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Biomedical subjects

D Clarke

Publications and source records attributed to D Clarke.

At least 109 records · Page 6Linked to original sources
PubMed1997

Longitudinal trends in late-life insomnia: implications for prescribing.

OBJECTIVE: To assess trends in insomnia and hypnotic drug use in a representative sample of elderly general practice patients. DESIGN: Longitudinal study with three interview waves--1985, 1989 and 1993. SETTING: Urban and suburban Nottingham. PARTICIPANTS: 1042 patients originally aged 65 and over randomly sampled from general practitioner lists. MAIN OUTCOME MEASURES: Point prevalence estimates, status (case/non-case/died) at 4-year follow-up, episode incidence and survival functions. RESULTS: At baseline (1985) 221 respondents met the survey criteria for insomnia. Of these, 36.1% continued to report severely disrupted sleep in 1989. Within this period 84 new cases of insomnia were identified (an incidence rate of 3.1% per person-year at risk). Controlling for age and sex, insomnia was unrelated to survival among prevalent cases, but significantly related to survival among incident cases (odds ratio = 1.7; 95% confidence interval = 1.1-2.5). Of 166 respondents using prescription hypnotics in 1985, 31.7% continued to report usage in 1989. Similarly, out of 41 new hypnotic drug users identified in 1989, 29.3% continued to report usage in 1993. CONCLUSIONS: Important clinical differences in the natural history of insomnia are evident when incident and prevalent cases are compared. Nevertheless, outcomes at 4-year follow-up suggest that, for the majority of surviving cases identified in a prevalence screen and for a substantial minority of incident cases, late-life insomnia shows a level of chronicity incompatible with hypnotic drug therapy as currently recommended.

Aged↗
PubMed1997

"I find the term customer offensive".

Explores the tensions between cost and quality, need and market, and the effects on patient care and service providers within today's NHS. Builds on research carried out in two hospitals during 1993 to 1995, focusing on perceptions of quality and its management in the context of the nursing discipline. Indicates a divergence of perspectives on "customer requirements" and the emergence of a cultural divide within the total care process. Identifies and illustrates the significant potential for cost savings in health care, which may be achievable while simultaneously improving quality, and suggests that the "prize" for bridging the cultural divide might include a substantial financial gain as well as improved standards of care. In the context of health care, need, expectation, and finite resources are inextricably linked. A shared understanding of the interdependence between the three, and of the balance to be struck, is essential in health care provision today and into the twenty-first century. Suggests that there is some way to go.

Attitude of Health Personnel↗
PubMed1997

Customary physical activity and survival in later life: a study in Nottingham, UK.

OBJECTIVE: To assess the value of broadly based customary physical activity scores, derived from a questionnaire inventory, in predicting 10 year mortality among elderly people. DESIGN: A 10 year survival analysis of participants in the first wave of the Nottingham longitudinal study of activity and ageing who, in face to face interviews in 1985, provided detailed information on customary physical activity, health, and lifestyle. SETTING: Urban and suburban Nottingham PARTICIPANTS: A total of 1042 people aged 65 years and over randomly sampled from general practitioner records. MAIN RESULTS: On the basis of factor scores derived from the interview questionnaire, activity levels were graded as "high", "intermediate", or "low". In Cox regression models controlling for age, health status, and cigarette smoking at the time of the activity assessment, these gradings were significantly related to 10 year survival. Relative to the "high" activity groups, the risk of dying was significantly increased in both the "intermediate" (hazard ratio (HR) 1.53; 95% CI 1.12, 2.09) and "low" (HR 2.07; 95% CI 1.53, 2.79) groups for women, and in the "low" group (HR 1.59; 95% CI 1.12, 2.25) for men (p < 0.01 throughout). CONCLUSION: Since the survival model controlled for age, health status, and cigarette smoking, it is unlikely that the activity gradings used here are simple proxies for physical health. It is concluded, therefore, that within the elderly population, recall based survey assessments covering a wide range of customary or habitual physical activities, can provide indices showing both cross sectional utility and predictive validity.

Activities of Daily Living↗
PubMed1997

Altered platelet function detected by flow cytometry. Effects of coronary artery disease and age.

