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Biomedical subjects

K Shaw

Publications and source records attributed to K Shaw.

At least 19 recordsLinked to original sources

Exercise for overweight or obesity.

BACKGROUND: Clinical trials have shown that exercise in adults with overweight or obesity can reduce bodyweight. There has been no quantitative systematic review of this in The Cochrane Library. OBJECTIVES: To assess exercise as a means of achieving weight loss in people with overweight or obesity, using randomised controlled clinical trials. SEARCH STRATEGY: Studies were obtained from computerised searches of multiple electronic bibliographic databases. The last search was conducted in January 2006. SELECTION CRITERIA: Studies were included if they were randomised controlled trials that examined body weight change using one or more physical activity intervention in adults with overweight or obesity at baseline and loss to follow-up of participants of less than 15%. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality and extracted data. MAIN RESULTS: The 43 studies included 3476 participants. Although significant heterogeneity in some of the main effects' analyses limited ability to pool effect sizes across some studies, a number of pooled effect sizes were calculated. When compared with no treatment, exercise resulted in small weight losses across studies. Exercise combined with diet resulted in a greater weight reduction than diet alone (WMD -1.1 kg; 95% confidence interval (CI) -1.5 to -0.6). Increasing exercise intensity increased the magnitude of weight loss (WMD -1.5 kg; 95% CI -2.3 to -0.7). There were significant differences in other outcome measures such as serum lipids, blood pressure and fasting plasma glucose. Exercise as a sole weight loss intervention resulted in significant reductions in diastolic blood pressure (WMD -2 mmHg; 95% CI -4 to -1), triglycerides (WMD -0.2 mmol/L; 95% CI -0.3 to -0.1) and fasting glucose (WMD -0.2 mmol/L; 95% CI -0.3 to -0.1). Higher intensity exercise resulted in greater reduction in fasting serum glucose than lower intensity exercise (WMD -0.3 mmol/L; 95% CI -0.5 to -0.2). No data were identified on adverse events, quality of life, morbidity, costs or on mortality. AUTHORS' CONCLUSIONS: The results of this review support the use of exercise as a weight loss intervention, particularly when combined with dietary change. Exercise is associated with improved cardiovascular disease risk factors even if no weight is lost.

Adult↗

Calcium supplementation for improving bone mineral density in children.

BACKGROUND: Clinical trials have shown that calcium supplementation in children can increase bone mineral density (BMD) although this effect may not be maintained. There has been no quantitative systematic review of this intervention. OBJECTIVES: . To determine the effectiveness of calcium supplementation for improving BMD in children. . To determine if any effect varies by sex, pubertal stage, ethnicity or level of physical activity, and if any effect persists after supplementation is ceased. SEARCH STRATEGY: We searched CENTRAL, (Cochrane Central Register of Controlled Trials) (Issue 3, 2005), MEDLINE (1966 to 1 April 2005), EMBASE (1980 to 1 April 2005), CINAHL (1982 to 1 April 2005), AMED (1985 to 1 April 2005), MANTIS (1880 to 1 April 2005) ISI Web of Science (1945 to 1 April 2005), Food Science and Technology Abstracts (1969 to 1 April 2005) and Human Nutrition (1982 to 1 April 2005). Conference abstract books (Osteoporosis International, Journal of Bone and Mineral Research) were hand-searched. SELECTION CRITERIA: Randomised controlled trials of calcium supplementation (including by food sources) compared with placebo, with a treatment period of at least 3 months in children without co-existent medical conditions affecting bone metabolism. Outcomes had to include areal or volumetric BMD, bone mineral content (BMC), or in the case of studies using quantitative ultrasound, broadband ultrasound attenuation and ultrasonic speed of sound, measured after at least 6 months of follow-up. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality and extracted data including adverse events. We contacted study authors for additional information. MAIN RESULTS: The 19 trials included 2859 participants, of which 1367 were randomised to supplementation and 1426 to placebo. There was no heterogeneity in the results of the main effects analyses to suggest that the studies were not comparable. There was no effect of calcium supplementation on femoral neck or lumbar spine BMD. There was a small effect on total body BMC (standardised mean difference (SMD) +0.14, 95% CI+0.01, +0.27) and upper limb BMD (SMD +0.14, 95%CI +0.04, +0.24). Only the effect in the upper limb persisted after supplementation ceased (SMD+0.14, 95%CI+0.01, +0.28). This effect is approximately equivalent to a 1.7% greater increase in supplemented groups, which at best would reduce absolute fracture risk in children by 0.1-0.2%per annum. There was no evidence of effect modification by baseline calcium intake, sex, ethnicity, physical activity or pubertal stage. Adverse events were reported infrequently and were minor. AUTHORS' CONCLUSIONS: While there is a small effect of calcium supplementation in the upper limb, the increase in BMD which results is unlikely to result in a clinically significant decrease in fracture risk. The results do not support the use of calcium supplementation in healthy children as a public health intervention. These results cannot be extrapolated to children with medical conditions affecting bone metabolism.

