127 records · Page 7Linked to original sources

How children and adolescents spend time across the world: work, play, and developmental opportunities.

The authors review studies on time use of children and adolescents around the world and discuss developmental implications of population differences. Industrialization and schooling are linked to dramatic declines in time spent on household and wage labor. This labor is often unchallenging, sometimes hazardous; developmental benefits often do not increase above a limited number of hours; hence, reduction in these activities opens time for activities that may be more developmentally beneficial. Adolescents in East Asian postindustrial societies spend this freed-up time in schoolwork, a use associated with lower intrinsic motivation but high achievement and economic productivity. Adolescents in North America spend more time in leisure, associated with greater self-direction but of an uncertain relation to development. Age, gender, and socioeconomic differences in activities and with whom time is spent are also considered.

Achievement↗

Diagnostic and therapeutic approaches for nonmetastatic breast cancer in Canada, and their associated costs.

In an era of fiscal restraint, it is important to evaluate the resources required to diagnose and treat serious illnesses. As breast cancer is the major malignancy affecting Canadian women, Statistics Canada has analysed the resources required to manage this disease in Canada, and the associated costs. Here we report the cost of initial diagnosis and treatment of nonmetastatic breast cancer, including adjuvant therapies. Treatment algorithms for Stages I, II, and III of the disease were derived by age group (< 50 or > or = 50 years old), principally from Canadian cancer registry data, supplemented, where necessary, by the results of surveys of Canadian oncologists. Data were obtained on breast cancer incidence by age, diagnostic work-up, stage at diagnosis, initial treatment, follow-up practice, duration of hospitalization and direct care costs. The direct health care costs associated with 'standard' diagnostic and therapeutic approaches were calculated for a cohort of 17,700 Canadian women diagnosed in 1995. Early stage (Stages I and II) breast cancer represented 87% of all incident cases, with 77% of cases occurring in women > or = 50 years. Variations were noted in the rate of partial vs total mastectomy, according to stage and age group. Direct costs for diagnosis and initial treatment ranged from $8014 for Stage II women > or = 50 years old, to $10,897 for Stage III women < 50 years old. Except for Stage III women < 50 years old, the largest expenditure was for hospitalization for surgery, followed by radiotherapy costs. Chemotherapy was the largest cost component for Stage III women < 50 years old. This report describes the cost of diagnosis and initial treatment of nonmetastatic breast cancer in Canada, assuming current practice patterns. A second report will describe the lifetime costs of treating all stages of breast cancer. These data will then be incorporated into Statistics Canada's Population Health Model (POHEM) to perform cost-effectiveness studies of new therapeutic interventions for breast cancer, such as the cost-effectiveness of day surgery, or of radiotherapy to all breast cancer patients undergoing breast surgery.

Age Factors↗

Screening for undetected mental disorders in high utilizers of primary care services.

OBJECTIVE: To define the prevalence and detection rates of mental disorders among high utilizers as compared with typical utilizers, and to examine the effect of case-mix adjustment on these parameters. DESIGN: Cross-sectional study. SETTING: General internal medicine outpatient clinic associated with an urban, academic medical center. PATIENTS: From patients attending a general medicine clinic, 304 were selected randomly in three utilization groups, defined by number of clinic visits: (1) high utilizers; (2) case-mix adjusted high utilizers; and (3) typical utilizers (control patients). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The presence of any mental disorder was ascertained by the PRIME-MD screening instrument. Chart review on all patients was performed to ascertain mental disorders detected by primary care physicians. The prevalence of mood disorders was markedly higher in high utilizers (29%) than in adjusted high utilizers (15%) or controls (10%) (p <.001). Anxiety disorders were slightly, but not statistically, more prevalent in the group adjusted for case mix (16%) than in other high utilizers (12%) or controls (9%). Alcoholism was significantly more prevalent in controls (12%) than in adjusted (6%) or other high utilizers (3%) (p <.03). The discrepancy in detection rates between PRIME-MD and chart review for any mental disorder was less for high utilizers (37% vs 31%) as compared with adjusted high utilizers (31% vs 11%) or controls (24% vs 8%). CONCLUSIONS: Mood disorders are associated with a high overall burden of illness, while anxiety disorders are more predominant among outliers after case-mix adjustment. Detection rates differ substantially by utilization pattern. Screening efforts can be more appropriately targeted with knowledge of these patterns.

