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Biomedical subjects

S Evans

Publications and source records attributed to S Evans.

At least 73 records · Page 4Linked to original sources

Acetylcholine induces cytosolic Ca2+ mobilization in isolated distal colonic crypts from normal and cystic fibrosis mice.

In intestinal biopsies from cystic fibrosis (CF) patients acetylcholine fails to elicit a chloride secretion response, and this observation can be explained by a defect in the Ca2+ signalling pathway in CF secretory cells. We tested the hypothesis that in CF intestine, the generation of an intracellular Ca2+ signal upon cholinergic stimulation is absent. A transgenic CF mouse model was used. Electrical measurements on intact jejunum and unstripped colon were performed in Ussing chambers. Intact distal colonic crypts were isolated, and the intracellular Ca2+ concentration was monitored using the Ca2+-sensitive dye fura-2. Acetylcholine increased the short-circuit current generated by wild-type jejunum and colon, but failed to induce a response in CF tissues. Acetylcholine caused a transient elevation in the intracellular Ca2+ concentration in colonic crypts from both wild-type and CF mice; the amplitude and timing of the response in CF crypts was indistinguishable from that in wild-type crypts. The response to acetylcholine was also observed in the absence of extracellular calcium, indicating intracellular stores as the source from which the cytosolic Ca2+ concentration increased. We conclude that the absence of a cholinergically-induced secretory response in CF intestine is not due to a defect in the generation of a Ca2+ signal in intestinal cells upon cholinergic stimulation.

Acetylcholine↗

The effect of flexible low glycemic index dietary advice versus measured carbohydrate exchange diets on glycemic control in children with type 1 diabetes.

OBJECTIVE: To determine the long-term effect of low glycemic index dietary advice on metabolic control and quality of life in children with type 1 diabetes. RESEARCH DESIGN AND METHODS: Children with type 1 diabetes (n = 104) were recruited to a prospective, stratified, randomized, parallel study to examine the effects of a measured carbohydrate exchange (CHOx) diet versus a more flexible low-glycemic index (GI) dietary regimen on HbA(1c) levels, incidence of hypo- and hyperglycemia, insulin dose, dietary intake, and measures of quality of life over 12 months. RESULTS: At 12 months, children in the low-GI group had significantly better HbA(1c) levels than those in the CHOx group (8.05 +/- 0.95 vs. 8.61 +/- 1.37%, P = 0.05). Rates of excessive hyperglycemia (>15 episodes per month) were significantly lower in the low-GI group (35 vs. 66%, P = 0.006). There were no differences in insulin dose, hypoglycemic episodes, or dietary composition. The low-GI dietary regimen was associated with better quality of life for both children and parents. CONCLUSIONS: Flexible dietary instruction based on the food pyramid with an emphasis of low-GI foods improves HbA(1c) levels without increasing the risk of hypoglycemia and enhances the quality of life in children with diabetes.

Australia↗

BMP signaling is required for heart formation in vertebrates.

In these studies, we have taken advantage of a transient transgenic strategy in Xenopus embryos to demonstrate that BMP signaling is required in vivo for heart formation in vertebrates. Ectopic expression of dominant negative Type I (tALK3) or Type II (tBMPRII) BMP receptors in developing Xenopus embryos results in reduction or absence of heart formation. Additionally, blocking BMP signaling in this manner downregulates expression of XNkx2-5, a homeobox gene required for cardiac specification, prior to differentiation. Notably, however, initial expression of XNkx2-5 is not affected. Mutant phenotypes can be rescued by co-injection of mutant with wild-type receptors or co-injection of mutant receptors with XSmad1, a downstream mediator of BMP signaling. Whole-mount in situ analyses indicate that ALK3 and XSmad1 are coexpressed in cardiogenic regions. Together, our results demonstrate that BMP signaling is required for maintenance of XNkx2-5 expression and heart formation and suggest that ALK3, BMPRII, and XSmad1 may mediate this signaling.

Activin Receptors↗

Attitudes of Australian veterinarians about the cause and treatment of lower-respiratory-tract disease in racehorses.

