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Biomedical subjects

M White

Publications and source records attributed to M White.

At least 181 records · Page 10Linked to original sources

Family dynamics of families with mental health problems in Finland.

This study forms part of the International Family Dynamics Project. Its purpose was describe the family functioning of families with mental health problems on the basis of Barnhill's framework for healthy family systems. The sample consisted of 160 families in which one family member had mental health problems. Both the patients and their relatives took part. The data were collected by questionnaires, i.e. The Family Dynamics Measure and The Family Dynamics Questionnaire. According to the results, mental health patients described family functioning as fairly poor, while relatives described it as fairly good. However, patients' and relatives' perceptions of family functioning did not differ significantly. There were some statistically significant differences between patients' and relatives' perceptions of different family dynamics dimensions. Relatives reported more mutuality (P = 0.006) and clearer communication (P = 0.009) than patients. Older mental health patients reported more isolation than patients under 30. Relatives who mentioned some serious illness in the family reported more role conflict than those who didn't. No differences were found by gender, family structure or education. The results indicated that the mental health problems of a single family member did not impair family dynamics. The study showed that the resources and functioning of families are fairly good in spite of the illness in the family.

Adult↗

Clinically used antimicrobial drugs against experimental pneumocystosis, singly and in combination: analysis of drug interactions and efficacies.

We analyzed single drugs and combinations of drugs used clinically in the treatment of opportunistic infections and other conditions for their activities against Pneumocystis carinii pneumonia in immunosuppressed rats. When they were used alone, atovaquone, rifabutin, and dapsone were more active than clarithromycin or trimethoprim. Drug combinations were evaluated for synergistic activity by an analysis of variance model for two-way factorial experiments and a response surface model. Atovaquone combined with trimethoprim trimethoprim and some combinations of dapsone and clarithromycin was synergistic; however, the activities of combinations of atovaquone and rifabutin, atovaquone and clarithromycin, and atovaquone and dapsone were simply additive. Lovastatin, which inhibits 3-hydroxy-methylglutaryl coenzyme A reductase, was inactive whether it was used alone or in combination with other agents. None of the synergistic drug combinations was as effective as trimethoprim-sulfamethoxazole. We conclude that the rat model can be used to test combinations of anti-P. carinii agents for synergistic activity by well-established statistical techniques. While some combinations of clinically used antimicrobial drugs have enhanced anti-P. carinii activity, further studies are needed before clinical trials can be contemplated.

Animals↗

Immunodeficient and immunosuppressed mice as models to test anti-Pneumocystis carinii drugs.

Congenitally immunodeficient and immunosuppressed normal mice with naturally acquired Pneumocystis carinii infection were compared as models for testing anti-P. carinii drugs. Among the immunodeficient mice, mice with severe combined immunodeficiency disease (scid), which lack B and T cells, had higher levels of P. carinii pneumonia than did microMT mice, which lack K cells. Normal mice administered dexamethasone in the drinking water had more extensive pneumocystosis than mice administered parenteral methylprednisolone or hybridoma cells making a monoclonal antibody to CD4 cells. The standard anti-P. carinii drugs trimethoprim (TMP)-sulfamethoxazole (SMX), pentamidine, and atovaquone, which work well in rats and humans, worked well in the mice. Clindamycin and primaquine were effective in the scid and microMT mice but not in the immunosuppressed normal mice. High doses of epiroprim, an analog of TMP, appeared to enhance the activities of low doses of SMX and dapsone, while high doses of TMP did not; however, further studies are needed before definitive conclusions about the actions of these drugs can be drawn. Taken together, the data obtained in this study support the growing body of literature suggesting that the mouse is a valid alternative to the rat as a model for testing anti-P. carinii drugs. Additional differences involving the activities of individual drugs in these models will probably emerge as more experience is gained.

Animals↗

Body mass index, waist circumference, waist-hip ratio, and glucose intolerance in Chinese and Europid adults in Newcastle, UK.

