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Biomedical subjects

A Cave

Publications and source records attributed to A Cave.

At least 19 recordsLinked to original sources

A qualitative study to identify factors influencing COXIB prescribed by family physicians for musculoskeletal disorders.

INTRODUCTION: Cyclo-oxygenase-2 inhibiting (COXIB) anti-inflammatories have been the drug class prescribed for a large number of cases of musculoskeletal (MSK) disorders in Canada over the past 5 years. The Alberta Improvements for MSK Disorders (AIMS) initiative sought to better understand the COXIB prescribing situation by funding several studies. The objective of this qualitative study was to determine the factors underlying primary care physicians' medication prescribing behaviour during an office visit for an MSK disorder, with particular emphasis on the prescribing of COXIBs. METHODS: The target respondents were Alberta primary care physicians chosen from a stratified random sample to meet a wide range of characteristics. Individual, semi-structured interviews were used to assess decision pathways in four real cases chosen by the physician. A total of 19 interviews were conducted and analysed using an analytic inductive approach. RESULTS: Factors judged as being important to decision pathways in relation to COXIB prescribing for MSK disease included safety, patient characteristics, affordability to patients, availability of samples, drug company marketing practices, habit formation, time contstraints, previous clinical experience of doctors and/or patient with certain drugs and doctors' perception of absolute versus relative risk. Interpretation. Most physicians preferentially prescribed COXIBs subsequent to a complicated, multifactorial, but essentially patient-centred, decision-making process.

Alberta↗

Socio-cultural factors influencing prevention and treatment of tuberculosis in immigrant and Aboriginal communities in Canada.

This multi-method study used a participatory action research approach to examine the complex net of socio-cultural factors that influenced behaviour related to tuberculosis (TB) prevention and treatment in the 10 highest risk cultural groups consisting of immigrant and Aboriginal populations in the province of Alberta, Canada. Trained community research associates collected qualitative interview data and helped with interpretation and evaluation. A community advisory committee established foundation principles and monitored the ethical and cultural appropriateness of the research process. A key finding is that although patients with active disease learn about TB from health professionals, people in high-risk populations need to learn more about TB transmission and prevention prior to contact. This is particularly important given that lack of knowledge of TB was strongly associated with negative attitudes towards TB and a worse experience of the disease. The study results underline the need for accessible and culturally appropriate health education about TB in the high risk groups. This can be accomplished in collaboration with lay people, particularly those who have recovered from active TB, their family members and health workers from the community.

Antitubercular Agents↗

Use of focus groups to assess the educational needs of the primary care physician for the management of asthma.

OBJECTIVES: To determine the educational needs of primary care physicians, in the management of patients with asthma. DESIGN: Focus group discussions with physicians, pharmacists, respiratory therapists and patients. SETTING: Metropolitan Edmonton, Alberta, Canada. PARTICIPANTS: Out of an original mail request to 100 potential recruits, 52 people attended the focus group sessions. These included physicians, pharmacists, respiratory therapists, adult patients and paediatric patients accompanied by their parents. MAIN OUTCOME MEASURE: Consensus of the specific group being interviewed using facilitator-mediated responses, to identify problems in the care of asthma patients and appropriate educational methods to improve the situation. RESULTS: Both diagnostic and treatment concerns were identified by the primary care physicians and others in the study. Confusion with infection was the most common diagnostic problem. Major treatment problems involved confusion about aspects of management strategy and a lack of communication between physicians, patients and other members of the health care team. Poor patient compliance and patients changing doctors frequently were also of major concern. There were inconsistencies in the treatment of asthma between physicians. While most physicians felt that they were up-to-date in management, Asthma Control Guidelines were seldom followed. CONCLUSIONS: There is an urgent need for continuing medical education, not only in management but also in communication with patients and with other members of the health care team. The data permit the development of an ongoing educational programme which is practical and designed to deal with the issues identified in this survey.

Alberta↗

Inhaled and nasal corticosteroids: factors affecting the risks of systemic adverse effects.

