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Biomedical subjects

D Atkins

Publications and source records attributed to D Atkins.

At least 73 records · Page 4Linked to original sources

Cholesterol reduction and the risk for stroke in men. A meta-analysis of randomized, controlled trials.

OBJECTIVE: Reducing serum cholesterol lowers the risk for ischemic heart disease, but its effects on other vascular diseases are unknown. Published trials were reviewed to determine the effect of cholesterol-lowering interventions on fatal and nonfatal stroke. DESIGN: Meta-analysis of randomized, controlled trials. DATA IDENTIFICATION: A literature search of English-language studies examining the effect of modified diets or medications on cardiovascular end points from 1965 to 1992 using MEDLINE and a review of references of five quantitative overviews of cholesterol reduction and coronary disease. DATA ANALYSIS: Thirteen studies met three eligibility criteria: patients randomized to intervention or control; fatal or nonfatal stroke reported separately; and end points assessed without knowledge of treatment status. Heterogeneity among studies and overall effects of treatment on fatal and nonfatal stroke were estimated using the Mantel-Haenszel-Peto method to combine independent study results. The influence of various study designs and interventions was explored using subgroup comparisons. RESULTS: For fatal stroke, the overall odds ratio associated with cholesterol-lowering interventions in 13 trials was 1.32 (95% Cl, 0.94 to 1.86), and the odds ratio for the 10 single-intervention trials was 1.34 (Cl, 0.91 to 1.96). Among eight trials reporting nonfatal events, the summary odds ratio for nonfatal stroke for treated participants compared with controls was 0.88 (Cl, 0.70 to 1.11), and the odds ratio for total strokes was 0.98 (Cl, 0.80 to 1.19). Among three trials using clofibrate, treatment significantly increased the risk for fatal stroke (odds ratio, 2.64; Cl, 1.42 to 4.92) but not for nonfatal stroke (odds ratio, 0.87; Cl, 0.61 to 1.26). Regression analysis showed no statistical association between the magnitude of cholesterol reduction and the risk for fatal stroke. CONCLUSIONS: Lowering serum cholesterol through modified diets or medications does not reduce stroke mortality or morbidity in middle-aged men. Clofibrate appears to increase the risk for fatal strokes, but the mechanism for this effect is unknown.

Anticholesteremic Agents↗

A review of the association of estrogens and progestins with cardiovascular disease in postmenopausal women.

The purpose of this article was to review, with special attention to the hypothesized mechanisms of atherosclerosis and thrombosis, the literature on the association of estrogens and progestins with cardiovascular disease. The data sources included recent reviews and their citations as well as literature searches of Medline. For coronary heart disease, we relied on a recent meta-analysis; for the lipid effects of estrogens and progestins, we refer to recent reviews and studies; for stroke, we identified all cohort and case-control studies; and for the effects of hormones on coagulation factors, we identified all relevant studies. The lipid effects of estrogens in postmenopausal women probably prevent atherosclerosis, and we would expect long duration of use rather than current use to provide the greatest benefit. Few epidemiologic studies have, however, assessed duration of estrogen use. High doses of estrogens are likely to be thrombogenic during current use, and it is possible that even moderate doses may increase the risk of clotting among women who smoke or who have existing coronary atherosclerosis. Compared with the lipid effects of estrogens alone, the lipid effects of combined therapy with progestins may increase atherosclerosis. The effect of progestins on coagulation factors is largely unknown, and no epidemiologic study has assessed the risk of cardiovascular disease associated with the use of combined hormone therapy in postmenopausal women. Cardiovascular risk or benefit associated with the use of postmenopausal hormones may involve several competing mechanisms, including effects on prostaglandins and vascular tone as well as atherosclerosis and thrombosis.

Aged↗

Vitamin content of camel milk.

The content of vitamin C, vitamin B2 and fat-soluble vitamins E and A in camel milk was studied. The milk samples were collected from 20 individual camels (Camelus dromedarius) in two different occasions. The study showed that camel milk contains considerably less vitamin A and B2 than cow milk while the content of vitamin E was about the same level. The level of vitamin C was in average three times higher than that of cow milk.

Animals↗

Syncope and orthostatic hypotension.