Adult↗

Vasculitic small bowel perforation masquerading as spontaneous bacterial peritonitis in a patient with decompensated liver disease.

We report on a young patient with decompensated alcohol-induced liver disease (Child-Pugh score C) who presented with clinical, biochemical and radiological evidence suggestive of spontaneous bacterial peritonitis. She was however subsequently found to have multiple small bowel perforations, which were diagnosed only at laparotomy. The histology of the bowel showed evidence of vasculitis. This case illustrates two important points. Firstly, even if a patient has all the prerequisites to develop spontaneous bacterial peritonitis, a secondary cause of peritonitis (eg. bowel perforation or intra-abdominal abscess) must always be considered as a differential diagnosis and a repeat ascitic tap is mandatory after 48 h of antibiotic therapy to confirm a decrease in the white cell count. Secondly, it shows the rare co-existence of alcoholic liver disease and vasculitis.

Bacterial Infections↗

BCR/ABL directly inhibits expression of SHIP, an SH2-containing polyinositol-5-phosphatase involved in the regulation of hematopoiesis.

The BCR/ABL oncogene causes chronic myelogenous leukemia (CML), a myeloproliferative disorder characterized by clonal expansion of hematopoietic progenitor cells and granulocyte lineage cells. The SH2-containing inositol-5-phosphatase SHIP is a 145-kDa protein which has been shown to regulate hematopoiesis in mice. Targeted disruption of the murine SHIP gene results in a myeloproliferative syndrome characterized by a dramatic increase in numbers of granulocyte-macrophage progenitor cells in the marrow and spleen. Also, hematopoietic progenitor cells from SHIP(-/-) mice are hyperresponsive to certain hematopoietic growth factors, a phenotype very similar to the effects of BCR/ABL in murine cells. In a series of BCR/ABL-transformed hematopoietic cell lines, Philadelphia chromosome (Ph)-positive cell lines, and primary cells from patients with CML, the expression of SHIP was found to be absent or substantially reduced compared to untransformed cell lines or leukemia cells lacking BCR/ABL. Ba/F3 cells in which expression of BCR/ABL was under the control of a tetracycline-inducible promoter showed rapid loss of p145 SHIP, coincident with induction of BCR/ABL expression. Also, an ABL-specific tyrosine kinase inhibitor, CGP57148B (STI571), rapidly caused reexpression of SHIP, indicating that BCR/ABL directly, but reversibly, regulates the expression of SHIP protein. The estimated half-life of SHIP protein was reduced from 18 h to less than 3 h. However, SHIP mRNA also decreased in response to BCR/ABL, suggesting that SHIP protein levels could be affected by more than one mechanism. Reexpression of SHIP in BCR/ABL-transformed Ba/F3 cells altered the biological behavior of cells in culture. The reduction of SHIP due to BCR/ABL is likely to directly contribute to the pathogenesis of CML.

Animals↗

In vivo regulation of protein-serine kinases by insulin in skeletal muscle of fructose-hypertensive rats.

The effects of tail-vein insulin injection (2 U/kg) on the regulation of protein-serine kinases in hindlimb skeletal muscle were investigated in hyperinsulinemic hypertensive fructose-fed (FF) animals that had been fasted overnight. Basal protein kinase B (PKB) activity was elevated about twofold in FF rats and was not further stimulated by insulin. Phosphatidylinositol 3-kinase (PI3K), which lies upstream of PKB, was increased approximately 3.5-fold within 2-5 min by insulin in control rats. Basal and insulin-activated PI3K activities were further enhanced up to 2-fold and 1.3-fold, respectively, in FF rats. The 70-kDa S6 kinase (S6K) was stimulated about twofold by insulin in control rats. Both basal and insulin-stimulated S6K activity was further enhanced up to 1.5-fold and 3.5-fold, respectively, in FF rats. In control rats, insulin caused a 40-50% reduction of the phosphotransferase activity of the beta-isoform of glycogen synthase kinase 3 (GSK-3beta), which is a PKB target in vitro. Basal GSK-3beta activity was decreased by approximately 40% in FF rats and remained unchanged after insulin treatment. In summary, 1) the PI3K --> PKB --> S6K pathway was upregulated under basal conditions, and 2) insulin stimulation of PI3K and S6K activities was enhanced, but both PKB and GSK-3 were refractory to the effects of insulin in FF rats.

