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Biomedical subjects

H Arthur

Publications and source records attributed to H Arthur.

At least 19 recordsLinked to original sources

Plasma esterase (ES) polymorphism in the tammar wallaby, Macropus eugenii.

The major plasma esterase in the tammar wallaby was identified as a carboxylesterase by inhibition studies and polymorphism with six variants was observed by isoelectric focusing (pH 4.2-4.9), followed by staining for esterase activity. Family studies demonstrated an inheritance of six codominant alleles, ESA,B,C,D,E,F, and population studies revealed marked differences in the allele frequencies in five Australian populations of tammar wallabies.

Animals

Further evidence for an association between a mutation in the APP gene and Lewy body formation.

There have been two detailed neuropathological reports of families with a valine to isoleucine substitution at position 717 of the amyloid precursor protein gene. Surprisingly, in one of these families substantial Lewy body formation occurred in addition to Alzheimer's disease, prompting the speculation that such a genetic mutation may predispose to both Lewy body and plaque formation. This report describes the neuropathology of an additional family with the same genetic mutation. Of two affected members who have come to autopsy, one had brainstem Lewy bodies. Some of these Lewy bodies had peripheral halos immunoreactive for beta-amyloid. These findings suggest a greater than chance link between genetic mutations for Alzheimer's disease and Lewy body formation.

Alzheimer Disease

Genetic polymorphism of cat (Felis catus) plasma orosomucoid.

Genetic polymorphism of orosomucoid (ORM) was observed in 22 breeds of cats (Felis catus) using isoelectric focusing (pH 4.0-6.5) of desialylated plasmas followed by immunoblotting with rabbit antiserum to human ORM. From a total of 943 plasma samples examined, 15 phenotypes were identified and family studies demonstrated an inheritance of five codominant alleles, ORMA, ORMB, ORMC, ORMD, and ORME, at a single locus.

Alleles

Women and heart attack: a study of women's experiences.

Cardiovascular disease in general, and myocardial infarction (MI) in particular, is the major health problem of females after 50 years of age. To date, heart disease research has focused primarily on males. The limited evidence suggests that the physical, psychological, and social ramifications of MI for women are significant, and different from those of men. Since the specific rehabilitation needs of women are not yet clear, this study was designed to explore the unique experiences and needs of women following a first MI. A phenomenological study using focus groups was used to explore the experiences, questions, concerns, and preferred interventions of women after a MI. Participants were female volunteers (n = 14) who had been hospitalized for a MI within the previous 6 months. Focus groups were audio taped and analysed by the investigators. Four major themes emerged: validation; perceived gender differences; role expectations/role tensions; and helps and hindrances to recovery.

Adult

Plasma protease inhibitor (PI) system in the laboratory opossum, Monodelphis domestica.

Protease inhibitor (PI) polymorphism was observed in the laboratory opossum, Monodelphis domestica, by either one-dimensional acid polyacrylamide gel electrophoresis (PAGE; pH 4.6) or isoelectric focusing (pH 3.5-5.0) followed by immunoblotting with rabbit antiserum to human alpha 1-antitrypsin; but acid PAGE produced superior resolution of the PI proteins. Family studies demonstrated an inheritance of nine codominant autosomal alleles, PID, PIE, PIF, PIG, PIH, PII, PIJ, PIK, and PIM, and a population study revealed frequencies of 0.411, 0.010, 0.341, 0.034, 0.023, 0.071, 0.035, 0.020, and 0.055, respectively.

Animals

Nursing curriculum content: an innovative decision-making process to define priorities.

Curriculum planning in the health sciences is becoming increasingly complex due to rapid societal change and scientific discovery. The half-life of most curricula is 5 years, which necessitates a periodic close examination and revision of both content and process. For nursing faculty, this exercise is often viewed as an arduous one and traditionally can lead to endless hours of circular debate. Planning is usually in two stages; the first stage being the development of or agreement about a theoretical framework and the second stage is deciding on core content and teaching methodologies. This article focuses on decisions in the second stage. Traditionally, decisions around curriculum are arrived at by much debate. Some argue that all health issues should be addressed in the curriculum in order that the graduate be prepared to deal with a breadth of issues. However, this approach often leads to what has been referred to as 'curriculum hypertrophy', where, in an attempt to be all-inclusive, the curriculum grows without bounds. Rarely is anything dropped from the curriculum when this approach is used. Sometimes priorities are established on the basis of what the individual teaching staff deems important. In other cases a consensus approach is chosen.

