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Biomedical subjects

M Dooley

Publications and source records attributed to M Dooley.

At least 37 records · Page 2Linked to original sources

Determinants of antepartum human immunodeficiency virus testing in a non-Medicaid obstetric population.

OBJECTIVE: To determine voluntary human immunodeficiency virus (HIV) testing rates and factors influencing testing in a private obstetric practice. METHODS: Antepartum patients were offered HIV testing after completing a self-assessment questionnaire. Perceived risks and demographics were correlated with testing rates. RESULTS: Overall, 348/600 (58%) women consented to HIV testing. In a univariate analysis, patients with "any" perceived risk(s) were more likely to be tested. Single women and those with an at-risk partner(s) or a history of sexually transmitted disease (STD) were more likely to desire testing. These factors remained independently associated with voluntary testing in a multivariate regression model. No patients tested positive for HIV. CONCLUSIONS: In our private obstetric practice, 26% of women perceived themselves at risk for HIV infection, and testing rates depended on the various risks identified. A history of STDs or an at-risk sexual partner were stronger predictors of voluntary testing than was marital status. Focused HIV counseling among pregnant women at relatively low risk for infection may be possible.

Blood Transfusion↗

Pramipexole. A review of its use in the management of early and advanced Parkinson's disease.

UNLABELLED: Pramipexole is an orally active non-ergoline dopamine agonist with selective activity at dopamine receptors belonging to the D2 receptor subfamily (D2, D3, D4 receptor subtypes) and with preferential affinity for the D3 receptor subtype. It is approved as monotherapy in early Parkinson's disease and as adjunctive therapy to levodopa in patients with advanced disease experiencing motor effects because of diminished response to levodopa. The potential neuroprotective effects of pramipexole have been shown in animal and in vitro studies. Data from relatively long term (10- or 31-week) studies suggest that pramipexole monotherapy (0.375 to 6.0 mg/day) can improve activities of daily living and motor symptoms in patients with early Parkinson's disease. Pramipexole (0.375 to 4.5 mg/day for 31 or 36 weeks), as an adjunct to levodopa in advanced disease, improved activities of daily living and motor symptoms, reduced the duration and severity of 'off' periods and allowed a reduction in levodopa dosage. Mentation, behaviour and mood [Unified Parkinson's Disease Rating Scale (UPDRS) part I], and timed walking test were not significantly improved. The extent of disability improved according to the UPDRS parts II and III but, when assessed by secondary efficacy parameters, it is unclear whether disability or the severity of disease improved. No significant differences were observed in patients randomised to pramipexole or bromocriptine according to a secondary hypothesis in a prospective study in which both drugs were better than placebo. Some quality-of-life measures improved with active treatment relative to placebo. Further studies comparing pramipexole with other dopamine agonists and levodopa in patients with early and advanced Parkinson's disease would be useful. In pramipexole recipients with early disease, the most commonly experienced adverse events were nausea, dizziness, somnolence, insomnia, constipation, asthenia and hallucinations. The most commonly reported adverse events in pramipexole recipients with advanced disease were orthostatic hypotension, dyskinesias, extrapyramidal syndrome (defined as a worsening of the Parkinson's disease), dizziness, hallucinations, accidental injury, dream abnormalities, confusion, constipation, asthenia, somnolence, dystonia, gait abnormality, hypertonia, dry mouth, amnesia and urinary frequency. The incidence of some adverse events did not greatly differ between pramipexole and placebo recipients. CONCLUSIONS: Pramipexole is effective as adjunctive therapy to levodopa in patients with advanced Parkinson's disease. However, the potential beneficial effects of pramipexole on disease progression need to be confirmed in clinical studies. The efficacy of pramipexole monotherapy in patients with early disease has also been demonstrated, although the use of dopamine agonists in early Parkinson's disease remains controversial.

Antiparkinson Agents↗

Fixed combination verapamil SR/trandolapril.

