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Biomedical subjects

P Shah

Publications and source records attributed to P Shah.

At least 37 records · Page 2Linked to original sources

Arginine supplementation for prevention of necrotising enterocolitis in preterm infants.

BACKGROUND: Immaturity, ischemia, and disturbances in gut mucosal integrity due to infections or hyperosmolar feeds are some of the suspected mechanisms in the development of necrotising enterocolitis (NEC) in preterm infants. Decreased concentration of nitric oxide is proposed as one of the possible cellular mechanisms for NEC. Plasma arginine concentrations were found to be lower in infants who developed NEC. Arginine can act as a substrate for the production of nitric oxide in the tissues and arginine supplementation may help in preventing NEC. OBJECTIVES: This review examines the efficacy and safety of arginine supplementation in decreasing the incidence of NEC among preterm neonates. SEARCH STRATEGY: A literature search was performed using the following databases: MEDLINE (1966 - June 2004), EMBASE (1980 - June 2004), CINAHL (1982 - June 2004), Cochrane Controlled Trials Register (Issue 2, 2004 of Cochrane Library) and abstracts from the annual meetings of the Society for Pediatric Research, American Pediatric Society and Pediatric Academic Societies published in Pediatric Research (1991-2004). No language restrictions were applied. SELECTION CRITERIA STUDY DESIGN: randomized or quasi-randomized controlled trials. POPULATION: preterm neonates. INTERVENTION: enteral or parenteral arginine supplementation (in addition to what an infant may be receiving from enteral or parenteral source), compared to placebo or no treatment; arginine administered orally or parenterally for at least 7 days in order to achieve adequate plasma arginine levels (145 umol/l). OUTCOMES: any of the following outcomes - NEC, death prior to discharge, death due to NEC, surgery for NEC, duration of total parenteral nutrition, plasma concentrations of arginine and glutamine at baseline and seven days after intervention, side effects of arginine. DATA COLLECTION AND ANALYSIS: The methodological quality of the trials was assessed using the information provided in the studies and by personal communication with the author. Data on relevant outcomes were extracted and the effect size was estimated and reported as relative risk (RR), risk difference (RD) and mean difference (MD) as appropriate. MAIN RESULTS: Only one eligible study was identified. The methodological quality of the included study was good. There was a statistically significant reduction in the risk of developing NEC (any stage) in the arginine group compared with the placebo group (RR 0.24 [95% CI 0.10, 0.61], RD -0.21 [95% CI -0.32, -0.09]). No significant side effects directly attributable to arginine were observed. REVIEWERS' CONCLUSIONS: The data are insufficient at present to support a practice recommendation. A multicentre randomized controlled study of arginine supplementation in preterm neonates is needed, focusing on the incidence of NEC, particularly stage 2 or 3.

Arginine↗

Injury to the eye.

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Burns, Chemical↗

Effect of maternal malnutrition and anemia on the endocrine regulation of fetal growth.

Fetal growth retardation is a result of a complex pathology caused by multiple factors of fetal, placental, and maternal origin. Hormones and growth factors released as a result of maternal-fetal physiological interactions play an importance role in fetal well being and fetal outcome. Intrauterine Growth Retardation (IUGR) is associated with significant perinatal and childhood morbidity. It is estimated that 13.7 million infants are born annually with IUGR, comprising 11% of all births in developing countries. Both maternal malnutrition and anemia are associated with various degrees of fetal growth retardation. The relationship between decreasing birth weight percentiles and increasing fetal morbidity and mortality has been demonstrated by several investigators and epidemiological studies suggest that IUGR is a significant risk factor for the subsequent development of chronic hypertension, ischemic heart disease, diabetes, and obstructive lung disease in adult life (Barker's Hypothesis). Maternal anemia and/or malnutrition are recognized to be the most frequent cause of IUGR and SGA birth in developing countries like India. In order to investigate adaptive mechanisms by the fetus to overcome the growth disadvantage caused due to maternal nutritional limitations, we examined the quantitative variations in hormonal and growth factor profiles in paired cord blood and maternal samples obtained from neonates born to malnourished and/or anemic mothers. The results of our study show that: 1) The percentage of small for gestational age (SGA) neonates born to malnourished and anemic mothers was significantly higher than those born to mothers who were either malnourished or anemic; 2) Significantly higher levels of GH, PRL, HPL and IGF-1 were observed in the cord blood of neonates born to malnourished and anemic mothers indicative of an adaptive response on part of the fetus to over come an in-utero growth disadvantage; 3) The anoxemia-related fetal perturbations may have unique features that make them distinct from nutrient deficiency-related IUGR. Thus, these novel observations are relevant to the context of the ongoing scientific debate on Barker's hypothesis.

