Comparative study of salt taste threshold of hypertensives, their normotensive relatives and non-relatives.

The role of salt in the genesis of hypertension has been well documented. Earlier studies have demonstrated higher salt taste threshold among hypertensives compared to normotensives. The aim of this study is to compare the salt taste thresholds of normotensive relatives of hypertensive patients with those of normotensives without family history of hypertension. Twenty-one hypertensives, 52 first degree relatives of these hypertensives and 99 normotensives without family history of hypertension were studied. They were made to taste different concentrations of solution from distilled water to 280 mmol of saline. The results showed that hypertensives had higher salt taste thresholds--detection (p < 0.0001), recognition (p < 0.0001) and maximum tolerable threshold (p < 0.05)--compared with normotensive relatives. The normotensive relatives of hypertensive patients in turn had higher salt taste thresholds--detection (p < 0.01), recognition (p < 0.0001) and maximum tolerable threshold (p < 0.001)--compared with normotensive controls; they also had significantly higher mean arterial pressure (p < 0.001). Health education with intervention directed at the hypertensives and their first degree normotensive relatives to willfully modify their desire and appetite for salt is of paramount importance.

WHO-ISH Guidelines for the management of hypertension: implementation in Africa--the Nigerian experience.

A 1990-91 country-wide survey in Nigeria showed the prevalence of hypertension to be 11.2% in those aged 15 years and above. The management, however, has been shown to be inadequate. At the instance of the Nigerian Hypertension Society a Consensus Meeting of National Medical Societies and other interest groups produced in 1996 Guidelines for the Management of Hypertension in Nigeria. Medical societies and the pharmaceutical industry have tried to increase awareness of the condition and its control through lectures, seminars, sponsor of essay competitions among secondary school and university students as well as canvassing against cigarette advertising and smoking in public places. However, their efforts are thwarted by luring advertisements by multinational tobacco companies driven from developed countries by anti-tobacco lobbies and legislation. A questionnaire survey showed that no other African country had produced similar guidelines in the past five years. In Sub-Saharan Africa there appears to be negligible implementation of the WHO-ISH Guidelines.

Effect of diabetes mellitus on glomerular filtration rate in an urban hospital diabetic population.

Glomerular filtration rate (GFR) as assessed by endogenous creatinine clearance was studied in 46 male and 38 female patients with diabetes mellitus (DM). Of these, 44 patients had uncomplicated DM (Group I) whilst 40 patients had complicated DM (Group II). There were 20 insulin-dependent diabetes mellitus (IDDM) patients in Group I and 5 in Group II, and 24 non-insulin dependent diabetes mellitus (NIDDM) patients in Group I and 35 in Group II. In Group I, 6 IDDM and 4 NIDDM patients had supranormal glomerular filtration rate (creatinine clearance 125 ml/min) and in Group II 1 IDDM and 6 NIDDM patients had supranormal GFR. The presence of diabetic complications and the mode of therapy of the diabetic state did not significantly affect the glomerular filtration rate. This concludes that glomerular hyperfiltration occurred in both IDDM and NIDDM Nigerian patients.

Impact of a short course in pharmacotherapy for undergraduate medical students: an international randomised controlled study.

Irrational prescribing is a habit which is difficult to cure. However, prevention is possible and for this reason the WHO Action Programme on Essential Drugs aims to improve the teaching of pharmacotherapy to medical students. The impact of a short problem-based training course in pharmacotherapy, using a WHO manual on the principles of rational prescribing, was measured in an international multi-centre randomised controlled study of 219 undergraduate medical students in Groningen (Netherlands), Kathmandu (Nepal), Lagos (Nigeria), Newcastle (Australia), New Delhi (India), San Francisco (USA), and Yogyakarta (Japan). The manual and the course presented the students, who were about to enter the clinical phase of their studies, with a normative model for pharmacotherapeutic reasoning in which they were taught to generate a "standard" pharmacotherapeutic approach to common disorders, resulting in a set of first-choice drugs called P(ersonal)-drugs. The students were then taught how to apply this set of P-drugs to specific patient problems on the symptomatic treatment of pain, using a six-step problem-solving routine. The impact of the course was measured by tests before training, immediately after, and six months later. After the course, students from the study group performed significantly better than controls in all patient problems presented (p < 0.05). The students not only remembered how to solve old problems, but they could also apply their skills to new problems. Both retention and transfer effect were maintained at least six months after the training session in all seven medical schools. In view of the impossibility of teaching students all basic knowledge on the thousands of drugs available, this approach seems to be an efficient way of teaching rational prescribing. However, the method should be accompanied by a change in teaching methods away from the habit of transferring knowledge about the drugs towards problem-based teaching of therapeutic reasoning.