Verapamil sustained-release (SR)/trandolapril is a combination of a phenylalkylamine calcium antagonist and an angiotensin converting enzyme inhibitor for the management of essential hypertension. Verapamil SR/trandolapril does not adversely influence glucose, insulin or lipid parameters in patients with mild to moderate essential hypertension and type 2 (non-insulin-dependent) diabetes mellitus with or without elevated cholesterol and/or triglyceride levels. Verapamil SR/trandolapril reduces proteinuria to a greater extent than the individual components in patients with diabetic or non-diabetic proteinuria. The antihypertensive efficacy of once daily verapamil SR/trandolapril (180/1 or 180/2 mg) for 8 weeks or 6 months is similar to that of atenolol/chlorthalidone (100/25 mg) and lisinopril/hydrochlorothiazide (20/12.5 mg), and was at least as good as that of metoprolol/hydrochlorothiazide (100/12.5 mg) in a small trial. The reduction in sitting or supine diastolic and systolic blood pressure is greater after verapamil SR/trandolapril (180/2 to 240/4 mg) than after monotherapy with verapamil SR (180 and 240 mg/day) or trandolapril (2 to 8 mg/day). Fewer cardiac events occurred after verapamil SR/trandolapril (240/1 to 360/2 mg/day) than after trandolapril (1 to 2 mg/day) in postmyocardial infarction patients with congestive heart failure. The incidence of adverse events after verapamil SR/trandolapril is similar to that of comparator drugs and the individual components of the combination.

Angiotensin-Converting Enzyme Inhibitors↗

Urapidil. A reappraisal of its use in the management of hypertension.

UNLABELLED: Urapidil is a peripheral postsynaptic alpha 1-adrenoceptor antagonist with central agonistic action at serotonin 5-HT1A receptors. It reduces blood pressure by decreasing peripheral vascular resistance. Oral urapidil decreases blood pressure in patients with mild to moderate essential hypertension and associated risk factors such as hyperlipidaemia or type 2 (non-insulin-dependent) diabetes mellitus with no effect on heart rate. The antihypertensive efficacy of urapidil is similar to that of most comparators in patients with mild to moderate essential or secondary hypertension and no concomitant risk factors. However, the antihypertensive efficacy of urapidil was lower than that of hydrochlorothiazide in a well designed trial. Lipid levels and glucose metabolism are not adversely affected and may improve with urapidil in patients with lipid or glucose abnormalities. Urapidil can be safely combined with other antihypertensive agents such as hydrochlorothiazide and nifedipine and improves blood pressure control in previous nonresponders to monotherapy. Intravenous urapidil reduces blood pressure in patients with pre-eclampsia or hypertension in pregnancy and in patients with hypertensive crises or peri- or postoperative hypertension. The decrease in blood pressure is similar to that observed after nifedipine, enalaprilat, sodium nitroprusside and dihydralazine, greater than that of ketanserin according to 1 larger study, and greater than that of sublingual nitroglycerin in 1 trial in patients with nonsurgical hypertensive crises and pulmonary oedema. However, more patients responded to treatment with urapidil than with enalaprilat or nifedipine. Heart rate is less likely to be altered by urapidil than with some comparator drugs. Urapidil appears to be well tolerated, with most adverse events being mild and transient. The incidence of adverse events with urapidil is similar to that with prazosin, metoprolol, atenolol, sodium nitroprusside and hydrochlorothiazide and less than that with nifedipine and clonidine. Urapidil may not be as well tolerated as captopril and, in 1 study, more urapidil than nitrendipine recipients discontinued treatment because of adverse events. CONCLUSIONS: urapidil reduces blood pressure without altering heart rate. The oral formulation is an effective choice in patients with hypertension and concomitant dyslipidaemia or type 2 diabetes mellitus, in whom the drug does not adversely affect and may improve lipid profiles and glucose metabolism. The intravenous formulation is effective in controlling various hypertensive crises and hypertension associated with pregnancy or surgery and is similar to or better than other first-line agents used in these conditions. Thus, urapidil may be a useful alternative to currently available antihypertensive agents.

Antihypertensive Agents↗

Community service needs of people with HIV infection in London.