Adolescent↗

Homicide of children aged 0-4 years, 2003-04: results from the National Violent Death Reporting System.

INTRODUCTION: To better understand, and ultimately prevent, infant/child homicide, it is imperative to more thoroughly elucidate the circumstances and conditions related to such instances. Data were obtained from the US National Violent Death Reporting System (NVDRS) to illuminate circumstances related to homicide among children aged 4 years or less, and to identify demographic groups which may be at increased risk. METHODS: The NVDRS is an active surveillance system that provides comprehensive information on all violent deaths that occur within participating states within the US. Standard statistical tests were conducted to determine homicide rates among children ages 0-4 across states that provided data for both 2003 and 2004 (Alaska, Maryland, Massachusetts, New Jersey, Oregon, South Carolina, and Virginia). These data were further used to investigate infant/child homicides by race, gender, and other relevant circumstances (for example, victim-suspect relationship, weapon type, and location of homicide). A Poisson regression model was fitted to the sample data to investigate the multivariate relationship between the infant/child homicide rate and available demographic information. RESULTS: The 2003 homicide rate for children ages 0-4 was 3.0 per 100,000 population. The 2004 homicide rate was 2.5 per 100,000 population. African Americans were 4.2 times as likely as whites to be victims of homicide. Suspects were commonly parents/caregivers. The vast majority of infant/child homicides occurred in houses or apartments, using weapons that include household objects. CONCLUSION: Homicides of infants and young children are most often committed in the home, by parents/caregivers, using "weapons of opportunity". This suggests that the risk of infant/child homicide is greatest within the primary care giving environment. Moreover, the use of "weapons of opportunity" may be indicative of maladaptive stress responses. Prevention and intervention strategies to reduce infant/child homicide should target the home environment and attend to maladaptive stress responses.

Black or African American↗

Relationship between impulsive sensation seeking traits, smoking, alcohol and caffeine intake, and Parkinson's disease.

BACKGROUND: An inverse relation exists between smoking and coffee intake and Parkinson's disease (PD). The present study explored whether this is explained by low sensation seeking, a personality trait believed to characterise PD. METHODS: A total of 106 non-demented patients with PD and 106 age and sex matched healthy controls completed a short version of Zuckerman's Sensation Seeking Scale (SSS), the Geriatric Depression Scale, and the Trait Anxiety Inventory. Data were collected on past and current cigarette smoking, and participants also completed food frequency questionnaires to estimate current caffeine and alcohol intake. RESULTS: Patients with PD had lower sensation seeking and higher depression and anxiety scores. They were also less likely to have ever smoked, and had lower caffeine and alcohol intakes. Analysis of the data using conditional logistic regression suggested that the inverse association of PD risk with sensation seeking was independent of smoking, and caffeine and alcohol intake. Moreover, low sensation seeking explained some of the apparent effect of caffeine and alcohol intake on PD. However, the effect of smoking was weakened only slightly when SSS was included in the regression model. CONCLUSION: This study raises the possibility that there is a neurobiological link between low sensation seeking traits--which might underlie the parkinsonian personality--and the hypothetical protective effect of cigarette smoking and caffeine consumption on PD.