Field tests for rational drug use in twelve developing countries.

Increasing efforts are being made to improve drug-use practices and prescribing behaviour in developing countries. An essential tool for such work is an objective and standard method of assessment. We present here a set of drug-use indicators produced and tested in twelve developing countries. We describe practical applications, which include the use of indicators to increase awareness among prescribers in Malawi and Bangladesh, to identify priorities for action (eg, polypharmacy in Indonesia and Nigeria, overuse of injections in Uganda, Sudan, and Nigeria, and low percentage of patients who understood the dosage schedule in Malawi), and to quantify the impact of interventions in Yemen, Uganda, Sudan, and Zimbabwe.

PIP: A set of drug-use indicators produced and tested in 12 developing countries and the recommended method for data collection are presented to improve drug use and prescribing behavior. The International Network for the Rational Use of Drugs in collaboration with the WHO Action Program on Essential Drugs undertook a project to develop and field-test a set of basic drug-use indicators. The method for collecting the data was first tested in Indonesia, Bangladesh, and Nepal; other tests took place in Guatemala, Malawi, Nigeria, Tanzania, and well as in Ecuador, Sudan, and Zimbabwe. In results from 12 developing countries, drug-use patterns were ascertained. The average numbers of drugs per encounter were high in Indonesia and Nigeria (3.3 and 3.8); the prescriptions of 1 or more antibiotics were also high in Uganda and Sudan (56% and 63%), similar to injectable drugs in Uganda, Sudan, and Nigeria (36-48%); and the availability of essential drugs was low in Ecuador (38%). 94% of drugs were prescribed by generic name in Zimbabwe, whereas only 37% were in Ecuador. In Yemen the comparison of an essential drugs project area to a control area demonstrated 1.5 and 2.4 drugs per encounter, 46% and 67% of them antibiotics and 22% and 45% of them injections, respectively. In Uganda, a study on the effect of training showed decline in the use of injections (50% to 41%), improvement in the use of oral rehydration treatment for diarrhea (52% to 89%), and reduction in antidiarrheal drug use (60% to 39%). In rural health facilities in Sudan the drugs prescribed by generic name increased from 17% to 70% between 1989 and 1991. In 10 developing countries the average number of drugs per prescription for general outpatient encounters ranges from 1.3 to 2.2., but in Indonesia and Nigeria it is 3.3 and 3.8. The median of 41% of antibiotics prescribed in the 12 countries reflects actual prescribing, not optimum values.

Acute renal failure at the Lagos University Teaching Hospital: a 10-year review.

The Dialysis Centre at the Lagos University Teaching Hospital was established in November 1981 as the first unit in West Africa to undertake chronic hemodialysis treatment. More than 500 patients have been managed in the center since then. Of these, 175 were cases of acute renal failure. The causes and outcome of these cases have been reviewed. There were 89 males (50.9%) and 86 females (49.1%). The majority, 111 (63.4%), were aged < 40 years. The main cause was sepsis, which occurred in 67 cases (38.3%). Gynecological and obstetric cases were 45 (25.7%), including 14 cases (8%) of pregnancy toxemia. Other causes were hemorrhage 18 (10.3%), obstructive uropathy 6 (3.4%), acute glomerulonephritis 8 (4.6%), and poisoning with "Holy Water" 6 (3.4%) and other nephrotoxins 9 (5.1%). Sixty-nine patients (39.4%) died in hospital, 92 (52.6%) recovered, and the fate of 14 (8%) was unknown as they were transferred from the hospital. Reasons for the high mortality included delayed hospitalization, selection of severe cases, and inability of patients to afford more than only one session of dialysis even though they needed more. It is hoped that as awareness of the value of dialysis increases and early treatment can be sought, the overall mortality will be reduced.

Effect of nifedipine on antipyrine and theophylline disposition.

