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Biomedical subjects

D Cook

Publications and source records attributed to D Cook.

At least 37 records · Page 2Linked to original sources
PubMed1995

Measurements of blood pressure, oedema and proteinuria in a pregnant population of New Zealand.

This is the first report of the largest study of blood pressure measurement in pregnancy in a New Zealand population using standardized definitions and methodology. Over 3,800 women who delivered in an 8-month period in the Wellington region were included in the study. Blood pressure measurement and the presence of oedema and proteinuria were recorded from booking until delivery and in the puerperium. Only 2.7% of women were unable to be contacted after delivery for details on outcomes. The results established normal ranges for blood pressure throughout pregnancy. The data show that blood pressure greater than 140/90 until 35 weeks' gestation is outside 2 standard deviations at all gestations and justifies using these measurements as the definition of hypertension in pregnancy. The fall in blood pressure in the 2nd trimester was less than 1 mm Hg per week in both the systolic and diastolic pressures. This fall was smaller than previously recorded in other studies. Gestational hypertension was the commonest blood pressure abnormality occurring in 15.2% of the population. This represented 69% of the pregnant women with a hypertensive disorder. The overall incidence of both gestational hypertension and preeclampsia was 18.5% which is higher than reported in other parts of the world. In this study obesity was significantly associated with hypertensive disorders in pregnancy. An arm circumference of > 33 cm, one of the measurements of obesity, was found in 6.8% of the study population. Even after the effect of arm circumference was taken into account, hypertensive disorders were also more common in Pacific Island women.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Pressure↗
PubMed1995

Interobserver variation in the computed tomographic evaluation of mediastinal lymph node size in patients with potentially resectable lung cancer. Canadian Lung Oncology Group.

OBJECTIVE: To measure the reliability of the assessment of mediastinal lymph node size in computed tomographic (CT) scans of the thorax. DESIGN: Observer agreement study in which radiologists, blinded to one anothers' interpretation, were randomized to read 30 scans each. POPULATION: Sixty scans from patients with apparently operable non-small cell carcinoma of the lung were read by radiologists responsible for clinical interpretation (clinical radiologists) and four radiologists with a special interest in thoracic CT (study radiologists). MEASUREMENTS: Radiologists measured the size of left and right superior mediastinal nodes, aortic nodes, and the subcarinal nodes and, on the basis of whether any nodes accessible to mediastinoscopy were greater than 1 cm, recommended whether mediastinoscopy be undertaken. Agreement was quantified using kappa, a measure of chance-corrected agreement. RESULTS: Among all radiologists, agreement on whether there were any nodes larger than 1 cm for right superior mediastinal nodes was 0.68; for left superior mediastinal nodes it was 0.28; for aortic pulmonary nodes it was 0.62; for subcarinal nodes it was 0.58; and for any node greater than 1 cm and accessible to mediastinoscopy it was 0.61. The agreement was very similar when the analysis was restricted to the study radiologists. CONCLUSION: Although the good level of overall agreement suggests that CT provides useful information in the evaluation of mediastinal lymph node size, the disagreement was sufficient that it likely contributes to suboptimal sensitivity and specificity of CT in detecting tumor spread reported in previous studies.

Carcinoma, Non-Small-Cell Lung↗
PubMed1995

Problem-based learning: its role in undergraduate surgical education.

OBJECTIVE: To familiarize the surgeon with problem-based learning (PBL) and to discuss the current and future role of PBL in undergraduate surgical education. DATA SOURCES: Two meta-analyses comparing the outcome of a PBL curriculum with a traditional curriculum and other studies in the English-language literature. STUDY SELECTION: Data on the effectiveness of PBL can best be assessed by a meta-analysis in which the conclusions of many studies are reviewed and combined to provide a more comprehensive picture. The studies chosen represent those from the only two recent meta-analyses of the problem that have appeared in reputable journals. DATA EXTRACTION: Results reported are those obtained using appropriate techniques and published in reputable journals. Information relevant to the major issues in undergraduate surgical training was selected for inclusion. DATA SYNTHESIS: PBL depends on self-directed learning, triggered by a clinical problem. The students meet in small groups led by a facilitator and discuss carefully designed clinical cases. At the conclusion, the students will have encountered all the information necessary to solve the case and, in so doing, will have gained knowledge that in a conventional curriculum would usually have been disseminated by lecture. There were only small differences between graduates from the two types of curricula. Those from a PBL curriculum had comparable examination results to those from a traditional curriculum on both basic science and clinically based examinations but were happier with their educational experiences. CONCLUSIONS: Centres that have adopted a PBL approach have found improved student motivation and enjoyment, but there has been no convincing evidence of improved learning. An intelligent combination of both traditional and PBL approaches will likely provide the most effective training for undergraduate surgical clerks.

