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Biomedical subjects

K Stone

Publications and source records attributed to K Stone.

At least 19 recordsLinked to original sources
PubMed1997

Low thyrotropin levels are not associated with bone loss in older women: a prospective study.

The relationship between excess thyroid hormone and bone loss is controversial. To determine whether low TSH levels, indicating excessive thyroid hormone, are associated with low bone mass or accelerated bone loss in older women, we performed a prospective cohort study of 458 women over age 65 yr participating in the multicenter Study of Osteoporotic Fractures. Three hundred and twenty-three women were randomly selected from the entire cohort of 9704; an additional 135 randomly selected thyroid hormone users were studied. Medical history, medication use, and calcaneal bone mineral density (BMD) were assessed at the baseline visit. Serum was collected and stored at -190 C. Hip and spine BMD were measured approximately 2 yr later, and follow-up calcaneal and hip BMD measurements were obtained after mean follow-up periods of 5.7 and 3.5 yr, respectively. TSH levels were determined in baseline serum samples using a third generation chemiluminescent assay. After adjustment for age, weight, previous hyperthyroidism, and use of estrogen, bone loss over 4-6 yr was similar in women with low, normal, or high TSH. For example, femoral neck bone loss was -0.3%/yr (95% confidence interval, -0.8%, 0.3%) among women with low TSH (< or = 0.1 mU/L) and -0.5%/yr (95% confidence interval, -0.7%, -0.3%) in those with normal TSH (0.1-5.5 mU/L). There were no statistically significant differences in baseline bone mass of the calcaneus, spine, or femoral neck or trochanteric hip subregions. Baseline total hip BMD was 6% lower (P = 0.01) in women with low TSH. Similar results were obtained in analyses confined to women not taking estrogens. We found no consistent evidence that low TSH, a sensitive biochemical marker of excess thyroid hormone, was associated with low BMD or accelerated bone loss in older ambulatory women.

Aged↗
PubMed1996

Aspirin and NSAID use in older women: effect on bone mineral density and fracture risk. Study of Osteoporotic Fractures Research Group.

Prostaglandin inhibition by aspirin or nonsteroidal anti-inflammatory drug (NSAIDs) may inhibit bone loss and preserve bone mineral density (BMD) in vitro and in animal models. The effect of these agents on BMD and fracture risk in postmenopausal women in unknown. We assessed the risk factors for osteoporosis and the use of aspirin and NSAIDs in 7786 white women over age 65. Axial BMD was measured at the same time, and fractures were prospectively documented over the subsequent 4 years of follow-up. In age-adjusted analyses, daily use of aspirin or NSAIDs was associated with a 2.3-5.8% increase in BMD of the hip and spine. The relationship persisted even after adjustment for weight, a variety of medications, self-reported arthritis, and for radiographic findings of osteoarthritis, but the multiply adjusted increase in BMD was only 1.0-3.1%. Fracture risk was similar among daily users of aspirin and NSAIDs and nonusers. After adjustment for potential confounders, among daily aspirin users the relative risk of hip fracture was 1.1 (95% confidence interval [CI]: 0.7, 1.6), and among daily NSAID users the risk was 0.9 (CI: 0.6, 1.4). Considering all nonspine fractures together, the risk among aspirin users was 1.0 (CI: 0.8. 1.2), and among NSAID users the risk was also 1.0 (CI; 0.8, 1.2). Regular use of aspirin or NSAIDs may have a modest beneficial effect on BMD in postmenopausal women. This effect persists after adjustment for obesity and the presence of osteoarthritis. However, among women who take aspirin or NSAIDs regularly, there is no clinically significant protective effect on the subsequent risk of fractures.

Aged↗
PubMed1996

Measurement of pulmonary artery diastolic pressure from a right ventricular pressure transducer in patients with heart failure.

