Effect of interferon alpha-2b in advanced multiple myeloma.

The antitumour effect of recombinant human interferon (rh-IFN) alpha-2b was studied in 22 patients with advanced multiple myeloma (MM). Nine of 14 evaluable cases were refractory to cytostatic therapy; five were in relapse. rh-IFN was administered s.c. three times per week, in escalating doses starting with 2 x 10(6) IU m-2 and if possible up to 15 x 10(6) IU m-2. Two patients (one refractory, one relapsing) showed a partial response, defined as a 50% reduction of the serum M-component. Three further patients had a minor, significant but short-lived response. Subjective side-effects grade 1-2 were noted during rh-IFN therapy in all patients. In three cases thrombocytopenia necessitating platelet transfusions occurred. Although a fraction of patients with advanced MM obviously respond to rh-IFN, this type of therapy may be more effective, alone or in addition to chemotherapy, in patients with a low tumour cell burden.

Plasma fibronectin deficiency during chemotherapy of acute myeloid leukaemia.

Plasma fibronectin was determined using a laser nephelometric method in 10 patients with acute myeloid leukaemia undergoing chemotherapy. There was a continuous fall during the first 3 weeks to about 50% of the normal level. The decrease of fibronectin may contribute to the lowered resistance against infection characteristic of these patients.

A case-referent study on acute myeloid leukemia, background radiation and exposure to solvents and other agents.

The effect of potential risk factors for acute myeloid leukemia was evaluated in a case-referent study encompassing 42 cases and 244 referents, all deceased. Information on exposure was obtained with questionnaires mailed to the next of kin. Particularly the effect of background radiation was evaluated, as assessed with a gamma radiation index weighing the time spent outdoors and indoors and considering the building material (stone, wood, etc.) in the homes and the workplaces of the subjects. Especially between the ages of 20 and 49 a, to some extent also between 50 and 69 a but not above 70, there seemed to be an effect from background radiation and a trend suggesting an exposure-effect relationship. There was also about a sixfold increase in the rate ratio with regard to solvent exposure, which also seemed to modify the effect of background radiation. Other exposures were associated with relatively modest increases in the rate ratios and/or very small numbers of exposed individuals. It would be worthwhile to undertake further cancer epidemiologic studies of background radiation in which effective study designs are applied and a variety of potential confounders and modifiers of effect are identified and accounted for.

Legionnaires' disease in leukaemic reticuloendotheliosis.

At our hospital 15 cases of leukaemic reticuloendotheliosis and 4 cases of legionnaires' disease have been diagnosed. 3 patients had both diseases. The clinical findings are reported. It is probable that patients with leukaemic reticuloendotheliosis have an increased susceptibility to Legionnaires' disease. Possible reasons for the decreased resistance are discussed.

Studies on plasma lipid and phospholipid composition in pernicious anemia before and after specific treatment.

Patients with pernicious anemia (PA) have been compared with a reference group concerning the concentration of lipids in plasma before (34 cases) and after (15 cases) treatment with vitamin B12. The lipid parameters in plasma and in postheparin plasma have been measured before and after 6 hours' incubation at 37degree C before and after specific treatment. In a limited number of cases the lecithin: cholesterol acyl transfer (LCAT) rate has been determined. In relapse, the PA cases showed increased free fatty acid (FFA) and triglyceride (TG) concentrations but decreased concentrations of total cholesterol (TC), unesterified cholesterol (UC) and all examined phospholipid fractions. After treatment, FFA remained unchanged and TG decreased, while TC and possibly also UC and the phospholipid frations were in line with reference levels. After incubations, UC and phosphatidylcholine (PC) decreased and lysolecithin (LL) increased. FFA increased and TG decreased. Incubation of postheparin plasma resulted in an augmented decrease in TG and PC and increase in FFA and LL, In relapse, the changes on incubation were less pronounced than after treatment. The LCAT was low but within the normal range before treatment in the six cases examined. After treatment, LCAT rates increased but were still normal in relation to the plasma lipid concentrations. The study showed a decreased net esterification of cholesterol and LL formation on incubation of plasma in PA cases in relapse. This finding might be explained by the low concentration of plasma substrates for the LCAT reaction and phospholipases. After treatment the concentration of lipid substrates was restored to normal, with subsequent normal LL formation and cholesterol esterification. The observations could also explain the frequent lack of stabilization of erythrocytes suspended in plasma of PA after incubation, resulting in virtually the same ESR after as before this procedure. Due to low LL formation following the insufficient substrate availability for LCAT and phospholipase, the previously reported critical level of the LL concentration is not reached and cannot achieve its normal reduction of the ESR.