There has been increasing concern in the medical literature about the safety of inhaled and nasal corticosteroids, since many patients, both adults and children, are increasingly prescribed these drugs for the long-term prophylactic treatment of asthma and rhinitis. It is well recognised that systemic absorption occurs following inhaled and nasal administration of corticosteroids, but the dose at which clinically relevant side effects occurs is controversial. The controversy stems from the fact that the degree of systemic absorption depends not only upon the prescribed dose, but also upon the mode of delivery and the severity of the underlying disease. From a regulatory view, it is essential that the Product Information (Summary of Product Characteristics and Patient Information Leaflet) reflects the available evidence to enable a doctor to make an informed decision when prescribing these medicines. This article assesses the potential for inhaled and nasal corticosteroids to cause systemic adverse effects by analysing the published literature and spontaneously reported suspected adverse drug reactions reported to the Committee on Safety of Medicines and Medicines Control Agency. Five main areas of concern were reviewed: hypothalamic-pituitary-adrenal axis suppression, osteoporosis or changes in bone mineral density, growth retardation in children, cataracts, and glaucoma. Conclusions regarding these side effects at licensed doses of inhaled and nasal corticosteroids are reached and the clinical relevance is discussed, particularly following long-term therapy. The recommendations of the Committee on Safety of Medicines and Medicines Control Agency are included.

Administration, Inhalation↗

Study of Cardiovascular Risk Intervention by Pharmacists (SCRIP): a randomized trial design of the effect of a community pharmacist intervention program on serum cholesterol risk.

OBJECTIVE: To determine the efficacy of a program of intervention by pharmacists on lipid risk management in patients at high risk for cardiovascular events. METHODS: Randomized, multicenter (44 sites in Alberta and Saskatchewan) study of community pharmacist intervention versus usual care in 1000 patients. Patients are those at high risk of vascular events (existing atherosclerotic vascular disease, or diabetes with > or = 1 other risk factor). After obtaining consent, the pharmacist calls the Project Office to randomize. Patients allocated to intervention receive a brochure and education about cardiovascular risk factors. Pharmacists also complete a physician contact form, which lists the patient's risk factors, medications, and any recommendations. A point-of-care cholesterol test is performed, the result is discussed with the patient, and it is entered on the contact form. If appropriate, the patient is asked to see his or her primary care physician for further assessment and/or treatment, and the form is faxed to the physician. Patients are followed up at two, four, eight, 12, and 16 weeks. During follow-up visits, pharmacists provide educational reinforcement and check for primary end point occurrence. Patients allocated to usual care receive the brochure only, with minimal follow-up. The primary end point is a composite of measurement of a complete lipid panel by the physician, or addition or modification of lipid-lowering drug therapy. Substudies will evaluate economics (third-party payer and pharmacy manager perspective), patient satisfaction, and quality of life. CONCLUSIONS: SCRIP (Study of Cardiovascular Risk Intervention by Pharmacists) is a unique ongoing trial that is evaluating a community pharmacist intervention designed to optimize cholesterol risk management in patients at high risk for cardiovascular events.

Aged↗

cis-monotetrahydrofuran acetogenins from the roots of annona muricata1

Phytochemical investigation of roots of Annona muricata led to the identification of seven mono-tetrahydrofuran (mono-THF) acetogenins. Six new acetogenins having the unusual cis-configuration of the THF ring, cis-solamin (1), cis-panatellin (2), cis-uvariamicin IV (3), cis-uvariamicin I (4), cis-reticulatacin (5), and cis-reticulatacin-10-one (6) were identified, in addition to a known compound, solamin.

Journal Article↗

A phorbol ester-insensitive AP-1 motif mediates the stimulatory effect of insulin on rat malic enzyme gene transcription.

In liver, insulin stimulates the transcription of the gene encoding the cytosolic form of malic enzyme (ME) and modulates protein binding to two putative insulin response sequences (IRSs) in the ME promoter. One of these IRSs resembles that identified in the phosphoenolpyruvate carboxykinase (PEPCK) gene, whereas the other resembles that defined in the glyceraldehyde-3-phosphate dehydrogenase (GAPDH) gene. To assess the functional significance of these changes in protein binding, a series of truncated ME-chloramphenicol acetyl-transferase (CAT) fusion genes were transiently transfected into rat H4IIE hepatoma cells. Deletion of the PEPCK-like IRS motif had no effect on the stimulation of CAT expression by insulin. Instead, the stimulatory effect of insulin was mediated through an AP-1 motif and an Egr-1 binding site that overlaps the GAPDH-like IRS motif. Both the ME AP-1 motif and the AP-1 motif identified in the collagenase-1 gene promoter were able to confer a stimulatory effect of insulin on the expression of a heterologous fusion gene, but surprisingly only the latter was able to confer a stimulatory effect of phorbol esters. Instead, the data suggest that AP-1 binds the ME AP-1 motif in an activated state such that phorbol ester treatment has no additional effect. The collagenase and ME AP-1 motifs were both shown to bind mainly Jun D and Fra-2, with similar affinities. However, the results of a proteolytic clipping bandshift assay suggest that these proteins bind the collagenase and ME AP-1 motifs in distinct conformations, which potentially explain the differences in phorbol ester signaling through these elements.