Animals↗

Symptomatic anterior uveitis in HIV-positive patients.

Symptomatic anterior uveitis is rare in HIV-positive patients. The uveitis associated with cytomegalovirus retinitis (CMVR), the commonest ocular manifestation in AIDS patients, is rarely symptomatic and patients do not typically present with a red painful eye in conjunction with blurred vision. In this article we report 12 cases of symptomatic anterior uveitis in HIV-positive patients and discuss the aetiology. The case notes of all HIV-positive patients presenting to the eye department with symptoms of uveitis over a 4-year period were studied retrospectively. The notes were analysed for age, sex, race, risk factors of HIV, features of the uveitis, concurrent disease and CD4 counts. Only 12 patients were identified to have symptomatic uveitis out of a total 172 patients. There were 9 males and 3 females with an average age of 35 years. None of these patients were taking either rifabutin, protease inhibitors or cidofovir. Seven out of the 12 patients had granulomatous uveitis. Of these 7 patients, 4 had CD4 counts over 200 and no other concurrent illness whilst 3 patients, with CD4 counts between 130-200, were subsequently found to have an underlying aetiology namely lymphoma, tuberculosis and candida. The remaining 5 patients, all with CD4 counts below 40, had a history of systemic illness with herpes zoster preceding the onset of the uveitis. HIV-positive patients with symptoms of uveitis do not have active CMVR and the ophthalmologist must search for other causes such as tuberculosis or lymphoma in those with granulomatous uveitis or herpes zoster in those with non-granulomatous uveitis. The CD4 count may be helpful.

AIDS-Related Opportunistic Infections↗

Managing pain and comorbid depression: A public health challenge.

Many millions of Americans suffer chronic medical conditions complicated by both depression and pain. Chronic pain disorders may be classified as being caused by one or more mechanisms, such as nociceptive (inflammatory), neuropathic (peripheral and central), and myofascial, each associated with a complex substrate of neurophysiologic changes. Specific treatment approaches have been developed for different pain mechanisms. Because all pain sensation is personal and subjective, all pain is affected to some degree by emotional states, and, therefore, by psychosocial factors. Major depression commonly complicates chronic pain and adds to impairment and disability. There is evidence that patients with depression occurring after the onset of chronic pain have the same rates of affective disorders in family members as in the general population, and significantly lower rates than in families of patients with major depression alone. This suggests that it is the stress of living with chronic pain, not personal or family predisposition, that causes depression in these patients. Optimal treatment includes treatment of both pain and depression, together with a focus on symptom control and functional restoration.

Adult↗

cDNA cloning and sequence analysis of bubaline growth hormone.

The cDNA for Bubalus bubalis growth hormone (GH) has been cloned and sequence determined through RT-PCR approach. The nucleotide sequence of bubaline GH cDNA was in a single reading frame coding for a protein of 191 residues comprising a putative signal sequence of 27 amino acids. Homology comparison of the sequence with other mammalian GH cDNAs showed a very high degree of evolutionary conservation. Bubaline GH sequence shared a homology of 99.5%, 99.5%, 98.6%, 87.6% and 61.9% with that of ovine, caprine, bovine, porcine and human, respectively at amino acid level.

Amino Acid Sequence↗

Relationship between Oil-Water Interfacial Tension and Oily Soil Removal in Mixed Surfactant Systems.

Detergency of oily soil is a complex kinetic process that includes contributions from the wash system physical properties, time and temperature of wash, and the hydrodynamic forces exerted during the wash process. Generally, surfactant mixtures that exhibit a low oil-water interfacial tension are considered to provide superior oily soil detergency. In our investigations, we measured the oil-water interfacial tension for C12EO3/NaLAS and C12EO7/NaLAS blends as a function of temperature (18-80 degreesC) and time (0-60 min). The oil-water interfacial tension was found to decrease as a function of time for all blends containing nonionic surfactants, and this decline was most rapid for blends containing a higher fraction of ethoxylated alcohol with less than 3 mol of ethylene oxide. It is proposed that the diffusion of this hydrophobic fraction into the oil phase leads to the measured decline in the oil-water interfacial tension. Also, due to this limitation, no general correlation of oil-water interfacial tension with oily soil removal was observed. In view of these observations, it appears that the measurement of the oil-water interfacial tension (using a spinning drop tensiometer) for solutions containing hydrophobic surfactants may give misleading results. Copyright 1998 Academic Press.