PURPOSE: The purpose of this study was to determine the postural blood pressure response over time, the prevalence of orthostatic hypotension in patients with syncope, and the relationship of orthostatic hypotension to recurrence of symptoms. PATIENTS AND METHODS: We prospectively evaluated 223 patients with syncope in a standardized manner. Orthostatic responses were measured in a standardized fashion at 0, 1, 2, 3, 5, and 10 minutes or until symptoms occurred. Follow-up was obtained at 3-month intervals. Causes of syncope were assigned by predetermined criteria. RESULTS: Orthostatic hypotension (20 mm Hg or greater systolic blood pressure decline) was found in 69 patients (31%). The median time to reach minimal standing systolic blood pressure was 1 minute for all subjects. In patients with orthostatic hypotension (20 mm Hg or greater), mean time to reach minimum blood pressure was 2.4 minutes. The vast majority of patients with significant orthostatic hypotension had this finding within 2 minutes of standing. Orthostatic hypotension was common in patients for whom other probable causes of syncope were assigned. The recurrence of syncope was not related to the degree of orthostatic hypotension; however, the recurrence of dizziness and syncope as end-points was lower in patients with 20 mm Hg or greater systolic blood pressure reductions as compared with patients with lesser degrees of orthostatic blood pressure declines. CONCLUSION: Orthostatic hypotension is common in patients with syncope and is detected in the vast majority of patients by 2 minutes. Although symptom recurrence on follow-up was lower in patients with more severe orthostatic hypotension, the clinical significance of this finding needs to be further defined by future studies.

Adolescent↗

The tobacco mosaic virus 30K movement protein in transgenic tobacco plants is localized to plasmodesmata.

Transgenic tobacco plants expressing a gene encoding the tobacco mosaic virus (TMV) movement protein (30K) were studied using immunocytochemical techniques. The movement protein was shown to be localized within or on most of the plasmodesmata observed in the transformed plant. These results are consistent with the idea that the movement protein interacts with the plasmodesmata to facilitate the cell-to-cell spread of TMV.

Capsid Proteins↗

Expression of the tobacco mosaic virus movement protein using a baculovirus expression vector.

A cDNA clone of the tobacco mosaic virus 30K movement protein (MP) gene was constructed and introduced into an Autographa californica nuclear polyhedrosis baculovirus expression vector. Infection of Spodoptera frugiperda cells with the vector resulted in the synthesis of low levels of MP, which was detected by anti-MP serum as two closely related species of Mr approximately 34K and a third species of 32K. The authenticity of the recombinant MP was confirmed by comparison of the protein, on the basis of migration during SDS-PAGE, with authentic MP from several sources. It appeared that the recombinant MP was not modified by N-linked glycosylation, but was phosphorylated. The recombinant MP was produced in both a phosphorylated and an unphosphorylated state and the former species was shown to comigrate with plant-expressed MP during SDS-PAGE.

Animals↗

Oophorectomy leads to a selective decrease in 1,25-dihydroxycholecalciferol receptors in rat jejunal villous cells.

The distribution of 1,25-dihydroxycholecalciferol [1,25-(OH)2D3] receptors in isolated rat jejunal cells was investigated in normal and oophorectomized female rats and also in vitamin D-deficient animals. Oophorectomy caused a selective reduction in 1,25-(OH)2D3 receptor numbers in villous cells, the reduction being similar (37%) in both normal and vitamin D-deficient animals. The data suggest that this effect of oophorectomy reflects a direct effect of oestrogens in the intestinal synthesis of 1,25-(OH)2D3 receptors, independent of the renal synthesis of 1,25-(OH)2D3. It is proposed that this phenomenon may, in part, explain the reduction in calcium absorption which occurs after oophorectomy or the menopause.

Animals↗

The temporal distribution of the 1 alpha,25-dihydroxycholecalciferol receptor in the rat jejunal villus.

The distribution of the 1 alpha,25-dihydroxycholecalciferol receptor was studied in enterocytes isolated from the upper, mid and lower villus and crypt cells of the jejunum of normal and rachitic rats. In all cell fractions a high-affinity receptor (KD congruent to 0.07 nmol/l) with a sedimentation coefficient of 3.5S was demonstrated. In normal rats there was a 60% reduction in receptor numbers in crypt cells compared with the mid and upper villous cells. Vitamin D deficiency led to a reduction in receptor numbers in all cell fractions (45% upper villus, 78% crypt cells). The data are compatible with the concept of calcium absorption occurring in the differentiated villous cells and also account for the reduction in absorption in rachitic animals.

Animals↗

Mechanism of the regulation of the 1 alpha,25-dihydroxyvitamin D3 receptor in the rat jejunum by glucocorticoids.

The distribution of 1 alpha,25-dihydroxyvitamin D3 (1,25-(OH)2D3) receptors in isolated jejunal villous and crypt cells was investigated in normal and adrenalectomized male rats, and also in animals treated with the synthetic glucocorticoid, dexamethasone, and/or the glucocorticoid antagonist, 11-deoxy-cortisol. Adrenalectomy caused an increase in 1,25-(OH)2D3 receptors whilst dexamethasone treatment led to a reduction in receptor number. 11-Deoxy-cortisol was able to reverse the 'down-regulation' effect caused by glucocorticoids. In all cases, the changes in receptor numbers were more pronounced in crypt cells. The data suggest that, in the small intestine, glucocorticoids may control the synthesis of 1,25-(OH)2D3 receptors via the mediation of a glucocorticoid receptor, and that the adrenal hormones mainly express their effect in crypt cells. It is proposed that this phenomenon may, in part, explain the reduction in calcium absorption which occurs in man after chronic glucocorticoid treatment.