Curriculum

An analysis of the impact of a management system on patients waiting for cardiac surgery.

The Cardiac Surgery Management System (CSMS) was developed in the Central West region of Ontario to support patients who are waiting for cardiac surgery. This management system provides a consistent mechanism to communicate preoperative information to patients and their families. A questionnaire was developed to analyze the impact of the CSMS on patients waiting for elective surgery in this health region. This descriptive study assesses the patients' perception of the assistance they received preoperatively, through the nurse coordinator. One hundred and fifty study patients were randomly selected from patients who had undergone elective surgery during the previous calendar year and these subjects received questionnaires. The final response rate was 81%. Ninety-three percent of respondents had telephone contact with the coordinator, and 89% of these patients received information/education by mail. Sixty percent of respondents admitted to some degree of anxiety, and 46% of these patients discussed their feelings with the coordinator. Increased levels of anxiety were associated with an increased likelihood of a patient-initiated contact with the coordinator. This contact was associated with decreased levels of anxiety. Patients waiting for surgery demonstrated preoperative anxiety, and opportunities to discuss this should be provided. Patients also feel they benefit from receiving educational material preoperatively. The use of the nurse in an expanded role needs to be maximized, with focus on the nurse as a facilitator for problem solving.

Adaptation, Psychological

Student self-evaluations: how useful? How valid?

Skill in self-evaluation is necessary for life-long learning, for competent performances--in short, for professional practice in the health sciences. In addition, self-evaluation skills can be learned and can be taught, although they are not now purposefully taught in most programs. There is research evidence that self-evaluation is more useful for learners as a formative rather than a summative tool. The purposes of this paper are (a) to provide a critical review of the literature on the accuracy of student self-evaluation and (b) to describe our experience and preliminary research findings at McMaster University regarding the most profitable approach to incorporating self-evaluation in baccalaureate nursing education.

Clinical Competence

Polymorphic drug metabolism in schizophrenic patients with tardive dyskinesia.

The metabolism of many neuroleptics cosegregates catalyzed by the polymorphic cytochrome P450 CYP2D6. The population can be phenotyped into extensive metabolizers (EM) and poor metabolizers (PM) with respect to this enzyme's activity. PM are likely to achieve higher than average concentrations of neuroleptic drugs in plasma, with an increased risk of extrapyramidal side effects, possibly including tardive dyskinesia. Sixteen white schizophrenic patients who had developed tardive dyskinesia during long-term neuroleptic treatment were phenotyped with debrisoquine and genotyped by CYP2D6-specific DNA amplification and EcoRI restriction fragment length polymorphism analysis. Only 1 (6%) of the 16 patients had a PM genotype, 8 (50%) were homozygous, and 7 (44%) were heterozygous EM. None had a CYP2D6 genotype indicative of ultrarapid debrisoquine hydroxylation capacity. The patients were also phenotyped with mephenytoin, a probe drug for another polymorphic cytochrome P450, CYP2C19. One patient was a PM of S-mephenytoin, which corresponds to the frequency found in healthy white volunteers. In conclusion, there was no overrepresentation of PM of debrisoquine or of S-mephenytoin among the 16 patients with neuroleptic-induced tardive dyskinesia. However, the PM of debrisoquine had the highest score on the Simpson-Angus Rating Scale and the second highest on the Abnormal Involuntary Movement Scale, despite a very low neuroleptic dose. Also, the debrisoquine MR correlated significantly with the SARS score (rs = 0.685, p < 0.05, N = 10), indicating a relationship between the degree of impaired CYP2D5 activity and the severity of extrapyramidal side effects during neuroleptic treatment.

