Ergonomics in consumer product evaluation: an evolving process.

As part of its commitment to empowering people to make informed consumer decisions, the Consumers' Association investigates the convenience aspects of a vast range of products, from cars to garden spades. Evaluation approaches include user trials, convenience checklists and expert appraisals. Our methodology is subject to constant review and refinement to ensure the highest levels of reliability, validity and auditability. We have a distinctive approach: our tests are designed to reflect consumer usage and to provide comparative data which is absolutely fair to all products. This paper discusses the evolving nature of that methodology within the "lifetime" of a product. Reasons for choosing each method are given as practical guidance for those involved in comparative testing.

Atenolol in essential hypertension during pregnancy.

OBJECTIVE: To determine the effect of atenolol on the outcome of pregnancy in women with essential hypertension. DESIGN: Prospective, randomised, double blind, placebo controlled study. SETTING: Hospital clinic. PATIENTS: 33 Women with mild essential hypertension (systolic blood pressure 140-170 mm Hg or diastolic pressure 90-110 mm Hg on two occasions at least 24 hours apart) consecutively referred to two obstetric medical clinics. Four patients in the placebo group were withdrawn from the study: control of blood pressure was inadequate in two, one developed breathlessness, and one changed her mind about participating. The mean gestation in the 29 remaining women on entry to the study was 15.9 weeks. MAIN OUTCOME MEASURES: Blood pressure and birth weight. INTERVENTION: 14 Women received placebo. 15 Women received atenolol 50 mg daily initially, increasing until either the blood pressure was less than 140/90 mm Hg or a dose of 200 micrograms daily was reached. RESULTS: The mean blood pressure on entry was 148/86 mm Hg in the group given atenolol and 144/86 mm Hg in the group given placebo. During treatment the mean diastolic pressure was significantly reduced by atenolol compared with placebo (to 74 v 81 mm Hg; difference in means (95% confidence interval) 7.0 (2.9 to 10.0) mm Hg) but the effect on systolic pressure was marginal (132 v 136 mm Hg; 4.0 (-1.4 to 8.6) mm Hg). Babies in the atenolol group had a significantly lower birth weight than those in the placebo group (2620 g v 3530 g; 910 (440 to 1380)g). CONCLUSION: Atenolol given from the end of the first trimester in patients with mild hypertension is associated with intrauterine growth retardation. When taken in conjunction with the results of a previous study in which methyldopa was given these findings indicate that benefit is unlikely to result from treating mild essential hypertension in pregnancy.

Awareness among pregnant women of the effect on the fetus of commonly used drugs.

Epidemiological studies have shown that pregnant women continue to take substantial quantities of drugs, particularly those readily available to them without prescription. Little is known of the attitudes and knowledge among pregnant women of the effects of these substances on the fetus. Awareness of the effects on the fetus of commonly used drugs, cigarettes and alcohol among 514 women in the postnatal wards of two maternity units in Glasgow was assessed by self completion questionnaire between October 1987 and April 1988. Most of the women recognised that the fetus is most at risk of being harmed by drugs during the first 3 months of pregnancy. The majority felt it was safest not to smoke cigarettes and were aware of the adverse effects of smoking on fetal growth. Over half thought smoking was harmful while breastfeeding. Over half thought that alcohol should be avoided altogether in pregnancy and that drinking could harm the fetus. Most women considered alcohol harmful to the breast feeding baby. The majority of the women would opt for paracetamol containing analgesics only and only a small proportion would take one containing aspirin. Only half the study population would take a prescribed antibiotic. A generally high level of awareness of commonly used drugs was demonstrated although there are areas where further health education could be directed. The study has highlighted areas worthy of further research.

A comparison of the effects of human alpha calcitonin gene-related peptide and glyceryl trinitrate on regional blood velocity in man.

1. Human alpha calcitonin gene-related peptide (h alpha CGRP) is a potent vasodilator which in doses up to 1.5 micrograms min-1 i.v. produces little or no fall in blood pressure in normal volunteers, but does cause a substantial tachycardia. 2. We have explored the underlying mechanism of this effect by comparing h alpha CGRP infused so as to maintain heart rate 25-30% above baseline with glyceryl trinitrate (GTN) in a dose sufficient to maintain a throbbing headache. 3. Ten normal volunteers were studied. In addition to blood pressure and heart rate, blood velocity and pulsatility index (PI) were determined from Doppler signals recorded from the internal and external carotid, renal and femoral arteries. 4. Following h alpha CGRP blood pressure (mean +/- s.d., mm Hg) did not significantly change: 120 +/- 10/70 +/- 7 before compared with 121 +/- 12/67 +/- 7 during h alpha CGRP infusion. Heart rate (mean +/- s.d., beats min-1) increased from 62 +/- 8 to 86 +/- 10 (P less than 0.0001). In contrast the blood pressure fell following GTN: 124 +/- 12/74 +/- 8 before compared with 111 +/- 13/62 +/- 6 following treatment (P less than 0.02). Heart rate did not change following GTN: 64 +/- 9 compared with 69 +/- 10. 5. GTN significantly increased PI (mean +/- s.d.) in the common carotid artery from 2.8 +/- 0.5 to 3.4 +/- 0.5 (P less than 0.003) while h alpha CGRP increased PI in the internal carotid from 1.3 +/- 0.2 to 2.1 +/- 0.4 (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Platelet intracellular free calcium concentration in normotensive and hypertensive pregnancies in the human.