Journal Article↗

Molecular cloning of human testis mRNA specifically expressed in haploid germ cells, having structural homology with the A-kinase anchoring proteins.

We have cloned a human testis specific gene (hi), which encodes for a protein having regional homologies to the domain of A-kinase anchoring proteins. Open reading frame encodes a protein of 860 amino acids. The predicted protein has a molecular weight 95.8 kD and contains 32 cysteine residues and 34 potential phosphorylation sites. The deduced protein analysis revealed an eukaryotic secretory signal with a potential cleavage site. Northern blot analysis detected a single transcript of approximately 3.0 kb in testis and not in any other somatic tissues. Expression of hi transcript was observed only in round spermatids indicating post meiotic haploid gene expression.

Amino Acid Sequence↗

Dependence of mammalian putrescine and spermidine transport on plasma-membrane potential: identification of an amiloride binding site on the putrescine carrier.

The mechanism of mammalian polyamine transport is poorly understood. We have investigated the role of plasma-membrane potential (DeltaPsipm) in putrescine and spermidine uptake in ZR-75-1 human breast cancer cells. The rate of [3H]putrescine and [3H]spermidine uptake was inversely correlated to extracellular [K+] ([K+]o) and to DeltaPsipm, as determined by the accumulation of [3H]tetraphenylphosphonium bromide (TPP). Inward transport was unaffected by a selective decrease in mitochondrial potential (DeltaPsimit) induced by valinomycin at low [K+]o, but was reduced by approximately 60% by the rheogenic protonophore carbonylcyanide m-chlorophenylhydrazone (CCCP), which rapidly (<=15 min) collapsed both DeltaPsipm and DeltaPsimit. Plasma-membrane depolarization by high [K+]o or CCCP did not enhance putrescine efflux in cells pre-loaded with [3H]putrescine, suggesting that decreased uptake caused by these agents did not result from a higher excretion rate. On the other hand, the electroneutral K+/H+ exchanger nigericin (10 microM) co-operatively depressed -3H-TPP, [3H]putrescine and [3H]spermidine uptake in the presence of ouabain. Suppression of putrescine uptake by nigericin+ouabain was Na+-dependent, suggesting that plasma-membrane repolarization by the electrogenic Na+ pump was required upon acidification induced by nigericin, due to the activation of the Na+/H+ antiporter. The sole addition of 5-N, N-hexamethylene amiloride, a potent inhibitor of the Na+/H+ antiporter, strongly inhibited putrescine uptake in a competitive fashion -Ki 4.0+/-0.9 (S.D.) microM-, while being a weaker antagonist of spermidine uptake. The potency of a series of amiloride analogues to inhibit putrescine uptake was clearly different from that of the Na+/H+ antiporter, and resembled that noted for Na+ co-transport proteins. These data demonstrate that putrescine and spermidine influx is mainly unidirectional and strictly depends on DeltaPsipm, but not DeltaPsimit. This report also provides first evidence for a high-affinity amiloride-binding site on the putrescine carrier, which provides new insight into the biochemical properties of this transporter.

Amiloride↗

Enhanced T cell engraftment after retroviral delivery of an antiviral gene in HIV-infected individuals.

Intracellular expression of gene products that inhibit viral replication have the potential to complement current antiviral approaches to the treatment of AIDS. We previously have shown that a mutant inhibitory form of an essential viral protein, Rev M10, prolongs the survival of T cells transduced with a nonviral vector in HIV-infected individuals. Because these gene-modified cells were not observed in patients beyond 8 weeks, efforts were made to improve the duration of engraftment. In this study, we used retroviral vector delivery of Rev M10 to CD4(+) cells and analyzed relevant immune responses in a pilot study of three HIV-seropositive patients. DNA and RNA PCR analyses revealed that cells transduced with Rev M10 retroviral vectors survived and expressed the recombinant gene for significantly longer time periods than those transduced with a negative control vector in all three patients. Immune responses were not detected either to Rev M10 or to Moloney murine leukemia virus gp70 envelope protein. Rev M10-transduced cells were detected for an average of 6 months after retroviral gene transfer compared with approximately 3 weeks for the previously reported nonviral vector delivery. These findings suggest that retroviral delivery of an antiviral gene may potentially contribute to immune reconstitution in AIDS and could provide a more effective vector to prolong survival of CD4(+) cells in HIV infection.