A questionnaire was administered to members of the Australian Equine Veterinary Association to investigate their attitudes and behaviours regarding the cause, diagnosis and treatment of lower-respiratory-tract disease in racehorses. The most-important perceived risk factors related to the level of exposure and resistance to infectious agents, whereas factors associated with racing and climatic factors were lower ranked. By far the most-commonly implicated primary cause of disease was respiratory viruses. However, specific diagnostic tests (such as viral serology or virus isolation) were rarely performed. By far the most-common diagnostic procedure was auscultation (without a rebreathing bag). The relative importance of diagnostic procedures was influenced by the proportion of total workload comprising horse work. Many respondents believed that bacteria become secondarily involved in disease; accordingly, antibiotic therapy was the most-commonly reported therapy. However, bacteriology of lower-airway-fluid samples was not commonly performed. The most-commonly used antibiotics were the potentiated sulphonamides (either alone or in combination with mucolytics or bronchodilators), followed by procaine penicillin and penicillin combined with gentamicin. Mainly, treatment would appear to be based on empirical beliefs rather than exhaustive investigation of individual cases.

Adrenal Cortex Hormones↗

Issues associated with the application to veterinarians of a mailed questionnaire regarding lower respiratory-tract disease in racehorses.

This study evaluated a questionnaire investigating the attitudes and behaviours of veterinarians regarding the cause, diagnosis and treatment of lower respiratory-tract disease in racehorses. The questionnaire was sent to all non-student members (648) of the Australian Equine Veterinary Association: two mailings and a single telephone contact (each separated by four weeks). Subsequent phases were only administered to those who had not responded to earlier phases. In total, 467 (72.1%) of the 648 mailed questionnaires were returned. Of these, 354 were usable. The remaining 113 respondents gave various reasons for not completing the questionnaire; the most common (68%) was that horses were not a component of their practice. Those respondents working primarily with horses required fewer phases to return the questionnaire. Although deviating from previously described questionnaire designs, the described protocol provided a reasonable response rate.

Animals↗

Candidate genes for the hypoxic tumor phenotype.

In this study, we have analyzed changes induced by hypoxia at the transcriptional level of genes that could be responsible for a more aggressive phenotype. Using a series of DNA array membranes, we identified a group of hypoxia-induced genes that included plasminogen activator inhibitor-1 (PAI-1), insulin-like growth factor-binding protein 3 (IGFBP-3), endothelin-2, low-density lipoprotein receptor-related protein (LRP), BCL2-interacting killer (BIK), migration-inhibitory factor (MIF), matrix metalloproteinase-13 (MMP-13), fibroblast growth factor-3 (FGF-3), GADD45, and vascular endothelial growth factor (VEGF). The induction of each gene was confirmed by Northern blot analysis in two different squamous cell carcinoma-derived cell lines. We also analyzed the kinetics of PAI-1 induction by hypoxia in more detail because it is a secreted protein that may serve as a useful molecular marker of hypoxia. On exposure to hypoxia, there was a gradual increase in PAI-1 mRNA between 2 and 24 h of hypoxia followed by a rapid decay after 2 h of reoxygenation. PAI-1 levels were also measured in the serum of a small group of head and neck cancer patients and were found to correlate with the degree of tumor hypoxia found in these patients.

Animals↗

Electromagnetic rewarming: the effect of CPA concentration and radio source frequency on uniformity and efficiency of heating.

The relevant dielectric properties of a practical perfusate formula have been measured at radiofrequencies from 27 to 2954 MHz and temperatures from -75 to +25 degrees C. Both dimethyl sulfoxide and 2,3-butanediol were investigated as the cryoprotectant component at concentrations from 15 to 50%. The dielectric properties are considered in terms of new indices which characterize uniformity of heating, the power delivered and the efficiency of heating, and the avoidance of localized thermal runaway during very rapid heating. It becomes clear that a compromise must be accepted between nonuniformity of heating at the higher frequencies and inconveniently low power delivery at the lower frequencies. The choice of CPA and the concentration are found to be not very significant in these respects.

Butylene Glycols↗

Health locus of control, distress, and utilization of protease inhibitors among HIV-positive men.

OBJECTIVE: To investigate the relationship between health locus of control (HLOC), distress, and protease inhibitor (PI) utilization in gay/bisexual men in all stages of HIV illness. METHOD: A total of 173 men participating in a longitudinal study of the psychological effects of HIV illness were administered a number of psychological distress measures and the HLOC scale. The association between the HLOC subscales, distress, and PI utilization was evaluated. RESULTS: In addition to physical symptoms, the attribution of health status to chance or fate significantly predicted depressive symptoms, feelings of hopelessness, and recent life stress. Results also demonstrated a significant relationship between strong, positive beliefs in doctors and other health care professionals and PI utilization. CONCLUSION: The results of this study point to a strong association between beliefs that health status is related to chance or fate and distress. In addition, beliefs in physicians and other health care providers appear to contribute to decisions to initiate PI therapy.

Adult↗

Fraud in medical research: an international survey of biostatisticians. ISCB Subcommittee on Fraud.