Adult↗

Multiorgan dysfunction in infants with post-asphyxial hypoxic-ischaemic encephalopathy.

BACKGROUND: Multiorgan dysfunction (MOD) is one of four consensus based criteria for the diagnosis of intrapartum asphyxia. The theoretical concept behind MOD is the diving reflex (conservation of blood flow to vital organs at the cost of non-vital organs). OBJECTIVES: To assess the patterns of involvement of each major organ/system and combinations of involvement in infants with post-asphyxial hypoxic-ischaemic encephalopathy (HIE), and to describe this in relation to long term outcome. DESIGN: Retrospective cohort study. SETTING: Regional tertiary neonatal intensive care unit at the Hospital for Sick Children, Toronto, Canada. PATIENTS: Term neonates with post-intrapartal asphyxial HIE assessed for kidney, cardiovascular system, lung, and liver function. OUTCOME: Death and presence or absence of severe neurodevelopmental disability. RESULTS: Out of 130 of 144 eligible infants with outcome data, 80 (62%) had severe adverse outcome and 50 (38%) had good outcome. All infants had evidence of MOD (at least one organ dysfunction in addition to HIE). Renal, cardiovascular, pulmonary, and hepatic dysfunction was present in 58-88% of infants with good outcome and 64-86% of infants with adverse outcome. CONCLUSIONS: MOD was present in all the infants with severe post-asphyxial HIE. However, there was no association between MOD and outcome in these infants. No relation between individual or combinations of organ involvements and long term outcomes was observed.

Apgar Score↗

Does HIV adversely influence the outcome in advanced non-small-cell lung cancer in the era of HAART?

The objectives of the study are to assess the impact of HIV status on the outcome of patients with non-small-cell lung cancer (NSCLC) in the era of highly active antiretroviral therapy (HAART). Patients diagnosed with HIV-related NSCLC in the HAART era (since January 1996) were identified from a prospective single-centre lung cancer database. The clinicopathological characteristics and outcome of each HIV-positive patient were compared to three age- and stage-matched HIV-negative controls with NSCLC who were diagnosed over the same time period and treated in an identical manner. The results showed that the two groups had similar disease characteristics and received a similar amount of chemotherapy. The median overall survival of the two groups was the same (4 months, log rank P=0.55). None of the HIV-positive patients developed an AIDS defining illness or died of HIV during treatment or follow-up. In conclusion, in this cohort, HIV status does not influence the prognosis of advanced NSCLC. This suggests that the survival of patients with HIV-related NSCLC may have improved since the introduction of HAART, and this may be due to a decrease in HIV-related deaths.

Adult↗

Glucose-induced suppression of endogenous glucose production: dynamic response to differing glucose profiles.

To determine whether, in the presence of constant insulin concentrations, a change in glucose concentrations results in a reciprocal change in endogenous glucose production (EGP), glucagon ( approximately 130 ng/l) and insulin ( approximately 65 pmol/l) were maintained at constant "basal" concentrations while glucose was clamped at approximately 5.3 mM (euglycemia), approximately 7.0 mM (sustained hyperglycemia; n = 10), or varied to create a "postprandial" profile (profile; n = 11). EGP fell slowly over the 6 h of the euglycemia study. In contrast, an increase in glucose to 7.13 +/- 0.3 mmol/l resulted in prompt and sustained suppression of EGP to 9.65 +/- 1.21 micromol x kg-1 x min-1. On the profile study day, glucose increased to a peak of 11.2 +/- 0.5 mmol/l, and EGP decreased to a nadir of 6.79 +/- 2.54 micromol x kg-1 x min-1 by 60 min. Thereafter, the fall in glucose was accompanied by a reciprocal rise in EGP to rates that did not differ from those observed on the euglycemic study day (11.31 +/- 2.45 vs. 12.11 +/- 3.21 micromol x kg-1 x min-1). Although the pattern of change of glucose differed markedly on the sustained hyperglycemia and profile study days, by design the area above basal did not. This resulted in equivalent suppression of EGP below basal (-1,952 +/- 204 vs. -1,922 +/- 246 mmol. kg-1. 6 h-1). These data demonstrate that, in the presence of a constant basal insulin concentration, changes in glucose within the physiological range rapidly and reciprocally regulate EGP.

Adult↗

A novel acrylic copolymer for a poly(alkenoate) glass-ionomer cement.

