Efficacy and safety of combination therapy using high- or low-dose hydrochlorothiazide with valsartan or other Angiotensin-receptor blockers.

Only a minority of patients treated for hypertension achieve controlled blood pressure (BP) levels. Therapy with fixed-dose combinations of an angiotensinreceptor blocker (ARB) and low-dose hydrochlorothiazide (HCTZ) is commonly prescribed but not always sufficient to achieve the target BP. The efficacy and safety of the fixed-dose combination of valsartan 160 mg and HCTZ 25 mg was evaluated in patients in whom BP had not been controlled with a fixed-dose combination of another ARB and low-dose HCTZ (12.5 mg) in a multicenter trial. After a wash-out period for antihypertensive drugs, patients with a mean sitting diastolic BP (DBP) at trough (3)100 mm Hg but <110 mm Hg were treated with candesartan cilexetil 16 mg plus HCTZ 12.5 mg or telmisartan 80 mg plus HCTZ 12.5 mg for 4 weeks (phase 1). Patients whose BP was still uncontrolled (DBP (3)90 mm Hg) after 4 weeks of therapy were then given valsartan 160 mg plus HCTZ 25 mg for an additional 4 weeks (phase 2). The primary efficacy parameter was the reduction in DBP between week 4 and week 8 in the intention-to-treat (ITT) population. BP reduction during phase 1 was -14.3+/-11.3/-7.5+/-3.9 mm Hg. DBP was controlled in 26% of the patients after phase 1. In patients treated with valsartan 160 mg plus HCTZ 25 mg during phase 2, DBP decreased by an additional 10.3+/-6.5 mm Hg and the mean sitting systolic BP (SBP) by an additional 11.0+/-11.7 mm Hg. The additional decrease was significant (P<.0001) for both parameters and independent of the fixed-dose combination used during phase 1. Among patients whose BP remained uncontrolled during phase 1, 74% achieved a controlled DBP after phase 2. The incidence of adverse events during both phases was comparably low and the results of laboratory tests were unremarkable. Treatment with valsartan 160 mg/HCTZ 25 mg offered a substantial benefit for patients with hypertension not controlled with the combination of candesartan cilexetil 16 mg or telmisartan 80 mg and low dose HCTZ, while maintaining a comparable safety and tolerability profile.

Age-dependent excretion of alanine aminopeptidase, alkaline phosphatase, gamma-glutamyltransferase and N-acetyl-beta-D-glucosaminidase in human urine.

Urinary excretion of alanine aminopeptidase, alkaline phosphatase, gamma-glutamyltransferase and N-acetyl-beta-D-glucosaminidase was determined in gel-filtered samples of morning random urine specimens of 442 subjects of various ages (5 days to 58 years). Enzyme excretion related to urinary creatinine (enzyme/creatinine ratio; U/mmol creatinine) significantly decreased with increasing age. Sex-related differences of some enzyme excretions were found in age groups over 6 years. From these investigations, we calculated upper reference intervals (97.5 percentiles) for 5 age-dependent groups of children and adolescents and for one group of adults.

[Clinical value of N-acetyl-beta-D-glucosaminidase and alpha-galactosidase in liver diseases]. / Zur klinischen Wertigkeit der N-Azetyl-beta-D-Glukosamminidase and alpha-Galaktosidase bei Lebererkrankungen.

N-acetyl-beta-D-glucosaminidase is a lysosomal glycosidase, which participates in the catabolism of the mucopolysaccharides and of the glycoproteins. For the determination of this enzyme the production of the substrate and a modified methodology are described. Measurements of the activity were performed by 4-nitrophenyl-alpha-D-galactopyranoside and 4-nitrophenyl-N-acetyl-beta-D-glucosaminide as substrates. Examinations of this enzyme were performed in patients with acute virus hepatitis, chronic hepatitis, liver cirrhosis and healthy test persons. In acute hepatitis and liver cirrhosis and significant increase of enzyme is provable, but not in protracted hepatitis.

[D-thyroxin in the therapy of type IIa and IIb hyperlipoproteinemias]. / D-Thyroxin in der Therapie von Hyperlipoproteinämien des Typs IIa und IIb.

21 patients with hyperlipoproteinaemias of type IIa and IIb were treated with D-thyroxin (4 mg/die) after a placebo phase. The observed changes of the cholesterol and triglyceride level in the serum are described. Hypermetabolic and cardiac side effects did not appear in the patients. The possible sites of action of D-thyroxin in the intermediary lipid metabolism are discussed.