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Biomedical subjects

L M Wing

Publications and source records attributed to L M Wing.

At least 37 records · Page 2Linked to original sources

Effects of age and isolated systolic hypertension on cardiovascular reflexes.

OBJECTIVES: Given the reported relationship between systolic hypertension and orthostatic hypotension in the elderly, to test the hypothesis that systolic hypertension causes impairment of the cardiovascular reflex function additional to the effects of age alone. DESIGN: Responses were compared in normotensive healthy young (n = 12) and elderly (n = 15) participants and elderly participants with disproportionate supine systolic hypertension (n = 11) using a baroreceptor-mediated stress (head-up tilt) and two non-baroreceptor-mediated stimuli (cold pressor test and isometric exercise). METHODS: Blood pressure and heart rate were measured by oscillometry before and during the three stress tests. Forearm blood flow was measured by venous occlusion plethysmography and pulse wave velocity (PWV) by Doppler ultrasound. RESULTS: Percentage changes in systolic/diastolic (SBP/DBP) blood pressure with head-up tilt were 0/+11, -3/0 and -6/+1 mmHg in the young and elderly normotensives and elderly systolic hypertensives, respectively. Both elderly groups had reduced DBP responses to tilt compared with the young (P < 0.01). All three groups had similar percentage changes in blood pressure responses to non-baroreflex-mediated stresses (cold pressor test: +10/+23, +11/+11, +10/+15; sustained isometric exercise: +18/+33, +22/+24, +13/+17 in the young and elderly normotensives and elderly systolic hypertensives, respectively). Aorto-iliac PWV adjusted for blood pressure was significantly higher in both elderly groups compared with the young (P < 0.01) but there was no difference between elderly normotensives and hypertensives. Unadjusted PWV was higher in elderly hypertensives than in elderly normotensives (P < 0.05). CONCLUSIONS: Compared with healthy young participants, both elderly groups had similarly attenuated blood pressure responses to tilt and reduced arterial compliance. Systolic hypertension is not associated with additional impairment of cardiovascular reflex function over and above the effects of age. The reported association between supine systolic hypertension and orthostatic hypotension does not appear to be a causative one.

Adolescent↗

Comparison of felodipine and enalapril monotherapy in essential hypertension.

This study compared the efficacy and tolerability of monotherapy with felodipine and enalapril in patients with essential hypertension using a double-blind randomised crossover design. Thirty-five subjects (22 male, 13 female--ages: median 48 years, range 31-69 years) entered the randomised phases of the study and 32 subjects completed the study. Following a 4-week run-in placebo phase, the treatments were felodipine ("Plendil ER") 5-20 mg and enalapril 5-20 mg orally once daily for 8 weeks, each with matching placebos. Dose titration was at 2 and/or 4 weeks in each phase. Number of subjects with each different end-of-phase dose were for felodipine: 5 mg--8, 10 mg--11, 20 mg--13 and enalapril: 5 mg--6, 10 mg--9, 20 mg--17. Predose supine blood pressure (mean +/- SEM) was reduced in both active treatment phases compared with the run-in phase (159 + 2/101 +/- 1), but there was no significant difference in blood pressure between the active phases: felodipine 143 +/- 2/90 +/- 1 and enalapril 146 +/- 2/92 +/- 1. The most common adverse effects were for felodipine: headache, flushing, ankle swelling; and for enalapril: cough. Felodipine and enalapril as once daily monotherapy are thus of similar antihypertensive efficacy but with predictably different adverse effect profiles.

Adolescent↗

A low-sodium diet supplemented with fish oil lowers blood pressure in the elderly.