The interest in the clinical use of polyalkenoate cements stems mainly from their behavior as bioactive adhesive materials with therapeutic action. Glass-ionomer cements set by an acid-base reaction between a degradable glass and a poly(alkenoic acid) and the therapeutic action is related to the release of fluoride ions which are present in the hardened cement that show a sustained release over years, responsible for caries inhibition in teeth. Conventional glass-ionomers, however, suffer from some disadvantages such as short working time, initial moisture sensitivity and prone to desiccation after setting and are generally brittle. In the present study, a poly(alkenoic acid) copolymer was synthesized based on acrylic acid and 2-hydroxyethylmethacrylate (HEMA) using azobisisobutyronitrile as the initiator and characterized. The acid-base reaction was carried out by reacting aqueous solutions of the new copolymer (40 and 60%) with a commercial aluminofluorosilicate glasses as used in conventional glass-ionomer cements. The results showed that the copolymer of HEMA and acrylic acid was a viable poly(alkenoic) acid for formation of glass-ionomer cements.

Journal Article↗

Current trends in large cell lymphoma.

For the last decade, cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) has been the best available standard of care for aggressive non-Hodgkin's lymphoma (NHL), based on equivalent therapeutic results with other multiagent chemotherapy accompanied by lower costs and lesser toxicity. However, only 40-45% of these patients are cured with CHOP. New treatment strategies have been employed, including the addition of Rituximab to CHOP in elderly patients; dose escalation using granulocyte-colony-stimulating factor; overcoming the multidrug resistance phenotype with infusional chemotherapeutic regimens and use of some newer agents. Furthermore, the International Prognostic Factor index (IPI) has permitted identification of subsets of patients with large variations in prognosis, allowing prognosis specific therapy to be tested. There is now accumulating evidence that the clinical behavior of certain NHL can be profiled by the expression of certain molecular markers, which will undoubtedly play a role in the development of new prognostic models that may refine our ability to identify poor-risk patients. Regardless, there is still significant opportunity for improving survival in large cell lymphomas.

Antineoplastic Combined Chemotherapy Protocols↗

Inhibition by red wine extract, resveratrol, of cytokine release by alveolar macrophages in COPD.

BACKGROUND: The pathophysiology of chronic obstructive pulmonary disease (COPD) features pulmonary inflammation with a predominant alveolar macrophage involvement. Bronchoalveolar macrophages from patients with COPD release increased amounts of inflammatory cytokines in vitro, an effect that is not inhibited by the glucocorticosteroid dexamethasone. Resveratrol (3,5,4'-trihydroxystilbene) is a component of red wine extract that has anti-inflammatory and antioxidant properties. A study was undertaken to determine whether or not resveratrol would inhibit cytokine release in vitro by alveolar macrophages from patients with COPD. METHODS: Alveolar macrophages were isolated from bronchoalveolar lavage (BAL) fluid from cigarette smokers and from patients with COPD (n=15 per group). The macrophages were stimulated with either interleukin (IL)-1beta or cigarette smoke media (CSM) to release IL-8 and granulocyte macrophage-colony stimulating factor (GM-CSF). The effect of resveratrol was examined on both basal and stimulated cytokine release. RESULTS: Resveratrol inhibited basal release of IL-8 in smokers and patients with COPD by 94% and 88% respectively, and inhibited GM-CSF release by 79% and 76% respectively. Resveratrol also inhibited stimulated cytokine release. Resveratrol reduced IL-1beta stimulated IL-8 and GM-CSF release in both smokers and COPD patients to below basal levels. In addition, resveratrol inhibited CSM stimulated IL-8 release by 61% and 51% respectively in smokers and COPD patients, and inhibited GM-CSF release by 49% for both subject groups. CONCLUSIONS: Resveratrol inhibits inflammatory cytokine release from alveolar macrophages in COPD. Resveratrol or similar compounds may be effective pharmacotherapy for macrophage pathophysiology in COPD.

Aged↗

Identification of surface-membrane P-type ATPases resembling fungal K(+)- and Na(+)-ATPases, in Trypanosoma brucei, Trypanosoma cruzi and Leishmania donovani.