Animals↗

Wellness programs: a review of the evidence.

OBJECTIVE: To review studies that have examined an association between wellness programs and improvements in quality of life and to assess the strength of the scientific evidence. DATA SOURCES: A MEDLINE search was constructed with the following medical subject headings: "psychoneuroimmunology," "chronic disease" and "health promotion," "chronic disease" and "health behaviour," "relaxation techniques," "music therapy," "laughter," "anger," "mediation" and "behavioural medicine." Searches using the text words "wellness" and "wellness program" were also carried out. References from the primary articles identified in the search and contemporary writing on wellness were also considered. STUDY SELECTION: Selection was limited to randomized controlled trials or prospective studies published in English that involved human subjects and that took place between 1980 and 1996. All studies with an intervention aimed at promoting wellness and measuring outcomes were included, except studies of patients with cancer and HIV and studies of health promotion programs in the workplace. Of the 1082 references initially identified, 11 met the criteria for inclusion in the critical appraisal. DATA EXTRACTION: The following information was extracted from the 11 studies: characteristics of the study population, number of participants (and number followed to completion), length of follow-up, type of intervention, outcome measures and results. All 11 studies were assessed for the quality of their evidence. DATA SYNTHESIS: All studies reported some positive outcomes following the intervention in question, although many had limitations precluding applicability of the results to a wider population. CONCLUSIONS: Despite the suggested benefit associated with wellness programs, the evidence was inconclusive. Whether the composition of the target group or the type of intervention has a role in determining outcomes is unknown. Although trends suggest that wellness programs may be cost-effective, further research is needed for confirmation.

Evidence-Based Medicine↗

Mitoxantrone, prednimustine, and vincristine for elderly patients with aggressive non-Hodgkin's lymphoma.

Elderly patients with intermediate- or high-grade non-Hodgkin's lymphoma have a worse outcome than those who are younger than 60 years. It has been shown that aggressive combination chemotherapy is poorly tolerated in older patients resulting in a subsequent decrease in dose intensity. A phase II trial was conducted with mitoxantrone, prednimustine, and vincristine (NSO) in this group of patients. NSO consists of mitoxantrone 12 mg/M2 intravenously on day one, vincristine 1.4 mg/M2 intravenously on day 1 (maximum dose of two mg), and prednimustine 100 mg/M2 orally once a day for four days. NSO was repeated every 21 days. Thirty-six patients were able to be evaluated. There were 18 males and 18 females with the median age of 71 (range 60-85). NSO was well tolerated and nonhematological toxicities were uncommon. More than 80% of the patients received 90% or greater of the intended dose. The complete response rate was 60.6% and partial response was 21.8%. At 60 months the Kaplan-Meier estimate of progression-free survival was 47.9% (standard error 8.6%) and actual survival was 40.6% (standard error 8.8%). There were no differences in outcome between those with performance status (PS) of zero or one and those with PS > 1. NSO is well tolerated by elderly patients including those with PS > 1. These results compare favorably with other combinations in elderly patients with aggressive non-Hodgkin's lymphoma.

Aged↗

Insulin-induced vasodilation is dependent on tetrahydrobiopterin synthesis.

Insulin has been shown to elicit vasodilation through increases in nitric oxide (NO) production. To examine whether insulin may modulate the availability of tetrahydrobiopterin (BH4) (an absolute cofactor requirement for NO synthase activation), we studied the effects of insulin (150 nmol/L) on femoral arterial reactivity (to norepinephrine [NE]) in the presence and absence of 2,4-diamino-6-hydroxypyrimidine (DAHP), a specific inhibitor of BH4 production. Our data indicate that inhibition of BH4 synthesis results in an attenuation in the vasodepressor effect of insulin. One possibility is that insulin may regulate NO production by increasing cofactor (BH4) availability for activation of NO synthase.

Animals↗