OBJECTIVE: To examine effects of dietary fish oil supplementation with sodium restriction on blood pressure in the elderly. DESIGN: In a double-blind dietary intervention lasting 4 weeks, parallel comparisons of blood pressure were made in volunteers assigned to one of four treatment groups: fish oil and low sodium; fish oil and normal sodium; sunflower oil and low sodium; or sunflower oil and normal sodium. SETTING: Subjects lived at home and attended our nutrition research clinic at fortnightly intervals for dietary counselling and blood pressure measurement. PARTICIPANTS: Health volunteers aged 60-80 years were sought by advertisement. A total of 114 men and women were enrolled in two cohorts; 106, with an initial mean blood pressure of 132/77 mmHg, satisfactorily completed the study. INTERVENTION: All subjects adopted a low-sodium diet and dietary changes were effected by double-blind administration of slow-release sodium chloride or placebo tablets, along with capsules containing either fish or sunflower oil. MAIN OUTCOME MEASURE: The primary measure was the within-subject change in blood pressure after 4 weeks of intervention in each dietary treatment group. RESULTS: Urinary sodium excretion in subjects on low-sodium diets decreased whilst potassium excretion was unaffected. Systolic blood pressure (SBP) fell in the group taking sunflower oil with low sodium, but there was only a transient fall in diastolic blood pressure (DBP). In those taking fish oil with normal sodium, the change in blood pressure was not significant, except after adjustment for initial blood pressure and weight changes. When fish oil was combined with low sodium, however, both SBP and DBP were substantially reduced; the reduction in DBP was significantly greater than in the other treatment groups. CONCLUSION: Dietary fish oil and sodium restriction can interact to lower DBP in the elderly.

Aged↗

Afferent baroreflex dysfunction and age-related orthostatic hypotension.

1. To test the hypothesis that in apparently healthy elderly subjects with orthostatic hypotension there is afferent baroreflex dysfunction, cardiovascular and neurohumoral responses were measured after separate stimuli which activated baroreceptor (head-up tilt) and non-baroreceptor (cold stress, isometric exercise) afferent pathways. 2. In 15 healthy elderly control subjects blood pressure did not change with 60 degrees head-up tilting and there was a moderate increase in heart rate, whereas in 13 subjects with age-related orthostatic hypotension head-up tilting was associated with a marked fall in blood pressure but a similar heart rate response to that in the elderly control group. In contrast, both groups of subjects had similar blood pressure and heart rate responses to cold stress and sustained isometric exercise. 3. Nine subjects with autonomic neuropathy also showed a marked hypotensive response to head-up tilt, but produced no pressor response to cold stress or isometric exercise. 4. The plasma concentrations of noradrenaline, adrenaline and neuropeptide-Y-like immunoreactivity rose and that of atrial natriuretic peptide fell after head-up tilt in the study population as a whole. There were no significant differences between groups despite the much greater blood pressure drops in the subjects with autonomic neuropathy and in those with age-associated orthostatic hypotension. 5. The aorto-iliac pulse wave velocity index was significantly higher in subjects with age-associated orthostatic hypotension compared with that in control subjects. 6. The pattern of responses to the separate stresses observed in the group with age-associated orthostatic hypotension is characteristic and different from that in the elderly control subjects and the subjects with autonomic neuropathy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Stereospecific high-performance liquid chromatographic assay for the enantiomers of phenylpropanolamine in human plasma.

A stereospecific high-performance liquid chromatographic assay for the enantiomers of phenylpropanolamine (PPA) in human plasma has been developed. The method is based on reaction of extracted PPA with the chiral derivatizing agent 2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosyl isothiocyanate to form diastereomeric thiourea derivatives. These thiourea derivatives are stable for at least 24 h, readily separable by reversed-phase chromatography, and amenable to ultraviolet detection at 254 nm. Standard curves for each of the PPA enantiomers are linear over the concentration range 10-250 micrograms/L. Over the approximate range of the standard curve, precision (intra- and interday) ranged from 2.2-7.0% while accuracy ranged from 99.2-107.3%. The method has been shown to be free from interference from endogenous plasma constituents and from a range of drugs containing a primary or secondary amine function. Individual PPA enantiomer plasma concentration-time profiles measured for a subject administered racemic PPA are included to demonstrate the utility of the assay.

Chromatography, High Pressure Liquid↗

Effects of dietary sodium restriction and fish oil supplements on blood pressure in the elderly.