The objectives of this study were to describe the expressed needs for community services of HIV-infected individuals by disease stage, gender and transmission category and the barriers which prevent the receipt of such services. Structured interviewer-administered questionnaires concerning a 6-month retrospective period were used to obtain information on need for community services and problems which prevented the receipt of services. The study sample included 70 homosexual men with asymptomatic HIV disease, 42 homosexual men with symptomatic non-AIDS, 53 homosexual men with AIDS, 23 heterosexual men, 29 heterosexual women, 9 male and 9 female injecting drug users. The main outcome measures were the extent to which needs for community services were met and person/service combinations for which problems or barriers prevented the receipt of community services. On average, subjects expressed a need for 10 categories of community services over the 6-month period: homosexuals expressed a mean of 10, heterosexuals 10, injecting drug users 11, subjects with asymptomatic HIV infection 9, subjects with symptomatic non-AIDS 11, subjects with AIDS 13, men 9 and women 14. A total of 58% of community service needs were always met, 6% were rarely not met, 16% were sometimes not met, 6% were often not met and 14% were not met at all. The extent to which subjects felt that their needs were met was similar for the different study groups, but the needs of women were met somewhat less frequently than those of men. Similarly, people with AIDS felt that their needs were met slightly less often. Reported levels of unmet need were high for a wide range of services. The most common reason subjects gave for not having received a community service for which they expressed a need was ignorance of where or how to obtain the service. This was mentioned in one-third of all such cases. Anxieties over the competence with which a service would be rendered was mentioned in 13% of cases and long waiting times in 11%. The frequencies of unmet need for many community services were high and often seemed to arise either from a lack of awareness on the part of subjects on how and where services could be obtained or from doubts about the relevance of services offered. Both of these barriers should be surmountable through the provision of better information to patients, extending user involvement in service development and the better co-ordination of service delivery through care management approaches.

Adult↗

The economic costs of caring for people with HIV infection and AIDS in England and Wales.

The objectives of this study were firstly to estimate total lifetime care costs for an individual with HIV/AIDS, and secondly to estimate the total costs of caring people with HIV infection and AIDS in England and Wales between 1992 and 1997 inclusive. Questionnaires and monthly diaries were used to collate data on healthcare utilisation from patients with HIV infection over a 6-month period. These data were then used to estimate the annual total direct costs of care (stratified by disease stage), total lifetime costs of care, and present and future total national care costs for England and Wales. Costing data were obtained from providers of services throughout Greater London. In total, 235 patients with HIV infection were recruited from 2 clinics in Greater London. All costs were calculated in 1992-93 pounds sterling (pound; 1 pound = $US1.58, December 1995). Annual care costs were estimated at 4515 pounds ($US7134) for a person with asymptomatic HIV disease, 8836 pounds ($US13,961) for a person with symptomatic non-AIDS and 15 268 pounds ($US24,123) for a person with AIDS. Lifetime care costs were estimated at 84,522 pounds ($US133,545) per patient. The total costs of care for England and Wales were forecast to increase from 116,627,400 pounds ($US184,271,300) in 1992 to 162,638,100 pounds ($US256,968,200) in 1997. In conclusion, our study further emphasises the continued shift in hospital services from the inpatient sector to the outpatient sector. The importance of community care and informal care, in terms of the associated direct economic costs, is also highlighted. This emphasises the need for close collaboration between different agencies and strategic coordination of services. Finally, the study forecasts an increase in care costs in England and Wales during the 1990s.

Acquired Immunodeficiency Syndrome↗

Cost and utilisation of community services for people with HIV infection in London.

This study aimed to describe the use and costs of community services for HIV-infected people by disease stage, sex and transmission category (homosexual, heterosexual, injecting drug use) by use of a prospective cohort study in which people were followed up for six months. There were two major components; gathering quantitative information on service utilisation from people with HIV infection using two interviewer-administered questionnaires and six self-completed monthly diaries; and estimating the costs of the services provided. People were recruited from two London clinics: the Jefferiss Wing Genito-urinary Medicine (GUM) clinic at St. Mary's Hospital, Paddington, and the Patrick Clements GUM clinic at the Central Middlesex Hospital, Harlesden. Costing data was obtained from providers of community services throughout Greater London. The main outcome measures were contacts per person-year, and costs per person-year, for all community services stratified by service sector. The people studied each made, on average, 139 community service contacts per year at a cost of 2,806 pounds; there was little difference in average utilisation between the three transmission categories. There were differences in both the utilisation of services and costs within the formal and informal sectors for subjects from different disease stages. Although the average number of contacts per person-year were similar for women and men, the total cost of community services was higher for women than for men, reflecting the differences in types of services used. The results indicated a high proportion of total care costs for people with HIV and AIDS is incurred through community-based social care.(ABSTRACT TRUNCATED AT 250 WORDS)

Community Health Services↗

Production of autostimulatory growth factors by the human carcinoma line, RPMI 2650.

