Detection of microalbuminuria in diabetic patients using a simple latex agglutination test.

The adaptation of an immunoturbidimetric assay to quantitatively measure urinary albumin is described and this was used to evaluate a commercial latex agglutination slide test, Albuscreen, with a sensitivity of 25 mg/l. Excellent agreement was observed between the two methods, and in clinical studies an acceptable classification of patients was made using Albuscreen, an albumin: creatinine ratio of less than or equal to 2.5 being used to indicate possible microalbuminuria. A small number of false negative and false positive results occurred in some dilute and concentrated urine samples, respectively.

Effects of atenolol withdrawal in patients on triple antihypertensive therapy.

The objective of this study was to examine the contribution of beta-blockade to antihypertensive treatment regimens including an angiotensin converting enzyme inhibitor or a calcium antagonist. The effects on BP control, adverse events, and plasma active renin concentration of removing atenolol from standard triple therapy (bendrofluazide and atenolol together with captopril or nifedipine) were assessed in a double-blind, randomised, parallel-group study, of eight weeks' duration in 46 patients from the Glasgow Blood Pressure Clinic. Blood pressures rose in patients randomised to placebo-atenolol compared with those who continued active-atenolol although the difference did not achieve statistical significance. However, the proportion of patients with controlled blood pressure (supine systolic BP < 140 mmHg plus supine diastolic BP < 95 mmHg) fell from 31% to 0% over the study period in patients given placebo-atenolol. There was a trend for BP control to deteriorate most when atenolol was withdrawn from nifedipine treated patients, but the 95% confidence intervals for the difference from captopril-treated patients were wide. Few side-effects were seen and these did not differ quantitatively between the study groups. Plasma active renin concentration was initially higher in captopril-treated patients, and increased on withdrawal of atenolol in both groups. Our findings suggest that beta-blockers make a clinically relevant contribution to treatment regimens including angiotensin converting enzyme inhibitors or calcium antagonists when given as part of standard triple antihypertensive therapy.

Comparison of captopril, hydralazine and nifedipine as third drug in hypertensive patients.

The antihypertensive, biochemical and adverse effects of captopril, hydralazine, nifedipine and placebo were compared in 160 patients with BP inadequately controlled by atenolol 100 mg daily plus bendrofluazide 5 mg daily. Treatments were given for up to 12 weeks. Beta-blocker and thiazide were continued unchanged. All three active drugs reduced supine BP relative to placebo; mean BP changes attributable to active treatment (95% confidence intervals): captopril 13.4/10.3 mmHg (0.6/4.0 to 26.2/16.6), hydralazine 15.0/10.0 mmHg (1.7/3.4 to 28.3/16.6), nifedipine 16.8/8.1 mmHg (4.0/1.8 to 29.6/14.4). There were no significant differences between the agents. Results for erect BP were similar. Target BP (< 140/95 mmHg) was achieved more frequently on captopril (33%), hydralazine (29%) and nifedipine (17%) than on placebo (10%). Compared with the other treatments captopril increased serum potassium concentration (P = 0.01), and hydralazine reduced serum cholesterol concentration (median changes: captopril -0.2 mmol/l, hydralazine -0.8 mmol/l, nifedipine -0.2 mmol/l, and placebo +0.2 mmol/l, P < 0.001). Overall, side-effects did not differ significantly between the groups; withdrawals resulting from adverse reactions: captopril 15%, hydralazine 24%, nifedipine 22%, and placebo 3% (chi 2 = 8.2, P = 0.04). Captopril, hydralazine and nifedipine did not differ significantly in efficacy and tolerability when added to atenolol and bendrofluazide. However, there were trends in favour of captopril, on which drug the highest proportion of patients had their BP controlled and the lowest proportion were withdrawn because of side-effects. Thus, of the drugs tested, captopril appears to be the best option as third drug in hypertension.

Effect on blood pressure or changing from high to low dose steroid preparations in women with oral contraceptive induced hypertension.

