Autoantibodies with antilipoprotein specificity and hypolipoproteinemia in patients with cancer.

Sera from 151 patients with a variety of cancers were screened for antibody-like activity against lipoproteins. Eighteen % of the sera exhibited activity against autologous and homologous high-density lipoproteins and 3% exhibited activity autologous and homologous low-density lipoprotiens. Antibody-like binding was proven by its restriction to the Fab fragment of IgG. The reactive part of the lipoprotein molecule was shown to be the appoprotein. Quantiation of the serum lipoproteins indicated that thehigh-density lipoprotien concentration in the sera of cancer patients was significantly lower (psmaller than 0.01) when antibody was present. These observation suggest that autoimmune mechanisms may be responsible for the decreased high-density lipoprotein serum levels in some patients with cancer.

[Fats and oils (including omega3, omega6)]. / Fette und Ole (unter anderem Omega 3, Omega 6).

Saturated fatty acids contribute essentially to atherogenesis, especially to coronary artery disease. In contrast, the protective effect of monounsaturated fatty acids such as oleic acid, contained in olive oil and as a constituent of a Mediterranean diet is very well shown epidemiologically. There is a modest beneficial effect on the clinical manifestation of coronary heart disease when saturated fatty acids of animal provenience are partially replaced by omega 6 fatty acids (linoleic acid). However, studies with the addition of omega-3-fatty acids in the diet (fish oil rich in eicosapentaenoic and docosaexaenoic acid and rape seed oil rich in alpha linolenic acid) demonstrate a significant decrease of sudden cardiac death and non fatal myocardial infarction. Long-chain omega-3-fatty acids have a direct antiarrhythmic effect on myocytes. The reduction of non-fatal myocardial infarctions during consumption of diets rich in long chain omega-3-fatty acids could at least in part be attributed to inhibitory effects on platelet aggregation and thus on thrombus formation and to a stabilization of atherosclerotic plaques.

Controlled evaluation of pantethine, a natural hypolipidemic compound, in patients with different forms of hyperlipoproteinemia.

Pantethine (P), the stable disulphate form of pantetheine, major component and precursor of coenzyme A, was evaluated within a double-blind protocol (8 weeks for P or for a corresponding placebo) in 29 patients, 11 with type IIB hyperlipoproteinemia, 15 with type IV, and 3 with an isolated reduction of high density lipoprotein cholesterol (HDL-C) levels. In type IIB patients, P (300 mg t.i.d.) determined a highly significant lowering of plasma total and low density lipoprotein (LDL) associated cholesterol (-13.5% for both parameters). In the same patients, HDL-C levels increased about 10% at the end of treatment. Switching from P to placebo was associated with a rapid return to the baseline cholesterolemia. Both in type IIB and type IV patients, plasma triglyceride levels were reduced around 30%, when P was given as the first treatment; when it was preceded by placebo, reductions were less striking (respectively, -17.8% for type IIB and -13.0% for type IV, at the end of P treatment). HDL-C levels were not increased by P, either in type IV, and in the patients with low HDL cholesterolemia. In type IV, LDL cholesterol levels showed a variable response to P: they tended to increase when below 132 mg/dl, prior to treatment, and to be reduced when above this level. This study provides evidence for a significant hypocholesterolemic effect of P, a natural compound free of overt side effects. It also indicates that P may raise HDL-C levels in type IIB patients, while moderately reducing triglyceridemia.

Fecal cholesterol excretion studies in type II hypercholesterolemic patients treated with the soybean protein diet.

The fecal steroid elimination profile was studied in 7 type II hyperlipoproteinemic patients given a low-lipid diet with textured soybean proteins, in order to define the mechanism of the hypocholesterolemic activity of this new dietary regimen. Four of the patients followed a 3- + 3-week cross-over protocol, comparing the soybean diet with a reference low-lipid diet with animal proteins. In these, fecal neutral steroids and bile acids were analyzed by chromatography during the two dietary periods. In spite of the clear hypocholesterolemic effect, no significant differences in steroid output were noted between the two dietary periods. In the 3 remaining patients, a chromatographic + isotopic method (by injecting 14C-labelled cholesterol i.v. 4-6 weeks prior to the dietary study) was employed. Again, no marked changes were noted in the fecal neutral steroid and bile acid outputs and the slope of the decay curve of the plasma cholesterol-specific activity was not changed by the experimental diet, in spite of the remarkable decrease in plasma cholesterol. The reported results do not provide a definitive contribution to the mode of action of the soybean protein diet. They suggest, however, that it is not an effect mediated by undigestible dietary components. The possibility of a cholesterol redistribution from plasma to tissue pools should be considered.

Lipid-free apolipoprotein (apo) A-I is converted into alpha-migrating high density lipoproteins by lipoprotein-depleted plasma of normolipidemic donors and apo A-I-deficient patients but not of Tangier disease patients.