The human carcinoma line RPMI 2650 produces autocrine factors; they are detected by the ability of RPMI 2650 conditioned medium (CM) to stimulate growth in soft agar of RPMI 2650 cells plated at low density. The autocrine activity in crude CM can be fractionated by ultrafiltration into a lower molecular weight (MW) fraction (R1-30), which concentrates molecules in the 1000-30,000 Da range; and a higher MW fraction (R30) with molecules greater than 30,000 Da in a more concentrated form. R1-30 is labile to acid, base, and heat treatment, whereas R30 is stable to (and sometimes activated by) these treatments. Boiling of R30, however, renders it labile to acid, base, and trypsin treatments. CM can be separated into a weakly heparin-binding fraction (with stability properties similar, but not identical, to R1-30), and a non-heparin binding fraction (with stability properties similar to R30). RPMI 2650 cells secrete transforming growth factor (TGF)alpha- and TGF beta-like molecules, but the R1-30 fraction can be distinguished from these TGFs, and from most other known growth factors, by its unusual combination of acid lability and weak affinity for heparin. Since the R30/non-heparin binding fraction is rendered labile by boiling or acid treatment, it may represent a bound or conformationally stable form of a growth factor.

Carcinoma, Squamous Cell↗

The use of role-play in teaching medical students obstetrics and gynaecology.

There is a great need to review and critically assess medical education. Role-play has seen increasing use as an educational tool. We investigated its role in a 'conventional speciality', Obstetrics and Gynaecology. This is a part of the medical curriculum where communication skills are particularly important, but difficult to learn in practice. Twenty-one medical students took part in three role-play case studies. An innovation we implemented was the use of 'time outs' which could be called at any time through a session. After the exercise students were required to complete a questionnaire designed to probe their attitudes towards the experience. The results indicate that this technique can be successfully used in teaching a conventional speciality. Unlike some previous studies we also found this to be a satisfactory tool in teaching the factual part of the course. We found the 'time out' innovation to be an important aid. We argue that there is an important niche for role-play in medical education.

Clinical Competence↗

Cytological differences between normal and malignant human cell populations in culture.

Cells from early-passage cultures of normal and malignant human tissues were analyzed for the presence of multiple nucleoli and tri- or multipolar mitoses; these properties are characteristic of malignant cell populations in tissue sections. For the cell types examined the presence of tri- or multipolar mitoses was characteristic of cells of malignant origin. Within epithelial cell populations, cells containing more than 4 nucleoli were found in populations of malignant but not of normal origin; this distinction did not apply to fibroblast populations. Large numbers of cells must be analyzed quantitatively to establish the distinctions described here, since they are properties characteristic of populations, not of individual cells. This approach may facilitate identification of normal and malignant cell populations in primary and early-passage culture.

Cell Nucleus↗

Radiation quality and rat motor performance.

The effects of bremsstrahlung, electron, gamma, and neutron radiations were investigated on the motor performance of male Sprague-Dawley rats. Rats were irradiated at a midline tissue dose rate of 20 Gy/min +/- 1 with one of the following: 18.6-MeV electrons (N = 40) or 18.1-MVp bremsstrahlung (N = 57) from a linear accelerator, 60Co 1.25-MeV gamma-ray photons (N = 48), or reactor neutrons at 1.67 MeV tissue-kerma weighted-mean energy (N = 43). Radiation effects were determined by establishing median effective doses (ED50) for rats trained on an accelerod, a shock-avoidance motor performance test. ED50's were based on 10-min postexposure performance. The ED50's were 61 Gy for electrons, 81 Gy for bremsstrahlung, 89 Gy for gamma-ray photons, and 98 Gy for neutrons. In terms of relative biological effectiveness to produce early performance decrement (10 min from the start of irradiation), significant differences existed between the electrons and the other three fields and between the bremsstrahlung and neutron fields. These differences could not be explained by macroscopic dose distribution patterns in the irradiated animals. The data imply that different radiation qualities are not equally effective at disrupting performance, with high-energy electrons being the most effective and neutrons the least.

Animals↗

Skeletal effects of oral oestrogen compared with subcutaneous oestrogen and testosterone in postmenopausal women.