OBJECTIVE: To compare the prevalence of glucose intolerance (impaired glucose tolerance and diabetes), and its relationship to body mass index (BMI) and waist-hip ratio in Chinese and Europid adults. DESIGN: This was a cross sectional study. SETTING: Newcastle upon Tyne. SUBJECTS: These comprised Chinese and Europid men and women, aged 25-64 years, and resident in Newcastle upon Tyne, UK. MAIN OUTCOME MEASURES: Two hour post load plasma glucose concentration, BMI, waist circumference, and waist-hip ratio. METHODS: Population based samples of Chinese and European adults were recruited. Each subject had a standard WHO oral glucose tolerance test. RESULTS: Complete data were available for 375 Chinese and 610 Europid subjects. The age adjusted prevalences of glucose intolerance in Chinese and Europid men were 13.0% (p = 0.04). Mean BMIs were lower in Chinese men (23.8 v 26.1) and women (23.5 v 26.1) than in the Europids (p values < 0.001), as were waist circumferences (men, 83.3 cm v 90.8, p < 0.001; women, 77.3 cm v 79.2, p < 0.05). Mean waist-hip ratios were lower in Chinese men (0.90 v 0.91, p = 0.02) but higher in Chinese women (0.84 v 0.78, p < 0.001) compared with Europids. In both Chinese and Europid adults, higher BMI, waist circumference, and waist-hip ratio were associated with glucose intolerance. CONCLUSIONS: The prevalence of glucose intolerance in Chinese men and women, despite lower BMIs, is similar to or higher than that in local Europid men and women and intermediate between levels found in China and those in Mauritius. It is suggested that an increase in mean BMI to the levels in the Europid population will be associated with a substantial increase in glucose intolerance in Chinese people.

Adult↗

Low levels of cardiovascular risk factors and coronary heart disease in a UK Chinese population.

OBJECTIVE: To compare the prevalence of cardiovascular risk factors and coronary heart disease in Chinese and Europid adults. DESIGN: Population based, cross sectional survey. SETTING: Newcastle upon Tyne, UK, 1991-93. SUBJECTS: Altogether 380 Chinese and 625 Europid adults, aged 25-64 years. MAIN OUTCOME MEASURES: Fasting lipid levels, blood pressure, body mass index (BMI), the proportions who smoked, and the prevalence of coronary heart disease based on the Rose angina questionnaire and major electrocardiographic abnormalities on resting 12 lead electrocardiogram (Minnesota codes 1.1-1.2). All figures were age adjusted to the 1991 England and Wales population. RESULTS: Altogether 183 and 197 Chinese, and 310 and 315 Europid men and women respectively were seen. Compared with Europid men, Chinese men had a lower mean total cholesterol concentration (5.1 versus 5.6 mmol/l, p < 0.001) and LDL cholesterol (3.2 versus 3.6 mmol/l, p < 0.001); lower BMI values (23.8 versus 26.1 kg/m-2, p < 0.001); and smoked less (23% versus 35%, p < 0.01)). Compared with Europid women, Chinese women also had lower mean lipid levels (total cholesterol: 4.9 versus 5.4 mmol/l p < 0.001, LDL cholesterol: 2.8 versus 3.1 mmol/l p < 0.001); BMI values (23.5 versus 26.1 kg/m-2, p < 0.001); and far fewer were smokers (1.4% versus 33%, p < 0.001). Chinese women, however, had higher mean systolic (121 versus 117 mmHg, p > 0.05) and diastolic (75 versus 68 mmHg, p < 0.001) blood pressures. The prevalence of coronary heart disease was significantly lower in Chinese than Europid men (4.9% versus 16.6%, p < 0.001) but not significantly different in women (7.3% versus 11.1%, p = 0.16). CONCLUSION: Strategies for UK Chinese are needed to maintain this favourable risk factor profile and prevent any potential increase in the risk of coronary heart disease associated with increasing acculturation.

Adult↗

Muscle fatigue in spinal muscular atrophy.

We previously reported that patients with spinal muscular atrophy do not lose muscle strength over time as measured quantitatively. However, we noted that many patients with spinal muscular atrophy suffer from what they call fatigue. We wondered if we could measure fatigue during a single maximal voluntary contraction, whether fatigue might increase with time, independent of muscle strength, and whether increasing fatigue might correlate with loss of function in some patients. We measured fatigue during a single maximal voluntary contraction in a cohort of patients having spinal muscular atrophy using quantitative strength testing. We included only patients with spinal muscular atrophy aged 5 years or older, so they could follow instructions regarding muscle contraction, and who were followed for at least 2 years. Seventy-six children with spinal muscular atrophy and 24 untrained individuals, aged 5 to 57 years (mean, 16.8 years), were studied. There was no discernible abnormal fatigue in patients with spinal muscular atrophy compared to untrained controls using our methodology. Thus, spinal muscular atrophy may not be associated with fatiguability. Moreover, spinal muscular atrophy does not appear to cause progressive muscle fatigue with age or loss of function. It is possible that fatigue was undetectable by our methods. An alternative explanation is that what patients describe as fatigue may be caused by factors outside the neuromuscular system. Such factors may include chronic respiratory insufficiency with hypoventilation and carbon dioxide retention as well as chronic malnutrition and negative nitrogen balance.

