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Biomedical subjects

J S Carroll

Publications and source records attributed to J S Carroll.

16 recordsLinked to original sources

Leading organisational learning in health care.

As healthcare organisations seek to enhance safety and quality in a changing environment, organisational learning practices can help to improve existing skills and knowledge and provide opportunities to discover better ways of working together. Leadership at executive, middle management, and local levels is needed to create a sense of shared purpose. This shared vision should help to build effective relationships, facilitate connections between action and reflection, and strengthen the desirable elements of the healthcare culture while modifying outdated assumptions, procedures, and structures.

Attitude of Health Personnel↗

A low abundance pool of nascent p21WAF1/Cip1 is targeted by estrogen to activate cyclin E*Cdk2.

Estrogens regulate cell proliferation in target tissues, including breast cancer by stimulating G(1)-S phase transition. Activation of cyclin E.Cdk2 through abrogation of the ability of p21(WAF1/Cip1) to bind to and inhibit cyclin-CDKs is a pivotal event in this process in MCF-7 breast cancer cells. A proposed mechanism is p21 sequestration into cyclin D1.Cdk4/6 complexes driven by estrogen-induced transcriptional activation of cyclin D1 gene expression. However, we now show that some E(2)-induced cyclin E.Cdk2 activation occurs in the absence of increased cyclin D1 levels and requires decreased p21 protein synthesis. Both mechanisms operate in the absence of major changes in total p21 protein levels and instead target a low abundance subset of newly synthesized p21. E(2)-induced activation of cyclin E.Cdk2 is mimicked by targeted inhibition of nascent p21 expression by antisense p21 oligonucleotides. Cyclin E.Cdk2 activation is completely inhibited by a combination of antisense cyclin D1 oligonucleotide transfection and elimination of the decrease in nascent p21 by infection with adenoviral-p21. These findings strongly support a central role for p21 in the early phase of E(2)-induced mitogenesis and highlight a major functional role for newly synthesized CDK inhibitory proteins.

Blotting, Northern↗

Digitalis-like factor response to hyperinsulinemia accompanying a euglycemic hyperinsulinemic clamp or oral glucose tolerance test.

Many studies of essential hypertension find evidence of insulin resistance in the same individuals, leading some to postulate a hypertensive role for insulin. However, the mechanisms by which insulin might exert a hypertensive effect are not fully resolved. An endogenous sodium pump inhibitor or digitalis-like factor (DLF) has been proposed as a hypertensive agent and its plasma concentrations are elevated in hypertension and in Type II diabetes, where insulin levels are elevated. Hence, we studied the effect of insulin on DLF using two approaches to achieve hyperinsulinemia. Normotensive men and women underwent a hyperinsulinemic, euglycemic clamp (40 mU/m2/min insulin, 40 mU = 1.6 x 10(-6) g) in which plasma insulin concentration was kept at high, but physiologic levels. Serum DLF (measured as inhibition of [Na,K]ATPase activity) and insulin levels were measured at baseline and every 30 min throughout the 2 hr clamp. Additionally, other subjects underwent an oral glucose tolerance test (OGTT) as a second means of increasing insulin levels. Insulin and DLF levels were measured prior to and hourly for 3 hours after receiving 100 gm of oral glucose. Serum DLF increased significantly during the clamp from a baseline of 4.6 +/- 0.81 to a peak of 8.7 +/- 1.2% inhibition (p=0.001). Comparison of the baseline and peak DLF levels with concomitant plasma insulin levels revealed a significant correlation (R=0.60, p=0.003). During the OGTT, DLF levels rose from a baseline of 2.4 +/- 1.0 to a peak level of 5.0 +/- 0.4%, p = 0.04. These results suggest that DLF, a factor that can cause vascular smooth muscle contraction and potentially influence blood pressure, is increased by hyperinsulinemia and provides a mechanism by which insulin may increase blood pressure.

