Biomedical subjects
Publications and source records attributed to J Scott.
Hybrid organo-silica materials possessing uniform nanoscale porosity in the super-micropore size range (1.0-2.0 nm diameter) have been prepared using neutral alkylamine and non-ionic alkyl(phenyl)polyethylene oxide surfactants as structure-directing agents.
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BACKGROUND: Lowering serum homocysteine levels with folic acid is expected to reduce mortality from ischemic heart disease. Homocysteine reduction is known to be maximal at a folic acid dosage of 1 mg/d, but the effect of lower doses (relevant to food fortification) is unclear. METHODS: We randomized 151 patients with ischemic heart disease to 1 of 5 dosages of folic acid (0.2, 0.4, 0.6, 0.8, and 1.0 mg/d) or placebo. Fasting blood samples for serum homocysteine and serum folate analysis were taken initially, after 3 months of supplementation, and 3 months after folic acid use was discontinued. RESULTS: Median serum homocysteine level decreased with increasing folic acid dosage, to a maximum at 0.8 mg of folic acid per day, when the homocysteine reduction (placebo adjusted) was 2.7 micromol/L (23%), similar to the known effect of folic acid dosages of 1 mg/d and above. The higher a person's initial serum homocysteine level, the greater was the response to folic acid, but there were statistically significant reductions regardless of the initial level. Serum folate level increased approximately linearly (5.5 nmol/L for every 0.1 mg of folic acid). Within-person fluctuations over time in serum homocysteine levels, measured in the placebo group, were large compared with the effect of folic acid, indicating that monitoring of the reduction in an individual is impractical. CONCLUSIONS: A dosage of folic acid of 0.8 mg/d appears necessary to achieve the maximum reduction in serum homocysteine level across the range of homocysteine levels in the population. Current US food fortification levels will achieve only a small proportion of the achievable homocysteine reduction.
The active form of many helicases is oligomeric, possibly because oligomerization provides multiple DNA binding sites needed for unwinding of DNA. In order to understand the mechanism of the bacteriophage T4 Dda helicase, the potential requirement for oligomerization was investigated. Chemical cross-linking and high pressure gel filtration chromatography provided little evidence for the formation of an oligomeric species. The specific activity for ssDNA stimulated ATPase activity was independent of Dda concentration. Dda was mutated to produce an ATPase-deficient protein (K38A Dda) by altering a residue within a conserved, nucleotide binding loop. The helicase activity of K38A Dda was inactivated, although DNA binding properties were similar to Dda. In the presence of limiting DNA substrate, the rate of unwinding by Dda was not changed; however, the amplitude of product formation was reduced in the presence of increasing concentrations of K38A Dda. The reduction was between that expected for a monomeric or dimeric helicase based on simple competition for substrate binding. When unwinding of DNA was measured in the presence of excess DNA substrate, addition of K38A Dda caused no reduction in the observed rate for strand separation. Taken together, these results indicate that oligomerization of Dda is not required for DNA unwinding.
BACKGROUND: Although lithium has been the most commonly used maintenance treatment in bipolar disorder for several decades, valproate is being used increasingly - especially in the United States of America. There is a need to clarify whether the increasingly prominent prophylactic role of valproate in bipolar disorder is justified. OBJECTIVES: To review the effectiveness of valproate, relative to placebo, other mood stabilisers and antipsychotics, in the prevention and/or attenuation of acute episodes of bipolar disorder. The effectiveness of valproate was considered in terms of mood symptoms, mortality, general health, social functioning, adverse effects and overall acceptability to patients. SEARCH STRATEGY: The CCDAN group search strategy was used. The following databases were searched: The Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register (CCDANCTR), The Cochrane Controlled Clinical Trials Register (CCCTR), EMBASE, MEDLINE, LILACS, PsycLIT and Psyndex. Reference lists of relevant papers and major textbooks of mood disorder were examined. Authors, other experts in the field and pharmaceutical companies were contacted for knowledge of suitable published or unpublished trials. SELECTION CRITERIA: Randomised controlled trials which compared valproate with placebo, alternative mood stabilisers (including lithium and carbamazepine) or neuroleptics, where the stated intent of intervention was the maintenance treatment of bipolar disorder. Participants were males and females of all ages with a diagnosis of bipolar disorder however diagnosed, approximating to ICD 10 Code F31 and DSM IV 296, but including patients diagnosed as ICD-9 manic depressive psychosis and DSM-III and DSM-IIIR bipolar disorder. DATA COLLECTION AND ANALYSIS: Data were extracted from the original reports individually by two reviewers. The main outcomes to be assessed were: 1. The effectiveness of valproate treatment in preventing or attenuating further episodes of bipolar disorder, including its effectiveness in rapid cycling disorder. 