Aged↗

The alpha-synuclein gene in multiple system atrophy.

BACKGROUND: The formation of alpha-synuclein aggregates may be a critical event in the pathogenesis of multiple system atrophy (MSA). However, the role of this gene in the aetiology of MSA is unknown and untested. METHOD: The linkage disequilibrium (LD) structure of the alpha-synuclein gene was established and LD patterns were used to identify a set of tagging single nucleotide polymorphisms (SNPs) that represent 95% of the haplotype diversity across the entire gene. The effect of polymorphisms on the pathological expression of MSA in pathologically confirmed cases was also evaluated. RESULTS AND CONCLUSION: In 253 Gilman probable or definite MSA patients, 457 possible, probable, and definite MSA cases and 1472 controls, a frequency difference for the individual tagging SNPs or tag-defined haplotypes was not detected. No effect was observed of polymorphisms on the pathological expression of MSA in pathologically confirmed cases.

Gene Expression↗

Closer to an ideal solution for inguinal hernia repair: comparison between general surgeons and hernia specialists.

BACKGROUND: It is accepted a priori that specialists of hernia surgery have better results than general surgeons who use the same or different techniques as part of their complete surgical repertoire. METHODS: Results of general surgeons trained in the technique of hernia repair using a bilayer connected mesh device (BCMD) was compared to results of specialists and other general surgeons who used other techniques. RESULTS: One report from hernia specialists and three additional reports from trained general surgeons showed similar results using a BCMD. These results were better than results of all other mesh repairs. DISCUSSION: This study shows the value of surgeon-training as well as the value in the design of a particular mesh device for hernia repair. The three components of this device offer three separate, yet connected, barriers to the formation of a recurrent hernia. CONCLUSION: General surgeons trained to use a bilayer mesh device repeatedly duplicated the results of specialists who used it.

General Surgery↗

Psychological interventions for overweight or obesity.

BACKGROUND: Overweight and obesity are global health problems which are increasing throughout the industrialised world. If left unchecked, they will continue to contribute to the ever increasing noncommunicable disease burden. OBJECTIVES: To assess the effects of psychological interventions for overweight or obesity as a means of achieving sustained weight loss. SEARCH STRATEGY: Studies were obtained from searches of multiple electronic bibliographic databases. The date of the latest search was June 2003. SELECTION CRITERIA: Trials were included if the fulfilled the following criteria: 1) they were randomised controlled clinical trials of a psychological intervention versus a comparison intervention, 2) one of the outcome measures of the study was weight change measured by any method, 3) participants were followed for at least three months, 4) the study participants were adults (18 years or older) who were overweight or obese (BMI > 25 kg/m(2)) at baseline. DATA COLLECTION AND ANALYSIS: Two people independently applied the inclusion criteria to the studies identified and assessed study quality. Disagreement was resolved by discussion or by intervention of a third party. Meta-analyses were performed using a fixed effect model. MAIN RESULTS: A total of 36 studies met the inclusion criteria and were included in the review. Overall, 3495 participants were evaluated. The majority of studies assessed behavioural and cognitive-behavioural weight reduction strategies. Cognitive therapy, psychotherapy, relaxation therapy and hypnotherapy were assessed in a small number of studies. Behaviour therapy was found to result in significantly greater weight reductions than placebo when assessed as a stand-alone weight loss strategy (WMD -2.5 kg; 95% CI -1.7 to -3.3). When behaviour therapy was combined with a diet / exercise approach and compared with diet / exercise alone, the combined intervention resulted in a greater weight reduction. Studies were heterogeneous however the majority of studies favoured combining behaviour therapy with dietary and exercise interventions to improve weight loss. Increasing the intensity of the behavioural intervention significantly increased the weight reduction (WMD -2.3 kg; 95% CI -1.4 to - 3.3). Cognitive-behaviour therapy, when combined with a diet / exercise intervention, was found to increase weight loss compared with diet / exercise alone (WMD -4.9 kg; 95% CI -7.3 to - 2.4). No data on mortality, morbidity or quality of life were found. AUTHORS' CONCLUSIONS: People who are overweight or obese benefit from psychological interventions, particularly behavioural and cognitive-behavioural strategies, to enhance weight reduction. They are predominantly useful when combined with dietary and exercise strategies. The bulk of the evidence supports the use of behavioural and cognitive-behavioural strategies. Other psychological interventions are less rigorously evaluated for their efficacy as weight loss treatments.