Adolescent↗

Correlation between the glucose clamp technique and the homeostasis model assessment in hypertension.

The homeostasis model assessment (HOMA) has been extensively used as a reliable surrogate marker for measuring insulin resistance in patients with diabetes mellitus and in normal subjects. Comparative data in another insulin resistance state, hypertension, is lacking. The goal of the present study was to obtain that information by testing the correlation of HOMA with the euglycemic hyperinsulinemic clamp in 36 hypertensive and 27 normotensive subjects. Clamp-derived insulin sensitivity was calculated as the glucose disposal rate over steady-state plasma insulin concentration. Homeostasis model assessment was computed using the formula (fasting glucose x fasting insulin)/22.5. There was significant correlation between the clamp and HOMA for both the hypertensive (r = -0.64, P < .0001) and normotensive subjects (r = -0.58, P = .002). The HOMA can be used reliably as a less expensive and less cumbersome alternative for measuring insulin resistance in hypertension.

Adult↗

Translation and validation of the Spanish version of the RELATE questionnaire using a modified serial approach for cross-cultural translation.

This article describes the initial translation and validation of the Spanish version of the RELATionshhip Evaluation (RELATE) questionnaire with a sample of monolingual English speakers (n = 78), a sample of monolingual Spanish speakers (n = 18), and two samples of Spanish/English Bilinguals (n = 27 and n = 34). Cross-cultural and cross-language equivalence of the Spanish version of RELATE to the original English version were assessed using a Modified Serial Approach (MSA) for instrument translation. Face and content validity of the Spanish RELATE were established. Test-retest reliability indices obtained with the translated version among the monolingual and bilingual Spanish speaking groups were consistently equivalent to, and in some cases higher than, the baseline reliability obtained with the monolingual English speaking group. Applications of the Spanish version of RELATE and use of the MSA for researchers and practitioners are presented.

Adult↗

A pure estrogen antagonist inhibits cyclin E-Cdk2 activity in MCF-7 breast cancer cells and induces accumulation of p130-E2F4 complexes characteristic of quiescence.

Estrogen antagonists inhibit cell cycle progression in estrogen-responsive cells, but the molecular mechanisms are not fully defined. Antiestrogen-mediated G(0)/G(1) arrest is associated with decreased cyclin D1 gene expression, inactivation of cyclin D1-cyclin dependent kinase (Cdk) 4 complexes, and decreased phosphorylation of the retinoblastoma protein (pRb). We now show that treatment of MCF-7 breast cancer cells with the pure estrogen antagonist ICI 182780 results in inhibition of cyclin E-Cdk2 activity prior to a decrease in the G(1) to S phase transition. This decrease was dependent on p21(WAF1/Cip1) since treatment with antisense oligonucleotides to p21 attenuated the effect. Recruitment of p21 to cyclin E-Cdk2 complexes was in turn dependent on decreased cyclin D1 expression since it was apparent following treatment with antisense cyclin D1 oligonucleotides. To define where within the G(0) to S phase continuum antiestrogen-treated cells arrested, we assessed the relative abundance and phosphorylation state of pocket protein-E2F complexes. While both pRb and p107 levels were significantly decreased, p130 was increased 4-fold and was accompanied by the formation of p130.E2F4 complexes and the accumulation of hyperphophorylated E2F4, putative markers of cellular quiescence. Thus, ICI 182780 inhibits both cyclin D1-Cdk4 and cyclin E-Cdk2 activity, resulting in the arrest of MCF-7 cells in a state with characteristics of quiescence (G(0)), as opposed to G(1) arrest.

Breast Neoplasms↗

The effect of droloxifene and estrogen on thyroid function in postmenopausal women.