2. The acceptability of valproate treatment to patients. 3. The prevalence of side-effects. 4. Mortality on valproate treatment. Outcomes concerning relapse/recurrence were analysed excluding data from discontinuation studies, which were to be analysed separately. Sub-group analyses were to be performed to examine the effects of valproate treatment in rapid cycling bipolar disorder and previous mood stabiliser non-responders. Data were analysed using Review Manager version 4.1. MAIN RESULTS: One trial of 12 months duration with 372 participants was identified comparing lithium, divalproex and placebo. It had several methodological limitations. The primary analysis of time to occurrence of mood episode described in the main trial report found no reliable difference between the treatments, although there was a trend for divalproex to be more effective than lithium. In the analysis in this review, patients taking divalproex who left the study because of the occurrence of an mood episode were significantly less in number than those on placebo (RRR 37%; RR 0.63; 95% CI 0.44 to 0.90). There was no significant difference in the numbers of patients in receipt of divalproex compared with those in receipt of lithium who left the study because they suffered any mood episode. (RRR 22%; RR 0.78; 95% C.I. 0.52 to 1.17). There was insufficient information to allow sub-group analyses of rapid-cycling disorder. The divalproex group had significantly more patients suffering tremor (RRI 223%; RR 3.23; 95% C.I. 1.85 to 5.62), weight gain (RRI 187%; RR 2.87; 95% C.I. 1.34 to 6.17) and alopecia (RRI 143%; RR 2.43; 95% C.I. 1.05 to 5.65) than the placebo group. In comparison with the lithium, divalproex was associated with more frequent sedation (RRI 58%; RR 1.58; 95% C.I. 1.08 to 2.32) and infection (RRI 107%; RR 2.07; 95% C.I. 1.16 to 3.68), but less suffered thirst (RRR 62%; RR 0.38; 95% C.I. 0.18 to 0.81) and polyuria (RRR 57%; RR 0.43; 95% C.I. 0.22 to 0.82). REVIEWER'S CONCLUSIONS: In view of the equivocal findings of this review, conclusions about the efficacy and acceptability of valproate compared to placebo and lithium cannot be made with any degree of confidence. With current evidence, patients and clinicians would probably wish to use lithium before valproate for maintenance treatment. At present, the observed shift of prescribing practice to valproate is not based on reliable evidence of efficacy
In this paper we use the 1994-1997 Youth Surveys of the British Household Panel Study to examine the wellbeing of young adolescents. We conceptualize wellbeing as a multi-dimensional construct and we develop and test models of gender and age differences. Using confirmatory factor analysis, we find clear gender differences in self-esteem, self-efficacy, unhappiness and worries. We confirm that wellbeing and some health-risk behaviours (fighting and smoking) are linked. We test models that examine how family structure, father's occupation, tenure, and household income, affect adolescent wellbeing. While socio-economic factors affect health-risk behaviours and also adolescents' reported worries, they have little impact on other aspects of youth wellbeing. The implications of these findings are discussed.
OBJECTIVE: This paper addresses the prevention and treatment of depression in the general population. It argues that the public health burden of depression cannot be effectively tackled solely at the level of the treatment of individuals; in addition, coherent strategies by national governments are required. It summarises some of the public health interventions that were undertaken in England by the government to reduce the risk factors associated with depression in increase detection and treatment and to destigmatise this disorder. Lessons learned from this experience are described. METHODS: To assess the scope for collective public interventions, a national psychiatric morbidity study was commissioned. The Government set targets for reducing psychiatric morbidity and suicide. Research related to depression was commissioned. A public information strategy was launched to increase understanding and reduce stigma, including a five year 'Defeat Depression' Campaign. Particular attention was paid to updating General Practitioners in the recognition, detection and management of depression. Government departments worked with employers and trade union organisations to attempt to reduce work-induced stress. Universal and selective prevention measures aimed to reduce factors associated with depression, such as unemployment. Measures to reduce suicide include education of health and social care professionals, supporting high-risk groups and restricting access to means of suicide. The impact of these strategies is difficult to assess and will not be apparent until the national psychiatric morbidity study is repeated in 2001. The overall suicide rate fell by 11.7% in five years.
