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Biomedical subjects

C J O'Callaghan

Publications and source records attributed to C J O'Callaghan.

At least 55 records · Page 3Linked to original sources

Who mixes with whom? A method to determine the contact patterns of adults that may lead to the spread of airborne infections.

Although mixing patterns are thought to be important determinants of the spread of airborne infectious diseases, to our knowledge, there have been no attempts to directly quantify them for humans. We report on a preliminary study to identify such mixing patterns. A sample of 92 adults were asked to detail the individuals with whom they had conversed over the period of one, randomly assigned, day. Sixty-five (71%) completed the questionnaire, providing their age, the age of their contacts and the social context in which the contacts took place. The data were analysed using multilevel modelling. The study identified, and allowed the quantification of, contact patterns within this sample that may be of epidemiological significance. For example, the degree of assortativeness of mixing with respect to age was dependent not only on the age of participants but the number of contacts made. Estimates of the relative magnitude of contact rates between different social settings were made, with implications for outbreak potential. Simple questionnaire modifications are suggested which would yield information on the structure and dynamics of social networks and the intensity of contacts. Surveys of this nature may enable the quantification of who acquires infection from whom and from where.

Adult↗

A comparison of different models for assessing variations in the sero-prevalence of infectious bovine rhinotracheitis by farm, area and district in Kenya.

The relative variability of the sero-prevalence of antibodies to infectious bovine rhinotracheitis (IBR) due to cow, farm, and agroecological area levels were investigated for three contrasting districts in Kenya: Samburu, an arid and pastoral area; Kiambu, a tropical highland area; and Kilifi, a typical tropical coastal area. Cattle were selected by two-stage cluster sampling and visited once between August 1991 and 1992. Data on animal, farm, and area factors were analyzed using Schall's algorithm and MLn (multi-level, n-level), two generalized mixed-model programs suitable for multi-level analysis. Most variation in IBR sero-prevalence was from farm-to-farm. This was reflected by the many farm-level fixed effects (farm size, disease control measures and type of breeding) significant in models both ignoring and accounting for single variance components (clustering) at farm, area, and district levels. Area-to-area and district-to-district variations were noted but the area and district variance components were one-third and one-fifth the size of the farm variance components for both methods. As farm-to-farm variation differed markedly by farm size and district, models in MLn were extended to allow for multiple farm-level variance components by these categories. For each, sero-prevalence of IBR increased with age and was significantly decreased on small-sized zero-grazing farms. These models, particularly the model with different farm variance components by districts, fit the data better and highlighted well that there was considerable farm-to-farm variation--differing by district--and that the available farm-level fixed effects did not predict IBR sero-prevalence well.

Algorithms↗

'Physiological' hyperinsulinaemia increases distal artery systolic blood pressure without changing proximal blood pressure.

1. Although epidemiological data links essential hypertension with insulin resistance, 'physiological' insulin concentrations have not had pressor effects in humans. Our previous studies suggested that hyperinsulinaemia might have effects on distal blood pressure which are not detected more proximally. Therefore, we used non-invasive techniques to determine the acute effects of insulin on proximal and distal blood pressure. 2. Blood pressure was measured in the finger (Finapres) and arm (Dinamap monitor) during a two-stage euglycaemic clamp. Values obtained during the insulin infusion were compared with a control infusion. 3. Plasma insulin concentrations were 7.0 +/- 1.0 mu-units/ml at baseline and remained within the accepted post-prandial 'physiological' range during low- and high-dose insulin infusions (28.9 +/- 2.1 and 101.7 +/- 6.8 mu-units/ml respectively). From a baseline value of 130 +/- 3 mmHg, finger systolic blood pressure rose by 9.9 +/- 1.9 mmHg during the low-dose infusion (compared with 7.5 +/- 2.7 mmHg in control, P < 0.05) and by 21.9 +/- 2.3 mmHg during the high-dose infusion (compared with 14.6 +/- 3.1 mmHg in control, P < 0.01). Compared with control, insulin did not have an additional effect on arm pressures. 4. Although finger systolic pressure was increased by hyperinsulinaemia, this occurred in the absence of a change in mean blood pressure or in arm pressures. These data therefore suggest that insulin augmented pulse wave reflection. This novel haemodynamic effect of insulin could contribute to the association of insulin resistance with essential hypertension.

Adult↗

Epidemiological patterns of hepatitis B virus (HBV) in highly endemic areas.

This paper uses meta-analysis of published data and a deterministic mathematical model of hepatitis B virus (HBV) transmission to describe the patterns of HBV infection in high endemicity areas. We describe the association between the prevalence of carriers and a simple measure of the rate of infection, the age at which half the population have been infected (A50), and assess the contribution of horizontal and perinatal transmission to this association. We found that the two main hyper-endemic areas of sub-Saharan Africa and east Asia have similar prevalences of carriers and values of A50, and that there is a negative nonlinear relationship between A50 and the prevalence of carriers in high endemicity areas (Spearman's Rank, P = 0.0086). We quantified the risk of perinatal transmission and the age-dependent of infection to allow a comparison between the main hyper-endemic areas. East Asia was found to have higher prevalences of HBeAg positive mothers and a greater risk of perinatal transmission from HBeAg positive mothers than sub-Saharan Africa, though the differences were not statistically significant. However, the two areas have similar magnitudes and age-dependent rates of horizontal transmission. Results of a simple compartmental model suggest that similar rates of horizontal transmission are sufficient to generate the similar patterns between A50 and the prevalences of carriers. Interrupting horizontal transmission by mass immunization is expected to have a significant, nonlinear impact on the rate of acquisition of new carriers.

