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.

[Acute poisoning with L-triiodothyroinine, L-thyroxine and phendimetrazine bitartrate with suicidal intention]. / Akute Intoxikation mit L-Trijodthyronin, L-Thyroxin und Phendimetrazinbitartrat aus suizidaler Absicht

It is reported on an acute intoxication after application of 8 mg L-thyroxin, 2 mg L-triiodotyronine (200 tablets Thyreotom) and 4.5 g hendimetrazine bitartrate (100 tablets Sedafamem). The clinical picture is described. An endangering of the vital function of the organism was not observed. The symptoms disappeared after 4 days. The pharmacological aspects of the intoxication after application of the hormone of the thyroid gland, its significance for the pathogenesis of the thyreotoxic crisis and its therapy are discussed

[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.

[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.

[Aminopeptidases in the serum and urine of patients with hyperthyroidism]. / Aminopeptidasen im Serum und Harn bei Schiddrüsenüberfunktion

In patients with hyperthyroidism the serum activities of the leucine aminopeptidase (LAP) and the alanine aminopeptidase (AAP) as well as the alanine aminopeptidase excretion in the urine were determined. A significantly increased activity of the leucine aminopeptidase in the serum and an increased excretion of alanine aminopeptidase in the urine were found. The AAP in the serum did not show a significant increase of activity. On account of the changes in the serum and in the urine before and during therapy a low-grade participation of the hepatobiliary and renal systems which are clinically not uppermost is to be assumed. Increased excretion of AAP and hyperthyroidism coincide nearly without exception in out patients. Correlation-statistical investigations make it probable to regard the increased excretion of AAP in the urine as an indirect parameter of the peripheral metabolism in hyperthyroidism.

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.

[Alanine aminopeptidase and creatinine excretion under various conditions of diuresis in man]. / Alaninaminopeptidase-und Kreatininausscheidung unter verschiedenen Diuresezuständen beim Menschen

In 10 female test persons Volhard's water and concentration experiment was carried out. It exists a highly significant correlation between the alanine aminopeptidase activity and the creatinine concentration in the urine. The relation of the two factors to the urine minute volume is hyperbolic. The creatinine in the urine may be regarded as a favourable reference parameter for the excretion of alanine aminopeptidase.

[Experiences in the determination of thyroxine iodine in serum in various functional conditions of the thyroid gland]. / Erfahrungen mit der Thyroxinjodbestimmung im Serum bei verschiedenen Funktionszuständen der Schilddrüse

A report is given on the method of the thyroxine iodine determination in the serum. Of 213 patients the result of the thyroxine iodine determination was compared with the clinically and radiologically established functional condition of the thyroid gland. The findings are discussed. Similar results were also reported of other in-vitro-tests (T3-test, T4-test, BEJ and PBJ). According to our experiences we consider the thyroxine iodine determination in the serum siutable as screening test which - when there is a suspicion of a hypo- or hyper- thyroidism - needs the supplementation by the radio-iodine functional and localisation tests.