Canada↗
PubMed1995

Lazaroids and deferoxamine attenuate the intracellular effects of oxyhaemoglobin in vascular smooth muscle.

OBJECTIVES: While it is probable that the cerebrovascular spasm which occurs after subarachnoid haemorrhage results from the action of haemoglobin, the mechanism of that process remains unclear. These studies were thus designed to test the hypothesis that the action of oxyhaemoglobin results from the iron-catalyzed formation of free radicals and subsequent lipid peroxidation resulting in intracellular changes in the second messengers for contraction. METHODS: Levels of intracellular calcium and of inositol (1,4,5)-trisphosphate were measured in cultured vascular smooth muscle cells derived from primate cerebral arteries. Contractility of rings of canine cerebral vessels were examined in vitro using standard pharmacological techniques. Vessels in spasm were obtained from the "two haemorrhage" canine model and the presence of vasospasm was confirmed angiographically. In each case, the effects of oxyhaemoglobin and sometimes of free radicals generated from iron salts were examined in the presence and in the absence of free-radical scavenging agents or the iron chelating agent, deferoxamine. RESULTS: Oxyhaemoglobin produces a slowly-developing sustained contraction of arterial rings which is accompanied by a sustained elevation of intracellular calcium. It also produces a transient but significant elevation of inositol (1,4,5)-trisphosphate, but this is not correlated with the development of sustained constriction. Deferoxamine and the lazaroid compounds U-74389G and U-83836E were effective in preventing the effects of oxyhaemoglobin and free radicals in the models tested, although in vessels in spasm, all effects were smaller. CONCLUSIONS: The present study provides results which are consistent with the hypothesis that the actions of haemoglobin on vascular smooth muscle are mediated by the formation of free radicals which subsequently affect intracellular calcium concentrations. This also implies that agents which impair free radical production or other processes leading to iron-catalyzed lipid peroxidation, are of potential value in cerebrovascular spasm.

Animals↗
PubMed1994

Spectrum of quality of life impairment in hypothyroidism.

The aim of this study is to evaluate the frequency and relative importance of different aspects of health related quality of life (HRQOL) impairment in patients with hypothyroidism. A survey of 200 patients with treated hypothyroidism was undertaken. Patients were identified and questionnaires distributed through family physicians, endocrinologists, and regional branches of the Thyroid Foundation of Canada. Frequency of importance of patients' symptoms attributed to hypothyroidism and resolved or improved with treatment were measured. Establishing the wide variety of patient-specific complaints associated with hypothyroidism provides guidance for clinicians dealing with hypothyroid patients, and investigators interested in HRQOL impairment in these patients.

Humans↗
PubMed1994

Cerebral vascular smooth muscle potassium channels and their possible role in the management of vasospasm.

One of the promising therapeutic uses of the potassium channel openers is in the management of cerebral vasospasm, a prolonged vasoconstriction of major cerebral arteries which follows aneurysmal subarachnoid haemorrhage. In this review, we first summarize the properties of potassium channels in cerebral vascular smooth muscle. Calcium-activated and ATP-dependent potassium channels are the major potassium channels identified in the cerebrovascular smooth muscle and both are believed to play a role in the regulation of cerebrovascular smooth muscle tone. The calcium-activated potassium channels can be activated by depolarization, by elevation of internal calcium and by some vasodilators. Some neuropeptides and potassium channel openers open the ATP-dependent potassium channels and produce vasodilation. We then review the effects of both synthetic and endogenous potassium channel openers in the cerebrovascular system, discuss their efficacy in the management of models of cerebrovascular spasm, and outline the clinical promise of these agents.

Adenosine Triphosphate↗
PubMed1994

Effect of increasing doses of beta agonists on spirometric parameters, exercise capacity, and quality of life in patients with chronic airflow limitation.

