Low-density lipoprotein plasmaphaeresis with and without lovastatin in the treatment of the homozygous form of familial hypercholesterolaemia.

A 7-year-old girl with homozygous familial hypercholesterolaemia and plasma low-density lipoprotein(LDL)-cholesterol levels of 820 mg/dl (21.2 mmol/l) and progressive xanthomata was treated with heparin extracorporeal low-density lipoprotein precipitation (HELP) to lower her plasma LDL. On weekly HELP treatment she maintained her pre-HELP treatment LDL-cholesterol levels at 409 mg/dl (10.6 mmol/l). The long-term HELP treatment was well tolerated and led to regression of her xanthomata. Subsequently, lovastatin [Mevacor; Merck Sharp & Dohme, Westpoint, Pa., USA (20 mg/day)] was added to the regimen, causing a further 20% decrease in her pre-HELP treatment plasma LDL-cholesterol levels. Lovastatin alone did not sufficiently lower her plasma LDL and could not replace the weekly HELP therapy. Our data show that lovastatin is an effective adjunctive therapy for lowering plasma LDL-cholesterol in a homozygous patient, once plasma LDL levels have already been lowered by regular HELP treatment.

Improved haemorheology associated with a reduction in plasma fibrinogen and LDL in patients being treated by heparin-induced extracorporeal LDL precipitation (HELP).

Heparin-induced Extracorporeal LDL-Precipitation (HELP) is an effective procedure for the elimination of both plasma LDL and fibrinogen. In 10 adult patients with severe type II hyperlipoproteinemia, a single HELP treatment of 3 1 plasma led to an acute decrease in the average plasma viscosity (PV) from 1.30 to 1.1 mPas. At the same time, an even more marked decrease in the mean erythrocyte aggregation rate from a pathological value of 7.9% to a value of 3.7% (normal range less than 5%) was observed. Long-term studies on five patients demonstrated a lasting improvement in these two haemorheological variables. The acute rheological changes were also accompanied by an improvement in polarographically determined muscle oxygen tension. Mean oxygen tension values measured in both the m.biceps brachii and the m.tibialis anterior in five patients before and after a single HELP treatment increased from 30 +/- 4 to 37 +/- 7 mmHg and from 27 +/- 2 to 31 +/- 3 mmHg respectively. These results may provide an explanation for the rapid improvement in patients' clinical symptoms such as angina pectoris and in stress electrocardiogram which have been observed during HELP therapy.

Application of urinary indicator proteins in the non-invasive assessment of glomerulo-tubular lesions in patients with chronic glomerulonephritis and rheumatoid arthritis.

As the semiautomated electrophoretic analysis of proteinuria still needs technical experience, interest was focused on easy-to-perform methods of urinary protein measurement. SRID-tests for albumin, transferrin, IgG, alpha-1-microglobulin and a spectrophotometrical test for beta-NAG were carried out in 50 normal controls and compared to PCI/ECI-values of patients suffering from rheumatoid arthritis (n = 52) and various types of chronic glomerulonephritis (n = 41). Elevated levels of alpha-1-M and beta-NAG in chronic glomerulonephritis were interpreted as indicative for tubulointerstitial involvement in the chronic inflammatory process. PCI/ECI elevation in individual RA-samples may be caused by functional impairment of tubular protein handling due to chronic ingestion of non-steroid analgesics. The serum assays for transferrin (TF) and IgG based on SRID technique turned out to be too insensitive for the application on unconcentrated urine of normal control persons. In renal patients, however, TF-PCI values above 30 mg/g crea and IgG-PCI values above 50 mg/g crea have to be interpreted as pathologic indicating damage of the glomerular basement membrane. To elucidate TF- and IgG-values in urines with low protein content, highly sensitive nephelometric methods should be used. Concentration of urinary proteins using membrane filters may lead to protein losses, resulting in miscalculation of PC-indices.

Acute and long-term effects of low-density lipoprotein apheresis on the serum concentrations of vitamins E and A.

Serum alpha-tocopherol and retinol concentrations were followed in four heterozygous adults and one homozygous child with familial hypercholesterolemia being treated by regular low-density lipoprotein (LDL) apheresis. Approximately 50% of plasma alpha-tocopherol was eliminated during a single apheresis procedure in the heterozygous adults, while a complete elimination of this vitamin along with LDLs was observed in the homozygous child. Absolute losses of alpha-tocopherol amounted to 13.4-22.5 mg/apheresis and are equivalent to the recommended dietary intake for 1.5 to 2 days. Despite these losses, no changes were observed either in serum alpha-tocopherol levels or in the ratio of alpha-tocopherol/total serum lipids after 12 months regular apheresis treatment. Serum retinol concentrations only showed a small decrease on apheresis, there being apparently no specific elimination of this vitamin. The absolute losses ranged from 42-422 micrograms/apheresis and were, therefore, much lower than the recommended dietary intake of the equivalent of 1500 micrograms retinol/day. It is concluded that no extra supplementation of these vitamins is required during LDL-apheresis therapy, although it may be advisable to monitor vitamin E status in patients on long-term, intensive therapy.

Prolonged cholestatic jaundice and leukopenia associated with piroxicam.

A case of prolonged cholestatic jaundice and leukopenia occurring in a 60 year old wh piroxicam--a non-steroidal antiinflammatory agent--is reported. Histological examination of liver biopsy revealed pronounced canalicular and intracellular bile retention. After discontinuation of the drug serum bilirubin declined to normal values over a period of 10 weeks.