Recent studies have demonstrated that pulmonary artery diastolic (PAD) pressure can be measured from a transducer positioned in the right ventricle (RV) based on the finding that PAD and RV pressures are equal at the time of pulmonary valve opening, which is associated with the time of maximum positive rate of pressure development (dP/dtmax) in the ventricle. The objective of this study was to assess the correlation between estimated PAD (ePAD) pressure, obtained through a RV transducer, and actual PAD (aPAD) pressure in patients with heart failure who have abnormal hemodynamics, reduced systolic function, and variable degrees of mitral regurgitation (MR) and tricuspid regurgitation (TR). Simultaneous measurements of pulmonary artery and RV pressures were obtained with a high-fidelity Millar catheter (Millar Instruments, Houston, TX) in 10 patients with New York Heart Association class III-IV heart failure who were being evaluated for cardiac transplantation. The overall correlation between ePAD and aPAD pressures was .92 (R2 = .878). This was not significantly different during the Valsalva maneuver (r = .96, R2 = .943), submaximal bicycle exercise (r = .87, R2 = .756), or infusions of dobutamine and nitroglycerin (r = .82, R2 = .730). The overall average difference between the average ePAD (24.6 +/- 7.0 mmHg) and aPAD (23.6 +/- 7.0 mmHg) pressures was 1.0 +/- 3.4 mmHg. The average difference between the two pressures in patients with mild to severe MR or TR was not different compared to those patients with no or trace MR or TR. The estimation of PAD pressure from an RV transducer is valid in patients with heart failure who have abnormal hemodynamics, reduced systolic function, and variable degrees of MR and TR. This correlation was observed at rest and during several provocative maneuvers. These data will be important for the development of a chronic, implantable hemodynamic monitor for patients with heart failure.

Adult↗
PubMed1996

Osteoporosis: association of recent fractures with quantitative US findings.

PURPOSE: To study the association of quantitative ultrasound (US) parameters and bone mineral density (BMD) in patients with and patients without recent fractures. MATERIALS AND METHODS: The authors studied 4,698 women (69 years or older) who had sustained 1,363 new fractures, including 106 hip fractures, during the 7 years prior to the study. Broadband ultrasound attenuation (BUA) and other velocity parameters were measured by means of quantitative US of the calcaneus. BMD was measured at the spine, hip, and calcaneus. RESULTS: The standardized age-adjusted odds ratio for all fractures was 1.5 (95% confidence interval [CI] = 1.4, 1.7) for BUA and up to 1.6 (95% CI = 1.5, 1.7) for BMD. For hip fractures, the odds ratio was 1.9 (95% CI = 1.5, 2.4) for BUA and up to 2.6 (95% CI = 2.0,3.4) for BMD. Sensitivity and specificity with BUA, velocity parameters, and BMD were comparable. Results of multivariate analysis showed that both BUA and BMD were independently associated with fractures and that combined measurements improved sensitivity and specificity. CONCLUSION: Quantitative US parameters are strongly associated with risk of fracture and partly independent of BMD. This simple, low-cost, portable, and radiation-free approach may complement bone densitometry in assessing risk of osteoporotic fracture.

Aged↗
PubMed1995

Peroxynitrite causes DNA nicks in plasmid pBR322.

Peroxynitrite causes single-strand breaks in pBR322 supercoiled DNA as evidenced by agarose gel electrophoresis analysis. The effect of three free radical scavengers, namely mannitol, benzoate and dimethylsulfoxide, were studied. Mannitol failed to protect DNA from damage by peroxynitrite while benzoate and dimethylsulfoxide amplified the damage. These results suggest the damage caused by peroxynitrite alone is not mediated by free radicals since typical free radical scavengers fail to prevent the damage.

Benzoates↗
PubMed1995

The ESR properties, DNA nicking, and DNA association of aged solutions of catechol versus aqueous extracts of tar from cigarette smoke.