Adolescent↗

Comparison of Neoral and Sandimmune cyclosporine for induction of immunosuppression after heart transplantation.

OBJECTIVE: To compare the efficacies of Neoral cyclosporine (N-CSA [Sandoz]) and Sandimmune cyclosporine (S-CSA [Sandoz]) in induction of immunosuppression immediately after heart transplantation. DESIGN: A prospective and a retrospective cohort. SETTING: Patients who underwent heart transplant operations at the Montreal Heart Institute, Montreal, Quebec. PATIENTS: To evaluate the results of both formulations of cyclosporine (CSA), a cohort of 20 consecutive patients who underwent heart transplant operations between 1994 and 1995, and who were administered N-CSA, azathioprine, prednisone and intravenous CSA (10 patients) or rabbit antithymocyte globulin (RATG) (10 patients) were compared with 21 patients who underwent heart transplant operations between 1993 and 1994, and were treated with RATG, S-CSA, azathioprine and prednisone. Preoperative patient characteristics were similar in all groups. RESULTS: There were no significant differences in daily CSA doses after the fourth day following transplantation. Higher trough levels of CSA were observed during the first four days, from days 12 to 14 and one month after transplantation in the two groups that were administered N-CSA. Serum levels of creatinine were significantly higher three to five days after transplantation in both groups who received N-CSA. Creatinine levels were also higher between days 13 and 14 in patients who received N-CSA and intravenous CSA. Oral administration of N-CSA was stopped temporarily in two patients (20%) who received intravenous CSA because of a sudden decrease in urine output and rise in serum creatinine. Three months after transplantation actuarial freedom rate from acute rejection averaged 33 +/- 10% in the S-CSA group, 10 +/- 9% in patients treated with N-CSA and intravenous CSA and 24 +/- 15% in patients treated with N-CSA and RATG (P = 0.25). The risk (hazard) of early rejection was higher in the group that received intravenous CSA and N-CSA. CONCLUSIONS: While similar averaged doses of N- and S-CSA were administered early after transplantation, the use of N-CSA resulted in higher blood levels of CSA. N-CSA appears to be well absorbed early after cardiac transplantation, but renal toxicity remains a significant concern.

Administration, Oral↗

Pharmacokinetic, hemodynamic, and metabolic effects of cyclosporine sandimmune versus the microemulsion neoral in heart transplant recipients.

BACKGROUND: Cyclosporine is a potent immunosuppressive agent that is, however, associated with systemic hypertension and renal dysfunction. The purpose of this investigation was to study the pharmacokinetic and long-term renal and hypertensive effects of Sandimmune (Sandoz) versus the new Neoral (Novartis) formulation of cyclosporine in heart transplant recipients. METHODS: Twenty heart transplant recipients with stable conditions and aged 54 +/- 9 years were studied in an open-labeled single-arm conversion protocol. Twelve-hour pharmacokinetic studies were performed on Sandimmune and after 4 weeks of treatment with Neoral at similar dosage. The 24-hour blood pressure monitoring, creatinine clearance, and complete biochemistry profile were studied simultaneously to the pharmacokinetic studies. Six-month follow-up with serial measurements of cyclosporine levels, and biochemistry profile was completed. RESULTS: Conversion to Neoral resulted in a 24% increase in area-under-the-curve in spite of no significant changes in cyclosporine trough levels (165 +/- 48 [Sandimmune] vs 169 +/- 32 nmol/L; p = 0.26). Respectively, 16%, 68%, and 16% were poor, average, and good absorbers on Sandimmune versus 26% and 74% being average or good absorbers on Neoral. Averaged systolic and diastolic blood pressure were not affected by Neoral, but blood pressure readings increased in 20% of patients previously known as having hypertension. The 24-hour blood pressure data yielded no significant changes with Neoral, but the nocturnal drop in systolic blood pressure was attenuated by Neoral. Twenty-four-hour creatinine clearance was not affected by Neoral, but serum magnesium levels decreased significantly at 6 months. CONCLUSIONS: Neoral resulted in 24% increase in cyclosporine exposure without significant changes in trough levels, and improved absorption status. This greater drug exposure is well tolerated and resulted in a slight increase in blood pressure in a subset of patients and some decrease in magnesium levels, but it had no effect on renal function.

