heme-arginate and Liver-Diseases

Topics: Adult; Arginine; Female; Heme; Humans; Liver Diseases; Metalloporphyrins; Porphyrias; Prospective Studies; Protoporphyrins

A double-blind study comparing placebo and haem arginate was conducted in 12 patients with acute intermittent porphyria. 2 days after admission in attack patients were randomised to receive intravenous haem arginate 3 mg/kg per 24 h for 4 days or placebo. 9 patients were readmitted with a further attack and were given the alternative treatment. Before randomisation the paired attacks were of similar severity with respect to urinary porphobilinogen (PBG) excretion and clinical manifestations. With haem arginate the median PBG excretion of the 9 patients with two attacks (normal range 0-16 mumol per 24 h) fell significantly from 332 mumol per 24 h (range 137-722) on admission to a median lowest level of 40 (range 22-105). On placebo, median PBG excretion was 382 (range 196-542) on admission, falling to 235 (range 128-427). Median duration of admission after the start of treatment was 11 days (range 2-28) for placebo and 8 days (3-26) for haem arginate. Median total analgesic requirement between the start of treatment and discharge was 8150 mg pethidine equivalents (range 0-17,650) with placebo versus 6425 (range 50-20,650) with haem arginate. Phlebitis occurred in 5 patients on haem arginate and in 2 on placebo. Haem arginate effectively reduces porphyrin precursor overproduction in the acute porphyric attack but this reduction is not accompanied by striking resolution of the clinical manifestations of the attack.

Topics: Acute Disease; Adolescent; Arginine; Clinical Trials as Topic; Double-Blind Method; Female; Heme; Heroin; Humans; Infusions, Intravenous; Injections, Intravenous; Liver Diseases; Male; Meperidine; Pain; Phlebitis; Porphyrias; Random Allocation; Recurrence; Severity of Illness Index

An 11 year old boy presented with severe acute hereditary coproporphyria. Despite supportive measures his condition deteriorated after admission. Haem arginate, started two days after presentation, produced appreciable inhibition of porphyrin precursor overproduction and clinical improvement.

Topics: Arginine; Child; Coproporphyrins; Heme; Humans; Liver Diseases; Male; Porphyrias

Sex hormone-binding globulin (SHBG), thyroxine-binding globulin (TBG) and cortisol-binding globulin (CBG) were measured in plasma of 26 patients with acute intermittent porphyria (AIP). Twelve patients had clinically manifest disease and all had elevated SHBG levels. All but one of 14 patients with latent porphyria had normal SHBG levels. TBG was elevated in 9 of the patients with clinically manifest porphyria and CBG elevated in three. Levels of TBG and CBG were either normal or only slightly elevated in those with latent porphyria. In a prospective study of 30 attacks of AIP in 7 patients, SHBG levels fell between admission and discharge, the fall being significant in the group of 21 attacks treated with haem arginate (p less than 0.001). Our findings suggest that a close correlation exists between elevated SHBG and clinical expression of AIP.

Topics: Adolescent; Adult; Aminolevulinic Acid; Arginine; Carrier Proteins; Heme; Humans; Hydrocortisone; Liver Diseases; Porphobilinogen; Porphyrias; Prospective Studies; Sex Hormone-Binding Globulin; Testosterone; Thyroxine-Binding Proteins

In three patients with attacks of acute intermittent porphyria we found markedly impaired functions of the left ventricle accompanied by ECG changes that returned to normal after administration of heme arginate or cytochrome C administration. In nine patients with other types of porphyria, and in one patient with acute intermittent porphyria not suffering an attack, no significant changes of left ventricle function were observed. The changes seen in patients with an acute attack may be ascribed to acute myocardial hypoxia resulting from defective biosynthesis of heme. We assume that the exogenous supply of heme may improve cellular hypoxia.

Topics: Acute Disease; Adult; Arginine; Cytochrome c Group; Female; Heart; Heme; Humans; Liver Diseases; Male; Middle Aged; Porphyrias

The effect of haem arginate on porphyrin metabolism and haemoprotein function was studied during seven attacks of acute hepatic porphyria in 5 patients. In each attack it greatly reduced the overproduction of porphyrin precursors and repressed the overactivity of the rate-controlling enzyme of haem synthesis delta-aminolaevulinic acid (ALA) synthase measured in leucocytes. Antipyrine clearance, an index of the oxidative function of cytochromes P-450, the major group of hepatic haemoproteins, was increased during haem therapy. Thus, haem arginate not only suppresses the overproduction of haem precursors but also improves hepatic oxidative metabolism in acute porphyria.

Topics: Acute Disease; Adult; Antipyrine; Arginine; Cytochrome P-450 Enzyme System; Depression, Chemical; Female; Heme; Humans; Hydroxymethylbilane Synthase; Leukocytes; Liver; Liver Diseases; Male; Mitochondria, Liver; Mixed Function Oxygenases; Porphobilinogen Synthase; Porphyrias; Porphyrins

Topics: Acute Disease; Arginine; Heme; Humans; Liver Diseases; Porphyrias