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Biomedical subjects

A Gordon

Publications and source records attributed to A Gordon.

At least 73 records · Page 4Linked to original sources

Predictors of compliance with naltrexone among alcoholics.

OBJECTIVE: Naltrexone has been found to be an effective adjunct to treatment to reduce the rate of drinking among alcoholics. However, adherence to the medication has been of considerable concern; the high rates of noncompliance with the medication limits the benefits that could potentially be realized from this pharmacotherapy. Knowledge of predictors of noncompliance could result in interventions targeted at these variables. METHOD: Participants were 128 alcohol-dependent patients who participated in a clinical placebo-controlled trial of naltrexone. Upon discharge from a 1- to 2-week partial hospital program, patients were randomly placed into 12 weeks of naltrexone (50 mg/day) or placebo (n = 64 per condition). Patients met with a physician and a research assistant weekly for 4 weeks then biweekly for 8 weeks. RESULTS: Compliance (number of days taking medication) was not predicted by demographic or pretreatment alcohol use variables. Number and severity of side effects in the first week, particularly nausea and fatigue, predicted early termination. Compliance was not predicted by commitment to abstinence or self-efficacy about abstinence, but was greater among patients who believed more strongly that the medication would help them stay sober. Compliance was not predicted by general level of urge to drink during the first week on medication but compliance was greater among those with a higher urge to drink in response to alcohol stimuli in the laboratory. CONCLUSIONS: Implications for approaches to increase compliance include reducing side effects and increasing patients' beliefs in the efficacy of naltrexone.

Adult↗

Life expectancy calculations for postcode sectors and their use for monitoring inequalities in the nation's health.

OBJECTIVE: To describe how life expectancy calculations can be used to demonstrate differences in mortality between populations of different socioeconomic status at each population census. DESIGN: Population data were obtained in five-year age-sex and deprivation groups at postcode sector level for the Greater Glasgow Health Board area for the censuses of 1981 and 1991. The numbers of deaths for the same groups were obtained for the three-year periods 1980-82 and 1990-92. Life expectancy tables were derived by applying mortality rates calculated from these data to a synthetic cohort of individuals. Regression analyses were applied to the tables thus derived to examine the relationships between census period, level of deprivation and life expectancy. RESULTS: Over the period 1980/82 to 1990/92 life expectancy of the age group 0-4 years increased by 2.1 years in males and 2.9 years in females, increases being greater in the more affluent areas. Differences in life expectancy between the geographically defined most deprived and most affluent areas increased from 7.4 to 9.0 years in males and from 5.9 to 6.0 years in females. CONCLUSION: Life expectancy is increasing in all socioeconomic groups, but particularly in the most affluent. We suggest that life expectancy values should be published routinely for different socioeconomic groupings. Over time these would illustrate more clearly the relationships between health policy and health outcomes, and would demonstrate whether policies are reducing inequalities and generally improving health.

Aged↗

Coordinated movement of RACK1 with activated betaIIPKC.

Protein kinase C (PKC) isozymes move upon activation from one intracellular site to another. PKC-binding proteins, such as receptors for activated C kinase (RACKs), play an important role in regulating the localization and diverse functions of PKC isozymes. RACK1, the receptor for activated betaIIPKC, determines the localization and functional activity of betaIIPKC. However, the mechanism by which RACK1 localizes activated betaIIPKC is not known. Here, we provide evidence that the intracellular localization of RACK1 changes in response to PKC activation. In Chinese hamster ovary cells transfected with the dopamine D2L receptor and in NG108-15 cells, PKC activation by either phorbol ester or a dopamine D2 receptor agonist caused the movement of RACK1. Moreover, PKC activation resulted in the in situ association and movement of RACK1 and betaIIPKC to the same intracellular sites. Time course studies indicate that PKC activation induces the association of the two proteins prior to their co-movement. We further show that association of RACK1 and betaIIPKC is required for the movement of both proteins. Our results suggest that RACK1 is a PKC shuttling protein that moves betaIIPKC from one intracellular site to another.

Animals↗

Aerobic training involving a minor muscle mass shows greater efficiency than training involving a major muscle mass in chronic heart failure patients.