Adult↗

Insulin as a pressor agent: effects of 'physiological' insulin concentrations on finger blood pressure.

Epidemiological evidence has linked essential hypertension with impaired tissue sensitivity to insulin (i.e. insulin resistance) and actions which could contribute to elevated blood pressure include renal sodium and water retention, sympathetic nervous system stimulation and effects on vascular smooth muscle cell growth and cation balance. Although insulin has pressor effects in some animal models, similar changes in human studies have only been demonstrable with supraphysiological insulin concentrations. We have recently measured finger blood pressure during a two stage hyperinsulinaemic euglycaemic clamp that produced insulin concentrations within the 'physiological' range. The plasma insulin concentration increased from 7.0 +/- 0.3 mu U.ml(-1) to 28.9 +/- 0.6 mu U.ml(-)and then to 101 +/-1.7 mu U.ml(-1) during the procedure and was associated with an increase in fingers but not arm systolic blood pressure during both low dose (i.e.+ 9.9 +/- 1.9 mmHg vs + 7.5 +/- 2.7 mmHg with control,p <0.05) and high dose insulin (21.9 +/- 2.3 mmHg vs 14.6 +/- 3.1 mmHg, p <0.01). Thus it appears that 'physiological' concentrations of insulin have pressor effects on finger systolic blood pressure that are not detectable more proximally and it is possible that such changes could contribute to the development of sustained elevations of blood pressure.

Adult↗

Total norepinephrine spillover, muscle sympathetic nerve activity and heart-rate spectral analysis in a patient with dopamine beta-hydroxylase deficiency.

Dopamine-beta-hydroxylase (D beta H) is the enzyme responsible for intraneural conversion of dopamine to norepinephrine. Its deficiency results in failure of norepinephrine synthesis, excessive dopamine release and orthostatic hypotension. We studied a young patient with this deficiency using the currently available methods to assess sympathetic function namely measurement of norepinephrine kinetics, microneurography to assess muscle sympathetic nerve activity (MSNA), and heart-rate spectral analysis. We compared these findings with those in 24 young healthy controls, and 4 patients with peripheral autonomic failure (PAF). Recordings were made in our subject before and after 5 months of treatment with L-threo-3,4-dihydroxyphenylserine (DOPS) (which is converted directly into L-norepinephrine bypassing the D beta H enzymatic step); measurements were made at rest in the supine position and after 15 min of 30 degrees head-up tilt. Our subject with D beta H deficiency had a high resting nerve firing rate (40.3 bursts/min) compared with the mean value in normal controls (19.3 bursts/min), and an appropriate increase in nerve firing rate during tilt. Total body norepinephrine spillover at rest was very low, 38 ng/min, compared with age-matched normals (519 +/- 43.3 ng/min, mean +/- SEM), and epinephrine secretion was undetectable. Conversely, the plasma concentrations of dopamine, DOPAC, HVA and DOPA were raised. At rest, low-frequency heart-rate variability (0.1 Hz) was absent with preservation of the respiratory-related high-frequency peak. In contrast, the PAF subjects had no detectable muscle sympathetic nerve activity, very low levels of norepinephrine spillover and epinephrine secretion and a reduction in heart rate variability at all frequencies. After 5 months treatment with L-threo-3,4-dihydroxyphenylserine (DOPS) in the D beta H deficiency patient there was a dramatic clinical improvement with resolution of the orthostatic symptoms, dramatic reduction in MSNA activity at rest, and return of plasma norepinephrine, norepinephrine spillover, DHPG and MHPG to within the normal range, indicating intraneuronal production of norepinephrine.

Adolescent↗

Efficacy of pravastatin in combination with captopril in hypertensive patients.

OBJECTIVE: To determine the efficacy of pravastatin in the treatment of primary hypercholesterolaemia in patients being treated with captopril for hypertension. DESIGN: A double-blind parallel group study comparing 12 weeks of pravastatin therapy (20-40 mg/day) with placebo. PARTICIPANTS: 25 patients (age, 37-73 years) with mild-to-moderate hypertension and hypercholesterolaemia (total cholesterol level, 5.5-8.8 mmol/L). RESULTS: Pravastatin reduced total cholesterol levels by 22% (from 7.1 +/- 0.29 [SEM] to 5.5 +/- 0.25 mmol/L; P < 0.001) and low-density-lipoprotein cholesterol levels by 32% (from 5.0 +/- 0.32 to 3.4 +/- 0.28 mmol/L; P < 0.001) in four weeks and these levels were maintained for the 12 weeks of therapy. Pre-pravastatin values returned three weeks after stopping therapy. Levels of total cholesterol, cholesterol fractions and triglycerides remained constant or deteriorated in the placebo group. Pravastatin therapy was well tolerated. An integrated coronary risk score showed a 40% reduction in risk. CONCLUSION: This study indicates that pravastatin (combined with captopril) is an effective cholesterol-lowering drug, but that treatment needs to be maintained.