Adult↗

Identifying Chinese populations in the UK for epidemiological research: experience of a name analysis of the FHSA register. Family Health Services Authority.

There is a paucity of research on health in the UK Chinese community partly due to the difficulties of identifying and accessing study populations. For a survey of cardiovascular disease we aimed to identify and recruit all Chinese adults aged 25-64 y living in Newcastle-upon-Tyne, UK. One thousand, eight hundred and sixty-five potential subjects were identified using a variety of methods. Of the 1702 potential subjects identified from a name analysis of the 1991 FHSA register (FHSA group), 638 students in halls of residence were excluded and the remaining 1064 were invited to participate. Non-respondents were followed up. Of the 1064, 658 (65.5%) addresses were no longer valid, 21 (2%) were reclassified as non-Chinese and no contact was made with 18 individuals (1.6%). A further 163 subjects (non-FHSA group) came forward in response to publicity, giving a total of 530 Chinese actually identified in Newcastle. Three hundred and eighty subjects took part in the study. Compared to the 1991 Census, the recruitment procedure underestimated the total population size, particularly for men and younger ages. In the FHSA group, men were significantly more likely to be current drinkers, and women were more likely to smoke and have a lower educational attainment that the non-FHSA group. There were no other important differences in the distribution of CHD risk markers in the two groups. Our experience indicates that the FHSA register is suitable for identifying Chinese but should be used alongside other complementary methods to augment samples for ethnicity and health research.

Adult↗

Tractional force generation by porcine Müller cells: stimulation by growth factors in human vitreous.

PURPOSE: To examine the levels of Müller cell contraction-stimulating activity in human vitreous, correlate these levels with clinical presentation, and identify, the causative growth factors. METHODS: Human vitreous was collected from patients undergoing pars plana vitrectomy (n = 84). Müller cells were isolated from porcine retina and maintained in tissue culture. Tractional forces generated by cells incubated on three-dimensional collagen gels were measured as changes in gel thickness. Contraction-stimulating activity in vitreous (VA) was calculated from the close-response profiles of gel contraction to vitreous protein. The contributions of individual growth factors to vitreous activity (n = 10) were assessed by inhibition with specific neutralizing antibodies. RESULTS: The mean VA of patients with retinal detachment (3.65) and proliferative vitreoretinopathy stages A, B, and C (2.06) were elevated above that of patients without retinal pathology (vitreous activity = 0.23) or retinal defects alone (0.57). Mean activities in patients with epimacular proliferation (1.22) and vitreous hemorrhage (1.40) were also significantly elevated. The percentage of this activity attributable to insulin-like growth factor 1 (IGF-1) varied from 9.2% to 84.5% with a mean of 61.3%. Similarly, the percent contribution of platelet-derived growth factor (PDGF) ranged from 6.8% to 49.0% with a mean of 26.5%. CONCLUSIONS: The vitreous of patients with retinal detachment, proliferative retinal disease, and vitreous hemorrhage contain varying amounts of growth factors that stimulate tractional force generation by Müller cells. The majority of the activity can be attributed to IGF-1 and a smaller proportion to PDGF.

Animals↗

Combination neurohormonal blockade with ACE inhibitors, angiotensin II antagonists and beta-blockers in patients with congestive heart failure: design of the Randomized Evaluation of Strategies for Left Ventricular Dysfunction (RESOLVD) Pilot Study.