BACKGROUND: Beneficial training outcomes have been reported in sedentary patients with chronic heart failure (CHF) after exercise training. However, data on training effects in previously trained patients, as well as comparisons of different exercise modes, are lacking. The aim of this study is to compare exercise training on a cycle ergometer (major muscle mass) and aerobic knee-extensor training (minor muscle mass) in previously trained patients with CHF. METHODS AND RESULTS: Twenty-four men and women (age, 63 +/- 10 years [mean +/- SD]) with stable, moderate CHF (left ventricular ejection fraction, 30% +/- 11%) who had completed their first exercise training period more than 1 year ago were allocated to either the exercise or control group. After stratification for sex, age, ejection fraction, and cardiac output response, the training group was further randomized to either cycle ergometer or knee-extensor training for 8 weeks. The control and training patients did not differ at baseline, and the measured variables did not change in the control group during the 8 weeks. Citrate synthase activity in skeletal muscle increased after cycle training (23%; P < .02) and knee-extensor training (45%; P < .008), and blood lactate concentration at submaximal intensities decreased (P < .04) in both groups. However, only after knee-extensor training did the peak oxygen uptake increase (19%; P < .01) and sympathetic nervous system activity, measured as plasma norepinephrine concentration at rest (P < .05) and during exercise (P < .008), decrease. Minnesota Living with Heart Failure questionnaire scores also showed improvement in the health-related quality of life (P < .05) only after knee-extensor training. CONCLUSION: Physical training is beneficial in previously trained patients with CHF. Aerobic training involving a minor muscle mass shows greater efficiency than training involving a major muscle mass.

Aged↗

Disruption of imprinted genes at chromosome region 11p15.5 in paediatric rhabdomyosarcoma.

Rhabdomyosarcomas are characterized by loss of heterozygosity (LOH) at chromosome region 11p15.5, a region known to contain several imprinted genes including insulin-like growth factor 2 (IGF2), H19, and p57(KIP2). We analyzed 48 primary tumour samples and found distinct genetic changes at 11p15.5 in alveolar and embryonal histological subtypes. LOH was a feature of embryonal tumours, but at a lower frequency than previous studies. Loss of imprinting (LOI) of the IGF2 gene was detected in 6 of 13 informative cases, all harbouring PAX3-FKHR or PAX7-FKHR fusion genes characteristic of alveolar histology. In contrast, H19 imprinting was maintained in 14 of 15 informative cases and the case with H19 LOI had maintenance of the IGF2 imprint indicating separate mechanisms controlling imprinting of IGF2 and H19. The adult promoter of IGF2, P1, was used in 5 of 14 tumours and its expression was unrelated to IGF2 imprinting status implying a further mechanism of altered IGF2 regulation. The putative tumour suppressor gene p57(KIP2) was expressed in 15 of 29 tumours and expression was unrelated to allele status. Moreover, in tumours with p57(KIP2) expression, there was no evidence for inactivating mutations, suggesting that p57(KIP2) is not a tumour suppressor in rhabdomyosarcoma.

Adult↗

Beneficial effects of exercise training in heart failure patients with low cardiac output response to exercise - a comparison of two training models.

BACKGROUND: Exercise capacity of patients with chronic heart failure (CHF) correlates poorly with estimates of cardiac function. Yet, it has been suggested that only patients without severely impaired cardiac output (CO) benefit from exercise training. Comparisons of different training models have not been made in the same study. AIMS: To evaluate whether the response to different training models diverges according to the cardiac output response to exercise in patients with chronic heart failure. METHODS: Sixteen CHF patients (63 +/- 11 years) with an ejection fraction of 30 +/- 11% underwent a baseline cardiopulmonary exercise test, right heart catheterization and leg muscle biopsy. Cardiac output (CO) response to exercise was defined as the ratio between CO increase and the increase in oxygen uptake (CO response index) during exercise. Patients were randomized into two training regimens, differing with regard to active muscle mass, i.e. whole body and one-legged exercise. RESULTS: Baseline exercise capacity expressed as W kg-1 correlated with the CO response index (r = 0.51, P < 0.05). Exercise capacity on the cycle ergometer increased in both groups but more in the one-legged than in the two-legged training group (P < 0.05). The improvement in exercise capacity did not correlate with base-line exercise capacity. It correlated with CO response index in the one-legged (r = 0.75, P < 0.01) but not in the two-legged training group. CO response index correlated negatively with the pulmonary capillary wedge pressure at peak exercise (r = - 0.60, P < 0.05). The increase in leg muscle citrate synthase activity after training correlated negatively with the baseline CO response index (r = - 0. 50, P < 0.05). CONCLUSIONS: The improvement of exercise capacity after one-legged training correlates with the CO increase in relation to the O2 uptake before training. In patients with low CO response, individualization of the exercise regimen is needed and the benefits of training a limited muscle mass at a time deserve further study.