1. The effects on blood pressure of dietary fish oil, sodium restriction and a combination of both strategies were examined in a short-term dietary intervention study of 50 healthy elderly subjects (average age 67 years) with mean initial systolic and diastolic blood pressures of 133 and 77 mmHg, respectively. 2. Subjects were allocated to one of four treatment groups: fish oil with normal sodium, fish oil with low sodium, sunflower oil with normal sodium and sunflower oil with low sodium for 4 weeks. They then crossed over to the alternative sodium treatment for a further 4 weeks whilst remaining on the same oil. 3. The combination of fish oil supplementation with dietary sodium restriction caused significant reductions of blood pressure in the first 4 weeks: systolic blood pressure (SBP) fell by 8.9 mmHg, mean arterial pressure (MAP) by 7.4 mmHg and diastolic blood pressure (DBP) by 6.0 mmHg. 4. Fish oil enhanced the effect of sodium restriction on blood pressure. In the crossover protocol, a change in sodium excretion of 92 mmol/day was accompanied by changes of 6.4, 3.3 and 2.2 mmHg for SBP, MAP and DBP, respectively, in the subjects taking fish oil. However in those taking sunflower oil, blood pressure did not change significantly. 5. The results indicate beneficial interactive effect of dietary fish oil and sodium intake on blood pressure.

Aged↗

Controlled release levodopa/carbidopa (Sinemet CR4) in Parkinson's disease--an open evaluation of efficacy and safety.

Twenty patients with moderately severe Parkinson's disease entered an open study of the efficacy and safety of a slow release preparation containing levodopa 200 mg and carbidopa 50 mg per tablet ('Sinemet CR4'). Following an initial four week baseline stabilisation period on conventional 'Sinemet' tablets, the patients were transferred to 'Sinemet CR4' and observed at intervals over the next 12 months. Fifteen patients completed the full year observation period. When compared with the baseline period, treatment with 'Sinemet CR4' was associated with longer periods of functional improvement and less fluctuation of response following each dose. The median (range) dose frequency was reduced from three (three-12) to two (two-seven) times daily (p less than 0.001) on 'Sinemet CR4' although median (range) total daily dose of levodopa was increased from 700 (375-2525) to 800 (400-2800) mg without any increase in adverse effects. Three patients developed peripheral neuropathy while receiving Sinemet CR4, but the association with this therapy is unclear. Overall 'Sinemet CR4' allowed a longer dosage interval and provided more stable control of disease manifestations than conventional 'Sinemet'.

Aged↗

Lack of effect of fish oil supplementation on blood pressure in treated hypertensives.

Fish and fish oils have been reported to reduce blood pressure in normotensives and untreated hypertensives. The present study examined the effect of dietary supplementation with fish oil on blood pressure in 20 treated hypertensives with controlled blood pressures who continued their usual antihypertensive drug treatment throughout. A double-blind, randomized crossover design was used, with two phases, each of 8 weeks' duration. In one phase, subjects took fifteen 1 g fish oil capsules (Lipitac; Reckitt and Colman Pharmaceuticals, Sydney, Australia) daily, and in the other, 15 capsules of identical appearance containing 1 g olive oil daily. There was no difference between the treatment phases for any blood pressure parameter, heart rate or body weight, but blood pressure was lower in both phases compared with pretreatment values. The fasting plasma triglyceride concentration was 30% lower in the fish oil phase (P less than 0.001), but there was no difference between the phases for plasma concentrations of total or high-density lipoprotein (HDL) cholesterol. We conclude that, in treated hypertensives with controlled blood pressures, any additional fall in blood pressure produced by dietary supplementation with fish oil is so small that the requirement for antihypertensive drug therapy is unlikely to be reduced.

Adult↗

Diltiazem and atenolol in essential hypertension: additivity of effects on blood pressure and cardiac conduction with combination therapy.