Genomic DNA fragments encoding nine, novel, P-type ATPases in trypanosomatid organisms were amplified in PCR, using degenerate oligonucleotide primers that recognize the ATP-binding and -phosphorylation sites present in all P-type ATPases. Subsequent phylogenetic analysis, based on the presence of conserved motifs in predicted peptide sequences for six Trypanosoma brucei, T. cruzi or Leishmania donovani PCR fragments, identified calcium-, proton- and phospholipid-translocating ATPases. DNA fragments that predict proteins homologous to the fungal, type-IID, P-type, ATPase pumps that transport Na(+) or K(+) ions were also present in T. brucei (TBCA1; 1022 nucleotides representing 340 amino acids), T. cruzi (TCNA1; 1022 nucleotides representing 340 amino acids) and L. donovani (LDCA1; 1031 nucleotides representing 343 amino acids). Southern blots showed that the Na(+)-ATPases were each present as a single-copy gene. The LDCA1 fragment was used to clone the complete LDCA1 gene from an L. donovani genomic-DNA library. The LDCA1 gene encodes a protein, of 1047 amino acids, with a predicted molecular mass of 115,501 Da. The results of analyses based on northern blots and the rapid amplification of cDNA ends (RACE) indicated that LDCA1 was expressed in promastigotes and amastigotes from axenic cultures and in animal-derived amastigotes. TBCA1 was expressed, as a 5.0-kb transcript, in procyclic culture stages and bloodstream trypomastigotes, with the 5.0-kb message up-regulated six-fold in the trypomastigote stage. Western blots probed with an antibody to the partial TBCA1 peptide identified a 150-kDa protein that was detected, by immunofluorescence, on the surface membrane of procyclic T. brucei.

Adenosine Triphosphatases↗

Lack of effect of exendin-4 and glucagon-like peptide-1-(7,36)-amide on insulin action in non-diabetic humans.

AIMS/HYPOTHESIS: The aim of this study was to determine whether rapid conversion to inactive and potentially antagonistic peptides could alter the response to GLP-1. METHODS: We evaluated the ability of exendin-4, a GLP-1 analogue resistant to degradation by dipeptidyl peptidase IV, to modulate insulin-induced stimulation of glucose uptake and suppression of glucose production in eight healthy subjects during infusion of GLP-1 (1.2 pmol.kg(-1).min(-1)), exendin-4 (0.12 pmol.kg(-1).min(-1)), or saline. Glucose was clamped at 5.3 mmol/l and insulin was infused to progressively increase insulin concentrations to about 65, 190 and 700 pmol/l, respectively. Endogenous insulin secretion was inhibited with somatostatin to ensure comparable portal insulin concentrations while glucagon and growth hormone were maintained at basal concentrations. RESULTS: Glucose, insulin, C-peptide, glucagon and growth hormone concentrations did not differ on the three occasions. In contrast, cortisol concentrations were greater during both exendin-4 (25.1+/-4.4 mmol/l per 7 h; p<0.01) and GLP-1, (17.0+/-2.0 mmol/l 7 h; p<0.05) than saline (13.5+/-1.5 mmol/l per 7 h). While insulin-induced stimulation of glucose disappearance at the highest insulin concentrations tended to be greater and insulin-induced suppression of glucose production lower in the presence of exendin-4 or GLP-1 than saline, the differences were not significant. CONCLUSION/INTERPRETATION: Exendin-4 and GLP-1 increase cortisol secretion in human subjects. However, neither alters insulin action in non-diabetic human subjects. These data also suggest that the lack of an effect of GLP-1 on insulin action is not likely to be explained by rapid degradation to inactive or antagonistic peptides.

Adult↗

Mental health needs of boys in secure care for serious or persistent offending: a prospective, longitudinal study.

BACKGROUND: The mental health needs of children and adolescents in secure care are a matter of concern, but little systematic research has been done. Our aim was to assess the mental health, social, and educational needs of these young people in a prospective, longitudinal study. METHODS: We enrolled 97 boys aged 12-17 years who had been admitted to secure care. We assessed their needs (n=97) at the time of admission and 3 months later (n=90) with standardised interviews and psychometric tests. RESULTS: 26 (27%) boys had an intelligence quotient (IQ) of less than 70. The need for psychiatric help was high on admission to a secure unit, with the most frequent disorders being depression and anxiety. There were high rates of aggression, substance misuse, self harm, and social, family, and educational problems, and associated needs. The mean number of needs was 8.5 (SD 2.9) on admission and 2.9 (SD 2.4) after 3 months (mean difference 5.6, 95% CI 5.0-6.3). Areas in which needs were mostly met included education, substance misuse, self care, and diet. Areas where the frequency of need fell substantially, but remained high, were social and family problems, and aggressive behaviours. Psychological needs persisted, with new onsets of depression, anxiety problems, and post-traumatic-stress symptoms shortly after admission. The most frequently required interventions were psychological assessment and cognitive behavioural work. INTERPRETATION: Boys in secure care have many needs and a high rate of psychiatric morbidity. During the admission period, secure care units address some domains of need, but others remain unchanged or get worse. Psychological and psychiatric provision in secure units need to be improved.

Adolescent↗