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Biomedical subjects

N Craft

Publications and source records attributed to N Craft.

31 records · Page 2Linked to original sources

Effects of age on intrinsic heart rate, heart rate variability, and AV conduction in healthy humans.

Heart rate, heart rate variability, and atrioventricular (AV) conduction were studied in 20 young (30 +/- 5 yr) and 19 older (69 +/- 7 yr) healthy men and women before and after single and double autonomic blockade (randomized order: atropine, 0.04 mg/kg i.v.; propranolol, 0.2 mg/kg i.v.). Basal R-R intervals did not differ, but older age increased P-R intervals (177 +/- 24 vs. 149 +/- 17 ms, P < 0.001) and decreased SD of R-R (43 +/- 17 vs. 70 +/- 18 ms, P = 0.001) and heart rate spectral content (area under the power vs. frequency curve from 0.04 to 0.32 Hz: 3.01 +/- 2.1 vs. 7.82 +/- 4.8 beats/min2, P < 0.009), as well as postural responses (R-R decreases of 107 +/- 80 vs. 250 +/- 72 ms, P < 0.002). Atropine decreased R-R intervals, SD of R-R, and high-frequency (0.24-0.32 Hz) spectral content less in elderly subjects compared with younger subjects. Propranolol increased R-R and P-R intervals equally in old and young and abolished low-frequency (0.04-0.12 Hz) increases with standing (P < 0.0008). After double blockade, R-R, P-R, and paced AV intervals were longer in old subjects. Mean values were as follows: R-R intervals, 859 +/- 176 vs. 677 +/- 106 ms, P < 0.001; P-R intervals, 179 +/- 23 vs. 149 +/- 17 ms, P = 0.0002; paced P-R intervals (500 ms), 251 +/- 39 vs. 215 +/- 47 ms; and AV block cycle length, 413 +/- 51 vs. 385 +/- 69 ms (multivariate analysis of variance, P < 0.03). After double autonomic blockade, heart rate variability was nearly eliminated in young and old (reduced > 98%, P < 0.0001). We conclude that age differences in heart rate variability can be explained by autonomic influences, but heart rate and AV conduction differences exist independently of beta-adrenergic and/or parasympathetic influences.

Adult↗

Secrecy in the NHS.

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Consumer Advocacy↗

Assessment of homology with the helical mimicry algorithm.

Homologies based on structural motifs characterize conserved structures and mechanisms of maintaining function. An algorithm was developed to quantitate homology among segments of two proteins based upon structural characteristics of an amphipathic alpha-helix. This helical mimicry algorithm scored homology among sequences of two proteins in terms of: (i) presence of Leu, Ile, Val, Phe, or Met in a longitudinal, hydrophobic strip-of-helix at positions n, n + 4, n + 7, n + 11, etc. in the primary sequence, (ii) identity or chemical similarity of amino acids at intervening positions and (iii) exchanges of amino acids from positions n to n - 1, n + 3, n + 4, n + 1, n - 3, n - 4 around n (on the surface of a putative helix). While such exchanges of amino acids on the surfaces of homologous helices may conserve function, they did not maintain specific interactions of those residues with apposing groups.

Algorithms↗

Calcium antagonists block angiotensin II-mediated vasoconstriction in humans: comparison with their effect on phenylephrine-induced vasoconstriction.

Calcium antagonists are known to decrease peripheral vascular resistance in vivo in humans. The mechanism of this vascular relaxation has not been clearly elucidated. Vascular tone is maintained by several endogenous neurohumoral systems including sympathetic nervous system activity and angiotensin II. We compared and contrasted the capacity of calcium antagonist drugs to prevent angiotensin II and phenylephrine-induced alpha-1 adrenergic vasoconstriction using brachial artery infusion and measurement of forearm blood flow by strain gauge plethysmography. In a dose-dependent manner, calcium antagonists blocked angiotensin II-induced vasoconstriction. The rank order of this blockade was nifedipine greater than verapamil greater than diltiazem. Nifedipine and verapamil, but not diltiazem blocked alpha-1 adrenergic (phenylephrine-induced) vasoconstriction. At 7.64 and 19.1 micrograms/min infusion rates for nifedipine and verapamil, respectively, they abolished the angiotensin II effect; however, the phenylephrine effect was incompletely blocked. Calcium antagonist-induced vascular relaxation in vivo in humans is in part explained by their capacity to block angiotensin II-mediated vasoconstriction. In addition, two calcium antagonists (nifedipine and verapamil) may inhibit alpha-1 adrenergic vasoconstriction.

Adult↗

Nutritional status and growth in juvenile rheumatoid arthritis.

The specific cause of short stature in juvenile rheumatoid arthritis (JRA) is unknown. One hypothesis links altered growth to inadequate dietary intake. In this study, nutritional status was assessed in 34 children with JRA (8 with systemic JRA, 14 with polyarticular JRA, and 12 with pauciarticular JRA) and 9 healthy controls using 3-day diet records, anthropometrics, and biochemical analyses. Differences in growth were found among the three types of JRA. One third of all subjects were at or below the 10th percentile in height for age (these being predominantly among the systemic and polyarticular groups). With few exceptions, the mean dietary intake for calories and essential nutrients was found to be adequate for each of the three groups. However, more than half of those with systemic JRA reportedly consumed less than the recommended caloric intake for their age and weight. No significant correlations were found linking dietary intake to growth percentiles in any of the groups studied. Biochemical abnormalities were found among the systemic and polyarticular groups. These abnormalities included low plasma levels of vitamins A and C, proteins (albumin, prealbumin, and retinol binding protein) and zinc; and increased levels of copper and glutathione peroxidase activity. Plasma selenium and vitamin E levels were unchanged. The discrepancy between intake and certain circulating nutrient levels may reflect alterations in the requirements, absorption, or use of these nutrients in the presence of chronic inflammation.