When the shot is released above a horizontal plane, range from this point depends on release height, speed and angle. Measured distance is the sum of this range and horizontal distance of the release point from the throwing circle edge. Optimal release conditions can be calculated only if the dependence of release velocity on other variables, due to thrower limitations, is known. Experiments on two shot-putters investigated the hypothesis that there are constraint relationships among these four release parameters. A variable scaling scheme, using measurement of impact point and the known magnitude of g, corrected 2D data from one camera for out-of-plane motion and yielded accurate estimates of release parameters. Multivariate regression analyses determined approximate constraint surfaces limiting performance. Achievable release speed decreases with increasing release angle at about 1.7(m/s)/rad and decreases with increasing release height at about 0.8(m/s)/m, with only small differences in sensitivities between the throwers. Horizontal release distance also decreases with increasing release angle at about 1.7m/rad and increases with increasing release height at about 1.3m/m, again with only small differences between the two throwers. Optimal release conditions producing maximum range for a particular athlete can be determined using similar constraints for that athlete.
BACKGROUND: The efficacy and effectiveness of cognitive therapy (CT) is well established for unipolar disorders, but little is known about its utility in bipolar disorders. This study aimed to explore the feasibility and efficacy of using CT as an adjunct to usual psychiatric treatment in this patient population. METHOD: Subjects referred by general adult psychiatrists were assessed by and independent rater and then randomly allocated to immediate CT (N = 21) or 6-month waiting-list control, which was then followed by CT (N = 21). Observer and self-ratings of symptoms and functioning were undertaken immediately prior to CT, after a 6-month course of CT and a further 6-months later. Data on relapse and hospitalization rates in the 18 months before and after commencing CT were also collected. RESULTS: At 6-month follow-up, subjects allocated to CT showed statistically significantly greater improvements in symptoms and functioning as measured on the Beck Depression Inventory, the Internal State Scale, and the Global Assessment of Functioning than those in the waiting-list control group. In the 29 patients who eventually received CT, relapse rates in the 1 8 months after commencing CT showed a 60 % reduction in comparison with the 18 months prior to commencing CT. Seventy per cent of subjects who commenced therapy viewed CT as highly acceptable. CONCLUSION: Although the results of this study are encouraging, the use of CT in subjects with bipolar disorders is more complex than in unipolar disorders and requires a high level of therapist expertise. The therapy may prove to be particularly useful in the treatment of bipolar depression.
Von Ebner's gland of ferret was examined by means of light microscopy, protein, mucosubstance and enzyme histochemistry, and neurohistology. Acinar cells were replete with granules containing neutral mucosubstances and disulphides, and showed strong diffuse acid phosphatase activity and weak granular staining for peroxidase. Staining for cytochrome oxidase, succinate dehydrogenase, and NADH and NAD(P)H dehydrogenases was also seen. Basolateral plasmalemma of acinar cells showed weak, ouabain-sensitive Na+,K+-ATPase activity. Ductal cells were of a simple appearance, contained thiols and showed variable staining for acid phosphatase, dehydrogenases and cytochrome oxidase. Variable amounts of beta-glucuronidase reaction product were localized in the glandular parenchyma, being marked in atrophic areas. Prominent stellate myoepithelial cells embracing acini and also basal ductal cells were demonstrated by alkaline phosphatase. Thiamine pyrophosphatase reaction product was concentrated in blood vessels around parenchyma, with little Golgi-like staining in acinar cells. Acetylcholinesterase activity was associated with an extensive network of nerve fibres embracing parenchyma, whereas catecholamine fluorescence was not seen. The results suggest that the acini of von Ebner's gland of ferret synthesise neutral secretory glycoproteins and peroxidase. Water mobilization is inconspicuous. Lysosomal activities feature in the parenchyma, possibly a consequence of processing secretory products in acini, absorption in ducts and/or adaptation atrophy. The gland receives a rich cholinergic-type innervation, and has extensive myoepithelial and microvascular networks.