Adult↗

Intrapartum umbilical artery Doppler velocimetry as a predictor of adverse perinatal outcome: a systematic review.

OBJECTIVE: To evaluate the diagnostic prediction of intrapartum umbilical artery Doppler velocimetry for adverse perinatal outcomes using systematic quantitative overview of the available literature. DESIGN: Online searching of MEDLINE database (January 1966-September 1997), scanning of bibliography of known primary and review articles, review of recent journal issues and that from personal files. Study selection, assessment of study quality and data extraction were all performed in duplicate under masked conditions. PARTICIPANTS: 2700 women (unselected, low, high, and combined low and high obstetric risk populations) included in eight studies selected for meta-analyses. MAIN OUTCOME MEASURES: Likelihood ratios (LRs) for positive and negative test results were generated for the following outcome measures: Apgar scores < 7 at 1 and 5 minute following delivery, small for gestational age fetus; intrapartum fetal heart rate abnormality, umbilical arterial acidosis at delivery; and caesarean section for fetal distress. RESULTS: For Apgar score < 7 at 1 minute following delivery, the pooled LR was 2.5 (95% CI 1.7-3.7) for a positive test and 1.0 (95% CI 0.9-1.1) for a negative test result. A positive test predicted an Apgar score < 7 at 5 minute following delivery with a pooled LR of 1.3 (95% CI 0.4-4.1) while a negative test had a pooled LR of 1.0 (95% CI 0.8-1.2). For the prediction of a small for gestational age fetus, the pooled LR was 3.4 (95% CI 2.3-5.1) for a positive test and 0.9 (95% CI 0.8-1.0) for a negative test. The prediction for fetal heart rate abnormality during labour was similarly disappointing: the pooled LR for a positive test result was 1.4 (95% CI 0.9-1.2) whereas a negative test result generated a pooled LR of 0.9 (95% CI 0.9-1.0). With umbilical acidosis at delivery, the pooled LR was 1.6 (95% CI 1.1-2.5) for a positive test and 1.1 (95% CI 1.0-1.2) for a negative test. The LRs for the prediction of caesarean section for fetal distress were 4.1 (95% CI 2.7-6.2) for a positive test result and 0.9 (95% CI 0.8-1.0) for a negative test result. CONCLUSION: Intrapartum umbilical artery Doppler velocimetry is a poor predictor of adverse perinatal outcomes.

Blood Flow Velocity↗

Naltrexone's effect on cue-elicited craving among alcoholics in treatment.

BACKGROUND: Advancing knowledge of biobehavioral effects of interventions can result in improved treatments. Thus, a standardized laboratory cue reactivity assessment has been developed and validated to assess the cognitive and psychophysiological responses to a simulated high-risk situation: alcohol cues. The present study investigates the effects of a pharmacotherapy (naltrexone) on a laboratory-based, cue-elicited urge to drink among abstinent alcoholics in treatment. METHODS: Alcohol-dependent subjects were randomized to 12 weeks of naltrexone or placebo after completing a partial hospital program. After approximately 1 week on medication, all received cue reactivity assessment. RESULTS: Significantly fewer patients taking naltrexone reported any urge to drink during alcohol exposure than did those on placebo. Those with any urges reported no decrement in level of the urges. Mean arterial pressure decreased significantly for those on placebo, but not for those on naltrexone, whereas cue-elicited decreases in heart rate were not affected by the medication. CONCLUSIONS: The results have implications for models of relapse and naltrexone's effects. Cue reactivity methodology has utility for investigating hypothesized mediators of therapeutic effects of pharmacotherapies as well as behavioral treatments.