Adult

Mutations in the equine plasma transferrin and esterase systems.

Eleven apparent mutations of the equine plasma transferrin and esterase gene (10 in TF and one in ES) were found in an analysis of approximately 240,000 thoroughbred horses. Eight of the transferrin mutations produced variants not previously recognized in horses. In the two remaining transferrin mutations and the esterase mutation, reduced plasma concentrations of the proteins were demonstrated by immunological techniques and together with the family data indicated the existence of 'null' alleles.

Animals

Potential oxyradical damage and energy status in individual muscle fibres from degenerating muscle diseases.

Inherited degenerating muscle diseases result in disintegration of muscle fibres, which is initiated by a lack of or alteration to a muscle protein. In Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) the protein is known to be dystrophin. The cellular function of dystrophin is not known in any detail but its absence appears to lead to a weakening of the sarcolemma. It has been proposed by Murphy and Kehrer that this leads ultimately to increased oxyradical production which may accelerate the degeneration. Studies have been carried out on individual muscle fibres derived from biopsy samples from patients with a number of degenerative muscle diseases. The glutathione cycling components, in particular glutathione and glutathione peroxidase, are significantly elevated in DMD, BMD and other diseases. Glutathione reductase is also elevated in some of these diseases. Energy producing systems are also affected particularly in intact fibres of muscle derived from muscle at an advanced stage of the disease. These results suggest that oxyradical damage may occur as a secondary consequence of muscle degenerating disease, leading to a breakdown in the glycogenolytic energy producing system.

Adenosine Diphosphate

Antithrombin III (AT3) polymorphism in the marsupial Monodelphis domestica: identification and genetics.

Antithrombin III polymorphism was observed in the gray short-tailed opossum, Monodelphis domestica, by either one-dimensional polyacrylamide gel electrophoresis (PAGE; pH 7.9), two-dimensional PAGE (agarose, pH 5.4; 12% T, pH 7.9), or isoelectric focusing (pH 4.2-4.9) followed by immunoblotting with rabbit antiserum to human antithrombin III. Family studies demonstrated an inheritance of three codominant autosomal alleles, AT3A, AT3B, and AT3C, and a population study revealed frequencies of 0.70, 0.10, and 0.20, respectively.

Alleles

A double-blind comparative multicentre study of remoxipride and haloperidol in schizophrenia.

In a double-blind multicentre study of parallel group design the efficacy and safety of remoxipride and haloperidol were compared in a total of 96 patients with acute episodes of schizophrenic or schizophreniform disorder according to DSM-III. There were 48 patients in each treatment group; 27 men and 21 women in the remoxipride group, 33 men and 15 women in the haloperidol group. The median duration of illness was 7 years in both groups. The mean daily dose was 437 mg for remoxipride and 10.6 mg for haloperidol during the last week of treatment. No statistically significant differences in total BPRS scores were found between remoxipride and haloperidol. The median total BPRS scores at the start of active treatment were 26 in the remoxipride and 27 in the haloperidol group; these were reduced to 16 and 12.5, respectively, at the last rating. According to Clinical Global Impression (CGI), 43% of patients in the remoxipride group and 68% of those in the haloperidol group improved much or very much during treatment. This difference was not statistically significant. Treatment-emergent extrapyramidal side effects such as akathisia, tremor, and rigidity occurred significantly more frequently in the haloperidol group; this group also made more frequent use of anticholinergic drugs. Neither of the trial drugs seriously affected laboratory or cardiovascular variables. It is concluded that remoxipride has an antipsychotic effect in a dose range of 150-600 mg per day comparable to that of haloperidol in doses up to 20 mg per day but with fewer extrapyramidal side effects.

Acute Disease

Micromethods in single muscle fibers. 1. Determination of catalase and superoxide dismutase.

