Significance of acetylator phenotype in pharmacokinetics and adverse effects of procainamide.

The pharmacokinetics and development of antinuclear antibodies (ANAs) during procainamide (PA) therapy were studied in 35 patients with ventricular arrhythmias. Sixteen of the subjects were rapid and 19 were slow acetylators. Twenty-six of them (13 rapid and 13 slow acetylators) received PA therapy (2.4g sustained-release PA X HCl daily in three doses) for at least 16 weeks. On maintenance therapy, rapid acetylators had insignificantly lower serum PA concentrations and slightly higher N-acetylprocainamide (NAPA) concentrations than slow acetylators. The unchanged PA fraction (PA/PA + NAPA) in the rapid acetylators was somewhat lower than in the slow acetylators. Rapid acetylators excreted more NAPA in urine than did slow acetylators (p less than 0.05), whereas the difference in PA excretion was not significant. More than 80% of the given drug was excreted as PA and NAPA. Spontaneous or exercise-induced arrhythmias were recorded in 6 rapid and 8 slow acetylators. ANAs (titre at least 20) appeared in 6 rapid and 8 slow acetylators. The mean time until ANA development in rapid acetylators was only marginally longer than in slow acetylators. The results suggest that acetylation phenotyping is not of great significance in predicting the development of ANAs during PA therapy.

The use of clonidine and practolol in the treatment of hypertension.

The antihypertensive effects of clonidine hydrochloride and practolol were compared in 42 men, aged 45 years, who had not received any antihypertensive therapy before, except one patient. The diastolic blood pressures were at least 110 mmHg on two successive visits to the health centre before their selection to the trial. One half of them were classified into the WHO group 1 and the other half into group 2. There was no statistical difference in the systolic and diastolic blood pressures between clonidine and practolol group at the end of placebo period. The study started with a three-week placebo period. Thereafter, 20 patients were given clonidine 0.225 mg and twenty-two practolol 200 mg daily. The next control was carried out after three weeks. The dosage was kept unchanged or increased according to the antihypertensive response. After three weeks, clonidine and practolol dosages were checked again, and 25 mg of chlorothiazide were added to the treatment in 15 clonidine cases and in 18 practolol cases. After the next three-week period, the same regimen was continued on most patients for 6-9 weeks. The daily dosage of clonidine varied from 0.225 to 0.900 (mean 0.394) mg and that of practolol from 200 to 600 (mean 382) mg. Both regimens resulted, when individually adjusted, in a mean systolic blood pressure level of less than 150 mmHg and diastolic pressures less than or equal to 100 mmHg. Hydrochlorothiazide potentiated the blood pressure effect almost equally in both regimens. The blood pressure reduction was statistically significant (p less than 0.05) both in the clonidine and practolol group. There was no significant difference of the mean blood pressures after the active drug therapy between these two groups. A moderate reduction of pulse rate was observed in both main groups, but it was not related to the antihypertensive efficacy. Side-effects were mild. Dryness of the mouth and sedation were more common in patients receiving clonidine. No oculocutaneous or other "immunological" manifestation were seen during the 15-18 weeks' practolol therapy.

Intravenous streptokinase treatment and serum C-reactive protein in patients with acute myocardial infarction.

Serum concentrations of C-reactive protein were studied in 23 patients with acute myocardial infarction. In 14 patients who did not receive thrombolytic treatment there was a linear relation between infarct size (determined by serial creatine kinase-MB determinations and thallium-201 isotope emission tomography) and the C-reactive protein response. The correlation coefficient between the concentration-time integrals of creatine kinase-MB and C-reactive protein was 0.96. The correlation coefficient between the creatine kinase-MB concentration-time integral and the peak serum value of C-reactive protein was 0.93. In the nine patients who received intravenous streptokinase treatment there was also a positive correlation between the concentration-time integrals of creatine kinase-MB and C-reactive protein. The relation, however, depended on the success of the treatment. In patients with successful reperfusion the C-reactive protein response was only approximately 20% of that in patients in whom reperfusion failed or who received no thrombolytic treatment and who were matched by infarct size. When thrombolysis was successful the correlation coefficient between the concentration-time integrals of creatine kinase-MB and C-reactive protein was 0.86. Daily measurement of serum C-reactive protein is useful in evaluating infarct size in patients with acute myocardial infarction who do not receive thrombolytic treatment. In patients treated with streptokinase C-reactive protein concentrations may be used to assess the success of thrombolysis.