Previous studies in our laboratories have shown that extracts from mainstream or sidestream tobacco smoke nick DNA. These solutions contain the tar semiquinone free radical, and the tar radical becomes associated with cellular DNA. Aged solutions of catechol contain a semiquinone species that has ESR properties similar to those of the radical in cigarette tar extracts, and we have used these catechol solutions as a model for the tar radical. Both the radical in aged catechol solutions and the cigarette tar radical become associated with the DNA in mammalian cells and also nick DNA. The nicking of DNA caused by both tar and aged catechol solutions follows saturation kinetics. Aged catechol solutions thus allow the study of a model for the radical present in cigarette tar, without interference from the other toxic constituents in tar extracts.

Animals↗
PubMed1995

Risk factors for hip fracture in white women. Study of Osteoporotic Fractures Research Group.

BACKGROUND: Many risk factors for hip fractures have been suggested but have not been evaluated in a comprehensive prospective study. METHODS: We assessed potential risk factors, including bone mass, in 9516 white women 65 years of age or older who had had no previous hip fracture. We then followed these women at 4-month intervals for an average of 4.1 years to determine the frequency of hip fracture. All reports of hip fractures were validated by review of x-ray films. RESULTS: During the follow-up period, 192 women had first hip fractures not due to motor vehicle accidents. In multivariable age-adjusted analyses, a maternal history of hip fracture doubled the risk of hip fracture (relative risk, 2.0; 95 percent confidence interval, 1.4 to 2.9), and the increase in risk remained significant after adjustment for bone density. Women who had gained weight since the age of 25 had a lower risk. The risk was higher among women who had previous fractures of any type after the age of 50, were tall at the age of 25, rated their own health as fair or poor, had previous hyperthyroidism, had been treated with long-acting benzodiazepines or anticonvulsant drugs, ingested greater amounts of caffeine, or spent four hours a day or less on their feet. Examination findings associated with an increased risk included the inability to rise from a chair without using one's arms, poor depth perception, poor contrast sensitivity, and tachycardia at rest. Low calcaneal bone density was also an independent risk factor. The incidence of hip fracture ranged from 1.1 (95 percent confidence interval, 0.5 to 1.6) per 1,000 woman-years among women with no more than two risk factors and normal calcaneal bone density for their age to 27 (95 percent confidence interval, 20 to 34) per 1,000 woman-years among those with five or more risk factors and bone density in the lowest third for their age. CONCLUSIONS: Women with multiple risk factors and low bone density have an especially high risk of hip fracture. Maintaining body weight, walking for exercise, avoiding long-acting benzodiazepines, minimizing caffeine intake, and treating impaired visual function are among the steps that may decrease the risk.

Aged↗
PubMed1995

Quantitative ultrasound and vertebral fracture in postmenopausal women. Fracture Intervention Trial Research Group.

Quantitative ultrasound is a promising technique to evaluate fracture risk. To test the hypothesis that reduction of one ultrasound measurement, broadband ultrasound attenuation (BUA), is associated with an increased risk of vertebral fracture in postmenopausal women, we performed a cross-sectional analysis of 442 women aged 55-80 years enrolling in a clinical trial of alendronate. Prior to randomization, we obtained bone mineral density (BMD) measurements of the hip, spine, and whole body, radiographs of lateral lumbar and thoracic spine, and duplicate measurements of calcaneal BUA with a Walker Sonix UBA575. Vertebral fractures were defined by morphometry and semiquantitative reading by a radiologist. After adjustment for potential confounders, the relative risk of vertebral fracture was 1.8 (95% CI 1.4-2.3) for each standard deviation reduction in BUA; for each standard deviation reduction in BMD, the relative risk was 1.7 (95% CI 1.3-2.1) at the femoral neck, and 2.2 (95% CI 1.7-2.9) at the spine. Adjustment for hip, spine, or whole body BMD did not significantly alter the relation between BUA and vertebral fracture. For example, after adjusting for spine BMD, the relative risk of vertebral fracture was 1.5 (95% CI 1.1-2.0) for each standard deviation reduction in BUA. We conclude that low BUA is associated with the presence of vertebral fractures in postmenopausal women. The relation between BUA and vertebral fracture is similar to that observed for BMD and vertebral fractures. Furthermore, the relation between BUA and vertebral fracture persists after adjustment for BMD.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1995

Detection of free radicals in aqueous extracts of cigarette tar by electron spin resonance.

