Differentiating between audit and research: postal survey of health authorities' views.
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Attitude to Health↗
Biomedical subjects
A Wilson
Publications and source records attributed to A Wilson.
Making use of guidelines in clinical practice
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Journal Article↗
Rethinking home healthcare. A love of the profession doesn't abate thoughts that home care's future may lie in hospitals.
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Centers for Medicare and Medicaid Services, U.S.↗
The protective effects of zinc on diethyldithiocarbamate cytotoxicity on rat astrocytes in vitro.
The neurotoxicity of diethyldithiocarbamate (DDC) has been documented for decades. In particular, cytotoxic effects against rat astrocytes have been noted by a decrease in cell viability and numerous ultrastructural defects. This study indicates an in vitro protective effect by zinc administration prior to DDC insult. Cell groups pre-treated with 50 microM ZnCl2 prior to the addition of 35 microg/ml DDC showed significant protection when compared with cells treated with DDC alone. Zinc reduced the DDC-mediated toxicity to astrocytes as indicated by an increase in cell adherence and viability. Morphological evaluation indicated a significant decrease in ultrastructural alterations. Metallothionein (MT), a metal regulatory protein known to be induced by zinc was studied to determine its role in this mechanism of protection. Immunocytochemistry and immunoblots showed increased presence of MT in all zinc treated groups. This suggests a protective effect against DDC cytotoxicity on rat astrocytes in vitro may be associated with an increase in MT concentration.
Animals↗
Managing smoking cessation.
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Family Practice↗
A conjoint phase of treatment involving a severely disturbed adolescent boy and his father.
A phase of father-son conjoint treatment during psychoanalytic psychotherapy of the son is described. The son, who met descriptive criteria for schizophrenia, felt most alive when planning revenge on his father; the father frantically dwelled on the son to the exclusion of virtually everything but work. The conjoint therapy complemented the son's individual therapy and led to a stable, hence analyzable transference. The outcome was generally positive in a case whose prognosis at the outset had appeared dismal. Questions concerning therapeutic change and clinical technique are raised. The author suggests that others in similar clinical circumstances might consider a phase of conjoint treatment.
Adolescent↗
A common variant in methionine synthase reductase combined with low cobalamin (vitamin B12) increases risk for spina bifida.
Impairment of folate and cobalamin (vitamin B(12)) metabolism has been observed in families with neural tube defects (NTDs). Genetic variants of enzymes in the homocysteine remethylation pathway might act as predisposing factors contributing to NTD risk. The first polymorphism linked to increased NTD risk was the 677C-->T mutation in methylenetetrahydrofolate reductase (MTHFR). We now report a polymorphism in methionine synthase reductase (MTRR), the enzyme that activates cobalamin-dependent methionine synthase. This polymorphorism, 66A-->G (I22M), has an allele frequency of 0.51 and increases NTD risk when cobalamin status is low or when the MTHFR mutant genotype is present. Genotypes and cobalamin status were assessed in 56 patients with spina bifida, 58 mothers of patients, 97 control children, and 89 mothers of controls. Cases and case mothers were almost twice as likely to possess the homozygous mutant genotype when compared to controls, but this difference was not statistically significant. However, when combined with low levels of cobalamin, the risk for mothers increased nearly five times (odds ratio (OR) = 4.8, 95% CI 1.5-15.8); the OR for children with this combination was 2.5 (95% CI 0.63-9.7). In the presence of combined MTHFR and MTRR homozygous mutant genotypes, children and mothers had a fourfold and threefold increase in risk, respectively (OR = 4.1, 95% CI 1.0-16.4; and OR = 2.9, 95% CI 0.58-14.8). This study provides the first genetic link between vitamin B(12) deficiency and NTDs and supports the multifactorial origins of these common birth defects. Investigation of this polymorphism in other disorders associated with altered homocysteine metabolism, such as vascular disease, is clearly warranted.
5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗
Effects of training dose and two- versus three-choice testing procedure on nicotine discrimination responding in humans.