Adult↗

The effects of short-term alcohol intake on clinic and ambulatory blood pressure in normotensive 'social' drinkers.

Office blood pressure (OBP), ambulatory blood pressure (ABP), and vascular reactivity were measured in 12 normotensive 'social' drinkers (mean alcohol consumption of 9.7 +/- 3.1 g/day) after 4 days of alcohol consumption (1 g/kg/day) and compared with the effects of an isocaloric substitute (sucrose, 1.75 g/kg/day) or no intervention. Alcohol consumption did not affect OBP or 24-mean ABP but appeared to decrease nocturnal systolic and diastolic blood pressure soon after consumption. Although vascular reactivity did not differ between the groups, the blood pressure rise in response to isometric exercise tended to be lower following alcohol. Thus, short-term alcohol ingestion by normotensive 'social' drinkers does not increase office or ambulatory blood pressure.

Adult↗

Rapidly developing pseudohypertension after renal transplantation diagnosed by non-auscultated blood pressure measurement.

Pseudohypertension has been reported in elderly, diabetic and uraemic patients. A variety of diagnostic methods have been used, generally with poor results with the exception of arterial catheterisation. We report a case of pseudohypertension that developed in the year following a renal transplant and was diagnosed by the use of oscillometric and photoplethysmographic blood pressure measurement.

Auscultation↗

Short term effects of pravastatin on blood pressure in hypercholesterolaemic hypertensive patients.

In this study, which was primarily designed to determine the lipid-lowering efficacy of pravastatin in the setting of background antihypertensive therapy with ACE inhibitors and calcium antagonists, we took the opportunity to examine whether pravastatin interacts with antihypertensive therapy to produce additional falls in blood pressure. This may help clarify the mechanism of action of pravastatin's rapid beneficial effects on cardiovascular morbidity. We treated 25 hypertensive hypercholesterolaemic patients with 12 weeks of either pravastatin or placebo in this double blind, placebo controlled parallel group study. Placebo treatment did not alter plasma lipids, whereas 12 weeks' treatment with pravastatin reduced total cholesterol by 27% (from 7.1 +/- 0.27 to 5.2 +/- 0.18, p < 0.001 compared with placebo) and low density lipoprotein cholesterol by 35% (from 4.9 +/- 0.36 to 3.2 +/- 0.17, p < 0.001). There were no changes in systolic or diastolic blood pressure either following 12 weeks' treatment or 3 weeks' withdrawal of pravastatin. Thus, pravastatin remains efficacious as a lipid lowering agent in the presence of antihypertensive therapy but does not enhance the blood pressure lowering action of these drugs. Therefore it is unlikely that blood pressure reduction is the mechanism by which pravastatin mediates its reported short term effects on cardiovascular morbidity.

Blood Pressure↗

Cardiac risk factor management. Experience of an outpatient hypertension clinic.

OBJECTIVE: To describe the outcome of the management of cardiovascular risk factors in the hypertension clinic of a teaching hospital over a five-year period. DESIGN: Retrospective analysis of risk factor data (blood pressure, plasma cholesterol level, body weight, smoking and drinking habits) obtained from computerised hypertension clinic progress report forms. SETTING: Public teaching hospital. PATIENTS: One hundred and thirty-one patients referred to the clinic from both general practice and from within the hospital who attended the clinic regularly during the five-year study period. INTERVENTION: Long term management of hypertension and coexisting coronary risk factors by dietary, medical and lifestyle intervention. RESULTS: There was a significant improvement in diastolic blood pressure control in 1990 versus 1986 in both men and women, while systolic blood pressure improved in women only. The number of patients controlled with monotherapy increased from 38% in 1986 to 45% in 1990. Eighty-nine per cent of the men and 85% of women remained above their maximum desirable weight. Reported levels of alcohol consumption were low and the proportion of smokers was below that of the general population. A significant decline in plasma total cholesterol levels was observed in the women. Despite dietary advice and a limited use of lipid lowering drugs, 53.2% of the men and 66.1% of the women continued to have total plasma cholesterol levels above 5.5 mmol/L in 1990. High density lipoprotein levels increased significantly in the women only. CONCLUSION: A high proportion of our clinic patients have well controlled hypertension, but the clinic program produced little evidence of improvement in risk factors in men stabilised by long term therapy. More intensive methods of achieving lifestyle modification and a wider use of lipid lowering drugs may be needed if we are to achieve satisfactory body weights and lipid profiles in hypertensive patients.

Ambulatory Care Facilities↗