[Zidovudine. The current status of its evaluation]. / Zidovudine. Etat actuel de son évaluation.

3'-azido-3'-deoxythymidine is a thymidine analogue with an in vitro as well as in vivo efficacy towards HIV-mediated infection. Zidovudine exerts its action, following an intracellular three-step phosphorylation, through viral reverse transcriptase inhibition. Its half-life is approximately one hour. Oral biodisponibility is 65%, and passage through blood-brain barrier results in therapeutic levels is CSF. Clinical evaluation has enabled demonstration of a beneficial effect on survival of stage IV AIDS patients, when treated after a PCP episode. In this setting, aggregate survival ratios reach 73% after one year of follow-up, and 41% after 2 years. In addition, zidovudine activity has been demonstrated in treatment of HIV-induced thrombopenias as well as HIV-related central nervous system disorders. Presently, zidovudine therapeutic evaluation proceeds through the following main axes: dosage tuning (either by lowering of standard dose, and/or dose interval modification); combination with other antiviral therapies; lastly, patient treatment et an early stage of disease.

Ultrastructural localization of aluminum in hepatocytes of hemodialyzed patients.

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.

[Prevention and treatment of cytomegalovirus infections after graft of allogenic bone marrow]. / Prévention et traitement des infections à cytomégalovirus après greffe de moelle osseuse allogénique.

Cytomegalovirus (CMV) infection is the most frequent cause of lethal infection after bone marrow transplantation. Viremia occurs in 50% of patients seropositive for CMV before transplantation. Interstitial pneumonitis due to CMV occurs in 10% to 20% of patients with 85% mortality. It is known that CMV infection is due to host reactivation of latent CMV infection or to the transmission of the virus by the marrow donor or by blood transfusions. Treatment of CMV infection has been disappointing in the past. All attempts to treat CMV pneumonia with available agents have failed. Recent studies have indicated the usefulness of prophylactic measures and the early treatment of CMV infections. The use of hyperimmune gammaglobulins has given contradictory results. The selection of seronegative marrow donors or blood donors is useful only if the recipient is seronegative. New antiviral drugs have been used recently in preliminary clinical trials. In preliminary studies a guanosine analogue similar to Acyclovir (DHPG Synthex or BWB 759 U Wellcome) has given reasonable hope of disease cure if it is used early before the occurrence of pneumonia. Phosphonoformate (Foscarnet) has also been shown to be active against CMV infection. Both drugs have good antiviral and clinical action in immunosuppressed patients but the results have been disappointing in cases of pneumonia. Relapse occurs frequently after cessation of the treatment and attempts are being made to use maintenance therapy.

[Trial treatment of severe Raynaud's phenomenon with prostacyclin (PGI2)]. / Essai de traitement du phénomène de Raynaud sévère par la prostacycline (PGI2).

Severe forms of Raynaud's phenomenon are very disabling. In a randomized, single-blind trial, we have evaluated the effects of PGI2, 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 PGI2 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 PGI2 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 PGF1 alpha levels during the infusion, without changes in thromboxane levels. A significant (p less than 0.05) reduction was observed in the number of attacks (2.6 +/- 2.5 per week) and in impairment (+ on average after PGI2 but not after the buffer). Improvement after PGI2 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 PGI2 infusion. In all patients with ulcerations of the finger tips, these healed more rapidly after PGI2. It is concluded that in spite of immediate discomfort, PGI2 in 24-hour infusions seems to be of value in the treatment of severe Raynaud's phenomenon.

[Determination of the dose-response curve for atracurium dibesylate in the anesthetized adult]. / Détermination de la courbe dose-effet du dibésylate d'atracurium chez l'homme adulte anesthésié.

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 in primary glomerular diseases.

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.

[Muscle relaxant effect of atracurium in patients with chronic renal failure]. / Effet myorelaxant de l'atracurium chez les patients insuffisants rénaux chroniques.

The muscle relaxant effect of atracurium was monitored by measuring the strength of the adductor pollicis muscle (TH) elicited by supramaximal stimulation of the ulnar nerve at the wrist. In order to facilitate tracheal intubation, a dose of 0.6 mg X kg-1 was administered in 10 patients with complete renal failure. The results were compared with those obtained from 20 normal patients. The dose of 0.6 mg X kg-1 produced adequate conditions for tracheal intubation. A 95% or more depression of TH was obtained in both groups after 3 min. The duration of effect was similar in both groups. The delay between injection and 75% recovery of TH was of 62 min in controls and 52 min in patients with renal failure. Only the recovery index (the time elapsed between 25% and 75% recovery) was shorter in patients with renal failure (p less than 0.01): 8 min instead of 14 min in the controls.

The effects of chronic renal insufficiency on the pharmacokinetics of doxycycline in man.

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.

Prophylaxis of herpes infections after bone-marrow transplantation by oral acyclovir.

In a double-blind controlled study, oral acyclovir was compared with placebo in 39 consecutive patients undergoing bone-marrow transplantation. Acyclovir was given at a dose of 200 mg every 6 h from 8 days before to 35 days after bone-marrow transplantation. Pharmacokinetic studies showed good absorption of the drug, despite intestinal damage related to chemoradiotherapy or gut graft-versus-host disease. There was no sign of toxicity. The protection against herpes simplex virus (HSV) infection was complete in the treated group compared with the placebo group even in patients with high anti-HSV antibody titres before transplantation. The same protection was observed against cytomegalovirus (CMV) infection. The frequencies of HSV and CMV infections were the same in both groups after the cessation of treatment.

