Blood pressure reduction by incremental infusion of labetalol in patients with severe hypertension.

1. Labetalol was given by incremental intravenous infusion to nineteen severely hypertensive patients, of whom nine were refractory to previous oral antihypertensive therapy. 2. Smooth reduction of arterial pressure was achieved in twelve subjects; one remained resistant to labetalol up to 160 mg/h; a sudden fall in pressure occurred in the remaining six. No serious complications were encountered. Blood pressure control was accompanied by slight byt significant reduction in heart rate and in plasma angiotensin II and aldosterone concentrations. 3. The administration of labetalol in this way appears to be a useful technique in patients requiring rapid reduction of arterial pressure, although close and continuous supervision is necessary.     

The effect of dosage forms on the duration and continuity of action of belladonna alkaloids

Summary A placebo-controlled, double-blind evaluation of encapsulated sustained release and nonsustained release forms of belladonna alkaloids was conducted to compare the effectiveness of these oral dosage forms. The evaluation was conducted according to a balanced, Latin Square design. A modified Mushin Salivary Suppression Test was used as the criteria for measuring results.Results of the evaluation indicate that (1) the Modified Mushin Salivary Suppression Test, under the conditions employed in this study, provides a reliable method of obtaining quantitative measurements of saliva flow; (2) a single dose of the nonsustained release form of belladonna produces effects that last less than six hours; (3) a single administration of the sustained release dosage form produces a prolonged (about 12 hours) pharmacological effect that is devoid of the pronounced peaks and valleys commonly observed with multidose administration of these drugs in nonsustained release form; (4) results with different lots of the sustained release dosage form are adequately reproducible, indicating the uniform formulation of this dosage form and the reliability of the test method; and (5) the Latin Square method of designing the evaluation minimizes many of the interacting variations that occur in evaluations of this type.Clinical work was done at the Section of Gastroenterology, Veterans Administration Center, Los Angeles, California, under the supervision of Dr. Grossman. All other laboratory work was done at Smith Kline and French Laboratories, Philadelphia, Pa.     

Plasma and cerebrospinal fluid probenecid concentrations as related to accumulation of acidic biogenic amine metabolites in man

The oral administration of probenecid (100 mg/kg/18 h) to depressed patients results in marked increases in the acidic metabolites of biogenic amines in the cerebrospinal fluid (CSF). In contrast to previous reports (where lower dose rates of probenecid were employed) the increases in 5-hydroxyindoleacetic acid and homovanillic acid were independent of plasma or CSF probenecid concentrations. Higher plasma and CSF probenecid concentrations were found in this study. The binding of probenecid to plasma proteins for each patient was also determined to examine the pharmacodynamics of probenecid distribution. The ratio of probenecid in CSF to the calculated free probenecid in plasma was higher (0.4) and more constant than previously noted. At these higher dose levels, probenecid successfully competes with the active transport process for biogenic amine acidic metabolites and also appears to block its own removal from CSF.A preliminary report of this work was presented (Fed. Proc. 32, 696 (1973).     

Further investigation and initial clinical use of advanced CT display capability.

The AUR Memorial Award Paper (this issue, pp. 403-416) described a technique for providing thin transverse CT sections and for redisplaying this transverse CT data as coronal or sagittal anatomic planes. This paper presents additional experience with cadaver models and the results of initial applications of the method to data obtained from living patients. The technique potentially enhances the clinical usefulness of CT scanning by providing precise triangulation and resolution of normal and abnormal structures.     

Transplantation of autoimmune potential. II. Glomerulonephritis in lethally irradiated DBA/2 recipients of NZB bone marrow cells.

Lethally irradiated (850 rads) DBA/2 mice which had been transplanted 10 months previously with 2 times 10-6 bone marrow cells from 3-week-old donors of the H-2-histocompatible NZB, BALB/c and DBA/2 strains were examined for manifestations of autoimmune disease. Also studied were lethally irradiated (950 rads) NZB mice grafted with NZB marrow. Strongly positive antinuclear antibody responses were present in all NZB and DBA/2 recipients of NZB marrow, but absent in DBA/2 mice grafted with BALB/c and DBA/2 marrow cells. The antinuclear antibody-positive animals had glomerulonephritis with the deposition of globulin in or along the basement membranes. These observations support the view that the potential for autoantibody formation and subsequent autoimmune disease development is inherent to the NZB hemopoietic stem cell and their progeny.