The characteristics of scientific fraud and its impact on medical research are in general not well known. However, the interest in the phenomenon has increased steadily during the last decade. Biostatisticians routinely work closely with physicians and scientists in many branches of medical research and have therefore unique insight into data. In addition, they have methodological competence to detect fraud and could be expected to have a professional interest in valid results. Biostatisticians therefore are likely to provide reliable information on the characteristics of fraud in medical research. The objective of this survey of biostatisticians, who were members of the International Society for Clinical Biostatistics, was to assess the characteristics of fraud in medical research. The survey was performed between April and July 1998. The participation rate was only 37%. We report the results because a majority (51%) of the participants knew about fraudulent projects, and many did not know whether the organization they work for has a formal system for handling suspected fraud or not. Different forms of fraud (e.g., fabrication and falsification of data, deceptive reporting of results, suppression of data, and deceptive design or analysis) had been observed in fairly similar numbers. We conclude that fraud is not a negligible phenomenon in medical research, and that increased awareness of the forms in which it is expressed seems appropriate. Further research, however, is needed to assess the prevalence of different types of fraud, as well as its impact on the validity of results published in the medical literature.

Biometry↗

Prevalence of celiac antibodies in children with neurologic disorders.

Neurologic complications are a recognized but unusual manifestation of celiac disease (CD) in adults and children. The use of antigliadin and antiendomysial antibodies in screening has revealed the frequency of CD among symptom-free individuals to be high. Recently, a high frequency (57%) of antigliadin antibodies was demonstrated in adult patients with neurologic dysfunctions of unknown cause. We investigated the yield of screening for CD in children with common neurologic disorders. One hundred sixty-seven children, 1-16 years of age, were included in the study: 41 with migraine headaches, 39 with attention-deficit disorder with or without hyperactivity, 36 with epileptic disorders, and 51 with hypotonia and motor abnormalities. Positive IgG antigliadin antibodies were evident in 22 children (13%) in the study group compared with three children (9%) in the control group. However, in all children, negative IgA and endomysial antibodies were observed; thus duodenal biopsies were not performed. Contrary to studies performed in adults, these results did not demonstrate any relationship between common neurologic disorders without a specific diagnosis during childhood and CD. Thus screening for CD does not need to be routinely included in the diagnostic evaluation of children with these disorders.

Adolescent↗

The efficacy, safety, and practicality of treatments for adolescents with attention-deficit/hyperactivity disorder (ADHD).

Studies examining interventions for adolescents diagnosed with attention-deficit/hyperactivity disorder (ADHD) were reviewed to evaluate their efficacy. These efficacy findings were supplemented with a preliminary system for judging safety and practicality. Results suggest that the stimulant drug methylphenidate (MPH) is safe and well-established empirically, but has some problems with inconvenience and noncompliance. Preliminary research supports the efficacy, safety, and practicality of some psychotherapeutic interventions, including behavioral classroom interventions, note-taking training, and family therapy. Treatment with tricyclic antidepressants was judged to have minimal empirical support and debatable safety. Very little is known about long-term effectiveness of treatments, long-term compliance, or multimodal treatments for adolescents such as stimulants plus behavior therapy.

Adolescent↗

Salivary, but not serum or urinary levels of progesterone are elevated after topical application of progesterone cream to pre-and postmenopausal women.

OBJECTIVE: The use of topically applied micronised ('natural') progesterone as a substitute for synthetic oestrogens and progestogen preparations is controversial. The aim of this study was to examine the changes in blood and salivary concentrations of progesterone following a single topical application of a progesterone cream. PATIENTS AND MEASUREMENTS: We investigated six premenopausal women in the luteal phase and six postmenopausal women to determine the short-term changes in serum, urinary and salivary progesterone concentrations following a single 64 mg topical application of micronised progesterone. RESULTS: Serum progesterone concentrations did not increase during the first 3 hours after application of progesterone cream, however, salivary values rose significantly in both premenopausal and postmenopausal women, consistent with the view that progesterone is absorbed and transported through the body. Salivary progesterone concentrations were significantly elevated above basal levels by 30-60 minutes and reached peak levels at 1-4 h, with mean levels approximately fivefold higher in premenopausal, than in menopausal women. CONCLUSIONS: Salivary progesterone measurements confirm that topically applied progesterone is absorbed, despite the lack of change in serum progesterone concentrations. However, at the dose administered, serum progesterone levels do not reach those observed after oral or vaginally delivered progesterone preparations. Higher doses may be required to induce biological responses within the endometrium.

Absorption↗