RATIONALE: Discrimination of a drug's interoceptive stimulus effects often depends substantially on training and testing conditions. OBJECTIVES: We examined changes in nicotine discrimination behavior in humans as a function of lowering the training dose and of varying the discrimination testing procedure. METHODS: Smokers and never-smokers (n=10 each) were initially trained to discriminate 20 microg/kg nicotine by nasal spray from placebo (0) and tested on generalization of discrimination responding across a range of doses from 0 to 20 microg/kg. Each subsequently learned to reliably discriminate progressively smaller doses of nicotine from placebo until his or her threshold dose for discrimination was identified (mean=2.7 microg/kg). A repeat testing of generalization responding across 0-20 microg/kg was then conducted, using placebo and the subject's threshold dose as training doses. Generalization testing involved both two-choice and three-choice (novel response option) quantitative procedures. RESULTS: A significant shift to the left was seen in nicotine-appropriate responding in the two-choice procedure when the nicotine training dose was lowered (i.e. from the first to the second test of generalization). In the three-choice procedure, however, there was no such leftward shift. Instead, in never-smokers, a flattening of nicotine-appropriate responding occurred with a lowering of the training dose, while novel-appropriate responding significantly increased. The subjective effects of "head rush" and, in never-smokers only, "jittery" also showed a shift to the left in their relationship with nicotine generalization dose when the training dose was lowered. CONCLUSIONS: These results confirm the importance of training and testing conditions on discrimination behavior and subjective drug responses within subjects and demonstrate the utility of the novel-response, three-choice procedure for assessing qualitatively different stimulus effects of novel drug doses.
Adult↗
Diffusing capacity limitations of the extent of lung volume reduction surgery in an animal model of emphysema.
OBJECTIVE: The purpose of this study was to investigate in an elastase-induced emphysema rabbit model the effects of increasing resection volumes during lung volume reduction surgery on pulmonary compliance, forced expiratory air flow, and diffusing capacity to assess factors limiting optimal resection. METHODS: Emphysema was induced in 68 New Zealand White rabbits with 15,000 units of aerosolized elastase. Static respiratory system compliance, forced expiratory flow, and single-breath diffusing capacity were measured before the induction of emphysema, after the induction of emphysema, and 1 week after a bilateral upper and middle lobe lung volume reduction operation. RESULTS: Static respiratory system compliance with 60 mL insufflation above functional residual capacity increased with emphysema induction and then decreased progressively with resection of larger volumes of lung tissue (P =.001 by analysis of variance). Expiratory flow improved after lung resection in the rabbits with large resection volumes. In contrast, diffusing capacity tended to deteriorate with larger resection volumes (P =. 18). CONCLUSION: Improvements in respiratory system compliance and forced expiratory flow after lung volume reduction operations may account for the improvements seen clinically. Declines in diffusing capacity with extensive lung reduction may limit the clinical benefits associated with greater tissue resection volumes. Future investigations with animal models may reveal other physiologic parameters that may further guide optimal lung volume reduction procedures.
Animals↗
Deficient T cell fate specification in mice with an induced inactivation of Notch1.
Notch proteins are cell surface receptors that mediate developmental cell specification events. To explore the function of murine Notch1, an essential portion of the gene was flanked with loxP sites and inactivation induced via interferon-regulated Cre recombinase. Mice with a neonatally induced loss of Notch1 function were transiently growth retarded and had a severe deficiency in thymocyte development. Competitive repopulation of lethally irradiated wild-type hosts with wild-type- and Notch1-deficient bone marrow revealed a cell autonomous blockage in T cell development at an early stage, before expression of T cell lineage markers. Notch1-deficient bone marrow did, however, contribute normally to all other hematopoietic lineages. These findings suggest that Notch1 plays an obligatory and selective role in T cell lineage induction.
Animals↗
Social interaction skills and theory of mind in young children.
Two studies explored relations between peer social skills and theory of mind in young children. In Study 1, a global teacher rating of social skills with peers, performance on a traditional false-belief task, a standardized assessment of auditory language comprehension, and a time sampling of amount of speech with peers were obtained. Positive, but moderate, zero-order correlations were observed between the false-belief measure and social skills, and false belief accounted for a significant amount of additional variance in social skills after covarying age and the 2 measures of language. Study 2 replicated the findings of Study 1 by using a larger sample and a standardized teacher questionnaire. The results are discussed with regard to the critical role of a mentalistic theory of behavior for human social interactions.
Child↗
The association of diet and thrombotic risk factors in healthy male vegetarians and meat-eaters.
OBJECTIVE: The aim of this study was to assess thrombosis tendency in subjects who were habitual meat-eaters compared with those who were habitual vegetarians. DESIGN: Cross-sectional comparison of habitual meat-eaters and habitual vegetarians. SETTING: Free living subjects. SUBJECTS: One hundred and thirty-nine healthy male subjects (vegans n = 18, ovolacto vegetarians n = 43, moderate-meat-eaters n = 60 and high-meat-eaters n = 18) aged 20-55 y who were recruited in Melbourne. OUTCOME MEASURES: Dietary intake was assessed using a semi-quantitative Food Frequency Questionnaire. The parameters of thrombosis were measured by standard methods. RESULTS: Saturated fat and cholesterol intakes were significantly higher and polyunsaturated fat (PUFA) was significantly lower in the meat-eaters compared with vegetarians. In the meat-eaters, the platelet phospholipids AA levels were significantly higher than in the vegetarians, but there was no increase in ex vivo platelet aggregation and plasma 11-dehydro thromboxane B2 levels. Vegetarians, especially the vegans, had a significantly increased mean collagen and ADP stimulated ex vivo whole blood platelet aggregation compared with meat-eaters. The vegan group had a significantly higher mean platelet volume than the other three dietary groups. However, meat-eaters had a significantly higher cluster of cardiovascular risk factors compared with vegetarians, including increased body mass index, waist to hip ratio, plasma total cholesterol (TC), triacylglycerol and LDL-C levels, ratio of TC/HDL-C and LDL-C/HDL-C and plasma factor VII activity. CONCLUSIONS: Consumption of meat is not associated with an increased platelet aggregation compared with vegetarian subjects.