Estrogen is known to increase serum T4-binding globulin (TBG) concentrations, thereby increasing serum total T4 concentrations. Serum free T4 concentrations, however, remain normal. Tamoxifen, a selective estrogen receptor modifier (SERM), also raises serum TBG concentrations, but whether newer SERMs with less stimulatory action on the endometrium do so is not known. We, therefore, compared the effect of droloxifene, a SERM, and conjugated equine estrogen on pituitary-thyroid function in normal postmenopausal women. Ten women were treated for 6 weeks with conjugated estrogen (Premarin), 0.625 mg/day, and droloxifene, 60 mg/day, in a double-blind crossover study with an intervening 4-week no-treatment period. We measured serum T4, T3, TBG, free T4 index, and TSH at baseline and at the end of each 6-week period. The baseline values were compared with the 6-week values using paired t tests. The mean (+/- SD) serum TBG concentrations increased significantly during both treatment periods (baseline, 1.5+/-0.4 mg/dL; conjugated estrogens, 2.7+/-0.6 mg/dL; droloxifene, 2.1+/-0.6 mg/dL; P < 0.001 and P = 0.001, respectively). There were no significant changes in the serum free T4 index. Serum T4 and T3 concentrations increased during both treatment periods, however, the increase was significant only for T4 during the conjugated estrogen treatment period. The serum TSH concentrations increased significantly during both treatment periods (18% during conjugated estrogen and 11% during droloxifene), and the values remained within the normal range in all women. Administration of both conjugated estrogen and droloxifene for 6 weeks increases serum TSH and TBG concentrations, but does not alter free T4 index values in postmenopausal women.

Aged↗

Higher cholesterol and insulin levels in pregnancy are associated with increased risk for pregnancy-induced hypertension.

Hyperinsulinemia and dyslipidemia are known to be associated with essential hypertension but their role in pregnancy-induced hypertension remains unclear. We performed a case-control study comparing cholesterol, insulin, and glucose levels in the early third trimester of pregnancy among 31 women who developed pregnancy-induced hypertension (PIH) (either preeclampsia [n = 6] or nonproteinuric gestational hypertension [n = 25]), with 31 women remaining normotensive through pregnancy. As compared with women remaining normotensive, women subsequently developing PIH had higher fasting cholesterol levels (279 v 247 mg/dL; P = .02) and higher fasting insulin levels (13.3 v 7.9 microU/mL; P = .03), although fasting glucose levels and levels of glucose and insulin after glucose load did not differ significantly between groups. In comparing hypertensive subgroups, fasting insulin levels were significantly higher among women who subsequently developed preeclampsia, but not among those subsequently developing nonproteinuric gestational hypertension. Although women developing PIH had higher pregravid body mass index (25.1 v 22.6 kg/m2, P = .06), fasting cholesterol and insulin levels were associated with risk for PIH even after adjustment for body mass index and age (relative risks for one unit increase, respectively: 1.02 (P = .03) and 1.12 (P = .03). Higher fasting cholesterol and insulin levels in mid- to late pregnancy are associated with increased risk for PIH. These observations support a role for insulin resistance in the development of this complication of pregnancy.

Case-Control Studies↗

Sleep and "sundowning" in nursing home patients with dementia.

"Sundowning," a term that is sometimes equated with sleep disturbance or nocturnal delirium in dementia, is a poorly understood psychiatric phenomenon. In this study, we performed systematic, temporally specific, behavioral observations of nine profoundly demented nursing home patients 4 times an hour over a 12-hour period (1300 to 0100h) to determine whether their agitation was more likely to occur at a particular time of day. Results indicated only equivocal evidence that agitation was any worse nocturnally or during the time near sunset, thus raising the possibility that at least some components of sundowning may reflect disruptive behaviors occurring with identical frequency throughout the day but with differential impact upon nursing staff. Additional data indicated that awakening from sleep during darkness was also associated with agitation. A final result was a trend indicating the apparent worsening of agitation seasonally (greater agitation during winter), which may suggest involvement of the circadian timing system.

Activities of Daily Living↗

Consent to mental health treatment: a theoretical analysis of coercion, freedom, and control.