BACKGROUND: The Randomized Evaluation of Strategies for Left Ventricular Dysfunction (RESOLVD) Pilot Study is a trial of combination neurohormonal blockade using an angiotensin II antagonist (candesartan), an angiotensin-converting enzyme inhibitor (enalapril) and a beta-blocker (metoprolol) in patients with congestive heart failure (CHF). OBJECTIVES: Primary objectives of stage I are to determine the efficacy (via the 6 min walk test) and safety of candesartan alone, and in combination with enalapril, versus enalapril alone. Secondary objectives are to determine the effect of the above combinations on neurohormones, ventricular function, quality of life and symptoms. Stage II objectives are similar, evaluating the effect of the addition of metoprolol or placebo to the above medication(s). DESIGN: Randomized, two-stage trial consisting of a three-way comparison (stage I), followed by a 3 x 2 partial factorial design (stage II). SETTING: Sixty out-patient clinics in five countries. PATIENTS: Patients with symptoms of CHF (New York Heart Association functional classes II to IV), ejection fraction less than 40% and 6 min walk distance of 500 m or less. INTERVENTIONS: In stage I, 770 patients are randomized to receive candesartan alone, enalapril alone, or candesartan plus enalapril. After five months (end of stage I), patients are assessed for eligibility to be randomized in stage II. Those who are not candidates for randomization to beta-blocker or placebo are followed on their stage I medications until the end of the study. In stage II, patients are randomized to receive metoprolol or placebo for a further six months in addition to their stage I medications. Endpoints are measured at baseline, end of stage I (week 20) and end of stage II (week 46). STUDY STATUS: The study has recently completed follow-up in both stages. The findings from this study will be used to design a large scale mortality study that will help further define the role of neurohormonal blockade in patients with CHF.

Adrenergic beta-Antagonists↗

Migration, fertility, and state policy in Hubei Province, China.

Despite China's one-child family planning policy, the nation experienced a slight rise in the birth rate in the mid-1980s. Many observers attributed this rise to the heightened fertility of those rural-to-urban migrants who moved without a change in registration (temporary migrants), presumably to avoid the surveillance of family planning programs at origin and destination. Using a sequential logit analysis with life-history data from a 1988 survey of Hubei Province, we test this possibility by comparing nonmigrants, permanent migrants, and temporary migrants. While changing family planning policies have a strong impact on timing of first birth and on the likelihood of higher-order births, migrants generally do not have more children than nonmigrants. In fact, migration tends to lower the propensity to have a child. More specifically, the fertility of temporary migrants does not differ significantly from that of other women.

Adolescent↗

Comparative hemodynamic, left ventricular functional, and antiadrenergic effects of chronic treatment with metoprolol versus carvedilol in the failing heart.

BACKGROUND: The basic pharmacology of the third-generation beta-blocking agent carvedilol differs considerably from second-generation compounds such as metoprolol. Moreover, carvedilol may produce different, ie, more favorable, clinical effects in chronic heart failure. For these reasons, we compared the effects of carvedilol and metoprolol on adrenergic activity, receptor expression, degree of clinical beta-blockade, hemodynamics, and left ventricular function in patients with mild or moderate chronic heart failure. METHODS AND RESULTS: The effects of carvedilol versus metoprolol were compared in two concurrent placebo-controlled trials with carvedilol or metoprolol that had common substudies focused on adrenergic, hemodynamic, and left ventricular functional measurements. All subjects in the substudies had chronic heart failure resulting from idiopathic dilated cardiomyopathy. Carvedilol at 50 to 100 mg/d produced reductions in exercise heart rate that were similar to metoprolol at 125 to 150 mg/d, indicating comparable degrees of beta-blockade. Compared with metoprolol, carvedilol was associated with greater improvement in New York Heart Association functional class. Although there were no significant differences in hemodynamic effects between the carvedilol and metoprolol active-treatment groups, carvedilol tended to produce relatively greater improvements in left ventricular ejection fraction, stroke volume, and stroke work compared with changes in the respective placebo groups. Carvedilol selectively lowered coronary sinus norepinephrine levels, an index of cardiac adrenergic activity, whereas metoprolol did not lower coronary sinus norepinephrine and actually increased central venous norepinephrine levels. Finally, metoprolol was associated with an increase in cardiac beta-receptor density, whereas carvedilol did not change cardiac beta-receptor expression. CONCLUSIONS: The third-generation beta-blocking agent carvedilol has substantially different effects on left ventricular function, hemodynamics, adrenergic activity, and beta-receptor expression than dose the second-generation compound metoprolol. Some or all of these differences may explain the apparent differences in clinical results between the two compounds.

Adrenergic beta-Antagonists↗