Platelet activation state and responsiveness to physiological agonists were measured in 65 patients with documented coronary artery disease (54 male and 11 female; mean age, 58 years). Twelve patients (mean age, 52 years), selected at random from the male cohort, were compared with 12 age-matched male control subjects (mean age, 52 years) and with 10 normal, young male subjects (mean age, 25 years). Whole-blood flow cytometry was used to measure platelet activation status ex vivo and platelet responsiveness to physiological agonists in vitro. Peripheral blood samples were analyzed for bound fibrinogen and expression of P-selectin, GPIb, and GPIIb-IIIa at rest and in response to ADP (0.1 to 10 mumol/L) and thrombin (0.02 to 0.32 mu/mL). No significant differences were seen in the basal levels of fibrinogen binding between any of the groups, but P-selectin expression was significantly lower in patients compared with age-matched control subjects (P = .0005). When stimulated with agonists, patients' platelets had significantly decreased fibrinogen binding (P < .03) but no difference in P-selectin expression compared with the age-matched group. Both agonist-induced fibrinogen binding and P-selectin expression were, however, higher in the young subjects compared with either the older control group or the patients (P < .05). GPIb and GPIIb-IIIa expression were lowest in the patients with angina and highest in the young control subjects, with levels in the age-matched control subjects falling between these values. Data from the total patient cohort (n = 65) were identical to those in the smaller cohort (n = 12). In conclusion, atherosclerosis impairs platelet aggregatory responses (fibrinogen binding) over and above the decreased response seen with age. Platelet degranulation (P-selectin expression) is also impaired in patients with coronary artery disease, but only in comparison with younger subjects, not age-matched controls.

Adult↗
PubMed1997

Mortality of captive British wartbiter crickets: implications for reintroduction programs.

A fungal infection was identified as the cause of a high mortality rate of captive wartbiter cricket (Decticus verrucivorus) nymphs at the London Zoo (United Kingdom) in 1994. This species is threatened with extinction in the United Kingdom and the animals concerned were part of a captive breeding and reintroduction program. Following these findings, reintroductions were postponed and release sites were used only where there were no extant wartbiter crickets.

Animals↗
PubMed1997

Evaluation of Caribbean strains of Macrocyclops and Mesocyclops (Cyclopoida:Cyclopidae) as biological control tools for the dengue vector Aedes aegypti.

Fifteen Caribbean strains of copepods were assessed for their predation ability against mosquito larvae. Macrocyclops albidus from Nariva. Mesocyclops aspericornis from Oropouche, and Mesocyclops longisetus from E1 Socorro, Trinidad, were most effective against Aedes aegypti but not against Culex quinquefasciatus. Mesocyclops longisetus and Me. aspericornis prevented any mosquito survival over 25 wk of observation despite weekly challenges with Ae. aegypti. The copepods were tolerant to dosages of the insecticide temephos that are usually toxic to mosquito larvae. This indicated that copepods could be incorporated into an integrated control system. To determine whether pathogenic microbes might be introduced with copepods into drinking water, microbial studies were done on the copepods. These showed the presence of only Aeromonas sobria, Pseudomonas sp., Alcalignes sp., and gram-positive bacilli. Although none of these are highly pathogenic to humans, the application of these copepods has not yet been recommended for use in drinking water.

Aedes↗
PubMed1997

Risk factors for late-life insomnia in a representative general practice sample.

BACKGROUND: Insomnia is widely reported and widely treated in general practice, yet relatively little research has focused on the natural history of the condition in primary care settings. As a result, there is at present little information to enable clinicians to assess insomnia risk, or anticipate outcomes in older general practice populations. AIM: To estimate, using 8-year longitudinal data, the risk of insomnia onset associated with selected health and lifestyle factors. METHOD: Survivors from a nationally representative sample (n = 1042) of elderly people originally interviewed in 1985 were reassessed in 1989 (n = 690) and 1993 (n = 410). At the first follow up in 1989, 84 new cases of insomnia were identified (a weighted incidence rate per person per year at a risk of 3.1%; 95% CI = 2.7-3.5). In logistic regression analyses controlling for age and sex, the risk of insomnia onset was then assessed in relation to the selected factors. RESULTS: Three factors assessed in 1985 were significantly and independently related to incident insomnia: psychometric ratings consistent with depressed mood odds ratio (OR) = 4.41; 95% CI = 3.32-5.43); health index scores indicating lower physical health status (OR = 1.19; 95% CI = 1.06-1.31 per unit change in scale score); and moderate and low levels of physical activity (OR = 1.91 and 2.14; 95% CI = 1.91-3.62 and 2.14-3.64 respectively). However, although depressed mood represented a major risk factor, the most likely source of risk was physical rather than mental ill-health. CONCLUSIONS: Psychiatric, somatic and lifestyle factors significantly and independently increase the risk of insomnia in older general practice patients. In predicting incident sleep disturbance, these factors exceed in importance the age and sex of patients.