PIP: Clinical hypertension is to be found in 1-4% of oral contraceptive (OC) users, and it is a major risk in the development of cardiovascular diseases. Most data on OC caused hypertension are based on high dose OC combinations, or those containing 50-100 mcg of estrogen and 1-4 mg of progestogen. 30 women with persistent hypertension induced by high dose combinations were divided into 4 groups. In group A the high dose combination was replaced by a lower dose combination; in group B the high dose combination was replaced by norethisterone only; in group C the high dose combination was stopped and barrier methods used for 6 months, after which a low dose combination was given for 6 months, followed by barrier methods for a further 6 months; in group D the same method as in group C was used, but norethisterone alone was substituted. In both groups A and B systolic and diastolic blood pressure experienced a significant drop; after 1 year group B, taking low dose progestin only, had shown a further small drop, with blood pressure significantly lower than that in group A. However, in neither group did the blood pressure return to pre-OC levels. When 30 mcg ethinyl estradiol and 150-250 mcg levonorgestrel was introduced (group C) blood pressure rose again after 6 months, but to levels which were significantly lower than those recorded in the higher combinations. Norethisterone 350 mcg alone (group D) also induced a small significant rise in blood pressure after 6 months. The results of this study suggest that women with hypertension caused by high dose OCs may experience great improvement by treatment with low dose combined OCs or by low dose progestogen alone.^ieng

Effects on blood pressure of low dose oestrogen and progestagen only oral contraceptives.

Oral contraceptives containing at least 50 micrograms oestrogen and 1-4 mg progestagen can raise blood pressure [1,2]. However, there is controversy about the effect of lower doses of oestrogen [3-5] on blood pressure and especially the role of the progestagen component [6-9]. We describe the results of a prospective, controlled study of the effects on blood pressure of contraceptive preparations containing different types and dosages of oestrogen and of progestagen.

The 'third drug' trial: a comparative study of anti-hypertensive agents added to treatment when blood pressure is uncontrolled by a beta-blocker plus thiazide diuretic.

Hydralazine, labetalol, methyldopa, minoxidil, prazosin and placebo were compared when added to atenolol 100 mg and bendrofluazide 5 mg daily in hypertensive patients inadequately controlled by the beta-blocker/diuretic combination. Atenolol was withdrawn in those allocated to labetalol and minoxidil was given only to men. The order of acceptability was: placebo, hydralazine, prazosin, methyldopa, minoxidil, labetalol. All the active agents were more effective than placebo. Minoxidil was more effective than the other active drugs, which had similar potency to one another. Hydralazine was the most generally suitable third drug, with prazosin a close second. Minoxidil was effective in the milder hypertensives, but in the present regimen caused fluid retention in those with more severe hypertension. Labetalol probably should be introduced at lower dose (150 mg daily) even as replacement for full doses of a previously administered beta-blocker.

Genetic variation in rooting ability of loblolly pine cuttings: effects of auxin and family on rooting by hypocotyl cuttings.

After about 20 days, hypocotyl cuttings from 20-day-old loblolly pine (Pinus taeda L.) seedlings rooted easily in the presence of the auxin indole-3-butyric acid (IBA), with roots forming directly from xylem parenchyma. In contrast, woody cuttings from 1-2-year-old hedged seedlings formed roots indirectly from callus tissue in 60-90 days, but IBA had little effect on rooting. Variation in rooting among hypocotyls from both half- and full-sib families was highly significant in response to IBA, and rooting did not occur within 20 days unless IBA was applied. Hypocotyls from poor rooting families tended to produce fewer roots per cutting than hypocotyls from good rooting families. Rooting by woody cuttings and hypocotyl cuttings from the same nine full-sib families was weakly correlated, raising the possibility that at least some common genetically controlled processes were affecting rooting by both types of cutting. The phytotropin N-1-naphthylphthalamic acid (NPA), supplied at 1 micro M with 10 micro M IBA, significantly inhibited rooting by hypocotyl cuttings from both good and poor rooting families, but there was no significant family x treatment interaction. Family variation in rooting ability may be a function of the frequency of occurrence of auxin-responsive cells in the hypocotyls.

A successful pregnancy following malignant phase hypertension.

We describe a patient who had a successful pregnancy three years after starting treatment for malignant phase renal hypertension and two years after a nephrectomy for right renal artery thrombosis and an aorto-femoral graft for right common iliac artery thrombosis.

Treatment of hypertension with a fixed ratio combination of long-acting propranolol and bendrofluazide, and influence of age of the subject.