Research has shown that substantial numbers of mental health patients may be coerced into 'voluntary' treatment. This article examines the concept of coercion to address the concerns of social scientists, treatment providers, and policy makers to know when coercion into treatment has occurred. This logically takes precedence over the second important question of whether or not coercion is desirable in some situations. A review of the scientific research on coercion and related topics of freedom, control, and choice leads to a theoretical framework in which coercion is defined in terms of opportunities to choose among courses of action. Implications of this analysis are drawn for mental health service delivery, mental health policy, and mental health research.

Choice Behavior↗

Predictors of observed sleep/wakefulness in residents in long-term care.

This cross-sectional study investigated predictors of sleep/wakefulness in residents in a skilled care nursing facility. Sleep/wakefulness was defined behaviorally by observations made four times an hour over four 12-hour observation periods. Predictors studied were mental status, functional capacity, relative likelihood of cardiovascular/respiratory, musculoskeletal, and endocrine disease, psychotropic medication intake, and presence of sleep apnea. Results based on 39 residents indicated that sleep apnea was a positive consistent predictor of observed sleep in the nursing home. Apnea generally was unrelated to other predictors. We discuss these findings in terms of the viability of this technique to study sleep as well as other potential predictors of sleep/wakefulness in elderly institutionalized patients.

Aged↗

A method for checking interobserver reliability in observational sleep studies.

Disturbances of the sleep/wake cycle occur frequently in nursing home residents. Because of the many technical difficulties in studying sleep and rhythms in such patients, systematic behavioral observations offer an alternative approach. In this study we describe a method for determining interrater reliability of such observations. Two individuals observed 39 nursing home residents four times per hour during daytime and nighttime hours. Results indicated high interrater reliability for both sleep/wake and the presence of apnea during sleep. Both day and night observations were made reliably. We found only 101 discrepancies of 1.160 tandem observations. These results suggests that behavioral observations are a viable approach in the study of the sleep/wake cycle in nursing home settings.

Aged↗

Sentencing goals, causal attributions, ideology, and personality.

Disparity in sentencing of criminals has been related to a variety of individual difference variables. We propose a framework establishing resonances or coherent patterns among sentencing goals, causal attributions, ideology, and personality. Two studies are described, one with law and criminology students, the other with probation officers. Relations among the different types of variables reveal two resonances among both students and officers. One comprises various conservative and moralistic elements: a tough, punitive stance toward crime; belief in individual causality for crime; high scores on authoritarianism, dogmatism, and internal locus of control; lower moral stage; and political conservatism. The second comprises various liberal elements: rehabilitation, belief in economic and other external determinants of crime, higher moral stage, and belief in the powers and responsibilities of government to correct social problems. Implications of these results are discussed for individual differences in sentencing, attribution theory, and attempts to reduce disparity.

Authoritarianism↗

Anaesthesia equipment malfunction.

Anaesthetic equipment was studied to determine whether the accuracy was improved and failure rate decreased by routine maintenance and calibration by a biomedical technician. Each piece was evaluated, and then repaired and rechecked at intervals by the same technician. Equipment failures were divided into three types: first, equipment that was completely nonfunctional; second, equipment that was functional but inaccurate; and third, equipment that was functional and accurate but needed minor repairs. The percentage of equipment failures in each group was compared on initial evaluation and after 6 months. Of the 311 pieces of equipment, 40% needed repair at the time of the initial survey; 80% was nonfunctional, and 18% was functional but inaccurate. After six months on a maintenance schedule, only 15% of the equipment needed repair, 3% was nonfunctional, and 6% was functional but inaccurate. The difference between the total percentage of equipment failure initially and after six months was statistically significant. After a regular maintenance, calibration, and checkout schedule by a biomedical technician was instituted, there was a significant improvement in the accuracy of the equipment and a reduction in the percentage of equipment needing repair.

Anesthesiology↗