On the basis of reports that some calcium channel blockers impair the elimination of some drugs, the effect of nifedipine on the disposition of antipyrine and theophylline was assessed in healthy volunteers. Antipyrine half-life of 10.04 +/- 1.43 h (mean +/- SD) after a week intake of nifedipine (20 mg twice daily) was not significantly different from the control value of 10.64 +/- 2.15 h; nor was that of 10.02 +/- 1.49 h after 2 weeks pretreatment with the calcium channel blocker in eight healthy volunteers. Control antipyrine clearance (ml min-1) of 44.40 +/- 10.58 was not significantly different from that of 45.66 +/- 9.34 and 46.87 +/- 9.63 after nifedipine pretreatment of 1 and 2 weeks, respectively. Similarly volume of distribution was unaltered: 0.601 +/- 0.074, 0.591 +/- 0.078 and 0.602 +/- 0.051 l kg-1, respectively. A week pretreatment with nifedipine did not significantly alter either of theophylline half-life (7.32 +/- 0.81 h (control) to 7.50 +/- 0.80 h) or clearance (42.10 +/- 5.84 ml min-1 (control) to 43.77 +/- 4.00 ml min-1) in six volunteers. However the change in volume of distribution: 0.451 +/- 0.053 l kg-1 (control) to 0.483 +/- 0.062 l kg-1 was significant (p less than 0.025). Generally, theophylline plasma levels were lower after nifedipine pretreatment and the difference was significant at 2 and 4 h post-dosing (p less than 0.05). It is suggested that nifedipine, unlike diltiazem and verapamil, is unlikely to interfere with the functional integrity of the hepatic mixed-function oxygenase enzymes, but might displace theophylline from plasma protein.

Debrisoquine oxidation phenotype and susceptibility to lung cancer.

1. It has been suggested that poor metabolisers of debrisoquine are at reduced risk of developing lung cancer from smoking cigarettes. This has been investigated in 82 patients with established cancer of the lung. 2. The frequency of poor metaboliser subjects was not different from that in the normal population. 3. There was no tendency for subjects with lung cancer to metabolise debrisoquine more rapidly than non-cancer subjects. 4. It is concluded that debrisoquine metabolic phenotype is not a good predictor of risk of developing lung cancer in the population at large.

Five years experience of haemodialysis at the Lagos University Teaching Hospital--November 1981 to November 1986.

The Dialysis Centre at the Lagos University Teaching Hospital became operational in November 1981 and caters for acute haemodialysis, chronic maintenance haemodialysis and continuous arteriovenous haemofiltration. In the past 5 years, over 600 patients had presented out of whom 245 could be accommodated within the realities of available facilities and patients' financial status. Of the 245 patients, 25 were discharged against medical advice and five were transferred to hospitals abroad but did not survive. There were 117 patients in end-stage renal failure (ESRF), 75 males, 42 females, ratio M:F 1.8:1, age range 13-69 years, mean 37.5. There were 51 males and 47 females in acute renal failure (ARF), ratio 1.1:1, age range 13-76 years, mean age 32.3 (Table 1). All patients in ESRF had moderate to severe hypertension (diastolic pressure of greater than or equal to 120 mmHg or 22.1 kPa) and a creatinine clearance of less than or equal to 5 ml/min and about 75% had established cardiac decompensation. Full pertinent investigations were precluded or contra-indicated in most patients in ESRF because of late presentation. In only 13 patients was renal biopsy performed and the pathohistologies were end stage renal disease (8), chronic glomerulonephritis (4) and glomerulosclerosis (1). In ARF the cause of the renal damage was multifactorial in 66.7%, with sepsis being the direct cause of death in 60.0%. The commonest conditions were septicaemia (61.4%), nephrotoxin (17.2%), trauma (31.3%), septic abortion (33.3%) and toxaemia of pregnancy (29.0%) (Table 2). The dialysis associated complications which were encountered included shunt infection (7%), burst membrane (9%), suspected pyrogen reaction (5.6%) and femoral vein perforation (0.9%).(ABSTRACT TRUNCATED AT 250 WORDS)

Attenuation of rifampicin-induced theophylline metabolism by diltiazem/rifampicin coadministration in healthy volunteers.

On the basis of reports that diltiazem binds to the hepatic microsomal enzymes and inhibits the metabolism of coadministered drugs, we investigated the effect of a 240 mg daily dose of the calcium channel blocker for a week on theophylline metabolism in 8 healthy male volunteers aged 20-24 years and weighing 56-68 kg. None of theophylline half-life (9.7 h), volume of distribution (0.514 l.kg-1) and total clearance (0.63 ml.min-1.kg-1) after pretreatment differed from the respective control value of 9.5 h, 0.519 l.kg-1 and 0.65 ml.min-1.kg-1. In 6 of the volunteers, 600-mg daily dose of rifampicin for a week induced theophylline metabolism. The control half-life of the bronchodilator (9.6 h) was reduced to 5.5 h and its total clearance (0.64 ml.min-1.kg-1) increased to 1.22 ml.min-1.kg-1. There was no change in volume of distribution. In these 6 volunteers, intake of diltiazem (240 mg daily), concurrently with rifampicin for a week, significantly elevated theophylline half-life to 6.2 h as well as reduced its clearance to 1.03 ml.min-1.kg-1. The volume of distribution did not change. Furthermore, diltiazem-induced absolute fall in theophylline clearance correlated significantly with its post-rifampicin value (r = 0.895). It is suggested that diltiazem has no effect on theophylline metabolism in non-induced subjects. However, rifampicin-induced metabolism of the bronchodilator could be attenuated by diltiazem when the two drugs are given concurrently.