BACKGROUND: A study was undertaken to determine the impact of different doses of inhaled terbutaline on peak flow rates, spirometric parameters, functional exercise capacity, and quality of life in patients with chronic airflow limitation. METHODS: A double blind, randomised, placebo controlled, multiple crossover trial was conducted with treatment periods of one week. Patients with a clinical diagnosis of chronic airflow limitation and FEV1 below 70% predicted after administration of bronchodilator were recruited from secondary care respiratory practices, and the effect of 500, 1000, and 1500 micrograms inhaled terbutaline four times daily on spirometric parameters (FEV1, FVC), maximum inspiratory pressures, six minute walking distance, and health-related quality of life (Chronic Respiratory Disease Questionnaire, Quality of Well Being, Standard Gamble) was measured. RESULTS: Twenty five patients completed the trial. Peak flow rates and FEV1 showed statistically significant but clinically trivial improvement on the higher drug doses. Results of maximum inspiratory pressure measurements, walk test distance, and quality of life measures showed minimal differences on the different dosages, and none of the differences approached conventional statistical significance. CONCLUSIONS: Regular use of beta agonists in doses higher than two puffs four times a day is very unlikely to provide additional functional or symptomatic benefit to patients with chronic airflow limitation.

Aged↗
PubMed1994

Antagonism of eicosanoid-induced contraction of rat aorta by sulphonylureas.

Glibenclamide and other sulphonylureas are extensively used as specific blockers for ATP-dependent potassium channels in vascular smooth muscle. However, glibenclamide has recently been shown to inhibit actions of some prostanoids in vascular smooth muscle. We extend our previous study by examining the relaxant actions of five different sulphonylureas in rat aorta. The inhibitory effects of sulphonylureas on the contractions induced by prostaglandins F2 alpha, E2 and D2, norepinephrine, 5-hydroxytryptamine (5-HT) or potassium chloride (KCl) were examined. Glibenclamide significantly inhibited the contractions produced by prostaglandins F2 alpha, E2 and D2 but was without effect on responses to norepinephrine, 5-HT or KCl. Glimepiride produced significant attenuation of the responses to all agents tested (5-HT, norepinephrine, KCl), although the inhibition of the responses to prostaglandin F2 alpha was most pronounced. Glipizide and tolbutamide had activities similar to that of glibenclamide, while chlorpropamide was devoid of any antagonist action in rat aorta. In rat aorta precontracted with norepinephrine, glibenclamide inhibited the relaxant responses to lemakalim and pinacidil. Thus, in addition to the effect on ATP-dependent potassium channels, glibenclamide inhibits responses to prostaglandins F2 alpha, E2 and D2 but not to other agents. This effect is shared by glimepiride, tolbutamide and glipizide.

Animals↗
PubMed1994

Maternal factors and development of cardiovascular risk: evidence from a study of blood pressure in children.

It has been suggested that risks of hypertension and cardiovascular disease begin in utero and that maternal nutrition plays an important role. We have examined the relation between maternal factors and BP in a study of 1,311 children in which physical measurements at 9-11 years of age have been linked to a parental questionnaire; birth record data were also available in a subsample of 662 children. Maternal height was inversely related to childhood BP after adjustment for the child's current height. However, several social factors related to maternal nutrition in pregnancy in earlier studies (including social class, housing tenure, maternal educational attainment and maternal smoking in pregnancy) showed weak and inconsistent relations with BP at 9-11 years. Minimum maternal haemoglobin in pregnancy and change in mean corpuscular volume in pregnancy (identified as potentially important markers of maternal nutrition in earlier studies) showed no consistent relationships either with placental weight to birthweight ratio or with childhood BP, although both factors showed strong inverse associations with birthweight. The association between maternal height and childhood BP may reflect the influence of early life factors on cardiovascular risk. However, the absence of consistent relationships between social factors and BP in offspring provides little support for the possibility that maternal diet is an important influence on cardiovascular risk factors in childhood. Minimum maternal haemoglobin and change in maternal mean corpuscular volume are unlikely to be specific markers of maternal nutrition in pregnancy. More specific hypotheses relating maternal nutrition to the development of cardiovascular risk in offspring are required.

Adult↗
PubMed1993

A measurement process for evaluating clinical teachers in internal medicine.

With input from faculty members and residents in the internal medicine residency training program at McMaster University, Hamilton, Ont., the authors developed a form to evaluate attending physicians in clinical teaching units according to 14 domains of performance. Although brief, the form included all main areas of teacher performance, allowed specification of attending physician behaviour and differentiated areas of strengths and weaknesses between and within attending physicians. The authors describe the new evaluation process and the results for 41 attending physicians.

Canada↗
PubMed1993

Maize Spm transposable element has an enhancer-insensitive promoter.