Adult↗

The effect of diclofenac sodium on the initial comfort of RGP contact lenses: a pilot study.

BACKGROUND: We conducted a pilot study to assess the effect of 0.1% diclofenac sodium eyedrops on the initial comfort of rigid gas permeable (RGP) contact lenses. METHODS: A double-masked, placebo-controlled, crossover trial was performed on 20 unadapted subjects. In Phase I, subjects used either 0.1% diclofenac or placebo eyedrops four times per day for 3 days before RGP lenses were dispensed. Contact lenses were inserted on Day 4 and worn for 8 continuous hours. Eyedrops were used twice during the 8-hour period. Ocular symptoms were graded on a visual analog scale at six points during the day. Visual acuity and slitlamp examinations were performed at the same six study points. After a 2-week wash-out period, subjects received the opposite treatment in Phase II, following the same protocol used in Phase I. RESULTS: The treatment effect was tested using the Mainland-Gart chi-square test. There was no statistically significant treatment effect (chi-square = 0.20, p = 0.653) on patient symptoms. Biomicroscopy findings were analyzed and, likewise, showed no significant treatment effect (chi-square = 2.10, p = 0.15). CONCLUSIONS: Data from this pilot study showed no statistically significant reduction in symptoms or signs with diclofenac eyedrops.

Adult↗

Genes, chromosomes, and rhabdomyosarcoma.

Rhabdomyosarcomas are a heterogeneous group of malignant tumors and are the most common soft-tissue sarcoma of childhood. Rhabdomyosarcomas resemble developing skeletal muscle, notably in their expression of the MRF family of transcription factors and the PAX3 and PAX7 genes. These PAX genes are also involved through specific translocations, t(2;13)(q35;q14) and variant t(1;13)(p36;q14) in the alveolar subtype, which result in PAX3-FKHR and PAX7-FKHR fusion genes, respectively. The fusion genes are thought critically to affect downstream targets of PAX3 and PAX7 or possibly have novel targets. Similar downstream changes may also be involved in embryonal and fusion gene negative cases. Genomic amplification of such genes as MYCN, MDM2, CDK4, and PAX7-FKHR is a feature mainly of the alveolar subtype, while specific chromosomal gains, including chromosomes 2, 8, 12, and 13, are associated with the embryonal subtype. Loss of alleles and imprinting at 11p15.5 and disruption of genes such as IGF2, ATR, PTC, P16, and TP53 have also been implicated in rhabdomyosarcoma development. Whereas there is now a realistic possibility of cure in the majority of cases, there remains a subset that is resistant to multimodality therapy, including high-dose chemotherapy. Characterization of the defining molecular features of tumors that are likely to behave aggressively represents a particular challenge. Current research is leading toward a better understanding of rhabdomyosarcoma tumorigenesis, which may ultimately result in novel therapeutic strategies that increase the overall cure. Genes Chromosomes Cancer 26:275-285, 1999.

Animals↗

Rectally administered misoprostol for the treatment of postpartum hemorrhage unresponsive to oxytocin and ergometrine: a descriptive study.

OBJECTIVE: To investigate whether rectally administered misoprostol is an effective treatment for postpartum hemorrhage unresponsive to conventional first-line management. METHODS: We studied 14 women with postpartum hemorrhage unresponsive to oxytocin and ergometrine (n = 10) or, when ergometrine was contraindicated, oxytocin alone (n = 4). While awaiting carboprost, misoprostol 1000 microg (five tablets) was administered rectally. RESULTS: In all 14 women, the hemorrhage was controlled, and sustained uterine contraction produced within three minutes of administration of misoprostol. CONCLUSION: Misoprostol appears to be absorbed effectively from rectal as well as oral and vaginal mucosa. Rectally administered misoprostol appears to be an effective treatment for postpartum hemorrhage unresponsive to oxytocin and ergometrine; therefore, it might be an alternative to parenteral prostaglandins or at least minimize the number of women requiring this invasive treatment. Given that it is an inexpensive and stable drug, misoprostol has considerable potential to reduce maternal mortality from postpartum hemorrhage in developing countries.

Administration, Rectal↗

Index finger lengthening by gradual distraction and bone grafting.