Comparative effects of labetalol and bromazepam on ambulatory blood pressure of Nigerians with labile and stress hypertension.

Twenty Nigerians with labile essential hypertension (LEH) were asked to record their blood pressure and pulse rate for 14-16 hours using the Remler Portable Ambulatory Blood Pressure Recorder while exposing themselves to the stress of Lagos traffic. The average blood pressure (systolic and diastolic) and pulse rate for the test day (ASBP, ADBP and APR) were determined in a cross-over randomised open design before (C), after one week on placebo bidaily (P1), after one week on bromazepam 1.5 mg bidaily (B), after one week on placebo bidaily (P2) and after one week on labetalol 100 mg bidaily (L). Allocation to the active drugs was randomised. All drugs were administered at 8.00a.m. and 8.00p.m. respectively. The maximum blood pressure (systolic and diastolic) and pulse rate MxSBP, MxDBP and MxPR were similarly determined. Both B and L significantly reduced ASBP, ADBP, APR, MxSBP, MxDBP and MxPR but L produced a much greater reduction in the above parameters than B. Side effects observed included drowsiness with B (two subjects) and postural dizziness with L (one subject). Both drugs were effective in controlling LEH but L was more effective than B in reducing stress hypertension.

Theophylline disposition--effects of cimetidine, mebendazole and albendazole.

On the basis of the report that benzimidazoles bind to and inhibit the hepatic cytochrome P-450 enzyme system, the effect of mebendazole and albendazole on theophylline disposition was studied in 12 volunteers. Mebendazole at a dose of 100 mg b.d. for 3 days did not significantly alter the theophylline half-life, volume of distribution or clearance in a group of six. In another group of six adult volunteers, albendazole (400 mg) pretreatment did not alter the same parameters. However, in this second group, pretreatment with cimetidine (400 mg t.d.s. for 5 days) significantly increased theophylline half life from 7.7 to 9.8 +/- 1.5 h (P less than 0.001) and reduced its clearance from 0.8 to 0.60 +/- 0.1 ml min-1 kg-1 (P less than 0.005). The volume of distribution was not altered significantly. It is concluded that at therapeutic doses it is unlikely that mebendazole or albendazole will induce theophylline toxicity if co-administered with the bronchodilator. Cimetidine-induced impairment of theophylline metabolism is such that toxicity will be more likely in individuals with initial high theophylline clearance.

Placental and milk transfer of chloroquine in humans.

The placental and milk transfer of chloroquine was studied in seven subjects and six subjects, respectively. Seven pregnant women at term were administered chloroquine phosphate (5 mg/kg) i.m. The maternal blood and arterial and venous umbilical cord blood were obtained during delivery. The maternal chloroquine blood levels varied from 0.438 to 1.193 micrograms/ml. The venous cord blood ranged from 0.607 to 0.869, whereas the arterial levels ranged from 0.480 to 0.905 micrograms/ml. Six subjects who were administered chloroquine phosphate (5 mg/kg) postpartum had chloroquine milk levels of 0.192-0.319 micrograms/ml. The milk:blood ratio ranged from 0.268 to 0.462. Chloroquine readily crossed the placenta and was excreted into the breast milk.

Lack of inhibitory effect of metronidazole on theophylline disposition in healthy subjects.

The effect of metronidazole, at a dose of 1.2 g daily, on theophylline disposition was studied in 10 healthy adult volunteers. Neither theophylline half-life, volume of distribution nor total body clearance was altered by the anti-microbial. It is concluded that metronidazole does not impair theophylline metabolism despite the fact that it is a substituted imidazole.

The effect of beta-adrenoceptor blockers on the absorption and excretion of chlorothiazide in man.

The effect of beta-adrenoceptor blockers on the absorption and elimination of the diuretic chlorothiazide was studied in healthy subjects. A week of pretreatment with either pindolol (10 mg twice daily) or propranolol (80 mg twice daily) resulted in significant reduction in 36 h mean cumulative urinary recovery of chlorothiazide in two groups of six subjects compared with a control (untreated) group. A week of pretreatment with atenolol (100 mg daily) did not significantly alter 36 h cumulative urinary excretion in another group of six subjects. None of the beta-blockers significantly changed chlorothiazide half-life. It is suggested that the non-selective (as opposed to the cardioselective) beta-blockers reduce chlorothiazide absorption by the mechanism(s) discussed.