Aged↗
PubMed1997

Cognition-enhancing drugs in dementia: a guide to the near future.

OBJECTIVES: To facilitate access to the available literature and to assist clinicians with the decision to recommend the use of medications for the enhancement of cognition in dementia. METHOD: A qualitative review of published research. Methodological issues confronting research in this area are described. An organizational scheme for the medication types, based on pathophysiologic processes relevant to Alzheimer's disease (AD), is reviewed. The paper makes extensive use of tablets to present the minimal data necessary for the reader to appraise critically all of the original publications found. The paper further presents in summary form the opinions of previous reviews on each of the medications. RESULTS: We identified 45 medications in the published research in which humans with dementia were assessed as having a change in cognition. Immediate use of tacrine is supported by the evidence, but the degree of benefit is modest, and side effects are problematic. CONCLUSION: A number of medications warrant further investigation. Tacrine can be offered to patients with careful education regarding the limited efficacy and potential side effects. Newer, perhaps safer, anticholinesterase inhibitors are now becoming available. Referral to a research study examining other medications is suggested, as are some "common sense" strategies.

Aged↗
PubMed1997

Our journey.

Explore the source record for details and available documents.

Canada↗
PubMed1996

Tenuous link between ischaemic threshold and both ambulatory ischaemia and symptom status over time in stable angina: a 5-year follow-up study.

This study evaluates changes in ischaemic threshold over a 5-year period in patients with stable angina pectoris, who did not suffer any intervening cardiac event. Changes in ischaemic threshold are related to alterations in symptomatic status and ambulatory ischaemia. Over long-term follow-up, there is a significant fall in ischaemic threshold in such patients (mean heart rate at onset of ischaemia fell from 104 +/- 17.8 to 97 +/- 17.4 bpm: P < 0.001), but this is not matched by a worsening of either symptoms or ischaemia during daily life. In the 68% of patients that had a reduction in ischaemic threshold of > or = 5 bpm, 68% had either definite reduction or no change in symptoms and 84% had either reduction, abolition or no change in transient ischaemic activity. The dissociation between ischaemic threshold, ambulatory ischaemia and symptoms has implications for long-term monitoring and management of the patient with stable angina.

Adult↗
PubMed1996

Effects of interleukin 6 administration on platelets and haemopoietic progenitor cells in peripheral blood.

Platelet numbers and circulating haemopoietic progenitor cells were examined in 12 patients with advanced malignancies who were receiving recombinant human interleukin-6 (rhIL-6) as part of an investigation of its thrombopoietic effects. Patients received recombinant glycosylated IL-6 by daily subcutaneous injection for 7 consecutive days in doses of 1, 3 or 10 micrograms/kg/day. Platelet numbers increased reaching a peak on days 12-15 with a mean on day 15 of 198.1% of pre-treatment values. This was accompanied by a significant fall in the mean platelet volume (mean decrease of 10.6%, P = 0.0044). No significant correlation was seen between the IL-6 dose and the change in platelet number. No significant differences were observed between pre- and post-treatment levels of circulating erythroid burst-forming units (E-BFU) and granulocyte macrophage colony-forming units (GM-CFU) but a small significant increase was seen in circulating primitive progenitor cells measured in a plastic-adherent (P delta) assay (P = 0.025). As positive controls, a group of patients treated with cyclophosphamide/G-CSF showed significant increases in GM-CFU (P = 0.018), E-BFU (P = 0.018) and P delta progenitors (P = 0.028). These data suggest that the thrombopoietic effects of IL-6 are mediated at a relatively late stage via effects on megakaryocyte differentiation, with a relatively small effect on circulating haemopoietic progenitors.

Adult↗
PubMed1996

Regulation of the human bilirubin UDP-glucuronosyltransferase gene.