Plasma of patients with Tangier disease (TD) is devoid of alpha-LpA-I (apolipoprotein A-I-containing lipoprotein), which in normolipidemic plasma constitutes the majority of high density lipoprotein (HDL). The residual amounts of apolipoprotein A-I (apo A-I) in TD plasma have electrophoretic prebeta1-LpA-I mobility. We have previously demonstrated that TD plasma does not convert prebeta1-LpA-I into alpha-LpA-I. In this study we found that plasmas of normolipidemic controls, apo A-I-deficient patients and patients with fish-eye disease, but not plasmas of six TD patients, convert biotinylated lipid-free apo A-I into alpha-LpA-I. Supplementation of plasma with free oleic acid or fatty acid free albumin neither inhibited conversion activity in normal plasmas nor reconstituted it in TD plasma. In normal plasma the conversion activity was assessed in HDL and in the lipoprotein-free fraction. The latter fraction, however, generated larger particles only in the presence of exogenous phospholipid vesicles. To obtain particles with alpha-mobility, these vesicles had to contain phosphatidylinositol and/or cholesterol. Lipoprotein-depleted TD plasma did not convert lipid-free apo A-I into alpha-LpA-I even in the presence of exogenous vesicles with phospholipids or cholesterol. Taken together we conclude that disturbed transfer of glycerophospholipds onto apo A-I or prebeta1-LpA-I prevents maturation of HDL and thereby possibly causes deficiency of HDL cholesterol in patients with TD. Moreover, the lack of alpha-LpA-I in TD plasma together with its failure to convert exogenous apo A-I into an alpha-migrating particle provide specific tests for the diagnosis of TD.

The dispositional enantioselectivity of indobufen in man.

The plasma pharmacokinetics and urinary elimination of the enantiomers of indobufen (2-[p-(1-oxo-2-isoindolinyl)-phenyl]butyric acid), a novel platelet aggregation inhibitor, have been studied in male healthy volunteers given either the racemic compound or the S-enantiomer (200 mg racemate, 100 mg S-enantiomer). Enantiospecific analysis of indobufen in plasma and urine was achieved by HPLC of its L-leucinamide diastereoisomers. After administration of the racemate, the pharmacokinetic behaviour of the R- and S-enantiomers differed, the plasma levels of the S form declining more rapidly [half-lives = 6.2 hr (S), 8.7 hr (R)]. No substantial differences were observed in terms of plasma level profile of S-indobufen when administered alone and in the racemic mixture. A statistically significant difference between the two enantiomers after administration of the racemate was found in the area under the curve (AUC), peak plasma levels (Cmax) and elimination half-life (t1/2 beta) whereas no statistically significant difference was detected in the time of peak (tmax). When the pharmacokinetic parameters Cmax, AUC, t1/2 beta and tmax of S-indobufen administered alone or as racemate were compared, there were no statistically significant differences between treatments as well as between periods and sequences. The urinary excretion of total S-indobufen (free + glucuronide) and of total R-indobufen after administration of the racemate was essentially the same. No difference was observed either in the urinary excretion of total S-indobufen after administration of the racemate or of the S-enantiomer.

Evaluation of efficacy and safety of erdosteine in patients affected by chronic bronchitis during an infective exacerbation phase and receiving amoxycillin as basic treatment (ECOBES, European Chronic Obstructive Bronchitis Erdosteine Study).