Animals↗

Physicians and immigrant patients. Cross-cultural communication.

OBJECTIVE: To formulate recommendations for facilitating communication and helping prevent misunderstandings during cross-cultural patient-physician interactions. DESIGN: Qualitative study using content and semantic analyses of information supplied in focus groups. SETTING: All family physician respondents were associated with departments of family medicine at two urban hospitals and had expressed interest in this study; all immigrant patients were recruited from the English-as-a-Second-Language program at a community agency. PARTICIPANTS: Thirteen immigrant patients, distributed in two groups (one of seven women and one man and one of three men and two women), and five family physicians (two women and three men). MAIN OUTCOME MEASURES: Responses to prepared questions asked in focus groups. RESULTS: Family physicians thought that understanding patients' cultures better would improve quality of care. Patients did not always understand why their physicians asked questions about their culture, sometimes finding these questions irrelevant or intrusive. Comments were used to formulate recommendations for patient-physician interactions. CONCLUSIONS: Physicians and patients are aware of culture as a factor in their relationships but differ on its importance to quality of care.

Adult↗

Effect of Pygeum africanum extract on A23187-stimulated production of lipoxygenase metabolites from human polymorphonuclear cells.

Pygeum africanum extract has been used for more than 20 years in France in patients suffering from benign prostatic hypertrophy (BPH). The extract displays anti-inflammatory activity and inhibits bladder hyperreactivity during the above conditions. However, the mechanism of action of P. africanum extract has never been clearly resolved. It has been recently demonstrated that infiltration by inflammatory cells may be involved in the development of BPH. Certain of these cell types, such as macrophages, are known to produce chemotactic mediators including leukotrienes, and thus may contribute to the development of the disease. In order to investigate the potential effect of P. africanum extract on arachidonate metabolism, we examined its effect in vitro on leukotriene (LT) synthesis in human polymorphonuclear cells stimulated with the calcium ionophore A23187. Two formulations of the extract were tested, one dissolved in DMSO and one aqueous solution obtained after alkalinization (0.1 N; NaOH/acidification (0.1 N; HCl). Neither formulation had any effect on cell viability which was above 95% in both cases. P. africanum extract dissolved in DMSO significantly inhibited the production of 5-lipoxygenase metabolites (5-HETE, 20-COOH LTB4, LTB4 and 20-OH LTB4) at concentrations as low as 3 micrograms/ml (p < 0.01), while the same extract dissolved in NaOH/HCl only exhibited an inhibitory effect at 10 micrograms/ml (p < 0.01). This difference apparently reflects the greater solubility of the active components in the extract in DMSO. The ability of P. africanum to antagonize 5-lipoxygenase metabolite production may contribute, at least in part, to its therapeutic activity in inflammatory component of BPH.

Anti-Inflammatory Agents, Non-Steroidal↗

Conformational stability of human skeletal tropomyosins modified by site-directed mutagenesis.

We have used human beta-tropomyosin produced in Escherichia coli and deletion mutants obtained by site-directed mutagenesis to analyse the conformational stability of this molecule under various experimental conditions. Protein engineering has allowed us to answer some questions raised by stability analysis of the wild-type tropomyosin. The complex pattern of denaturation is due neither to heterogeneity of the preparation nor to head-to-tail interactions. The N- and C-termini are not of importance for the thermal stability of the molecule. On the contrary, deletion of the 31 C-terminus amino acids leads to a dramatic decrease of the stability observed in guanidinium chloride. This lowering is interpreted as the participation of one more guanidinium chloride ions to the denaturation equilibrium. Analysis of the stability in presence of organic solvents reveals that acetonitrile and methanol induce opposite effects. Investigation of these effects by three methods (CD, fluorescence and electrophoresis that measure respectively the content in alpha-helix, the contact between the two strands and the strands exchange) leads to the conclusion that strand separation can precede the denaturation of the alpha-helix.

Circular Dichroism↗

[Active antihelminitic alkaloids: active in vitro against Leishmanic Tropica the protozoa involved in leishmaniasis].