This study examined the cognitive mediation of relapse prevention by cognitive therapy (CT) in a trial of 158 patients with residual depression. Scores based on agreement with item content of 5 questionnaires of depression-related cognition provided no evidence for cognitive mediation. A measure of the form of response to those questionnaires, the number of times patients used extreme response categories ("totally agree" and "totally disagree"), showed significant and substantial prediction of relapse, differential response to CT. and conformity to mediational criteria. CT reduced relapse through reductions in absolutist, dichotomous thinking style. CT may prevent relapse by training patients to change the way that they process depression-related material rather than by changing belief in depressive thought content.
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There is considerable empirical support for the use of cognitive therapy in the treatment of mild to moderately severe acute major depression. More recent research has focused on the utility of this approach in severe or chronic depressive disorders, in relapse prevention and also on the potential benefits of combining cognitive therapy with medication. This paper attempts to clarify the empirical data on these important issues in order to identify further the role of cognitive therapy in day-to-day clinical practice. It also provides an overview of findings regarding predictors of response to cognitive therapy and the possible mediators of its effects.
BACKGROUND: To analyze the use of admission angiography as a nonoperative adjunct for management of blunt splenic injury. METHODS: Retrospective chart review of all blunt splenic injuries to a Level I trauma center from March 1997 through July 1999. RESULTS: One hundred twenty-six patients underwent angiography for splenic injury. Eighty-six patients (68%) had a negative angiogram and were treated expectantly. Of these, seven patients (8%) required laparotomy, with a splenic salvage rate of 92%. Embolization was performed on 40 patients (32%) for evidence of vascular injury. Of these, three patients (8%) required laparotomy, for a total salvage of 92%. Repeat angiography was performed for suspicion of bleeding in 12 patients (10%), with 50% requiring embolization. Outcome based on CT grade demonstrated an average grade of 2.9, with a salvage rate of greater than 70% for grade IV and V injuries. CONCLUSION: Vascular injury increases with splenic injury grade. Embolization improves nonoperative salvage rates to 92%, even with high-grade injuries. Ten percent of patients require additional therapy including "second-look" angiography. A significant portion of patients with negative screening angiograms (10%) required either embolization or laparotomy to control delayed hemorrhage.
Primary care in the UK has been the subject of numerous changes and reorganizations since 1990. Each innovation in organization, with the exception of fundholding, has been the subject of evaluation. However, the complexities of some innovations make the evaluation process problematic and this is further complicated by the trend towards central policy decision making being subject to local interpretation and implementation, by means of simultaneous devolution and centralization. This paper discusses the challenges and problems posed by attempting to evaluate these new organizations, particularly with regard to whether or not they can be considered to be "successful". It draws specifically on the national evaluation of the total purchasing pilots and indicates how the findings can be applied to primary care groups.
The Na+/Ca2+ exchanger plays a prominent role in regulating intracellular Ca2+ levels in cardiac myocytes and can serve as both a Ca2+ influx and efflux pathway. A novel inhibitor, KB-R7943, has been reported to selectively inhibit the reverse mode (i.e., Ca2+ entry) of Na+/Ca2+ exchange transport, although many aspects of its inhibitory properties remain controversial. We evaluated the inhibitory effects of KB-R7943 on Na+/Ca2+ exchange currents using the giant excised patch-clamp technique. Membrane patches were obtained from Xenopus laevis oocytes expressing the cloned cardiac Na+/Ca2+ exchanger NCX1.1, and outward, inward, and combined inward-outward currents were studied. KB-R7943 preferentially inhibited outward (i.e., reverse) Na+/Ca2+ exchange currents. The inhibitory mechanism consists of direct effects on the transport machinery of the exchanger, with additional influences on ionic regulatory properties. Competitive interactions between KB-R7943 and the transported ions were not observed. The antiarrhythmic effects of KB-R7943 were then evaluated in an ischemia-reperfusion model of cardiac injury in Langendorff-perfused whole rabbit hearts using electrocardiography and measurements of left ventricular pressure. When 3 microM KB-R7943 was applied for 10 min before a 30-min global ischemic period, ventricular arrhythmias (tachycardia and fibrillation) associated with both ischemia and reperfusion were almost completely suppressed. The observed electrophysiological profile of KB-R7943 and its protective effects on ischemia-reperfusion-induced ventricular arrhythmias support the notion of a prominent role of Ca2+ entry via reverse Na+/Ca2+ exchange in this process.