In 15 patients with mild to moderate essential hypertension, the effects of diltiazem (120 mg twice daily) were compared with those of atenolol (50 mg once daily), the two drugs in combination, and placebo in a randomized double-blind cross-over study with treatment phases of 4 weeks duration. Blood pressure was reduced in the active treatment phases (supine blood pressure: diltiazem, 172/92 mmHg; atenolol, 172/92 mmHg; diltiazem plus atenolol, 164/88 mmHg; pooled estimate of s.e.m. by analysis of variance = 3/1) compared with placebo (180/101 mmHg). Factorial analysis confirmed fully additive antihypertensive effects of the drugs in combination. The time interval from the beginning of the P wave to the beginning of the QRS complex (P-R interval) was longer during combination therapy (0.184s) compared with either diltiazem (0.175s) or atenolol (0.174s) alone, or placebo (0.164s); s.e.m. by analysis of variance = 0.003. No clinically significant conduction disturbances occurred. Plasma atrial natriuretic peptide was elevated by atenolol but not diltiazem. Thus, in subjects with uncomplicated essential hypertension, diltiazem and atenolol had equal antihypertensive efficacy when used alone, and fully additive effects in combination, on both blood pressure and cardiac conduction.

Atenolol↗

Automated non-invasive measurement of cardiac output by the carbon dioxide rebreathing method: comparisons with dye dilution and thermodilution.

The accuracy and reproducibility of indirect measurement of cardiac output at rest by the carbon dioxide rebreathing (indirect Fick) method with an automated respiratory analysis system (Gould 9000IV) were compared with simultaneous measurements made in duplicate by dye dilution and thermodilution in 25 patients having cardiac catheterisation studies. Measurements of cardiac output by the carbon dioxide rebreathing method were not significantly different from those obtained with dye dilution (mean difference -0.3 l/min, SD 0.76, 95% confidence interval -0.7 to 0.1). Thermodilution significantly over-estimated cardiac output by a mean of 2.2 l/min or 39% (SD 1.5, 95% confidence interval 1.6 to 2.8) compared with the carbon dioxide rebreathing method and significantly overestimated cardiac output by 1.9 l/min or 31% (SD 1.2, 95% confidence interval 1.2 to 2.5) compared with dye dilution. The reproducibility of measurements of cardiac output in individual patients was satisfactory with the dye dilution method but was poor with carbon dioxide rebreathing and thermodilution. Indirect measurement of resting cardiac output by the Gould 9000IV automated carbon dioxide rebreathing method is more accurate but the variability inherent with this method requires that multiple measurements be taken for each determination. Measurement of cardiac output by the thermodilution method by a commercially available cardiac output computer was not satisfactory because not only was there considerable variability between repeat measurements but the method also consistently overestimated cardiac output compared with the dye dilution method.

Adult↗

Drug advertising.

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Advertising↗

Optimal size of cuff bladder for indirect measurement of arterial pressure in adults.

This study tested the hypothesis that a sphygmomanometer cuff bladder long enough to encircle the arm in most adults ('obese cuff') would provide a more accurate and precise estimate of intra-arterial pressure than the usual 'standard' cuff bladder. In 53 patients undergoing diagnostic coronary angiography (35 males, 18 females, aged 36-79 years), indirect blood pressure, measured in the left arm with a random-zero sphygmomanometer, was compared with simultaneously measured femoral intra-arterial pressure. Duplicate indirect measurements were made with each of two cuffs containing bladders measuring 39 x 15 cm ('obese') and 23 x 12 cm ('standard'). The obese cuff bladder encircled 80% or more of the arm circumference in all subjects, whereas the standard cuff bladder met this requirement in only 19% of the subjects. For both systolic and diastolic pressure there was marked interindividual variability in the differences between indirect and direct measurements with both cuffs. With the obese cuff there was no systematic error in the diastolic blood pressure measurement. The standard cuff consistently overestimated diastolic pressure by 7.7 +/- 8.3 mmHg (mean +/- s.d.). For both cuffs, the difference between indirect and direct diastolic pressure increased with arm size (P less than 0.05). Both cuffs underestimated systolic blood pressure, the obese cuff by 15.5 +/- 11.7 mmHg and the standard cuff by 7.6 +/- 12.1 mmHg. These systolic blood pressure underestimates were greater at higher blood pressures (P less than 0.01) and with smaller arms (P less than 0.05). Age was not related to measurement error with either cuff.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Accuracy of the Takeda TM-2420 ambulatory blood pressure monitor.

