The livers of 7 hemodialyzed patients have been studied by electron microscopy and electron probe X-ray microanalysis. In 6 patients dialyzed for a long time (at least 39 months), aluminum has been detected in high concentrations in phagolysosomes of hepatocytes; in these lysosomes aluminum is associated with phosphorus. In 2 of these 6 patients, a very large number of aluminum inclusion bodies were found inside hepatocytes and this aluminum accumulation was associated with severe ultrastructural lesions of the cells. In one patient dialyzed during a short period (4 months) no aluminum accumulation has been observed. In none of the 7 patients was aluminum accumulation detected inside the Küpffer cells. These observations show that the cell which accumulates aluminum in the liver of dialyzed patients is the hepatocyte and not the Küpffer cell and that this accumulation may be associated with serious hepatocellular lesions.

Bupropion, a novel antidepressant drug, is known to be a moderate hepatic metabolism‐inducer in rodents at high doses but not in young human volunteers. Eleven elderly depressed patients (mean age 76·9 ± 8·7 years) entered in the study and received 100 mg of bupropion t.i.d. for 28 days. An antipyrine test was performed before and at day 28 of therapy. Antipyrine was taken orally (15 mg/kg) at 8 a.m. and blood samples were drawn at 11 a.m., 2, 5, and 8 p.m. Plasma levels were assayed using a GLC method. Results show a slight but significant increase of apparent clearance (+30 per cent) and decrease in the half‐life (–14 per cent) of antipyrine. Difference between these results and previous results in young volunteers might be explained by the usual decrease of hepatic function described in elderly patients. Bupropion can be considered in elderly people as a slight hepatic enzyme‐inducer.

Trente-cinq patients adultes (âge moyen 38 ans), sous anesthésie générale comportant du thiopental, du fentanyl et du protoxyde d'azote, ont reçu une dose unique de dibésylate d'atracurium: 0,10 mg · kg−1 (n = 10), 0,15 mg · kg−1 (n = 10), 0,20 mg · kg−1 (n = 11) ou 0,30 mg · kg−1 (n = 4). La courbe dose-effet établie à partir des trois premières doses permet de fixer la DA50 à 0,13 mg · kg−1 et la DA95 à 0,20 mg · kg−1. A la dose de 0,20 mg · kg−1, le délai d'action est de 6,1±0,6 min, la durée d'action de 34,3±3,2 min, le temps de récupération 25–75 % de 10,9±1,0 min. A la dose de 0,30 mg · kg−1, le délai d'action est de 4,7±1,3 min, la durée d'action de 39,9±3,7 min et le temps de récupération de 10,7±1,8 min. Cela tend à faire du dibésylate d'atracurium un produit de puissance d'action intermédiaire entre le chlorure de d-tubocurarine et le bromure de pancuronium, ayant un délai d'action identique à la plupart des autres myorelaxants non dépolarisants, mais doté d'une durée d'action et d'un temps de récupération 25–75 % plus courts que la plupart des autres produits, hormis le bromure de vécuronium.

Severe forms of Raynaud's phenomenon are very disabling. In a randomized, single-blind trial, we have evaluated the effects of PGI 2 , a natural compound with strong vasodilator and anti-platelet activities, in 14 patients presenting with Raynaud's phenomenon. The patients received a 24-hour infusion of either PGI 2 in doses of 10 mg/kg.min, or only the solvent (glycine buffer). All patients recorded the frequency and severity of the attacks before and after treatment, and 7 of the 8 patients who received the solvent benefited from a PGI 2 infusion 30 to 60 days later. Among the 14 patients (6 men, 8 women), 10 had underlying collagen disease. The number of attacks per week was initially 15.9 ± 5.3 (mean ± s.e.). The resulting impairment was pronounced (+ + on a + to + + + scale). Radioimmunoassays of prostaglandins showed a strong increase in 6-keto PGF 1α levels during the infusion, without changes in thromboxane levels. A significant (p < 0.05) reduction was observed in the number of attacks (2.6 ± 2.5 per week) and in impairment (+ on average after PGI 2 but not after the buffer). Improvement after PGI 2 lasted from 0.5 to 12 months, and all but one patient regarded the treatment as effective in long-term, despite undesirable side-effects (flush, hypotension) which occurred regularly during PGI 2 infusion. In all patients with ulcerations of the finger tips, these healed more rapidly after PGI 2 . It is concluded that in spite of immediate discomfort, PGI 2 in 24-hour infusions seems to be of value in the treatment of severe Raynaud's phenomenon.