Methods have been developed for the measurements of catalase and superoxide dismutase (SOD) in single, isolated muscle fibers. These fibers are also classified according to fiber type. Catalase is determined using a fluorescent method for the measurement of hydrogen peroxide consumed. SOD measurements are carried out using a modification of established techniques whereby the inhibition of oxidation of epinephrine by SOD is assayed fluorometrically. Both enzymes may be determined in submicrogram samples of dried muscle. This approach avoids the complication of the inclusion of nonmuscle tissue with varying enzymatic activities which is frequently experienced when using homogenates of muscle, particularly diseased muscle. In addition, these techniques can be used to determine the inherent variation in SOD and catalase activities within individual fibers of the same fiber type. The Km and Vmax for catalase, determined using homogenates of human muscle, were found to be 12 mM and 1.45 mumol/min/mg dry wt, respectively. Catalase of muscle was inhibited 50% by 2 microM sodium azide. Mn-SOD contributes less than one-fifth of the total SOD activity. Therefore the activity is largely due to the Cu-Zn form of SOD. These methods are applicable to a wide variety of tissues.

Catalase

Micromethods in single muscle fibers. 2. Determination of glutathione reductase and glutathione peroxidase.

This paper extends the previous study for systems which control intracellular oxidative events in muscle and describes procedures suitable to assay glutathione peroxidase (GSHPx), glutathione reductase (GR), and total glutathione (GSH + GSSG) after fiber typing of individual muscle fibers. In human skeletal muscle, both GR and GSHPx activities were relatively low when compared to those of other tissue. No difference was found among fiber types (I, IIA, and IIB) with regard to GR activity, but in contrast GSHPx activity was significantly lower in type IIB fibers than in the other types. These results suggest that type IIB fibers may have a reduced ability to cope with hydroperoxides generated during oxidative stress, which, in turn, could lead to increased damage to membrane structures by lipid peroxidation or oxidation of sensitive intracellular thiol (-SH) enzymes by hydrogen peroxide. The Km of skeletal muscle GR for GSSG was 27 microM and for NADPH was 22 microM. If one assumes approximately 95% of total glutathione is present in the reduced state, then GSSG concentration would be of the order of 0.3 mmol/kg and under these conditions skeletal muscle GR would be efficient in all muscle fiber types.

Fluorescence

A pilot trial of plasma infusions in Duchenne muscular dystrophy.

It has been proposed that a defect in tocopherol transport may lead to a chronic vitamin deficiency in Duchenne muscular dystrophy (DMD). To test this hypothesis, a pilot clinical trial which involved the infusion of tocopherol-laden plasma was carried out. An increased uptake of tocopherol into erythrocyte membranes during infusions failed to produce a significant reduction in plasma enzyme levels or to arrest the dystrophic process in the two children examined. Further studies to investigate treatments with increased amounts of tocopherol, in conjunction with other antioxidants, may prove a more fruitful avenue of research.

Adolescent

Thermodynamic behaviour of membrane enzymes in Duchenne muscular dystrophy.

Erythrocyte ghost preparations have been prepared from blood of Duchenne patients (DMD), female carriers of the disease and controls. Arrhenius plots of Na+, K+-ATPase activity of these membrane preparations show a biphasic response for controls. For 75% of DMD and carriers the response is monophasic. This is not an inherent property of the membrane since it can vary over time in the one individual and it can be induced in normal membranes by preincubation with DMD plasma. Arrhenius plots of AChE activity showed no such difference between the three sources of blood.

Acetylcholinesterase

Plasma lipoproteins in Duchenne muscular dystrophy.

Plasma lipoproteins of Duchenne muscular dystrophy patients and carriers of the disease, together with age- and sex-matched controls, were examined by density gradient ultracentrifugation and agarose gel electrophoresis. Analysis of density gradient profiles revealed a significant reduction in absorbance (435 nm) by low density and high density lipoproteins from Duchenne patients when compared with controls. Although no abnormalities were observed on electrophoresis of whole plasma samples, the isolated low density lipoprotein fractions from Duchenne patients and carriers displayed increased electrophoretic mobility compared with controls. The results obtained implicate the plasma lipoproteins, in particular the low density lipoproteins, as the primary site of the lesion in this disease.

Adolescent