1. The accuracy of blood pressure measurement with the Takeda TM-2420 ambulatory blood pressure monitor and the TM-2020 data recorder have been assessed by comparison with simultaneous measurements taken using auscultation and direct femoral artery measurements. 2. Systolic blood pressure was underestimated by the TM-2420 by a mean of 10 mmHg (s.d. = 6, 95% confidence interval (CI) = -13 to -7) over the range of pressures measured by auscultation. It was underestimated by 23 mmHg (s.d. = 12, 95% CI = -28 to -18) compared with direct femoral artery measurements. 3. Diastolic pressure measurements were similar to those obtained by auscultation. When compared with direct femoral artery recordings, diastolic pressure was overestimated by about 5 mmHg (s.d. = 4, 95% CI = 3.4-6.6), which is consistent with indirect readings, taken with a 'standard' cuff (inflatable bladder 23 cm X 12 cm). 4. The TM-2420/2020 is thus suitable for ambulatory measurements of blood pressure when diastolic pressure is the criterion of interest.

Angiocardiography↗

Interactions of non-steroidal anti-inflammatory drugs.

As NSAIDs are commonly used in patients receiving concomitant drug therapy, there is a risk of clinically significant drug interactions. Important interactions with NSAIDs involve one or both of two major mechanisms: pharmacokinetic (e.g. lithium, phenytoin and barbiturates) and pharmacodynamic (e.g. antihypertensive agents, diuretics). Prescription of a NSAID should be preceded by a careful evaluation of any coexisting pathology (such as renal dysfunction or hypertension) or concurrent drug therapy (such as anticonvulsant or anticoagulant agents) which may predispose a patient to the development of an interaction with potentially severe effects.

Anti-Inflammatory Agents, Non-Steroidal↗

Enalapril and atenolol in essential hypertension: attenuation of hypotensive effects in combination.

In 16 patients with essential hypertension the effects of enalapril 20 mg once daily were compared with those of atenolol 50 mg once daily, with the two drugs in combination and with placebo using a double-blind cross-over design with allocation of treatment order by randomised Latin squares. For each patient there were four treatment phases, each of four weeks duration, which together comprised a 2 x 2 factorial experiment. All blood pressure parameters were reduced in the three active treatment phases compared to placebo (p less than 0.001). Supine blood pressures (group means) were 171/97 (placebo), 147/85 (enalapril), 154/84 (atenolol) and 144/78 (enalapril plus atenolol) (S.E.M. +/- 2/+/- 1-ANOVA), and standing blood pressures were 170/105 (placebo), 146/92 (enalapril), 154/92 (atenolol) and 147/86 (enalapril plus atenolol) (S.E.M. +/- 3/+/- 1). In the combination phase there was an additional hypotensive response but the potential fully additive effects of the two agents were attenuated by 30-50%. The mechanism of the attenuated hypotensive effect of the combined agents has not been determined. Plasma atrial natriuretic peptide (ANP) concentration was doubled in the presence of atenolol (P less than 0.01) suggesting that ANP may contribute to the hypotensive effect of the beta-blocker.

Aldosterone↗

Hypertension in the elderly: the role of calcium antagonists.

Calcium antagonists have a spectrum of actions that opposes many of the pathophysiological abnormalities found in hypertension in old age. There is good evidence that these drugs reduce blood pressure effectively in the elderly. There is no evidence from controlled studies to indicate that they are more effective in elderly than in young subjects. There is equally no convincing evidence that age is an independent predictor of hypotensive efficacy of calcium channel antagonists, after the effect of pretreatment blood pressure and random variation have been taken into account. There have been no studies comparing the efficacy of calcium antagonists with other classes of antihypertensive drugs in old age, and there is no evidence that any one group of calcium antagonists is superior in this age group. There have been no studies demonstrating that calcium antagonists have a beneficial effect on the morbidity and mortality associated with hypertension in the elderly, or indeed in any age group. Side effects are equally common in old and young subjects and are usually mild. Overall, calcium antagonists are valuable and appropriate drugs for the treatment of hypertension in the elderly. They may be particularly useful for treating hypertension associated with conditions that occur with increased frequency in the elderly such as peripheral vascular disease, ischemic heart disease, cardiac arrhythmias, and obstructive airways disease. Since plasma concentrations of these drugs may be elevated in elderly patients due to altered pharmacokinetics, therapy should be started with low doses and increased gradually.

Aged↗