17-Hydroxycorticosteroids↗

Distribution and properties of Ca2+-ATPase, phytase, and alkaline phosphatase in isolated enterocytes from normal and vitamin D-deficient rats.

The effects of vitamin D-deficiency and repletion on the distribution and activities of Ca2+-ATPase, phytase, and alkaline phosphatase in intact epithelial cells isolated from different regions of the villi and the crypts of the rat jejunum were studied. Similar distribution patterns of activities were found for the three enzymes. In all cases, the enzyme levels were the highest at the villus tip and gradually declined to low activities in the crypt. The Kms were very different between cells in the crypt base and those at the villus tip, the highest Kms being found in the crypt. The activities of these enzymes were reduced in the entire length of the villus in vitamin D-deficient rats. Recovery of the enzymatic levels was observed on vitamin D repletion, but at different rates. Total recovery of activity of Ca2+-ATPase, phytase, and alkaline phosphatase was observed after 18, 24, and 36 hours, respectively, after a single dose of 6.5 nmol (2.5 micrograms) vitamin D3. Enzymatic activities in the crypt cells were not affected by vitamin D3 treatment. These data suggest that Ca2+-ATPase, phytase, and alkaline phosphatase may be distinct entities, and that their activities in the crypt cells may not be vitamin D-dependent.

6-Phytase↗

Carcinogenic epoxides of benzo[a]pyrene and cyclopenta[cd]pyrene induce base substitutions via specific transversions.

We have determined the spectrum of base-pair substitution mutations induced in the lacI gene of a uvrB- strain of Escherichia coli by two polycyclic aromatic hydrocarbons--(+/-)7 alpha,8 beta-dihydroxy-9 beta,10 beta-epoxy-7,8,9,10 tetrahydrobenzo[a]pyrene (BPDE), and 3,4-epoxycylopenta[cd]pyrene (CPPE). Approximately 10% of all lacI mutations induced by either BPDE or CPPE are nonsense mutations, suggesting that base-pair substitutions are a large fraction of the mutational events induced by these agents in the uvrB- bacteria. Both carcinogens specifically induced the G . C leads to T . A and, to a lesser extent, the A . T leads to T . A transversions. One possible mechanism for transversion induction at G . C sites by BPDE might involve carcinogen binding to the exocyclic amino group of guanine in the template strand followed by a rotation of the modified base around its glycosylic bond from the anti to the syn conformation. This could allow specific pairing of modified bases with an imino tautomer of adenine.

Benzopyrenes↗

Prostaglandins as mediators of bone resorption in renal and breast tumours.

Amounts of prostaglandin E and prostaglandin F have been measured by radioimmunoassay in extracts of renal cortical carcinoma and benign and malignant breast tumours after solvent extraction and column chromatography. 2. Substantial amounts of prostaglandin E were found in extracts of benign and malignant breast tumours and in renal tumours. Much lower amounts of prostaglandin F were present in all tumour types. 3. Co-cultivation of tumour explants with mouse calvaria led to significant bone resorption in 10 of 13 renal carcinomas, three of eight malignant breast tumours, and two of nine benign breast tumours. Tumours associated with bone resorption had higher concentrations of prostaglandin E in culture media at the end of incubation than did non-resorbers. 4. Indomethacin (14 mumol/1) greatly reduced bone resorption in the presence of the tumour, but this was not always complete, particularly with breast tumours. Indomethacin had no effect on prostaglandin-induced bone resorption. Theophylline (2.2 mmol/1) significantly increased prostaglandin E production and resorption by an effect on the tumour. 5. It is concluded that prostaglandins may be important in mediating the effects of renal cortical carcinoma and possibly breast cancer on bone destruction. A non-prostaglandin mechanism may also contribute to bone destruction by breast carcinoma.

Animals↗

Drug therapy assessments by pharmacists.

Drug therapy assessments made for ambulatory patients by pharmacists and those made by the patients' primary physicians were compared. Using refill assessment guidelines, pharmacists evaluated the drug therapy regimens of patients attending a general medicine clinic before they were seen by their physicians. At the end of each clinic day, the pharmacists compared their assessments with the physician evaluations. Of the 155 drug regimens reviewed, the study pharmacists would have continued 104 (67.1%) without alteration, changed 48 (31.0%), and referred three patients (1.9%) with new problems for physician evaluation. The differences between pharmacist assessment and physician agreement were not significant (p greater than 0.2), but there was a significant difference between pharmacist assessment and physician actions (p less than 0.005), because the physicians actually changed only 52% of the drugs they agreed could be changed. The study suggests that the pharmacist is able to detect drug therapy problems and to recommend appropriate actions for resolving them.

Drug Prescriptions↗