Aqueous extracts of cigarette tar (ACT) autooxidize to produce semiquinone, hydroxyl, and superoxide radicals in air-saturated buffered aqueous solutions. The semiquinone species were detected by direct electron spin resonance (ESR) measurements and identified as o- and p-benzosemiquinone radicals by comparison with the ESR signals of catechol and hydroquinone radicals under similar conditions. The rate of formation of these radicals was dependent on pH. Hydroxyl and superoxide radicals were detected as 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) spin adducts by ESR spin trapping. Superoxide dismutase (SOD) (20 units/ml) inhibited the formation of the superoxide spin adduct of DMPO completely. Addition of Fe2+ to this system increased the ESR signal intensity of hydroxyl radical spin adduct of DMPO three to five times. These results indicate that superoxide and hydroxyl radicals are produced during the autooxidation of hydroquinone- and catechol-related species in ACT.

Cyclic N-Oxides↗
PubMed1994

Trypsin-Mn(2+)-resistant form of type 1 protein phosphatase in human muscle.

Reduced type 1 protein phosphatase (PP-1) activity in human muscle extracts may contribute to the reduced insulin-stimulated glycogen synthase activity associated with insulin resistance for glucose disposal in humans. Because inactive forms of PP-1 can be activated with trypsin plus Mn2+, these reagents were used to compare the PP-1 activities in skeletal muscle extracts before and after separation into cytosolic and glycogen microsomal (GM) fractions. PP-1 activities were reduced in the GM fraction from insulin-resistant subjects (54 +/- 2 vs. 61 +/- 1, P < 0.01) but, in contrast to our previously published results, were elevated in the extract (33 +/- 6 vs. 18 +/- 3, P < 0.05). Recombination of the cytosol and GM fractions (reconstituted extract) demonstrated that the low extract PP-1 activities could only be regenerated when the GM fraction from insulin-sensitive subjects was recombined with cytosol from either group. The results indicate that the elevated PP-1 activity observed in extracts of insulin-resistant compared with insulin-sensitive subjects is caused by an inhibitor of extract PP-1 activity that sediments with the GM pellet and is more active in the insulin-sensitive subjects.

Adult↗
PubMed1994

Implementing a research-based protocol: an interactive approach.

Endotracheal suctioning (ETS) is a common procedure done in the critical care environment. There are many different practices related to ETS. With the proliferation of research studies about ETS, a change in practice is needed to incorporate these research findings. The authors present a creative teaching strategy that was used to implement a research-based ETS protocol.

Clinical Nursing Research↗
PubMed1993

Fast axonal transport is required for growth cone advance.

Growth cones are capable of advancing despite linkage to a stationary axonal cytoskeleton in chick and murine dorsal root ganglion neurites. Several lines of evidence point to the growth cone as the site of cytoskeletal elongation. Fast axonal transport is probably the means by which cytoskeletal elements or cofactors are rapidly moved through the axon. We report that direct, but reversible, inhibition of fast axonal transport with laser optical tweezers inhibits growth cone motility if cytoskeletal attachment to the cell body is maintained. Advancement ceases after a distance-dependent lag period which correlates with the rate of fast axonal transport. But severing the axonal cytoskeleton with the laser tweezers allows growth cones to advance considerably further. We suggest that axon elongation requires fast axonal transport but growth cone motility does not.

Animals↗
PubMed1993

Psychiatric morbidity and compulsory admission among UK-born Europeans, Afro-Caribbeans and Asians in central Manchester.