Leishmaniasis caused by protozoan Leishmania ssp., is an endemic parasitic disease in Central and South America. The chemotherapeutic agents against Leishmania ssp. (pentavalent antimony compounds, pentamidine and amphothericine B) are toxic and expensive products. Basing on the Bolivian folk medicine, we tried to find new active principles. Fourteen isoquinoline alkaloids, especially bisbenzylisoquinoline alkaloids extracted from Annonaceae, Berberidaceae, Hernandiaceae and Menispermaceae, demonstrate highly effective activity against this protozoan. Among them gyrocarpine, daphnandrine and obaberine seem to be of particular interest. The therapeutic effect was studied by biological assays on culture forms in vitro three strains of Leishmania, L. donovani, L. braziliensis (cutaneous and mucocutaneous leishmaniasis), L. mexicana amazonensis (cutaneous) and L. donovani (visceral leishmaniasis).

Alkaloids↗

Synthesis of (pGlu-5, MePhe-8, Sar-9) substance P (5-11) (DiMe-C7) using a polyacrylamide resin and biological activity on guinea pig ileum and tracheal smooth muscle.

DiMe-C7 (pGlu-Gln-Phe-MePhe-MeGly-Leu-MetNH2), a metabolically stable analogue of Substance P, was prepared by solid-phase peptide synthesis using a polyacrylamide resin and a labile anchorage derived from glycolic acid. Myotropic activities in guinea pig ileum (ED50 = 4.0 +/- 1.5 10(-8) M) and guinea pig trachea (ED50 = 8.6 +/- 3.5 10(-8) M) are discussed in comparison with the corresponding activities of Substance P.

Animals↗

Absence of reflex sympathetic activation by the selective renal vasodilator CGP 22979A in the conscious rat.

The effects of the selective renal vasodilator prodrug CGP 22979A on mean arterial blood pressure (MAP), heart rate (HR) and sympathetic efferent splanchnic nerve activity (SpNA) were investigated in conscious normotensive rats, and compared with those of the active drug CGP 18137A, a hydrallazine-like systemic vasodilator. CGP 18137A (0.03 to 1mg/kg i.v.) produced a dose-dependent decrease in MAP, whereas HR and SpNA increased. CGP 22979A affected neither BP nor HR and SpNA at doses of 1 and 3mg/kg i.v. which induce a selective increase in renal blood flow. In contrast, a dose of 30mg/kg i.v., which produced systemic effects comparable to those of CGP 18137A, stimulated SpNA to the same extent as 18137A did. These results demonstrate that the rise in renal blood flow induced by low doses of CGP 22979A is not associated with an increase in efferent sympathetic nerve activity. They suggest also that selective renal vasodilatation can be accomplished without an activation of the sympathetic nervous system.

Animals↗

Altered glucose tolerance, insulin response, and insulin sensitivity after massive weight reduction subsequent to gastric bypass.

We have studied an otherwise normal group of morbidly obese subjects and compared them with patients who had experienced massive weight loss after loop gastric bypass. Compared to normal controls (NLCs), morbidly obese control patients (OBCs) had abnormal glucose tolerance curves (after glucose ingestion), elevated basal insulin levels, and increased plasma insulin concentrations, suggesting insulin insensitivity. The latter has been corroborated by the measurement of decreased insulin binding in these patients. Postoperative (PO) patients were hyperglycemic after taking oral glucose, but all PO patients had a rapid decrease in plasma glucose concentration, half reaching hypoglycemic levels. PO basal insulin levels and insulin receptor number were not statistically different from those in NLCs, indicating up-regulation of insulin receptors (and therefore, increased insulin sensitivity) postoperatively. Hyperinsulinemia seen in the PO group (greater than that in OBCs, P less than 0.001) after administration of oral glucose occurred simultaneously with a doubling of plasma concentration of gastric inhibitory polypeptide. Massive weight loss in patients after gastric bypass was accompanied by an improvement in insulin receptor number, basal hyperinsulinemia, and glucose tolerance. In addition, postoperative patients demonstrated symptomatic reactive hypoglycemia which may have resulted from the hyperinsulinemia seen subsequent to ingestion of glucose.

Adult↗

Conformational studies on muscular parvalbumins cooperative binding of calcium (II) to parvalbumins.

1H NMR and ORD were used to characterize the respective variations of tertiary structure and secondary structure of parvalbumins with calcium content ((Pa(O), without calcium and PaCa2 calcium saturated) and temperature. It has been observed that the tertiary structure can be lost without significant variation of the helical content. Cooperative binding of calcium to Pa(O) has been shown by NMR spectroscopy under low ionic strength conditions and at neutral pH. The present study shows that the calcium binding affinity of parvalbumin is dependent on the tertiary structure. Calcium binding and calcium release functions of parvalbumins in the muscle may be controlled by their tertiary structure.

Animals↗