The efficacy of sustained-release propranolol 160 mg (Inderal LA), bendrofluazide 5 mg and the combination preparation Inderex (bendrofluazide 5 mg and Inderal LA) in the treatment of hypertension was investigated. Twenty-one patients over a wide age range were studied, as it was of particular interest to find whether differing responses across a range of age groups might exist 24 hours post-dosing. Blood pressure control was greater with Inderex than with either Inderal LA or bendrofluazide. No significant difference between different age groups on the three treatments was demonstrated. There was some evidence, not statistically significant, suggesting potassium values to be lower on bendrofluazide and on Inderex. Serum glutamate oxaloacetate transaminase (SGOT) values were raised on bendrofluazide. Inderex is more effective in lowering blood pressure than either bendrofluazide or Inderal LA alone, and as a single capsule given once daily encourages compliance in comparison with combination treatments.

Subchronic inhalation toxicity of dimethylformamide in rats and mice.

Fisher F344 rats and B6C3F1 mice were exposed to concentrations of 0, 150, 300, 600 and 1200 ppm of dimethylformamide (DMF) for 6 hours a day, 5 days a week for 12 weeks. Detailed clinical observations were obtained weekly and body weights biweekly on all animals. Clinical chemistry and hematology evaluations were made on all rats and approximately half the mice at terminal sacrifice. Gross necropsy examinations were made on all animals. Histopathologic evaluations were conducted on selected tissues of animals of both species at all dose levels. Few overt signs of toxicity were seen in either rats or mice. There was a dose related depression in body weight gain in rats that was significant at the 1200 ppm level from the second week of study onwards. A total of 11 mice died or were sacrificed moribund during the study, 8 from the high dose and 2 from the 600 ppm dose level. Both clinical chemistry (in rats only) and gross necropsy observations, and histopathology of tissues indicate the possibility that liver may be the target in specific organ toxicity. The no-effect DMF dose was below the 150 ppm level for both rats and mice and the maximum tolerated dose was below the 600 ppm level.

A prospective controlled study of the effect on blood pressure of contraceptive preparations containing different types and dosages of progestogen.

A prospective controlled study investigated the effects of oral contraceptives on blood pressure in 485 women who were between 17 and 46 years of age and had blood pressures of less than 140/90 mmHg at entry. The women were divided into seven groups depending on the chosen method of contraception: intrauterine device or barrier method (control group): ethinyl oestradiol 30 micrograms plus levonorgestrel 150 micrograms (Microgynon-30 or Ovranette); norethisterone 350 micrograms (Micronor); norgestrel 75 micrograms (Neogest); norethisterone oenanthate 200 mg intramuscularly every 2 months for the first 6 months, then every 3 months thereafter; ethinyl oestradiol 30 micrograms plus ethynodiol diacetate 2 mg (Conova-30); and ethynodiol diacetate 500 micrograms (Femulen). Blood pressures were measured every 3 months by the family planning clinic nurse under standardized conditions using an Elag-Köln automatic sphygmomanometer. After one year, blood pressure had risen significantly (P less than 0.05) in the 137 women taking ethinyl oestradiol plus levonorgestrel (mean systolic and diastolic rises 6.4 and 2.7 mmHg respectively) and in the 91 women taking ethinyl oestradiol plus ethynodiol diacetate (mean systolic and diastolic rises 6.2 and 3.0 mmHg respectively). The 94 women taking the progestogen-only preparations and the 143 women in the control group showed no increases in blood pressure. These data were confirmed after 2 years of follow-up.