Adolescent↗

Concentrations of carotenoids, retinol, and tocopherol in plasma, in response to ingestion of a meal.

Field studies and epidemiological surveys may necessitate obtaining a blood sample from a nonfasted subject for nutritional assessments. We measured the effect of a standardized test meal, eaten after an overnight fast, on the concentrations of seven carotenoid fractions, retinol, and tocopherol in plasma of eight healthy adults. The 790-calorie test meal did not alter the measured concentrations. We conclude that blood sampled up to 4 h after breakfast can be validly used for these measurements.

Adult↗

Changes in pancreatic enzyme specific activities of rats fed a high-fructose, low-copper diet.

This study describes the progressive changes in exocrine pancreatic enzyme specific activities from rats provided with a diet containing either 62% starch (S) or fructose (F) with 6.0 ppm copper (+Cu) or 0.6 ppm (-Cu) from 21 to 61 days of age. Copper-deficient rats had significantly reduced pancreatic weight and DNA, RNA, protein and copper content and superoxide dismutase (SOD) activity after consuming diet for 39 days. These reductions were far more severe in F-Cu than in S-Cu rats. Copper deficiency significantly reduced pancreatic amylase and lipase specific activities, but the effect was more severe in the F-Cu dietary group. Chymotrypsinogen and trypsinogen specific activities were reduced only in the F-Cu dietary group and the CHO x Cu interaction was significant. High dietary fructose and low dietary copper in combination interact to produce severe reductions in pancreatic amylase, lipase, chymotrypsinogen, and trypsinogen specific activities which could not be explained by either copper deficiency or by an increase in dietary fructose alone.

Amylases↗

Alteration of pancreatic enzyme activities in small intestine of rats fed a high fructose, low copper diet.

This study describes the progressive effects on pancreatic enzyme activities from washings of the small intestine of rats fed diets containing either 62% starch (S) or fructose (F), with 0.6 mg copper/kg diet (-Cu) or 6.0 mg copper/kg diet (+Cu) from 21 to 61 d of age. Hepatic copper concentration of the copper-deficient groups was 50% of that of the copper-supplemented groups. Body and relative pancreatic weights were lower in the F-Cu dietary group than in any other group. Relative liver weight was significantly higher in the fructose dietary groups than in the starch dietary groups. There were significant carbohydrate (CHO) X week and Cu X week interactions for luminal amylase activities and the CHO X Cu X week interaction was significant for luminal lipase and trypsin activities. The lowest enzyme activities were observed in the F-Cu-fed rats. The CHO X week interaction was significant for chymotrypsin with the lowest enzyme activities in the fructose-fed rats. It appears that high dietary fructose and low dietary copper interact to produce greatly reduced pancreatic enzyme activities in small intestinal washings. We speculate that subsequent digestive and absorptive abnormalities during a period of rapid growth may account for the severe morbidity and mortality in copper-deficient, fructose-fed rats.

Amylases↗

Contrasting effects of the stomach and small intestine of rats on copper absorption.

Since the severity of copper deficiency has been shown to be enhanced by feeding diets containing fructose but ameliorated by diets containing starch, we decided to investigate the effect of fructose or starch on copper absorption. As copper transport has been reported to occur also from the stomach, it was possible that copper absorption is inhibited by fructose already from that tissue. Under anesthesia, stomachs of 72 rats fed copper-deficient or supplemented diets containing fructose or starch were ligated prior to the oral administration of 64Cu. Gastric absorption of 64Cu was studied when the isotope was administered by gastric tube either in diet containing fructose or starch or in water. 64Cu was not absorbed from the stomach regardless of the type of dietary treatment, copper status or whether the copper was administered either in diet or in water. In addition, the absorption of 64Cu from a diet containing either fructose or starch or from a saline solution was studied using the isolated ligated duodenal loop. When 64Cu was administered with dietary fructose 64Cu retention and absorption were impaired when compared to starch. When 64Cu was administered in saline solution, differences in retention and absorption between the four dietary groups disappeared. It is suggested that the requirements for copper rather than the decreased absorption of copper are responsible at least in part for the more pronounced severity of copper deficiency in rats fed fructose compared to those fed starch.

Absorption↗

Mechanistic concepts in androgen-dependence of prostate cancer.

Androgen blockade is the mainstay of therapy in the clinical management of advanced prostate cancer. Recent progress on two fronts--the development of newer xenograft and transgenic models and a greater understanding of nuclear receptor signaling--has provided new insight into mechanisms of androgen-dependence in prostate cancer. This review centers on the concept that perturbations in androgen receptor signaling are likely to occur early in prostate cancer and play a critical role in progression to end stage hormone-refractory disease.

Androgens↗