Adult↗
A high uptake eye and foot screening service for an urban population.
AIMS: A community diabetes eye screening service using slit-lamp biomicroscopy and colour fundus photography was set up in 1993 at the Barnsley District General Hospital Diabetes Centre with a foot screening service being added in 1994. The service is available for all diabetic patients in the Barnsley health district (encompassing 220,000 people). After 4 1/2 years, a survey was carried out to establish the uptake of this service. METHODS: All diabetic patients on the local diabetes register were checked for attendance at the eye screening service or the Barnsley District General Hospital Eye Department. Questionnaires were sent to general practitioners to establish what screening was received by those attending neither of these services. RESULTS: More than 10% of patients were found to be incorrectly registered. Of the 4000 correctly registered diabetic patients, 62% were screened annually by this service and 25% were under the care of the Department of Ophthalmology. Half of the remaining 13% were screened at other hospitals or by opticians or general practitioners and the other half were either too old or ill to be screened or were non-compliant. CONCLUSIONS: This service has a high uptake, and is recommended for a circumscribed urban population.
Diabetes Complications↗
Pseudosubluxation of C2 on C3 in polytraumatized children--prevalence and significance.
AIM: Pseudosubluxation of C2 on C3 is a recognized physiological variant in the upper cervical spine radiographs of normal children. The aim of this study was to determine the prevalence of this variant in children admitted with serious polytrauma, and to explore its significance in this setting. PATIENTS AND METHODS: A retrospective review was performed of 138 patients under 16 years of age admitted with polytrauma via The Helicopter Emergency Medical Service. All patients wore hard collars and underwent immediate horizontal beam lateral cervical spine radiography. Normal and C2/C3 pseudosubluxation groups were defined using standard criteria. The two groups were compared in terms of age, presence of an endotracheal tube, injury severity, and outcome. RESULTS: There were 108 (78.3%) children in the normal group and 30 (21.7%) in the C2/C3 pseudosubluxation group. No significant differences in sex ratio, intubation status, injury severity, or outcome were found. Patients in the pseudosubluxation group were significantly younger. CONCLUSION: In paediatric polytrauma it is essential to establish the integrity of the cervical spine promptly as this will deter unnecessary further imaging and investigation. In our study 21.7% of cases had C2/C3 pseudosubluxation on admission radiographs. We have shown that C2/C3 pseudosubluxation has no significant association with intubation status, injury severity, or outcome. We conclude that C2/C3 pseudosubluxation can be considered a benign variant even in the setting of polytrauma.
Adolescent↗
Prolonged fatigue, anxiety and depression: exploring relationships in a primary care sample.
OBJECTIVE: While prolonged fatigue states are frequently comorbid with other forms of distress, they are now the subject of independent aetiological and treatment research. The objective of this study was to use principal component analysis to clarify the relationships between proposed measures of prolonged fatigue and anxiety and depression in data obtained from patients attending primary care. METHOD: Self-report measures of prolonged fatigue and psychological distress (anxiety and depression) were administered to consecutive ambulatory care patients attending primary care. RESULTS: Data from 1593 subjects were obtained. A two-factor principal component solution (varimax rotation) demonstrated a clear separation between fatigue-related items (Cronbach's alpha = 0.81) as compared with those items describing anxiety and/or depression (Cronbach's alpha = 0.95). A four-factor solution produced similar results with two factors describing general psychological distress (contrasting anxiety and depression), with two other factors describing the profiles of mental and physical fatigue. CONCLUSIONS: The results lend weight to the argument that prolonged fatigue states can be measured independently of conventional notions of anxiety and depression in patients attending primary care. Epidemiological, aetiological and treatment research in psychiatry may need to focus greater attention on such prolonged fatigue states.
Adaptation, Psychological↗
Effect of dietary alpha-linolenic acid on thrombotic risk factors in vegetarian men.