Adult↗

Randomized trial of busulfan vs total body irradiation containing conditioning regimens for children with acute lymphoblastic leukemia: a Pediatric Blood and Marrow Transplant Consortium study.

Conditioning regimens for children with ALL have generally included total body irradiation (TBI), which may result in significant sequelae. The primary aim of this study was to evaluate the outcome for children with ALL undergoing allogeneic stem cell transplant (SCT) with either busulfan (Bu) or TBI regimens. Patients <21 years with ALL undergoing allogeneic SCT were eligible. Conditioning included either Bu or TBI, with etoposide 40 mg/kg and cyclophosphamide 120 mg/kg. Randomization was stratified based upon duration of remission, remission status, and prior cranial irradiation. A total of 43 patients were enrolled; 21 received Bu and 22 TBI. Median patient age was 8 years (0.5-20 years). Remission status included 12 patients in CR1, 25 in CR2, and six in CR3. At a median follow-up of 43 months, event-free survival (EFS) is 45% at 3 years, with 29% EFS in the Bu arm and 58% in the TBI arm (P=0.03). There was no significant difference between Bu and TBI for patients who received stem cells from related donors (36 vs 58%, P=0.3). However, for URD, EFS was 20% for Bu and 57% for TBI (P=0.04). Relapses were similar in both arms. This randomized prospective study suggests that Bu is inferior to TBI for pediatric patients with ALL undergoing allogeneic SCT.

Adolescent↗

A qualitative study of Australian GPs' attitudes and practices in the diagnosis and management of attention-deficit/hyperactivity disorder (ADHD).

BACKGROUND: The importance of general practice involvement in the care of attention-deficit/ hyperactivity disorder (ADHD) is increasing due to the rising numbers of patients who present with the disorder. It has been suggested by consensus bodies that GPs should be identifying and referring patients at the severe end of the ADHD spectrum and managing those with less severe symptoms. However, GPs' views of their role in ADHD care are unknown. OBJECTIVE: Our aim was to explore the attitudes and practices of Australian GPs towards the diagnosis and management of ADHD. METHODS: We conducted a series of focus groups to explore GPs' beliefs regarding the causes of ADHD, their perceived role in ADHD diagnosis and management and their views on the role of behaviour therapies and pharmacotherapies in ADHD management. The subjects were 28 GPs in six focus groups. RESULTS: GPs in this study did not want to be the primary providers of care for patients with ADHD. Participants indicated a preference to refer the patient to medical specialists for diagnosis and treatment of ADHD, and expressed low levels of interest in becoming highly involved in ADHD care. Concerns about overdiagnosis and misdiagnosis of the disorder, diagnostic complexity, time constraints, insufficient education and training about the disorder, and concerns regarding misuse and diversion of stimulant medications were the reasons cited for their lack of willingness. CONCLUSIONS: The Australian GPs in this study identify a role for themselves in ADHD care which is largely supportive in nature, and involves close liaison with specialist services.

Adult↗

Long-term potentiation and spatial learning are associated with increased phosphorylation of TrkB and extracellular signal-regulated kinase (ERK) in the dentate gyrus: evidence for a role for brain-derived neurotrophic factor.