1. Basal and stimulated platelet intracellular free calcium concentrations were measured in non-pregnant women and in third trimester patients who were either normotensive or who had pregnancy-induced hypertension or pre-eclampsia. There were 15 subjects in each group. 2. A trend for a reduction of the maximal response of platelet calcium levels to stimulation by 5-hydroxytryptamine was seen in pregnant groups compared with nonpregnant subjects, but this was significant only in pre-eclampsia. 3. No significant differences in basal or adenosine 5'-pyrophosphate-stimulated levels of platelet intracellular free calcium concentration were observed between the four groups. 4. These results illustrate that basal platelet calcium levels are unchanged in hypertension of pregnancy. Alterations in basal platelet calcium levels may not be involved in the platelet activation that is a feature of pre-eclampsia.

Nifedipine and platelets in preeclampsia.

In addition to its antihypertensive properties, nifedipine inhibits platelet aggregation in vitro. Because increased platelet aggregation is a feature of preeclampsia, we have investigated nifedipine in this condition. Ten women at 31 +/- 2.8 weeks gestation, with blood pressure 162 +/- 18/102 +/- 10 mmHg (despite atenolol 200 mg/day) and proteinuria 2.0 +/- 1.1 g/24 hr, were treated with nifedipine. Pregnancies were prolonged by 17 +/- 15 days (range 5 to 56). Blood pressure was controlled in eight of the ten patients, final values before delivery being 142 +/- 16/89 +/- 12 mmHg (P less than 0.02). Platelet count rose in all women from 190 +/- 80 to 261 +/- 78 X 10(9)/1 (P less than 0.001). Nifedipine appears to reverse the thrombocytopenia of pre-eclampsia, in addition to controlling the blood pressure.

Ethanol and platelet intracellular free calcium concentrations.

The effect of 0.8 g kg-1 absolute ethanol orally on platelet intracellular free calcium was assessed in a random order study in 24 normotensive subjects with an isocaloric control. Platelet calcium was measured 90 min and 12 h after treatment by the Quin 2 method. The study had 90% power of detecting a 16.5% change. After 90 min, breath ethanol was 37 +/- 9 micrograms 100 ml-1, blood pressure was unchanged and heart rate rose slightly. Platelet calcium was unchanged by ethanol after 90 min or 12 h.

The influence of pregnancy on drug action: concentration-effect modelling with propranolol.

The physiological changes of pregnancy have been shown to alter the disposition of some drugs. However, there are no data on the possible influence of pregnancy or its complications on drug effect. We have applied drug concentration-effect analysis to determine whether pregnancy influences the action of propranolol. Twelve women with pregnancy induced hypertension were studied during the third trimester and again 2-3 months post partum. On each occasion propranolol (10 mg) was given intravenously and measurements of heart rate, blood pressure and whole blood propranolol concentration were determined over the ensuing 8 h. Pregnancy did not alter propranolol disposition. Clearance was 0.63 +/- 0.18 and 0.71 +/- 0.24 litre h-1 kg-1, and volume of distribution at steady state was 4.02 +/- 2.98 and 3.07 +/- 1.58 litres/kg during and after pregnancy respectively. There was no fall in blood pressure over the period of the acute study. The reduction in heart rate (beats/min per ng of propranolol/ml) was greater during compared with after pregnancy: -0.61 +/- 0.23 and -0.39 +/- 0.19 respectively (F = 6.64; df 1.9; P less than 0.03). There was no relationship between blood pressure or pretreatment heart rate and the slope of the concentration-effect relationship. We conclude that pregnancy can significantly alter drug effect in the absence of any pharmacokinetic changes. These findings suggest that therapeutic ranges established in non-pregnant patients may not be applicable during pregnancy.

Plasma catecholamines in pregnancy induced hypertension.

Increased activity of the sympathetic nervous system has been implicated in the genesis of early hypertension in young people. Studies in pregnancy allow observations to be made on evolving, recently established and resolving hypertension in the human. We describe the results of two studies involving women who developed hypertension during pregnancy. In the first study, plasma concentrations of noradrenaline and adrenaline were measured in 17 women with pregnancy induced hypertension (PIH) and 17 normotensive pregnant control subjects. Plasma noradrenaline (nmol/l) was lower in the PIH group compared with control patients in both semi-recumbent (1.11 +/- 0.53 vs 1.98 +/- 0.96, P less than 0.001) and standing positions (1.31 +/- 0.65 vs 2.57 +/- 1.27, P less than 0.005). Five days post partum, plasma noradrenaline had risen in the PIH group compared with pregnant values in semi-recumbent (1.65 +/- 1.0 vs 1.11 +/- 0.52, P less than 0.05) and standing positions (2.46 +/- 1.5 vs 1.31 +/- 0.65, P less than 0.05). In the normotensive patients plasma noradrenaline did not differ between post partum and pregnant values (1.51 +/- 0.73 vs 1.98 +/- 0.96 semi-recumbent; 2.00 +/- 1.16 vs 2.57 +/- 1.7 standing). Logarithmic transformation of the noradrenaline concentration data resulted in a significant (P less than 0.02) negative correlation with diastolic blood pressure in the pregnant patients but not post partum. Plasma adrenaline concentration was the same in both groups. In the second study, plasma concentrations of noradrenaline and adrenaline were measured sequentially through pregnancy in five women who developed PIH and five control subjects who remained normotensive.(ABSTRACT TRUNCATED AT 250 WORDS)

