[Effectiveness and tolerance of combined verapamil retard and hydrochlorothiazide. Results of a double-blind, randomized study]. / Wirksamkeit und Verträglichkeit der Kombination Verapamil retard und Hydrochlorothiazid. Ergebnisse einer doppelblinden, randomisierten Studie.

AIM: To determine, in a multicenter study, whether the fixed combination of verapamil retard (240 mg) and hydrochlorothiazide (12.5 mg) is capable of lowering blood pressure more effectively than either of the substances alone or placebo, while retaining good tolerability. METHOD: A total of 173 patients who, after a four-week run-in period had a diastolic blood pressure of at least 100 and not more than 115 mm Hg, were randomized to six weeks of monotherapy with one of the two substances, placebo or the fixed combination. RESULTS: Combination treatment proved superior to monotherapy with either substance in lowering the diastolic blood pressure (p < 0.05). Also in terms of normalization (diastolic pressure < 90 mm Hg) the combination was clearly superior (p < 0.05). During the study no side effects beyond those associated with the single substances, occurred.

The addition of doxazosin to the treatment regimen of hypertensive patients not responsive to nifedipine.

The efficacy and safety of doxazosin, a selective alpha 1-inhibitor, were assessed in hypertensive patients who failed to respond to nifedipine. Fifty patients were entered into a study that involved three phases: (1) a 2-week baseline period, (2) a 10-week period in which patients received doxazosin, 1 to 8 mg, once daily, and (3) a 4-week maintenance period. After 14 weeks, all 43 efficacy evaluable patients were considered therapy successes (sitting diastolic blood pressure either less than or equal to 90 mm Hg or greater than or equal to 10 mm Hg reduction) at a mean daily dose of 3.1 mg. Ninety-three percent achieved blood pressure control (sitting diastolic blood pressure less than or equal to 90 mm Hg) at a mean dose of 3.1 mg once daily. By the final treatment visit, sitting systolic and diastolic blood pressures of efficacy evaluable patients were reduced (p less than 0.05) by 16/18 mm Hg from a mean baseline of 157/103 mm Hg to a final value of 141/85 mm Hg. The most prevalent side effect was vertigo (six patients). Most side effects were mild or moderate and disappeared or were tolerated with continued therapy. No clinically significant laboratory changes were apparent, and no trends were observed with regard to organ systems or correlations with dose or duration of treatment. The investigators' global assessment was excellent or good for 98% of patients for both efficacy and toleration. From baseline to final visit there was a highly significant reduction of 17% (p less than 0.001) in the calculated coronary heart disease risk score, which was based on the Framingham equation.

[Inherited hemolytic anemia due to pyruvate kinase deficiency: II. Density-layer centrifugation of erythrocytes (author's transl)]. / Familiäre hämolytische Anämie durch Pyruvatkinasedefekt. II. Nachweis der Enzyminstabililät durch Dichtezentrifugation der Erythrozyten.

Heterogeneous clinical features of inherited hemolytic anemia due to pyruvate kinase (PK) deficiency were observed in three related homozygous patients. Erythrocytes were separated into old and young cells by means of density-layer centrifugation using a new supporting medium: Stractan-Urografin gradients. Those fractions containing older RBC disclosed defective PK which resulted in an impaired metabolism. Following an intake of chloramphenicol the clinical course of one female family member converted to acute monocytic leukemia. Thus, the report of a PK instability trait, in one family member associated with pancytopenia which converted in leukemia, suggests that inherited red cell enzyme deficiency might be also an expression of the vulnerability of the hematopoietic stem cells.

[Glucocorticoid-induced effect of erythropoietin in haemolytic anaemia with uraemia and red cell enzyme deficiency (author's transl)]. / Glukokortikoid-induzierte Erythropoetinwikung bei urämischen und enzymopenischen Hämolysen.

The effect of 6-methylprednisolone (GCC) was studied on erythropoietin (ESF) levels and on the metabolic functions of erythrocytes (RBC). GCC (U mg/kg/day for 15 days) was administered to 6 patients with the haemolytic-uraemic syndrome (group B) and to 6 patients with non-spherocytic haemolytic anaemia due to hereditary pyruvate kinase enzyme deficiency (group C). 6 healthy persons served as control (group A). The metabolic functions of RBC were investigated by assaying HMPS activity, GSH/GSSG and lactate/pyruvate ratios, relevant glycolytic intermediates, 2,3-DPG, ATP, and key enzymes. A significant increase in ESF was observed in group B patients after GCC therapy, correlating with an improvement in the haemolytic state, and consequent rectification of the secondary disturbances of RBC metabolism. Group C patients already had raised ESF levels before GCC therapy; no further increase occured in response to treatment and no other clinical or haematological change was recorded. Hence, no harmonal influence of GCC on the disturbed RBC metabolic process was detectable in the cases.

Colony stimulating factor (CSF) in human mixed lymphocyte cultures: effect on human and mouse progenitor cells.

Supernatants from human two-way MLC, poor and rich in monocytes, were tested for their ability to induce colony growth of human and mouse progenitor cells in semi solid agar. Colony stimulating factor (CSF), with activity in both systems, indicated that allogenic lymphocytes require monocytes to produce CSF. Whereas human marrow showed an early kinetics of production, the liberation of CSF active on mouse marrow cells exhibited a delayed kinetics. These results, combined with other evidence, suggest that human lymphocytes produce two different factors.