We present the case of an 18-year-old woman with a shortened right index finger. The digit was stabilized and lengthened a total of 18 mm by external fixation and iliac bone grafting. A distal interphalangeal fixed flexion deformity of 60 degrees was corrected with external fixation and intermedullary wiring.

Adolescent↗

Exercise-based rehabilitation improves skeletal muscle capacity, exercise tolerance, and quality of life in both women and men with chronic heart failure.

BACKGROUND: Data of training effects in chronic heart failure patients are based on findings in men. The purpose of this study was to compare the effects of skeletal muscle endurance training between men and women with chronic heart failure. METHODS AND RESULTS: Twelve consecutive men (mean [+/- SD] age 58 +/- 9 years, left ventricular ejection fraction 29 +/- 9%) and 12 women (60 +/- 10 years, left ventricular ejection fraction 28 +/- 7%) with moderate, chronic heart failure stratified according to age and inclusion criteria were investigated at baseline and after 8 weeks of knee extensor endurance training. The activity of skeletal muscle citrate synthase and resting heart rate were similar in men and women at baseline and with training improved (P < .0001) similarly in both genders. Peak work rate (P < .0001), peak oxygen uptake (P < .001) and muscle strength (P < .05) at baseline were higher in men than in women. Training improved peak work rate (P < .0001) and muscle strength (P < .0001) similarly in both genders, while improvement in peak oxygen uptake was better in women (P < .001). The distance ambulated during 6 minutes was similar in both genders at baseline and increased after training more in men (P < .004). The overall and physical Sickness Impact Profile indicated similarly reduced health-related quality of life in men and women, while worse psychosocial quality of life was observed in men (P < .05). Both genders improved after exercise training in the overall, physical, and psychosocial Sickness Impact Profile (P < .01). CONCLUSIONS: Exercise-based rehabilitation improves skeletal muscle capacity, exercise tolerance, and the health-related quality of life in women as well as in men with moderate, chronic heart failure.

Aged↗

Effect of compounds with antibacterial activities in human milk on respiratory syncytial virus and cytomegalovirus in vitro.

The effect of some antibacterial compounds present in human milk were tested for antiviral activity against respiratory syncytial virus, Semliki Forest virus and cytomegalovirus. These included the gangliosides GM1, GM2 and GM3, sialyl-lactose, lactoferrin and chondroitin sulphate A, B and C, which were all tested for their ability to inhibit the viruses in cell culture. Of the compounds tested, only the ganglioside GM2, chondroitin sulphate B and lactoferrin inhibited the absorption and growth of respiratory syncytial virus in cell culture, and none inhibited the growth of Semliki Forest virus, indicating that lipid antiviral activity was not associated with any of the gangliosides. While the concentrations of these two compounds required to inhibit respiratory syncytial virus were in excess of those present in human milk, sialyl-lactose concentrations similar to those present in human milk increased the growth of cytomegalovirus. Lactoferrin was confirmed as inhibiting both respiratory syncytial virus and cytomegalovirus growth in culture even when used at lower concentrations than those present in human milk. The antiviral activities of GM2, chondroitin sulphate B and lactoferrin were tested when added to an infant formula. Lactoferrin continued to have antiviral activity against cytomegalovirus, but a lower activity against respiratory syncytial virus; ganglioside GM2 and chondroitin sulphate B still maintained antiviral activity against respiratory syncytial virus.

Animals↗

After-the-fact strategies Mexican Americans use to prevent HIV and STDs.

Hispanics make up less than 10% of the U.S. population but account for 83,923 (17%) of all U.S AIDS cases and are disproportionately affected by sexually transmitted diseases (STDs). Nurses have a mandate to provide culturally competent care, but to do so, they must understand what their clients' needs are and how best to deliver nursing care. A key finding of this exploratory focus group study with newly immigrated Mexican Americans in North Carolina was that respondents were actively striving to prevent HIV or STDs. Their preventive practices for both HIV and STDs centered around a "gonorrhea model" of prevention and casual transmission. The emphasis was not on the biomedical model of transmission or prevention (condoms use). The findings also suggested that the level of counseling for prevention needs to be targeted differently for men than for women.

Acquired Immunodeficiency Syndrome↗