Plasma catecholamines and modes of delivery: the relation between catecholamine levels and in-vitro platelet aggregation and adrenoreceptor radioligand binding characteristics.

Catecholamines were measured in maternal venous, and mixed umbilical cord blood. Maternal catecholamines were significantly (P less than 0.01) reduced by epidural analgesia with a 36% reduction in noradrenaline and a 33% reduction in adrenaline. Fetal catecholamines were elevated at birth with a 3-8 fold increase in noradrenaline but not adrenaline during spontaneous vaginal delivery. The lowest fetal catecholamines were obtained in the group delivered under epidural analgesia; lower plasma catecholamines were not associated with adverse respiratory effects. Fetal platelets showed impaired alpha 2-adrenoceptor function with absent aggregatory responses to adrenaline in vitro. The defect in platelet function was unlikely to be related to changes in the number of fetal platelet alpha-receptors or to changes in receptor affinity for adrenaline, as fetal platelets failed to aggregate to adrenaline from deliveries with high and low cord blood catecholamines.

First year of life after the use of atenolol in pregnancy associated hypertension.

We describe the results of a prospective study in which 120 women who developed hypertension in the last trimester of pregnancy were randomly allocated in double blind manner to atenolol or placebo. The mean duration of treatment was five weeks. The only difference between groups during the neonatal period was in respiratory distress syndrome, mainly related to spontaneous premature labour, which occurred in six placebo group babies but in none from the atenolol group. Fifty five children from each group have been followed to 1 year of age. All in the atenolol group are developing normally but one child from the placebo group is brain damaged. These findings do not suggest any short or medium term paediatric complications after the use of beta blockers in pregnancy.

Obstetric aspects of the use in pregnancy-associated hypertension of the beta-adrenoceptor antagonist atenolol.

The obstetric implications of the use of the beta-adrenoceptor antagonist atenolol have been evaluated in a prospective, randomized, double-blind, and placebo-controlled study involving 120 women with pregnancy-associated hypertension. The clinical interpretation of antenatal and intrapartum cardiotocographs was uninfluenced by atenolol. Human placental lactogen concentration fell in the atenolol group, but this was not an indicator of subsequent fetal distress. Other obstetric indices, such as urinary estriol excretion, were the same in both groups. Spontaneous premature labor occurred in five women receiving placebo but in none who received atenolol. Together with previously reported findings on pregnancy outcome, our study leads us to conclude that beta-blockers such as atenolol can appropriately be used in the management of hypertension during pregnancy.

Atenolol elimination in the neonate.

The elimination of the cardioselective beta-adrenoceptor antagonist atenolol has been studied in 35 neonates by measuring drug concentration in cord blood and in blood obtained at 24 h by heel stab. Elimination rate was assessed by calculating the slopes of lines joining these two concentration points. The slopes had a mean of 0.043 h-1 (equivalent to a half-life of 16 h) and were normally distributed with 95% of values being in the range 0.02-0.066. There was no relationship between slope and neonatal weight or skinfold thickness, but most babies were at term and the range of these indices was narrow. Babies who developed a bradycardia had cord atenolol concentrations and slopes which did not differ significantly from those in babies without bradycardia. We conclude that atenolol elimination in the neonate is reduced when compared to adults. This prolonged elimination is consistent with the physiological characteristics of this age group and with previous observations on drugs eliminated by renal excretion.

Clinical pharmacological studies with prazosin during pregnancy complicated by hypertension.

The disposition and effect of orally administered prazosin have been studied in eight women with hypertension which was uncontrolled by beta-adrenoceptor blockade during the last trimester of pregnancy. Results were compared with healthy men of similar age. The median time to peak concentration was 165 min during pregnancy and 120 min in the men (P less than 0.04). Area under the concentration vs time curve was 3914 ng l-1 min in pregnancy and 2439 ng l-1 min in the men (P less than 0.06). Mean elimination half-life was 171 min in the pregnant women and 130 min in the men (P less than 0.01). Blood pressure was lowered by prazosin in both supine and standing positions. Blood pressure control remained satisfactory in six of the eight women and the median prolongation of pregnancy was 22 days. Neonatal outcome was satisfactory and all babies are developing normally. We conclude that prazosin is more slowly, but apparently more completely, absorbed during pregnancy and that its half-life is slightly prolonged. Prazosin appears to be both effective and safe when used during the last trimester to control blood pressure.