Psychiatric admissions in Central Manchester of Europeans, Afro-Caribbeans, and Asians (within three age-bands) were studied over four years. Among the Afro-Caribbean group there were more single or unemployed persons than in either the Asian or European groups, which suggested greater socio-economic disadvantage. Rates for first admissions and readmissions among Afro-Caribbeans were greater; among Asians they were similar except for the 16-29-year age-group, who tended to have lower rates than Europeans. A higher proportion of Afro-Caribbeans and Asians were psychotic. In the Afro-Caribbean group, the raised rates of admission were largely attributable to increased rates of schizophrenia. The highest rate occurred in second-generation (UK-born) Afro-Caribbeans and was nine times that among Europeans. The police were more frequently involved in the admissions of Afro-Caribbeans compared with Europeans or Asians. Higher proportions of Afro-Caribbeans and Asians who were readmitted were detained under the Mental Health Act 1983, when compared with Europeans.

Adolescent↗
PubMed1993

Adhesions in gynecologic surgery.

The pathophysiology of adhesion formation continues to be perplexing. A delicate balance appears to exist between those wound factors that would initiate the physiologic process of peritoneal wound healing and those factors necessary for the lysis of fibrin, a major component of adhesions. Research continues to elucidate the roles of leukotrienes, prostaglandins, protein kinase-C, and transforming growth factors in adhesiogenesis. The ability to enhance plasmin's fibrinolytic activity or to impede plasminogen activator inhibitor factor may have important clinical ramifications in adhesiolysis. Clinical studies continue to address the effectiveness of intraperitoneal additives (dextran, lactated Ringer's solution, heparin) and barriers to adhesion formation (Interceed, TC7, Johnson & Johnson, New Brunswick, NJ; Gore-Tex, polytetrafluoroethylene, Gore & Assoc, Flagstaff, AZ). Surgical technique with attention to hemostasis, minimal trauma, proper suture selection, and peritoneal irrigation continues to be the mainstay in adhesion prevention.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1992

Defective insulin response of phosphorylase phosphatase in insulin-resistant humans.

Insulin-stimulated glycogen synthase activity in human muscle is reduced in insulin-resistant subjects. Insulin regulation of human muscle glycogen synthase may require activation of a type-1 protein phosphatase (PP-1). We investigated the change of phosphorylase phosphatase and glycogen synthase activities in muscle biopsies obtained during a 2-h hyperinsulinemic euglycemic clamp in 12 insulin-sensitive (group S) and 8 insulin-resistant (group R) subjects. Fasting phosphorylase phosphatase activity was lower in group R than in group S, and did not increase significantly with insulin infusion in group R until 20 min. In group S, phosphorylase phosphatase was significantly stimulated by 10 min, remaining significantly higher than in group R at all time points. The insulin-mediated changes in phosphatase activities were not decreased by 3 nM okadaic acid but were completely inhibited by 1 microM okadaic acid, thereby verifying that insulin-stimulated phosphorylase phosphatase is accounted for by a PP-1. Subcellular fractionation demonstrated reduced fasting PP-1 activities in both the glycogen and cytosolic fractions of muscle obtained from subjects in group R compared to those in group S. These results suggest that insulin activation of PP-1 could contribute to the stimulation of glycogen synthase by this hormone in human muscle. Lower fasting PP-1 activity in cytosol and glycogen fractions plus lower insulin-stimulated PP-1 activity could explain, in part, reduced insulin-stimulated glycogen synthase in skeletal muscle of insulin-resistant subjects.

Adult↗
PubMed1991

Amylin activates glycogen phosphorylase in the isolated soleus muscle of the rat.

The pancreatic beta-cell hormone amylin acts in isolated rat skeletal muscle to decrease insulin-stimulated incorporation of glucose into glycogen. It also increases blood levels of lactate and glucose in fasted rats in vivo. However, it remained uncertain whether amylin exerts direct effects to stimulate muscle glycogenolysis. We now report that amylin caused a dose-dependent increase in activity of muscle glycogen phosphorylase in isolated rat soleus muscle by stimulating phosphorylase a. Insulin inhibited amylin-stimulated activation of phosphorylase. Effects of amylin to stimulate muscle glycogenolysis are consistent with observed effects of amylin in vivo and could be a major mechanism whereby amylin modulates carbohydrate metabolism.

Amyloid↗