We have used a transient assay system to investigate the promoter region of the maize Suppressor-mutator (Spm) transposable element. All of the sequence required for constitutive promoter activity is confined to the 0.2-kb sequence upstream from the transcription start site of the element at nt 209 and designated the upstream control region. The element's promoter is weak, lacks a conventional TATA box, and depends on the presence of multiple, short repetitive sequence elements. The Spm promoter is quite insensitive to the enhancer sequence of the cauliflower mosaic virus 35S promoter. Enhancer sensitivity can be restored by providing a -30 TATA sequence and removing the G + C-rich sequence encoding the untranslated leader of the element, designated the downstream control region. Although the downstream control region is without effect on Spm promoter activity, it completely inhibits the 35S core promoter and markedly inhibits activity of the complete 35S promoter. The properties of the Spm element's promoter buffer it from both mutational and position-dependent changes in activity. We suggest that the inherent characteristics of the promoter are part of the genetic mechanism that controls the element's transposition frequency, ensuring it remains low and insertion-site independent.

Base Sequence↗
PubMed1993

Alternative mechanisms with and without steel factor support primitive human hematopoiesis.

As a first approach to defining the molecular requirements for supporting human hematopoietic stem cell maintenance and differentiation in vitro, we have analyzed and compared the ability of various factors to support the maintenance and initial differentiation of human long-term culture-initiating cells (LTC-ICs), a distinct, rare primitive hematopoietic cell type whose progeny after 5 weeks include cells detectable as colony-forming cells. Normal human marrow cells highly enriched in LTC-ICs (approximately 1% pure) were placed in cultures containing either preestablished, irradiated human marrow adherent feeder layers, or feeders consisting of Steel factor-deficient SI/SI, or normal +/+ murine fibroblasts, or no feeders. In some groups, either Steel factor alone, granulocyte colony-stimulating factor (G-CSF) and interleukin-3 (IL-3), or all three factors combined were also added repeatedly. SI/SI murine fibroblasts were equivalent to +/+ controls and to normal human marrow feeders in supporting both LTC-IC maintenance and clonogenic cell output over a 5-week period. Soluble Steel factor alone could, however, effectively substitute for human marrow feeders to support LTC-IC maintenance, although clonogenic cell output was markedly reduced under these conditions. Conversely, soluble Steel factor with G-CSF and IL-3 or with feeders (or all together) did not further enhance (or depress) LTC-IC maintenance, although under these conditions clonogenic cell output was markedly increased. These findings confirm previous evidence that LTC-IC maintenance and clonogenic cell production are differentially regulated and show for the first time that LTC-IC maintenance can be supported by different nonsynergizing factors that may, but need not, include Steel factor.

Animals↗
PubMed1993

Transfer of humoral immunity against cytomegalovirus proteins following transplantation of T-cell-depleted allogeneic bone marrow from seropositive donors.

Previous work by Grob et al. [Lancet i: 774, 1987] has demonstrated that allogeneic, T-cell-depleted bone marrow transplant recipients have a better prognosis for reactivated cytomegalovirus (CMV) infection if their donor is also immune. It was proposed that adoptively transferred humoral immunity was responsible for the protective effect of active infection. Immunoblot analysis using purified virions was used here to examine pre- and posttransplant antibody responses of seropositive recipients who had undergone active viral infection after transplantation. Immunoblots were assessed for the numbers of polypeptides recognised and reactivity against individual polypeptides. Immunoblots were also scanned by quantitative densitometry, and the intensity of antibody responses against total viral protein and individual polypeptides was determined. Sera from recipients with immune donors exhibited a secondary-type immune response in terms of both intensity and polypeptide specific pattern of antibody reactivity, compared with those recipients with nonimmune donors. In particular, recipients with immune donors appeared to show a greater reactivity against a protein of M(r) 55,000; this may represent the envelope glycoprotein gB, which is a major target for neutralising antibodies, and might also be utilised for preparing an effective vaccine for CMV.

Antibodies, Viral↗
PubMed1993

Strain variation in Epstein-Barr virus immediate early genes.

RNase protection analysis of mRNAs for Epstein-Barr virus (EBV) genes activated early in the induction of the productive cycle in Akata cells has confirmed that BZLF1 and BRLF1 behave as immediate early genes. These are likely to be the only virus immediate early genes since analysis of three other transcripts previously suggested to behave as immediate early genes in this system shows that they are, in fact, early genes. Western blotting of BRLF1 and BZLF1 demonstrates expression of these proteins early in induction of the productive cycle and reveals that the BZLF1 protein of Akata virus migrates more slowly on SDS gels than the BZLF1 protein of the prototypic virus strain B95-8. The nucleotide sequence of the BZLF1 gene and the immediate early promoters of Akata EBV have been determined and compared to other EBV strains. RFLP analysis of sequence variation in the BZLF1 gene of EBV strains from many different parts of the world shows a distribution of BZLF1 types which are not simply related to the established A and B EBV types.

Amino Acid Sequence↗