[Acute renal insufficiency in spontaneous septicemia of renal origin. Analysis of a series of 17 patients]. / Insuffisance rénale aiguë au cours des septicémies spontanées d'origine rénale. Analyse d'une série de dix-sept malades.

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.

A hypereosinophilic syndrome with retinal arteritis and tuberculosis.

A 35-year-old man was initially seen with a decrease in visual acuity, renal insufficiency, and elevation of the eosinophil count in the blood. The ocular syndrome was caused by extensive arterial occlusions of the retina. The subsequent apparition of cardiac, pulmonary, and neurologic signs fulfilled the criteria for the diagnosis of hypereosinophilic syndrome (HES). Most symptoms, including ocular, were temporarily but notably improved by hydroxyurea. The patient died after two years. An autopsy showed an endomyocardial fibrosis and disclosed destruction of the left kidney by an active tuberculosis. A pathogenic relationship between the infectious disease and the HES is envisaged.

[Suppression of proliferative allogenic response in patients receiving a programmed series of transfusions prior to renal graft]. / Suppression de la réponse proliférative allogénique chez des patients recevant des transfusions programmées en rue de greffe rénale.

The effects on the lymphocytic proliferative allogenic response of a protocol of planned blood transfusions have been studied in 12 patients with chronic renal failure. This study was prospective and the experiments were performed before kidney grafting. The results were then compared with the clinical results of the graft. These results have shown that the peak allogenic proliferation in the group of patients with good renal function was significantly decreased after transfusion. This decreased response was not observed in the groups of patients with either kidney rejection or immunisation and antibody formation. Most of the lymphocyte suspensions whose proliferation was decreased after transfusion were also capable of inhibiting the proliferation of autologous lymphocytes taken before transfusion. It is therefore legitimate to postulate that the decreased response was due to the generation of suppressor lymphocytes. This latter could be responsible for the beneficial effects of blood transfusion on kidney grafting.

[Scintigraphy with technetium dimercaptosuccinic acid (99 m TC DMSA). Contribution to the functional assessment of individual kidneys (author's transl)]. / La scintigraphie au dimercaptosuccinate de technetium: DMSA 99 m TC. Apport dans l'évaluation de la fonction rénale séparée.

Renal uptake of 99m Tc DMSA was used to evaluate the renal function of 16 healthy subjects (controls) and 115 patients with various urinary tract diseases. Scintigraphic examination was carried out 6 hours after an intravenous injection of the product. In the 16 controls Tc DMSA uptake was 25.7 +/- 2.48% in the right kidney and 24.4 +/- 2.86% in the left kidney. In 36 patients with one single hypertrophied kidney, there was a correlation (r = 0.850) between creatinine clearance and Tc DMSA uptake, which was higher than in normal subjects (39.23 +/- 9.9%). In the group of 68 patients with unilateral (31) or bilateral (37) renal disease, a significant correlation (r = 0,725) was observed between kidney-to-kidney ratios of urea clearance and Tc DMSA uptake, so that renal impairment could be quantified. Quantitative scintigraphy did not appear to be of assistance in the remaining 11 patients with obstructive uropathy, as it overestimated renal function. The results obtained with 99 m Tc DMSA scintigraphy should be helpful in choosing between nephrectomy and conservative surgery and in assessing the degree of compensatory hypertrophy in single kidneys.

[Significance of lymphocytotoxic antibodies in kidney transplantation revisited (author's transl)]. / Réévaluation de la signification des anticorps lymphocytotoxiques en transplantation rénale.

Lymphocytotoxic antibodies against peripheral blood lymphocytes (LT anti-PBL) were investigated in sera obtained before and after 148 kidney transplantations. Reactivity was assayed on a panel of unrelated donor cells and, in 15 cases, on the kidney donor's lymphocytes. Pretransplant LT anti-PBL, whether they persisted or not after grafting, were of no prognostic value. However, they were associated with longer periods of treatment by chronic hemodialysis, due to an increased frequency of positive cross-matches against potential donors. De novo occurrence of LT anti-PBL after transplantation was more frequently observed in mismatched kidney recipients, and they were significantly correlated to graft failure. In this respect, LT specifically directed to the kidney donor are of more avail than those directed to the panel. Anti-B lymphocyte LT do not seem to be more specific or more predictive for the follow-up of these patients.

[Removal of kidneys for transplantation. Experience in a French general teaching hospital (author's transl)]. / Prélèvements des reins en vue de transplantation. Expérience d'un centre hospitalo-universitaire multidisciplinaire.

A law issued on december 22, 1976 and aimed at increasing the number of kidney transplantations in France authorizes the removal of kidneys from deceased persons of full age provided they had not expressed refusal while still alive; for decreased persons under age, removal is subject to written consent of the legal representative. In a general teaching hospital of whose than 1 000 beds, 21 kidneys donors were operated upon between January 1, 1971 and December 31, 1975 (an average of 4.2 per year). A kidney transplantation team was developed in 1976. Between January 1, 1976 and August 31, 1979, 83 kidneys donors were operated, an average of 22.6 per year. Ninety-five per cent (59/62) of the kidneys removed and transplanted in the hospital began to function (diuresis greater than 2 ml/min) within minutes of releasing the clamp, no matter how long cold ischaemia had lasted. The increase in kidney removal and transplantation may be attributed to the fact that motivation was maintained among the various units concerned (anaesthesia and intensive care, neurosurgery, neuroradiology) by sustained information and teaching.