Self-poisoning patients in an intensive care unit.

The purpose of the present study was to analyze 147 self-poisoning cases, admitted within one year to an intensive care unit (ICU). About half the patients had taken only one substance. The most important poisons were alcohol (52% of the cases), neuroleptics (37%), anxiolytics (28%), hypnotics (27%), antidepressants (16%) and analgesics (13%). On admission, 25% of patients were hypotensive, 25% of patients had cardiac arrhythmias or conduction disturbances. Retention of carbon dioxide was found in 28% of cases. In 60% of the patients emptying of the stomach contents was performed. Four patients, all of whom survived, were treated with haemodialysis. Most of the patients were treated in the ICU for less than two days. Three patients died, all of whom had taken large amounts of poisons and/or were in a critical condition on admission. Among men the most common psychiatric disorder preceding the poisoning was alcoholism: among women it was depression. A very serious attempt at suicide was considered to be the reason with 38% of the cases. About two thirds of the patients were sent for psychiatric aftercare. To reduce further suicide attempts, large general hospitals should have psychiatric outpatient clinics or consultation facilities.

Treatment of hypertension successively with a diuretic, clonidine or a beta-blocking agent and hydralazine.

The present study was carried out in an homogenous group of 49 untreated hypertensive patients, all aged 45 years. Diastolic blood pressure was equal to or greater than 110 mmHg in successive measurements; eleven patients were classified as WHO group II, and the others as WHO group I. An initial placebo period of 3 weeks was followed by cyclothiazide medication with a good response in 6 patients. The remaining patients were given either clonidine or practolol, and by adjustment of the dose a good response was obtained in 31 patients. In these cases the treatment was exchanged after 6 weeks. The antihypertensive effect of relatively small doses of clonidine was equal to that of practolol. Since completion of the study practolol has been withdrawn because of the emergence of long term toxic effects. In 12 cases, hydralazine had to be added to obtain a satisfactory response. Mild side-effects were common, especially at the beginning of clonidine treatment, but they did not necessitate discontinuation of treatment. Further comparative studies of clonidine and beta-blockers should be carried out and more experience with the combination of clonidine and vasodilators in the treatment of hypertension is necessary.

Uriglox and quantitative urine microscopy in diagnosis of urinary tract infection.

The aim of this study was to find an alternative to the sole use of abundant cultural findings as a basis for the diagnosis of urinary tract infection (UTI). For this purpose, the results obtained from the bacteriological culture of daytime urine specimens from 154 students by the dip slide method were checked against the findings from the quantitative culture, microscopy and Uriglox testing of the first morning urines voided later at home. As a diagnostic criterion, the finding of 10(5) or more bacteria/ml urine in two successive cultures had an error of 19%. For the simultaneous occurrence in the morning urine of abundant bacteria (larger than or equal to 10(5)/ml) and a subnormal glucose concentration (as revealed by the Uriglox test), this error was 1.5%. Only the latter combination showed, therefore, the presence of UTI at the confidence level of larger than or equal to 95%, or was "clinically significant". The specificity indices for the Uriglox test and the quantitative culture were 0.99 and 0.97, respectively. Microscopy of the morning urine showed 10(3) or more bacteria/ml in all the subjects with infection but the number of leucocytes was normal in a fifth of them. The specificity indices for microscopic counts of 10(3) or more organisms/ml and 10 or more leucocytes/mm3 were 0.74 and 0.94, respectively. For higher counts, i.e. 10(5) or more bacteria/ml and 50 or more leucocytes/mm3, the specificity index of positive microscopy was 1.0. This specificity level was, however, attained at the expense of the sensitivity, which for 10(5) or more organisms/ml was 0.67 and for 50 or more leucocytes/mm3 0.53. It is concluded that abundant bacterial contamination of specimens often decisively complicates the diagnostic use of urine culture, and therefore the combined use of quantitative culture, microscopy and the Uriglox test is recommended as the principal tool for the diagnosis of UTI in ordinary hospital and ambulatory health services.