A controlled comparison of the antihypertensive effects of labetalol and alpha-methyldopa.

An open crossover study was carried out in 10 Arab patients with mild to moderate hypertension to compare the effectiveness and tolerability of labetalol with alpha-methyldopa. Patients were started on either 100 mg labetalol or 250 mg alpha-methyldopa 3-times daily and, if necessary, the dosage adjusted by standard increments every 2 weeks over a period of a month until satisfactory control was achieved. This dosage was then maintained for a further 6 weeks before the patients were crossed over to the alternative treatment, similarly adjusted, after a wash-out period of 2 weeks on placebo. The results showed that both treatments produced effective blood pressure control and there was no significant difference in the maximum reduction achieved. The effect of the two drugs on heart rate was also similar. Both treatments were generally well-tolerated and side-effects were mild and similar with either drug.

Tests of efficacy of antidotes for removal of methylmercury in human poisoning during the Iraq outbreak.

Three complexing agents and a thiolated resin were tested for their ability to reduce the T 1/2 of methylmercury in blood during an outbreak of human poisoning. The slope of the line relating the natural logarithm of the blood concentration to time during treatment was calculated by a parametric (linear regression) and a nonparametric (two-point) method. The mean slope for each treatment group was calculated and the T 1/2 was calculated from the mean slope. Both the linear regression and two-point methods yield similar mean values. The "two-point" T 1/2 will be quoted here. The mean T 1/2 in six patients receiving no specific treatment was 65 days and in 10 patients receiving placebo was 61 days, and these values did not differ from those reported in the literature. All four treatments significantly reduced the mean T 1/2 values below the mean for the combined placebo and no treatment groups. Sodium 2,3-dimercaptopropane-1-sulfonate was the most effective agent, reducing the mean T 1/2 in 10 patients to 10 days. The thiolated resin given to eight patients produced a mean T 1/2 of 20 days. The penicillamines also produced a significant reduction in T 1/2 values; the mean T 1/2 for D-penicillamine in 12 patients was 26 days and N-acetyl-DL-penicillamine in 17 patients yielded a mean T 1/2 of 24 days. This is the first report of the effects of sodium 2,3-dimercaptopropane-1-sulfonate and resin in human subjects exposed to methylmercury. No adverse effects were observed in any of the treatment groups. A clinical trial was not possible but it is concluded that agents that reduce blood levels and accelerate excretion are probably clinically useful if given before irreversible damage has occurred.

Clinical and epidemiological aspects of methylmercury poisoning.

An opportunity to study the effects of methylmercury poisoning in humans was provided by the large outbreak in Iraq in 1971-2. In adults, poisoning resulted from the ingestion of home-made bread prepared from methylmercury-treated seed grain and there was a highly significant correlation between the amount of bread ingested and blood mercury levels. Poisoning in infants resulted either from prior exposure in utero or from suckling or both. Blood mercury levels were higher in infants and children than in adults. There was no increased incidence of congenital defects. Symptoms and signs of poisoning and histopathological changes were mainly confined to the CNS. Symptoms developed, on average, 1-2 months after exposure. In children there was mental retardation with delayed onset of speech and impaired motor, sensory and autonomic function. Severely affected children were blind and deaf. In adults, the clinical picture could be classified as 1, mild (mainly of sensory symptoms) 2, moderate (sensory symptoms accompanied by cerebellar signs) and 3, severe (gross ataxia with marked visual and hearing loss which, in some cases, progressed to akinetic mutism followed by coma). Grades 1 and 2 carried a better prognosis thant grade 3. Interference with transmission at the myoneural junction was found in 14% of patients studied. There was no evidence of peripheral nerve involvement per se and sensory symptoms may be of central origin. The clinical differences between the Iraqi and Japanese outbreaks may be a result, in part at least, of the severe, prolonged and continuous exposure which occurred in the latter outbreak. Improvement was observed among the mild and moderate group. Treatment with chelating agents, thiol resin, haemodialysis and exchange transfusion lowered blood mercury concentrations but produced no convincing clinical benefit. To be effective, treatment may need to be instituted soon after exposure.

Intoxication due to alkylmercury-treated seed--1971-72 outbreak in Iraq: clinical aspects.

Sixty-six hospitalized patients suffering from chronic methylmercury poisoning were examined in Baghdad during 1972. The poisoning was attributed to consumption of home-made bread prepared from seed wheat treated with mercurial fungicide. The age incidence ranged between 4 and 70 years.Of the various clinical features encountered, neurological symptoms and signs were predominant and included muscular weakness, numbness, unsteady gait, paraesthesia, dysarthria, mental disturbances and, in severe cases, blindness, partial deafness, stupor, coma, and death. Involvement of the cardiovascular, urinary, gastrointestinal and haemopoietic systems, which was commonly encountered in ethylmercury poisoning in the 1960 outbreak in Iraq, was unusual.The severity of symptoms and signs was, broadly speaking, dose-dependent; high exposure led to severe clinical manifestations, but variations existed. Criteria, based on the clinical manifestations, were set for grading the severity of cases. The series included 2 asymptomatic cases, 20 mild, 20 moderate, 14 severe, and 10 very severe. In the latter group 5 patients died from failure of the central nervous system.The severely poisoned patients died irrespective of the medical treatment received. After 2 years of observation, most patients graded as mild or moderate cases lost their symptoms completely. Severe cases improved slowly, although ataxia, diminution of visual field and acuity and paraesthesia were still present. Thus, the previously accepted view that neurological signs were irreversible has been disproved.

Organomercury poisoning in Iraq: history prior to the 1971-72 outbreak.

Mercury has been used medically in the Middle East since time immemorial. Organomercury compounds were first used as seed dressings in Iraq in 1955. During the years 1955-59, 200 cases of poisoning occurred. A more clearly defined outbreak occurred in 1960, involving approximately 1000 hospital admissions. Twelve patients from two families affected in this outbreak were re-examined in 1973, and showed considerable improvement.

Electrophysiological studies of peripheral nerves in patients with organic mercury poisoning.

Nineteen patients with organic mercury poisoning were examined clinically and electrophysiological studies were carried out on their peripheral nerves. Four severely affected patients were disorientated, restless, and unable to speak. Vision was abnormal in nearly half the patients, usually consisting of gross constriction of visual fields with preservation of central acuity. Severe cerebellar abnormalities were present in most. Paraesthesiae were common. On sensory examination, all except three patients had one or more of the following abnormalities: reduced appreciation of pin prick peripherally, defective position sensation, abnormal two-point discrimination, astereognosis. Vibration sensation was normal in all. Despite these sensory findings no electrophysiological abnormality was demonstrated in the peripheral nerves. It is suggested that the sensory disturbances are predominantly or entirely due to damage to the central nervous system.

Sensitivity to mycobacterial antigens.

In a study carried out in 1971, each of 3 030 persons was tested simultaneously with tuberculin RT 23 and two other PPD sensitins-PPD-S and PPD-A, PPD-B and PPD-Y, or PPD-G and PPD-F. Of the 2 558 persons whose reactions were read, 20.2% had previously been vaccinated with BCG and 79.8% were unvaccinated. RT 23 and PPD-S produced almost identical mean indurations. Both elicited much higher reactions than the sensitins prepared from atypical mycobacteria. Correlation of the sizes of induration obtained with RT 23 and with the other sensitins showed that low-grade sensitivity was due to cross-reactions to human tuberculous infection and that in no case did an "atypical" sensitin produce an induration of wider diameter than RT 23 did. It is concluded that nonspecific tuberculin sensitivity was not demonstrated in this study.