PIP: A prospective, controlled study investigated the effects of oral contraceptives (OCs) on blood pressure in 485 women who were between 17-46 years old and had blood pressures of 140/90 mmHg at entry. The women were divided into 7 groups depending on the chosen method of contraception: 1) IUD or barrier method (controls); 2) ethinyl estradiol 30 mcg plus levonorgestrel 150 mcg (Microgynon 30 or Ovranette); 3) norethisterone 350 mcg (Micronor); 4) norgestrel 75 mcg (Neogest); 5) norethisterone enanthate 200 mcg intramuscularly every 2 months for the 1st 6 months, then every 3 months thereafter; 6) ethinyl estradiol 30 mcg plus ethynodiol diacetate 2 mg (Conova 30); 7) and ethynodiol diacetate 500 mcg (Femulen). Blood pressures were measured every 3 months by the family planning clinic nurse under standardized conditions using an Elag-Koln automatic sphygmomanometer. After 1 year, blood pressure had risen significantly (P0.05) in the 137 women taking ethinyl estradiol plus levonorgestrel (mean systolic and diastolic rises 6.4 and 2.7 mmHg respectively) and in the 91 women taking ethinyl estradiol plus ethynodiol diacetate (mean systolic and diastolic rises 6.2 and 3.0 mmHg respectively). The 94 women taking the progestogen-only preparations and the 143 women in the control group showed no increases in blood pressure. These data were confirmed after 2 years of follow-up.

Indoramin in the hypertensive diabetic patient.

In 32 hypertensive diabetic patients a study was performed to determine the effects of indoramin on blood pressure and blood glucose, plasma insulin, C-peptide, serum total cholesterol, and triglyceride levels. All patients evaluated showed a significant fall in blood pressure with daily doses of 50 to 200 mg of indoramin. In six insulin-dependent diabetic patients there was no change in diabetic control and no effect on the incidence of hypoglycaemia. In 18 noninsulin-dependent diabetics monitored for 3 months and in 14 followed for 12 months, there was no significant change in glucose tolerance after a 75 g glucose dose; mean plasma C-peptide levels and 2 h insulin levels were increased at 12 months. Mean weight and mean fasting cholesterol and triglyceride concentrations were unchanged. Nine patients withdrew because of side effects, mainly drowsiness and lethargy.

Blood pressure in women taking oral contraceptives.

A controlled prospective survey of women taking oestrogen-progestogen oral contraceptives showed increases in mean systolic and diastolic blood pressure of 14.2 mm Hg and 8.5 mm Hg respectively after four years. The largest increases in individual cases were 36 mm Hg systolic and 20 mm Hg diastolic. Blood pressure returned to pretreatment levels within three months after oral contraceptives had been stopped. These changes in blood pressure were unrelated to the progestogenic potencies of the preparations being taken.

Influence of cortisol on the larval bullfrog thyroid axis in vitro and in vivo and on plasma and ocular melatonin.

Adrenal (interrenal) steroids have an important role in amphibian development, antagonizing the metamorphic changes induced by the thyroid at first and then synergizing with the thyroid hormones as their level rises during metamorphosis. Because most of the studies of corticoids at metamorphosis have focused on peripheral tissues, we investigated the effect of cortisol (hydrocortisone; HC) in vitro and in vivo on the thyroid of Rana catesbeiana (bullfrog) tadpoles on 12:12 light/dark (LD) cycles. Plasma and ocular melatonin, which is altered by changes in thyroxine (T(4)) levels, were also assayed in some experiments. Thyroids from premetamorphic tadpoles secreted less T(4) into culture media when incubated with 10 micrograms/ml HC and 0.2 micrograms/ml ovine thyrotropin (TSH) than with TSH alone and when cultured in the absence of TSH following 5 days of 10-micrograms HC injections, indicating that HC inhibited the thyroid at young stages. The effect of 10 micrograms/ml HC at older stages was investigated by culturing thyroids and pituitaries separately on the first day in control or HC media and then incubating the thyroids on the second day in homologous pituitary-conditioned media as a bioassay for pituitary TSH. HC had no effect on baseline T(4) secretion by the thyroids of prometamorphic or climax tadpoles on the first day but increased T(4) secretion over the control on the second day. Thyroids cultured with TSH and HC showed no increase in T(4) secretion over the control TSH group on the second day, indicating that, in the previous experiments, HC had enhanced pituitary secretion of TSH, rather than the response of the thyroid to TSH. In vivo, 5 days of injections of 10 micrograms HC increased plasma T(4) at prometamorphosis and decreased it at climax. There was no marked effect of HC on plasma or ocular melatonin levels. The findings showed that the nature of the effect of HC on the thyroid axis changes during metamorphosis from inhibition at early stages to a positive influence at prometamorphosis and finally to a negative effect on the T(4) level in the plasma at climax.