The human UGT1 gene is a single copy gene consisting of four common exons and more than 13 variable exons which span more than 200 kb of the human genome. A single variable exon is spliced to the four common exons to form the mRNA for synthesis of a single UDP-glucuronosyltransferase (UGT) isoenzyme. Treatment of humans or hepatoma cell lines with drugs such as phenobarbital causes the induction of hepatic bilirubin UGT by increased transcription from the UGT1 gene. The upstream region of UGT1*1 (bilirubin UGT) was sequenced and found to contain consensus sequences for several transcriptional regulatory elements including a 'BARBIE box'. An unusual 'TATA' promoter sequence A(TA)6TAA was also observed. The 5' region flanking the UGT1*1 exon when cloned into reporter constructs and transfected into four cells lines was capable of promoting reporter gene expression, but not when transfected into monkey kidney cell fibroblasts (COS-7 cells) indicating a cell specific expression. Sequential deletion of the 5' flanking region in the plasmid constructs did not cause any significant reduction in reporter expression. Treatment of cells transfected with these plasmid constructs with drugs did not cause a significant increase in reporter expression except with retinoic acid plus WY 14643. Introduction of an additional two base pairs (TA) into the 'TATA' box of the 5' gene sequence (as observed in Gilbert's patients) did not significantly change reporter expression levels. The regulation of the biliruibin UGT gene by drugs is not yet understood and it will be important to identify additional genetic elements possibly further than -2kb upstream of the UGT1*1 coding region, which regulate the expression of this gene.

Base Sequence↗
PubMed1996

Does brachytherapy have a role in the treatment of prostate cancer?

The goal of radiation therapy is to deliver a high dose to the tumor while preserving normal surrounding tissue. For early-stage prostate cancer, the ultimate conformal irradiation is to place radioactive sources directly into the gland either as permanent or temporary seeds. Permanent seed implantation is capable of delivering two times the radiobiologically equivalent dose of external beam irradiation to the prostate and tumor. In the past, the results of prostate brachytherapy were likely poor owing to the technical difficulty in accurately placing the radioactive seeds uniformly throughout the prostate. The use of low-dose-rate I-125 to treat high-grade cancers probably also contributed to the poorer results as compared with external beam irradiation. Over the last 10 years, however, technologic advances in transrectal ultrasonography, computer dosimetry, and template-based transperineal techniques have dramatically improved the accuracy and consistency of the brachytherapist to place radioactive sources directly into the prostate gland. Transperineal ultrasound or CT directed seed implantation has replaced the older retropubic method. Brachytherapists are now able to accurately map out the gland prior to the implant and carefully evaluate preoperatively seed placement. The availability of such radioactive sources as iodine-125, palladium-103, and iridium-192 has also given the brachytherapist isotopes that can be more carefully matched to the biology and stage of the tumor. More sensitive definitions of failure have prompted radiation oncologists and urologists to carefully evaluate the efficacy of external beam irradiation and surgery. Accurate comparison of the efficacy of brachytherapy to surgery and to external beam radiation requires a randomized study. Comparisons of retrospective studies are fraught with the problems of the heterogeneous nature of early-stage prostate cancer. Imbalances in stage, grade, initial PSA extraprostatic disease, and nodal status of patient groups make comparisons difficult. Most of the long-term data for permanent seed implantation are the result of work at a single institution. These results will need to be repeated at other institutions treating patients in a similar manner. Because techniques vary from institution to institution, permanent implant results will need to be carefully evaluated for technique as well as stratified for pretreatment variables. Pretreatment PSA and grade appear to be more sensitive variables than stage in predicting failure after radiation. As more patients are diagnosed with very early and nonpalpable disease, future studies will need to stratify patients based on these pretreatment factors. Patients with early-stage disease but identified as high risk for extraprostatic disease will require more intensive regimens. The treatment outcomes based on biopsy results are inconclusive. A lack of consensus on the definition of a truly positive biopsy remains forthcoming. The value of a positive prostate biopsy as an outcome predictor for clinical failure is still unclear. The use of prostate nuclear cell antigen staining may help clarify the issue. Comparison of treatment outcome based on absolute PSA is also difficult. The Seattle series suggest that brachytherapy by permanent seed implantation is as efficacious as external beam irradiation for early-stage disease in patients with a low PSA (< 10 ng/mL). As the PSA value rises above 10 ng/mL, the probability of failure after external beam rises substantially. Results from the Seattle series suggest an advantage to seed implant alone or the judicious application of seed implant boost to external beam radiation for these patients with more advanced cancer. The most sensitive measurement of therapeutic outcome is progression-free survival. Few studies to date have evaluated progression-free survival.