STUDY OBJECTIVE: To compare oral and implanted oestrogens for their effects in preventing postmenopausal osteoporosis. DESIGN: Non-randomised cohort study of postmenopausal women treated with oral or depot oestrogens and postmenopausal controls. SETTING: Gynaecological endocrine clinic in tertiary referral centre. PATIENTS: Oral treatment group of 37 postmenopausal women (mean age 57.5 years, median 8.75 years from last menstrual period), compared with 41 women given oestrogen implants (mean age 56.2 years, median 9.5 years from last menstrual period) and 36 controls (mean age 51.8 years, median 2.0 years from last menstrual period). Weight was not significantly different among the groups. INTERVENTIONS: Oral treatment group was given continuous treatment with cyclic oestrogen and progesterone preparations (Prempak C or Cycloprogynova) for a median of 8.0 years. Implant group was given subcutaneous implants of oestradiol 50 mg combined with testosterone 100 mg, on average six monthly for a median of 8.5 years. Controls were not treated. END POINT: Significant increase in bone density. MEASUREMENTS AND MAIN RESULTS: Bone density measured by dual beam photon absorptiometry was 1.02 (SD 0.13) g hydroxyapatite/cm2 in implant group versus 0.89 (0.11) in oral group (p less than 0.01) and 0.87 (0.14) in controls (p less than 0.01). Serum oestradiol concentration in implant group was (median) 725 pmol/l versus 170 pmol/l in oral group (p less than 0.01) and 99 pmol/l in controls (p less than 0.01). Serum follicular stimulating hormone was median 1 IU/l (range 1-11) in implant group (equivalent to premenopausal values) versus 43 (4-94) IU/l in oral group (p less than 0.01) and 72 (28-99) IU/l in controls (p less than 0.01). CONCLUSIONS: Subcutaneous oestrogen is more effective than oral oestrogen in preventing osteoporosis, probably owing to the more physiological (premenopausal) serum oestradiol concentrations achieved. It also avoids problems of compliance that occur with oral treatment.

Administration, Oral↗

Early experience with gamete intrafallopian transfer (GIFT) and direct intraperitoneal insemination (DIPI).

We present our early experience with gamete intrafallopian transfer (GIFT) and direct intraperitoneal insemination (DIPI) combined with intrauterine insemination (IUI), two recently described methods of assisting conception in patients with patent fallopian tubes. Sixty-nine patients (93 cycles) were entered into the study. Thirty-three patients (51 cycles) entered the DIPI/IUI programme and 36 patients (42 cycles) entered the GIFT programme. The mean age, duration and aetiology of infertility were similar in both groups. In the GIFT programme 12 pregnancies occurred, which is a 29% pregnancy rate per cycle and a 33% pregnancy rate per patient. In the DIPI/IUI programme only 3 pregnancies occurred, being a 6% pregnancy rate per cycle and a 9% pregnancy rate per patient. With the live birth rate of in vitro fertilization (IVF) being 12% per embryo transfer, we conclude that GIFT is more successful than either DIPI/IUI or IVF in patients with patent fallopian tubes. Further controlled studies are required to assess the future role of DIPI/IUI in clinical practice.

Adult↗

Effect of lactate on glucose incorporation into fetal lung phospholipids.

Fetal rabbit lung explants were incubated with 3.0 mM glucose and varying levels of lactate. An increase in lactate concentrations resulted in a decrease in glucose incorporation into total disaturated phosphatidylcholine. Glucose utilization for surfactant phosphatidylcholine synthesis was also reduced by approximately 35% in the presence of 5.0 mM lactate. The decreased incorporation of glucose occurred in the fatty acid portion of both total tissue disaturated phosphatidylcholine and surfactant phosphatidylcholine. The effect of lactate on glucose incorporation into pulmonary phospholipids was not affected by the presence of pyruvate in concentrations up to 500 microM. Pyruvate alone produced only a slight decrease in glucose utilization for lung phospholipid production. These data indicate that glucose and lactate are competitive substrates for late gestation surfactant phospholipid fatty acid synthesis, and that lactate is potentially a very important substrate for fetal lung development.

Age Factors↗

Evidence for lactate utilization for fetal lung glycogen synthesis.

Fetal rabbit lungs from 23 day gestation animals were used to investigate the potential role of lactate as a substrate for fetal lung glycogen synthesis. Fetal lactate dehydrogenase activity was approximately twice that found in the adult lung, while the activity of phosphoenolpyruvate carboxykinase was elevated fourfold over the adult value. Pyruvate carboxylase activities were similar in both fetal and adult lungs. Studies employing fetal lung explants in organ culture indicated that the presence of both glucose and lactate may be necessary for glycogen accumulation in the developing fetal lung. These data support the hypothesis that lactate is an important precursor for fetal lung glycogen.

Animals↗