Influence of fat ingestion on lecithin:cholesterol acyl transfer rate in plasma of normal persons.

Lecithin:cholesterol acyl transfer (LCAT) rate in plasma and lipid concentrations in total plasma and high density lipoproteins (HDL) were determined before and after oral fat loads in healthy human subjects. The changes of LCAT rate after fat loading were compared to the effect of chylomicrons or lipid emulsions added in vitro to fasting plasma. After the fat loads there was an increase of mean molar LCAT rate simultaneous with an increase of mean phospholipid (PL) and HDL-PL concentration but not simultaneous with the increase of mean triglyceride (TG) concentration. Individual changes of molar LCAT rate correlated positively with changes of PL, HDL-PL, and unesterified cholesterol (UC) concentration but not with changes of TG concentration in the separate plasma samples after the fat loads. If only the maximal changes in each subject in any sample at any time after the loads were taken into account, the maximal increase of molar LCAT rate correlated positively with the maximal increase of TG concentration. Molar LCAT rate was not influenced by addition of chylomicrons in vitro but increased after addition of a PL emulsion. It is suggested that LCAT rate is stimulated by an excess of PL in plasma and substrate lipoproteins. This excess of PL may be created in vivo temporarily during chylomicron catabolism. The stimulation of LCAT rate by fat ingestion emphasizes the importance of LCAT as a connecting link between triglyceride and cholesterol metabolism.

Lecithin:cholesterol acyl transfer in plasma of normal persons in relation to lipid and lipoprotein concentration.

Information concerning variation in the lecithin:cholesterol acyl transfer (LCAT) rate in normal persons is scanty. We have therefore analyzed the LCAT rate and the lipid and lipoprotein concentrations in the plasma of healthy normolipidemic persons 20-60 years of age, 40 men and 40 women. 10 per decade and sex. Interindividual variation in molar LCAT rate was 57-130 mumol-u(-1)-h-1 (mean +/- 2 S.D.) with no sex difference. Intraindividual variation of molar LCAT rate studied in 8 women and 9 men was shown to be greater than expected from methodological error and was not explainable by the small changes in plasma lipid concentration during the observation period. In the women the molar LCAT rat was lower during the preovulatory phase of the menstrual cycle than during the postovulatory phase. There was positive correlations between the molar LCAT rate and most of the lipid parameters in plasma. By partial correlation analysis a positive correlation was shown between LCAT rate and triglyceride concentration irrespective of other lipid parameters. Keeping triglyceride concentration constant, there was a positive correlation between molar LCAT rate and total phospholipid, unesterified cholesterol, esterified cholesterol, or low-density lipoprotein (LDL) cholesterol concentration. No correlation was found between high-density lipoprotein (HDL) lipid concentration and LCAT rate. Thus in normal subjects there seems to be a direct relation between very low density lipoprotein and LDL lipid concentration and molar LCAT rate but no relation between HDL lipid concentration and LCAT rate.

Evaluation of an in vitro assay of lecithin:cholesterol acyl transfer rate in plasma.

Crucial and previously criticized points in a slightly modified version of the Stokke-Norum assay of fractional lecithin:cholesterol acyl transfer (LACT) rate in plasma were studied. LCAT activity in the albumin added to the assay medium and negative influence of remaining organic solvent were important sources of error that it was necessary to eliminate. The assumption of equilibration of labeled cholesterol among lipoproteins in vitro was supported experimentally. Addition of isolated chylomicrons had no influence on initial LACT rate. Incubation time was decreased to 20 minutes to obtain a better estimate of initial LCAT rate in normals. Using gas-liquid chromatography to determine unesterified cholesterol concentration, the precision of measurement of molar LCAT rate was 5.2 per cent (coefficient of variation). Molar LCAT rate in healthy males 20-60 years of age was 56-130 mumol-1(-1)-h-1 (mean +/- 2 S.D.) and compared well with reports from other laboratories and in vivo measurements. At present this methodology is considered to be suitable for studies of LCAT and cholesterol turnover in different metabolic situations and clinical materials.

Hypercalcaemia in chronic lymphatic leukaemia.

Hypercalcaemia developed in a patient with chronic lymphatic leukaemia. The hypercalcaemia did not respond to conventional treatment. At bone biopsy osteoclastic resorption was found (a photomicrograph is presented). 7 cases from the literature of hypercalcaemia and chronic lymphatic leukaemia are briefly reviewed. Possible mechanisms are discussed and it is suggested that osteoclast-stimulating factors may be of importance in the development of the hypercalcaemia.