BACKGROUND: Vegetarians have lower platelet and plasma concentrations of n-3 polyunsaturated fatty acids (PUFAs) than do omnivores. We recently showed that male vegetarians have higher platelet aggregability than do omnivores. OBJECTIVE: We investigated whether male vegetarians (n = 17) who consumed an increased amount of dietary alpha-linolenic acid (ALA) showed any changes in their tissue profile of PUFAs, plasma thromboxane concentrations, platelet aggregability, or hemostatic factors. DESIGN: During the study, all subjects maintained their habitual vegetarian diets except that a proportion of dietary fat was replaced with vegetable oils and margarines that were provided. Initially, all subjects consumed a low-ALA diet (containing safflower oil and safflower oil-based margarine) for 14 d; they then consumed either a moderate-ALA diet (containing canola oil and canola oil-based margarine) or a high-ALA diet (containing linseed oil and linseed oil-based margarine) for 28 d. Blood samples were collected at day 0 (baseline), day 14, and day 42. RESULTS: Eicosapentaenoic acid, docosapentaenoic acid, total n-3 PUFAs, and the ratio of n-3 to n-6 PUFAs were significantly increased (P < 0.05), whereas the ratio of arachidonic acid to eicosapentaenoic acid was decreased (P < 0.05), in platelet phospholipids, plasma phospholipids, and triacylglycerols after either the moderate-ALA or high-ALA diet compared with the low-ALA diet. No significant differences were observed in thrombotic risk factors. CONCLUSION: ALA from vegetable oils (canola and linseed) has a beneficial effect on n-3 PUFA concentrations of platelet phospholipids and plasma lipids in vegetarian males.
Adult↗
Urinary iodine concentrations and thyroid function in adult Zimbabweans during a period of transition in iodine status.
BACKGROUND: In 1993 the compulsory iodization of salt was introduced in Zimbabwe, a country that was previously an area of severe iodine deficiency. OBJECTIVE: The objective of this study was to document urinary iodine excretion and biochemical thyroid function in seemingly healthy, community-dwelling adults after the introduction of iodization. DESIGN: A multistage, random sampling method was used in rural and urban settings to identify households from which the senior household member (aged >35 y) was recruited (alternating male and female recruits). Demographic data were collected for each subject and urinary and venous blood samples were taken. Urinary iodine excretion and serum thyroid hormone status (thyrotropin and total thyroxin) were evaluated according to age, sex, and area of residence. RESULTS: A total of 736 adults were recruited (253 men; mean age: 64 y). Urinary iodine concentrations were high [median (first and third quartiles): 4.41 (2.84, 6.78) micromol/L, or 560 (360, 860) microgram/L] and were significantly higher in rural areas than in urban areas [4.73 (3.07, 7.14) micromol/L, or 600 (390, 906) microgram/L, compared with 3.47 (2.05, 4.73) micromol/L, or 440 (260, 600) microgram/L; P < 0.001]. Urinary iodine excretion declined significantly with increasing age (r = -0.29, P < 0.001). Serum thyroid status suggested that the prevalence of biochemical hyperthyroidism in the study was 3%, with 13 of 415 cases in rural and 3 of 149 cases in urban subjects. CONCLUSION: This study reaffirms the need to continuously monitor iodine replacement programs to ensure efficacy.
Adult↗
Molecular basis for methionine synthase reductase deficiency in patients belonging to the cblE complementation group of disorders in folate/cobalamin metabolism.
Methionine synthase reductase (MSR) deficiency is an autosomal recessive disorder of folate/cobalamin metabolism leading to hyperhomocysteinemia, hypo- methioninemia and megaloblastic anemia. Deficiency in MSR activity occurs as the result of a defect in the MSR enzyme, which is required for the reductive activation of methionine synthase (MS). MS itself is responsible for the folate/cobalamin-dependent conversion of homo- cysteine to methionine. We have recently cloned the cDNA corresponding to the MSR protein, a novel member of the ferredoxin-NADP(+)reductase (FNR) family of electron transferases. We have used RT-PCR, heteroduplex, single-strand conformation poly- morphism (SSCP) and DNA sequence analyses to reveal 11 mutations in eight patients from seven families belonging to the cblE complementation group of patients of cobalamin metabolism that is defective in the MSR protein. The mutations include splicing defects leading to large insertions or deletions, as well as a number of smaller deletions and point mutations. Apart from an intronic substitution found in two unrelated patients, the mutations appear singular among individuals. Of the eleven, three are nonsense mutations, allowing for the identification of two patients for whom little if any MSR protein should be produced. The remaining eight involve point mutations or in-frame disruptions of the coding sequence and are distributed throughout the coding region, including proposed FMN, FAD and NADPH binding sites. These data demonstrate a unique requirement for MSR in the reductive activation of MS.
5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