An international multicentric study was conducted with the aim of demonstrating that erdosteine improves the efficacy of amoxycillin in the treatment of infective exacerbation of chronic bronchitis mainly on the clinical symptomatology (primary objective), on spirometric tests and body temperature, without negatively influencing the tolerance (secondary objectives). The study was conducted as a prospective evaluation, with 2 comparative groups treated with erdosteine (300 mg x 2/day) or placebo in association with amoxycillin (1500 mg/day) for a maximum of 10 days. The design of the trial was double-blind and parallel group with 2 subgroups. The treatments have been assigned randomly to a population of chronic bronchitic patients in exacerbation phase of n = 237 subjects. The study was conducted according to the principles of the Declaration of Helsinki and its amendments (Hong Kong, September 1989). The primary end-point used to determine effectiveness in this study was the global clinical assessment (GCA) which was choosen as a general indication of activity with objective/subjective evaluation of the clinical picture. Secondary endpoints of efficacy are sputum parameters, functional signs of chronic obstructive bronchitis, spirometric tests and overall judgement of efficacy. Safety was evaluated with adverse drug reactions reporting, arterial blood pressure, heart rate and laboratory tests monitoring. The obtained values have been analyzed with two-way and factorial ANOVA, Least Squares Catmod-SAS, Wilcoxon and Chi-square tests. The number of patients included in the effectiveness analysis is of n = 226 subjects, due to the fact that 11 patients were lost due to different reasons. In term of results as far as the primary objective of the study was concerned, erdosteine resulted more active than placebo. The analysis evidenced a very significant difference for treatment, time and interaction time x treatment. No difference on the contrary was observed for center and the interaction center x treatment. Sputum volume, body temperature and spirometric parameters were not significantly influenced by both treatments. Viscosity, appearance as well as functional signs evidenced a modification over time in favour of erdosteine. As safety is concerned the majority of adverse events, both in the erdosteine and in the placebo group, were related to the gastrointestinal area. For erdosteine, of 9/17 side-effects, 3 were epigastralgias, 3 nauseas, 1 diarrhoea, 1 taste loss, 1 hemorrhoids. For placebo of 13/17 related events 3 were epigastralgias, 4 nauseas, 4 diarrhoeas, 1 pyrosis, 1 dry mouth. In terms of severity they have been all defined as mild or moderate degree. Also from a qualitative perspective it is clear that there are no relevant differences between the 2 treatments under evaluation, concerning safety. In conclusion of particular interest is the datum arising from the efficacy/safety evaluation, which indicates that the clinical picture is modified earlier and at deeper degree by the synergistic activity of erdosteine and of the antibiotic without the risk of an augmentation of side-effects incidence.

Comparative absorption kinetics of imidazole and salicylic acid in volunteers after administration of ITF 182 tablets and suppositories.

Comparative absorption kinetics in volunteers of a new antiinflammatory drug (Selezen), in the form of 750 mg tablets and suppositories, were studied. The two components of the drug, imidazole and salicylic acid were found in plasma. Pharmacokinetic parameters were calculated according to a first order absorption. Salicylic acid showed a maximum concentration 59.2 +/- 5 min and 75.4 +/- 7.6 min after the administration of the tablet and suppository respectively; and imidazole after 86.3 +/- 10.8 min and 75.2 +/- 5.4 min, respectively.

[Acute basal ganglia necrosis with favorable course during Mycoplasma encepahlitis]. / Nécrose aiguë des noyaux gris d'évolution favorable lors d'une encéphalite à mycoplasme.

BACKGROUND: Acute bilateral striatal necrosis complicating the course of a post-infectious encephalitis is rare. CASE REPORT: A previously healthy 5-year-old boy presented with an atypical pneumonia; he rapidly developed, encephalitis revealed by a generalized status epilepticus. After transient improvement, he became confused and mutic, with dystonic postures of his limbs. Painful stimulation resulted in prolonged facial grimacing and doleful cry. CT scan and MRI showed abnormal signals in the whole basal ganglia, typical of bilateral striatal necrosis. Serologic tests for Mycoplasma pneumoniae were positive. The child recovered almost completely. CONCLUSION: A parainfectious process is probably responsible for the transient bilateral striatal necrosis seen in this patient who had Mycoplasma pneumoniae infection several days before the onset of neurologic symptoms. MRI seemed more reliable than CT-scan for the diagnosis of this condition.

[Epidural hematoma in a child with hemophilia: diagnostic difficulties]. / Hématome épidural chez l'enfant hémophile: difficultés diagnostiques.

UNLABELLED: Spinal epidural hematoma is an uncommon complication in hemophilia. CASE REPORTS: The cases of an extensive epidural hematoma in two boys with severe hemophilia are reported. CONCLUSION: Acute onset of severe neck pain or backache leads to the diagnosis of epidural hematoma in children with hemophilia, even in the absence of neurologic symptoms. Early diagnosis is important and relies on magnetic resonance imaging. Replacement therapy is mandatory and must be prescribed before neuroradiologic imaging. Generally, children have a good neurologic outcome.

[Drug treatment of hyperlipidemia]. / Medikamentöse Behandlung der Hyperlipidämie.

The working panel of the Swiss Foundation for Cardiology has elaborated in 1989 new directives for the treatment of hyperlipaemias. Cholesterol values over 6.5 mmol/l with a cholesterol/HDL ratio over 5 and, in case of coronary heart disease, cholesterol values over 5.2 mmol/l should first be treated by diet. If after 3-6 months, in spite of dietary treatment, cholesterol values remain superior to 6.5 mmol/l or the cholesterol/HDL ratio superior to 6.5, drug treatment must be considered in case of coronary heart disease or arteriosclerosis, considerably abnormal lipid values (cholesterol greater than 7.8 mmol/l; in case of coronary heart disease: cholesterol greater than 6.5 mmol/l), other risk factors, positive family history for coronary heart disease and younger men. Most of the medicaments available today reduce total cholesterol by 10-30%. Combined therapies can be indicated, if in the presence of high risks the different possibilities of monotherapy have not led to the desired success.