In this study, the authors investigate changes in the presynaptic terminal of the dentate gyrus that accompany 2 types of hippocampal-dependent plasticity: spatial learning and long-term potentiation (LTP). Parallel changes occurred in the dentate gyrus of rats that had undergone training in the Morris water maze and had sustained LTP. In both cases, KCl-induced brain-derived neurotrophic factor release was increased, and this was accompanied by increased phosphorylation of TrkB and the mitogen-activated protein kinase, ERK. Glutamate release was also enhanced, and the data suggest that this may be a consequence of increased activation of TrkB and ERK. Because the data indicate that similar cellular modifications are shared by these 2 forms of plasticity, they provide circumstantial evidence that LTP satisfies some of the requirements of a memory-inducing cellular substrate.

Animals↗

Differentiation of dementia with Lewy bodies from Alzheimer's disease using a dopaminergic presynaptic ligand.

BACKGROUND: Dementia with Lewy bodies (DLB) is one of the main differential diagnoses of Alzheimer's disease (AD). Key pathological features of patients with DLB are not only the presence of cerebral cortical neuronal loss, with Lewy bodies in surviving neurones, but also loss of nigrostriatal dopaminergic neurones, similar to that of Parkinson's disease (PD). In DLB there is 40-70% loss of striatal dopamine. OBJECTIVE: To determine if detection of this dopaminergic degeneration can help to distinguish DLB from AD during life. METHODS: The integrity of the nigrostriatal metabolism in 27 patients with DLB, 17 with AD, 19 drug naive patients with PD, and 16 controls was assessed using a dopaminergic presynaptic ligand, (123)I-labelled 2beta-carbomethoxy-3beta-(4-iodophenyl)-N-(3-fluoropropyl)nortropane (FP-CIT), and single photon emission tomography (SPET). A SPET scan was carried out with a single slice, brain dedicated tomograph (SME 810) 3.5 hours after intravenous injection of 185 MBq FP-CIT. With occipital cortex used as a radioactivity uptake reference, ratios for the caudate nucleus and the anterior and posterior putamen of both hemispheres were calculated. All scans were also rated by a simple visual method. RESULTS: Both DLB and PD patients had significantly lower uptake of radioactivity than patients with AD (p<0.001) and controls (p<0.001) in the caudate nucleus and the anterior and posterior putamen. CONCLUSION: FP-CIT SPET provides a means of distinguishing DLB from AD during life.

Aged↗

Tyrosine hydrogen bonds make a large contribution to protein stability.

The aim of this study was to gain a better understanding of the contribution of hydrogen bonds by tyrosine -OH groups to protein stability. The amino acid sequences of RNases Sa and Sa3 are 69 % identical and each contains eight Tyr residues with seven at equivalent structural positions. We have measured the stability of the 16 tyrosine to phenylalanine mutants. For two equivalent mutants, the stability increases by 0.3 kcal/mol (RNase Sa Y30F) and 0.5 kcal/mol (RNase Sa3 Y33F) (1 kcal=4.184 kJ). For all of the other mutants, the stability decreases with the greatest decrease being 3.6 kcal/mol for RNase Sa Y52F. Seven of the 16 tyrosine residues form intramolecular hydrogen bonds and the average decrease in stability for these is 2.0(+/-1.0) kcal/mol. For the nine tyrosine residues that do not form intramolecular hydrogen bonds, the average decrease in stability is 0.4(+/-0.6) kcal/mol. Thus, most tyrosine -OH groups contribute favorably to protein stability even if they do not form intramolecular hydrogen bonds. Generally, the stability changes for equivalent positions in the two proteins are remarkably similar. Crystal structures were determined for two of the tyrosine to phenylalanine mutants of RNase Sa: Y80F (1.2 A), and Y86F (1.7 A). The structures are very similar to that of wild-type RNase Sa, and the hydrogen bonding partners of the tyrosine residues always form intermolecular hydrogen bonds to water in the mutants. These results provide further evidence that the hydrogen bonding and van der Waals interactions of polar groups in the tightly packed interior of folded proteins are more favorable than similar interactions with water in the unfolded protein, and that polar group burial makes a substantial contribution to protein stability.

