310 Southern Society for Clinical Research

CLINICAL PHARMACOLOGY OF FLUMETHIAZIDE, AN

ORALLY EFFECTIVE DIURETIC AND ANTIHYPER-

TENSIVE AGENT. Ralbh V. Ford,* A. C. Montero and J. B. Rochelle, III. Dept. of Medicine and Pharmacology, Baylor Univ. College of Medi- cine, and Medical Service of V. A. Hospital, Houston, Texas.

Flumethiazide [6-(trifluoromethyl)-1,4,2-ben- zothiadiazine-7-sulfonamide,1 ,l -dioxide] differs structurally from chlorothiazide in the presence of the tri-fluro group in place of the chloride. We have used previously described technics for the bioassay of diuretic potency, electrolyte excre- tion effects, serum biochemical changes, repeti- tive effectiveness and antihypertensive potency. The antihypertensive effects were observed in twenty-five outpatients while all other studies were carried out under controlled metabolic conditions.

Flumethiazide administered in doses of 1.0 and 2.0 gm., orally, is 0.7 times as potent as meralluride (Mercuhydrin@), intramuscularly, as a natriuretic agent. (Diuril is 0.8 times as potent.) However, there is an increase in sodium excretion at doses as low as 250 mg. The effects on electrolyte excretion are similar to those observed after the administration of chloro- thiazide (primarily changes in sodium and chloride, with small changes in potassium and bicarbonate). The drug is repetitively effective on continuous daily use and produces minor disturbances in serum biochemical architecture similar to that of chlorothiazide. There is no significant difference in its antihypertensive potency from that of chlorothiazide.

Flumethiazide appears to be another valuable agent in the management of edema and hypertension.

INVESTIGATIONS CONCERNING THE STAPHYLO-

COCCAL PROBLEM IN HOSPITALS. James B. Grogan and Curtis P. Ark * Surgical Bacteriology Labora- tory and Dept. of Surgery, Univ. of Mississippi School of Medicine, Jackson, Miss.

Phage type and sensitivity patterns were determined on staphylococci from two groups: (1) nose and throat cultures isolated from pa- tients and (2) clinical infections. Sixty-five per cent of hospital patients harbored coagulase- positive staphylococci of which 65 per cent were resistant to treatment with one or more anti- biotics. Resistant 80-81 strains were found to be carried by 20 per cent of the patients.

In 477 coagulase-positive cultures of staphylo- cocci isolated from patients with various infec- tions, 73 per cent were resistant to treatment with one or more antibiotics. Strain 80-81 was found in 22 per cent of these patients. A comparison of the resistant patterns between the two groups indicates that 80-81 strains from patients with infections are more resistant than those from cultures of the nose and throat.

When varying dilutions of staphylococci were injected intraperitoneally into mice the 80-81 strains appeared to kill more in high dilution.

Control of infections requires constant atten- tion to phage type and resistant patterns. The disc method has proved to be satisfactory for screening and an improved method permits the phage typing of 100 cultures daily.

STAPHYLOCOCCAL BACTEREMIA IN DOGS: EFFECT

OF UREMIA, SPLENECTOMY, AND SPLENECTOMY

PLUS PORTACAVAL SHUNT ON THE RATES OF

CLEARANCE FROM THE BLOOD STREAM. James B. Grogan, Richard S. Doyle and James D. Hardy,* Dept. of Surgery, Univ. of Mississippi Medical Center, Jackson, Miss.

Normal dogs, dogs with uremia, splenectomy, and splenectomy plus portacaval shunt were injected intravenously with 5 cc. of a heavy saline suspension of a coagulase-positive strain of Staphylococci aureus. Serial blood samples were taken from the femoral vein, diluted in sterile saline and plated.

The results from at least three dogs in each group have been studied and the clearance curves plotted on semilogarithmic paper. There was little difference in the first phase of clear- ance in the different groups. After a rapid initial clearance rate within the first thirty minutes, clearing was continued at a much slower rate. Bacteremia appeared to persist at a higher level in animals having splenectomy and portacaval shunt than in the normal control animals. While in the normal dogs the blood stream was sterile before injection, after injection bacteremia persisted for days until it finally cleared or until the defense mechanisms of the hosts were over- come and death occurred.

PULMONARY RESECTION: EFFECT OF INITIAL VEIN

LIGATION UPON SEQUESTRATION OF BLOOD IN LUNG.

James D. Hardy,* James T. Croley and James P. Spell. Dept. of Surgery, Univ: of Mississippi Medical Center, Jackson, Miss.

AMERICAN JOURNAL OF MEDICINE