Effects of doxycycline in actively purging cholera patients: a double-blind clinical trial

In 51 actively purging cholera patients the efficacy of doxycycline, a long-acting tetracycline, was compared with a placebo and tetracycline hydrochloride. Seventeen patients who were given doxycycline at the recommended dose of 2 mg/kg at the beginning of the study, at 12 h, and at the repeated dose once daily purged a mean volume of 5.1 liters of stool and received an average of 5.7 liters of intravenous fluid. Nineteen patients receiving the placebo purged 10.1 liters of stool and received 9.7 liters of fluid. Fifteen patients given tetracycline hydrochloride at 6-h intervals passed 4.8 liters of stool and received 5.5 liters of fluid. The durations of diarrhea calculated in 8-h periods were 3.5, 8.0, and 4.1 h in the respective groups receiving doxycycline, placebo, and tetracycline. The differences between the doxycycline and placebo treatments and the tetracycline and placebo treatments were statistically significant. Those receiving doxycycline became vibrio-free in about 3 days as compared with 2 days for those receiving tetracycline; the group given the placebo were vibrio positive for the duration of their hospitalization. The results show that in the treatment of cholera the administration of doxycycline once daily has effects equal to those when tetracycline is administered at 6-h intervals. This is a distinct advantage because it decreases the demand on nursing personnel in epidemics. Also, doxycycline may be safely administered in cases of suspected renal failure from prolonged shock in cholera.     

Differing effects of the vasodilator drugs, prazosin and diazoxide on plasma renin activity in the dog

1. The effects of intravenous (i.v.) administration of the vasodilator drugs prazosin or diazoxide on blood pressure and plasma renin activity were evaluated in the anaesthetized dog. 2. Prazosin and diazoxide both induced a rapid reduction in the mean arterial pressure to 73% and 75% of control values respectively. 3. Prazosin lowered plasma renin activity to 62% (P less than 0-025) of the control value whereas diazoxide raised plasma renin activity to 178% (P less than 0.05) of the control value. 4. The combination of vasodilatation and low renin activity observed following the administration of prazosin is unique, and may have clinical significance if these factors reduce the vascular complications of hypertension.     

Axonal excitability and motor propagation velocity of peripheral nerves in patients with acute vascular lesions of the brain

From measurements of maximum and minimum motor nerve propagation velocity and neuronal excitability we conclude that there is a functional loss of motor units and distal nerve "dying back" in persons affected with unilateral acute cerebral vascular lesions. The study also suggests that transynaptic degeneration affects the lower motor neurone function on both sides.     

Change in pulmonary venous admixture with varying inspired oxygen

Pulmonary venous admixture (Qsp/Qt) was analyzed as a function of fractional concentration of inspired O2 (FIO2) in 30 patients who required postoperative mechanical ventilation. Pulmonary and radial artery blood-gas tensions and pH were measured and Qsp/Qt was calculated with FIO2 ranging from 0.21 to 1. In all patients, Qsp/Qt decreased when FIO2 was increased from 0.21 to 0.4 and then stabilized to an FIO2 of approximately 0.6. As the FIO2 was increased to 1, Qsp/Qt increased. Since the inhalation of gas mixture with FIO2 greater than or equal to 0.6 increased right-to-left intrapulmonary shunting of blood, we recommend respiratory function be evaluated during inhalation of a clinically useful concentration of O2 rather than at an FIO2 of 1.     

Hypocholesterolemic agents V: Inhibition of beta-hydroxy-beta-methylglutaryl coenzyme A reductase by substituted 4-biphenylylalkyl carboxylic acids and methyl esters

Eleven substituted 4-biphenylylalkyl carboxylic acids and three methyl esters were synthesized and assayed for inhibition of rat liver beta-hydroxy-beta-methylglutaryl coenzyme A reductase. Five of the acids were analogs, resulting from various isosteric replacements of the carbonyl and ether oxygens of the previously described reversible inhibitor 1-(4-biphenylyl)pentyl hydrogen succinate. No significant change in activity was noted, except upon introduction of an amide linkage where a decrease in inhibition was found. Six carboxylic acids and three methyl esters, all containing the 4-biphenylyl radical but lacking the n-butyl side chain found in 1-(4-biphenylyl)pentyl hydrogen succinate, also were inhibitors of the reductase.     

Study of in vivo tumor state and response to therapy by analysis of DNA distribution

Comparative studies of cefamandole and cephalothin were carried out in 32 cancer patients. After rapid intravenous injection of 1 gm cefamandole or cephalothin, the peak mean serum concentrations in 11 patients achieved at 0.25 hr were 103.4 mcg/ml and 56.7 mcg/ml, respectively. Except at 6 hr, the serum concentration of cefamandole was higher (p less than 0.05) at all times. The terminal half-lives (t 1/2) were similar, being 1.2 hr for cefamandole and 1.0 hr for cephalothin. Cefamandole, 1 gm intramuscularly, induced a peak mean serum concentration of 26.6 mcg/ml at 1 hr, with a slow decay. Intermittent cefamandole (2 gm intravenously every 6 hr) induced very high mean serum concentrations (7 patients), but at 4 hr the concentrations were similar to those after 1 gm intravenously. Per cent of urinary excretion was similar for both drugs regardless of dose and mode of administration. Continuous-infusion cefamandole or cephalothin (2 gm loading followed by 2 gm every 6 hr) in 14 patients showed consistently higher serum concentrations for cefamandole (p less than 0.05) over a 5-day period. There was no evidence of drug accumulation in the multiple-dose studies. Both the single- and multiple-dose schedules were well tolerated.     

Urography during pregnancy

A review of 22,971 pregnancies from 1969-74 reveals that the reasons for requesting excretory urography were renal colic of pregnancy 11, pyelonephritis 8, renal contusion 2, threatened abortion 1, and suspected degeneration of fibroid 1. The final diagnoses were similar except that two patients with torsion of ovarian cysts and a renal calculus were discovered. The only intravenous pyelographic examination that was decisive for diagnosis was in a patient with a ureteric calculus. Careful clinical correlation should reduce excretory urography during pregnancy.     

Stimulation of nucleic acid and protein synthesis in the epididymis and accessory organs of the rat by testosterone

The metabolism of 3H-testosterone by the epididymis and accessory organs of adult male rats exposed continuously to microdoses of cyproterone acetate from subcutaneous capsules were studied. The major metabolite of 3H-testosterone in the epididymis, vas deferens and ventral prostate of control rat was dihydrotestosterone while the formation of androstanediol by these tissues was low. The highest percentage of DHT was formed by the ventral prostate and cauda epididymis. In rats exposed to cyproterone acetate for four months, the conversion of testosterone to DHT was inhibited in all the tissues but maximally in the ventral prostate and cauda epididymis. In these rats, the secretory function of the ventral prostate was normal while that of the epididymis was markedly decreased. These data are discussed based on the differential thresholds of androgens required to regulate the functions of the accessory organs.     

A new method of treatment for mallet finger. A preliminary report

An infant with a typical Edwards syndrome and a modal chromosome number of 46 is reported. In all cells analyzed one chromosome G was missing and an additional chromosome similar to a pair No. 16 was present. The phenotype of the child indicates that the extra element is a translocation between G and 18 chromosomes as in one case described previously.