Biopsy↗
PubMed1996

Dementia and 'borderline dementia' in Britain: 8-year incidence and post-screening outcomes.

Survivors from a nationally representative sample of elderly people originally screened in 1985 were reassessed in 1989 and again in 1993. On each occasion respondents were rated as cognitively impaired, borderline impaired or unimpaired (using a brief information/orientation scale), with the validity of these ratings assessed in subsequent clinical interviews. Where follow-up screening was not possible, information was derived from death certificates and hospital case-notes. Over 8 years (1985-93) the overall incidence rate per person-year at risk was 1.58%, giving age-specific rates of 0.72, 1.32, 1.63, 3.46, 2.55 and 1.41% for the age groups 65-69, 70-74, 75-79, 80-84, 85-89 and > or = 90 respectively. Of 43 individuals classified at screening as borderline impaired in 1985 and 1989, 19 were diagnosed as demented at clinical interviews conducted within 16 weeks of screening. Four-year follow-ups among the remaining 24 showed that 15 had died, while 6 showed a worsened cognitive status. Controlling for both age and sex, aggregated 4-year mortality was significantly higher among those defined at screening in 1985 and 1989 as either impaired or borderline, when compared with the unimpaired.

Aged↗
PubMed1996

The results of water fluoridation in Ireland.

The visit of Dr. Trendley Dean to Dublin in the mid-1950s helped accelerate the decision to introduce water fluoridation as a public health measure in the prevention of caries in the Republic of Ireland. A challenge to the constitutional validity of the Health (Fluoridation of Water Supplies) Act 1960 failed and in 1964 the water supplies of Dublin city were fluoridated. Over the next seven to eight years all the major urban communities in the Republic of Ireland were fluoridated. Currently, 67 percent of the 3.5 million people in the country reside in fluoridated communities. Studies conducted over the last 20 years show that residents of fluoridated communities have better dental health than those in nonfluoridated communities--the mean dmft is lower in children and the number of natural teeth present in adults is higher.

Adolescent↗
PubMed1996

Endothelial control of lower limb blood flow in chronic heart failure.

BACKGROUND: Limitation of the blood supply to skeletal muscle in chronic heart failure may contribute to the symptoms of fatigue and diminished exercise capacity. The pathophysiology underlying this abnormality is not known. The purpose of this study was to assess the effect of endothelium dependent and independent vasodilator agents on blood flow in the leg of patients with heart failure. METHODS AND RESULTS: Blood flow in the leg was measured in patients with heart failure (n = 20) and compared with that in patients with ischaemic heart disease and normal left ventricular function (n = 16) and patients with chest pain and normal coronary arteries (n = 8). External iliac artery blood flow was measured using intravascular Doppler ultrasound and quantitative angiography. Flow was recorded at rest and in response to bolus doses of the endothelium independent vasodilator, papaverine. Endothelium dependent responses were measured by infusion of acetylcholine and substance P. Mean (SEM) baseline blood flow was reduced at rest (2.9 (0.4) v 4.5 (0.3) ml/s, P < 0.001) and vascular resistance was raised (37.4 (3.6) v 27.1 (3.0) units, P < 0.05) in patients with heart failure compared with that in controls. The peak blood flow response to papaverine (8 mg), acetylcholine (10(-7)-10(-5) mol/l), and substance P (5 pmol/min) was reduced in heart failure, with greater impairment of the response to acetylcholine than substance P. There was a correlation between baseline blood flow in the heart failure group and diuretic dose (r = -0.62, P = 0.003), New York Heart Association classification (r = -0.65, P = 0.002), and left ventricular ejection fraction (r = 0.80, P = 0.0004). CONCLUSIONS: There is reduced blood flow and raised vascular resistance at rest in the legs of patients with heart failure. The degree of impaired blood flow in the leg correlates with the severity of heart failure. There is impairment of the response to both endothelium dependent and independent vasodilators. Abnormal function of the vascular myocyte in heart failure may explain these results as would structural abnormalities of the resistance vessels.

Acetylcholine↗