Amino Acid Substitution↗

Tryptophan and 5-hydroxytryptophan for depression.

BACKGROUND: 5 Hydroxytryptophan (5-HTP) and tryptophan are so-called natural alternatives to traditional antidepressants, used to treat unipolar depression and dysthymia. OBJECTIVES: To determine whether 5-HTP and tryptophan are more effective than placebo, and whether they are safe to use to treat depressive disorders in adults. SEARCH STRATEGY: Trials were searched in computerized general (Medline, Psychlit, and Embase) and specialized databases (Cochrane Controlled Clinical Trials Register, Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trial Register); by checking reference lists of relevant articles; by handsearching relevant specialist journals; and by contacting relevant authors where appropriate. Publications in all languages were sought. SELECTION CRITERIA: Trials were included if they were randomized, included patients with unipolar depression or dysthymia, compared preparations of 5-HTP or tryptophan with placebo, and included clinical outcomes assessed by scales assessing depressive symptoms. DATA COLLECTION AND ANALYSIS: Data was extracted independently by the three reviewers, onto data collection forms. Inclusion criteria were applied to all potential studies independently and a coefficient of agreement (Kappa) was calculated for them. Disagreement was resolved by reaching consensus. Trial quality was scored according to risk of bias. Analysis for 5-HTP and tryptophan were combined due to the small number of included trials. MAIN RESULTS: 108 trials were located using the specified search strategy. Of these, only two trials, involving a total of 64 patients, were of sufficient quality to meet inclusion criteria. The available evidence suggests these substances were better than placebo at alleviating depression (Peto Odds Ratio 4.10; 95% confidence interval 1.28-13.15; RD 0.36; NNT 2.78). However, the evidence was of insufficient quality to be conclusive. REVIEWER'S CONCLUSIONS: A large number of studies appear to address the research questions, but few are of sufficient quality to be reliable. Available evidence does suggest these substances are better than placebo at alleviating depression. Further studies are needed to evaluate the efficacy and safety of 5-HTP and tryptophan before their widespread use can be recommended. The possible association between these substances and the potentially fatal Eosinophilia-Myalgia Syndrome has not been elucidated. Because alternative antidepressants exist which have been proven to be effective and safe the clinical usefulness of 5-HTP and tryptophan is limited at present.

5-Hydroxytryptophan↗

Effect of four laboratory decontamination procedures on the quantitative determination of cocaine and metabolites in hair by HPLC-MS.

The testing for drugs of abuse in hair is increasingly used to detect illicit substances. Laboratories have implemented various decontamination, or washing, procedures in order to eliminate concerns regarding potential contamination of the hair with drug from the environment. However, the effect of these decontamination procedures on drug incorporated into the hair shaft via systemic exposure is unknown. This study evaluated the effect of four simple laboratory wash procedures on the quantitative measurement of cocaine and its metabolites in hair from rats administered cocaine by intraperitoneal injection. Washes included (1) methanol only; (2) 0.1 M phosphate buffer, pH 6.0; (3) 0.1 M phosphate buffer, pH 8.0; and (4) isopropanol and phosphate buffer, pH 5.5. Cocaine and its major metabolites, benzoylecgonine, norcocaine, ecgonine methyl ester, and cocaethylene, were analyzed using high-performance liquid chromatography coupled to atmospheric pressure electrospray ionization mass spectrometry. All four washes resulted in significant differences from unwashed hair controls (p < or = 0.05) for some or all of the detectable analytes. Because different wash procedures lead to significant differences in the measured concentrations of analytes in hair known to contain drug, quantitative data must be interpreted cautiously based on the wash procedures employed.

Animals↗