Les formes sévères de phénomène de Raynaud entraînent une invalidité majeure. Nous avons évalué l'effet de la prostacycline (PGI2), un composé naturel puissamment vasodilatateur et antiplaquettaire, chez 14 de ces malades selon un protocole randomisé en simple aveugle, les patients recevant une perfusion unique de PGI2 (24 h à la dose de 10 ng/kg.min) ou seulement du solvant (tampon glycine). Les patients ont tenu un cahier de la fréquence et de l'intensité de leurs crises avant et après traitement, et 7 des 8 patients ayant reçu le solvant ont bénéficié d'une perfusion de PGI2, 30 à 60 jours plus tard. Parmi les 14 patients (6 hommes, 8 femmes), 10 avaient une collagénose sous-jacente. La fréquence hebdomadaire de base des crises était de 15,9 ± 5,3 (moyenne ± écart type). La gêne occasionnée était notable (cotation + + sur une échelle de + à + + +). Les dosages radio-immunologiques de prostaglandines montrèrent une forte augmentation du 6-céto-PGF1-alpha urinaire et plasmatique durant les perfusions sans modification du thromboxane B2. Après traitement, la fréquence des crises a été significativement (p < 0,05) plus basse: 2,6 ± 2,5 crises par semaine, et l'intensité de la gêne cotée + en moyenne après PGI2 mais non après tampon. La durée de l'amélioration après PGI2 a été de 0,5 à 12 mois et tous les patients sauf un ont considéré le traitement comme un succès à long terme, malgré les effets indésirables constants (flush, hypotension) au cours de la perfusion de PGI2. Tous les patients ayant des ulcérations pulpaires les ont vues cicatriser plus rapidement après PGI2. Malgré ses inconvénients immédiats, la PGI2 en perfusion de 24 heures à 10 ng/kg.min semble donc un traitement intéressant dans les phénomènes de Raynaud sévères.

The mechanical response of the adductor pollicis to a 0.15 Hz stimulation of the ulnar nerve was studied in 35 unpremedicated adult patients (mean age 38 yr) under general anaesthesia using thiopentone, fentanyl and a N2O/O2 mixture under mechanical ventilation. PaCO2, pH, K, Ca, Mg plasma levels and temperature were in the normal range. Each patient received a single bolus of atracurium dibesylate: 0.10 mg . kg-1 (n = 11), 0.15 mg . kg-1 (n = 10), 0.20 mg . kg-1 (n = 11) or 0.30 mg . kg-1 (n = 4). The dose-response curve was constructed using the log-probit method for 0.10, 0.15, 0.20 mg . kg-1 doses, giving neuromuscular blocks greater than 0% and less than 0.20 mg . kg-1. The 0.20 mg . kg-1 dose had an onset time of 6.1 +/- 0.6 min, duration 0-90% of 34.3 +/- 3.2 min and a recovery index 25-75% of 10.9 +/- 1.0 min. The 0.3 mg . kg-1 dose resulted in onset time of 4.7 +/- 1.3 min, duration of 39.9 +/- 3.7 min and a recovery index of 10.7 +/- 1.8 min. Thus atracurium dibesylate seemed to be an agent of intermediate potency. Onset time was approximately the same as that for other non-depolarizing neuromuscular blocking drugs, but duration of action and recovery index were quite shorter, except for vecuronium bromide.

Serum IgE was measured by RIST test in 181 adult subjects, with log transformation. In 24 controls the geometric mean was 109 IU/ml, with an upper limit (geometric mean +/- 2 SD) of 460 IU/ml. 157 cases of glomerulonephritis (GN) classified according to light and immunofluorescence microscopy were studied. Serum IgE was significantly elevated in 39 lipoid nephrosis patients (p less than 0.001, with 21 levels greater than 460 IU/ml), 21 focal and segmental glomerulosclerosis (p less than 0.05, with 8 levels greater than 460 IU/ml) and 42 membranous GN (p less than 0.01, with 10 levels greater than 460 IU/ml). In 27 membrano-proliferative GN and 28 IgA GN, serum IgE was not different from controls with respectively 4 and 3 levels greater than 460 IU/ml. In addition, the lipoid nephrosis IgE geometric mean is 493 IU/ml, which is keeping with the high incidence of atopic troubles. The significance of raised serum IgE was discussed.

L'effet myorelaxant d'une dose de 0,6 mg · kg−1 d'atracurium utilisée comme dose d'intubation a été évalué chez 10 patients ayant une insuffisance rénale terminale en comparaison avec un groupe de 20 patients bien portants. Le monitorage de la myorelaxation a été réalisé chez tous les patients. La dose de 0,6 mg · kg−1 d'atracurium procure une myorelaxation supérieure à 95 % dans un délai moyen de 3 min, identique dans les deux groupes : le délai entre l'injection du myorelaxant et le retour à une force de 75 % de la valeur initiale est de 62 min chez les sujets sains et de 52 min pour les insuffisants rénaux chroniques. Par contre, le délai de récupération entre la force 25 % et la force 75 % de la valeur de contrôle est plus court chez les insuffisants rénaux : 8,2 min au lieu de 13,7 min chez les sujets sains (p <0,01).

The pharmacokinetics as well as erythrocyte and plasma protein binding of doxycycline were studied in fifteen patients with various renal function impairments after oral doxycycline polyphosphate single administration. Plasma half-life (t 1/2), area under the plasma concentration-time curve (AUC), urinary excretion, renal clearance, erythrocyte and plasma protein binding (%) were regressed vs creatinine clearance. No significant correlations were observed between t 1/2 or AUC and renal function nor plasma protein binding and plasma albumin concentrations. Significant correlations were obtained between urinary excretion, renal clearance, erythrocyte binding, plasma protein binding and creatinine clearance. Significant correlation was obtained between haematocrit and erythrocyte binding. Constancy of overall elimination parameters in renal failure is due to parallel increase in plasma free fraction of doxycycline.

Seventeen recent cases of spontaneous renal septicemia with acute renal failure are reviewed, confirming the need for a diagnostic and therapeutic strategy to restore the fluid balance, if necessary with the aid of an artificial kidney, and the urgency of treating local infection and the pathogenic agents involved. The case review also suggest that the high mortality rate of this infection, estimated by some observers at 50 p. cent, can be greatly reduced by early radical urological treatment.