Uricosuric agents in uremic sera. Identification of indoxyl sulfata and hippuric acid.

Serum and urine from chronically uremic patients and normal individuals were subjected to gel filtration of Sephadex-G10. The effects of the eluted fractions on the uptake of urate and para-aminohippurate by isolated cortical tubules of rabbit kidney were investigated. According to the origin of the samples, one to three major groups of fractions inhibiting both urate and para-aminohippurate transport were disclosed. The first eluted group occurred for all the samples under study. The second one was demonstrated in both sera and urines from uremic patients but only in urines from normal individuals. The third one was exclusively detected in uremic sera and urines. Among all the compounds identified, only hippuric acid, eluted in the fractions of the second group, was capable of inhibiting the uptake of urate and para-aminohippurate in vitro. The concentration for which this inhbiitory effect of hippuric acid occurred was in the range of that existing in uremic sera. Indoxyl sulfate, which accumulates to very high concentrations in uremic serum, could not be disclosed in the above-mentioned fractions. This is explained by the strong adsorption of this indole derivative to Sephadex gel. Potassium indoxyl sulfate, when tested in vitro at the concentration existing in uremic serum, substantially inhibited the uptake of both urate and para-aminohippurate. In normal subjects, ingestion of hippuric acid or potassium indoxyl sulfate significantly increased fractional urinary excretion of uric acid. On the basis of these results, it is suggested that progressive retention of hippuric acid, indoxyl sulfate, and other yet unidentified inhibitors may explain the gradual increase in urinary fractional excretion of urate observed in uremia. The present results may be viewed as an example of a mechanism in which retention of normally excreted end products is responsible for adaptation of tubular transport in uremic subjects.

Clinical significance of anti-Sm antibodies in systemic lupus erythematosus.

Case records of 34 patients with systemic lupus erythematosus (SLE) were analyzed. Twelve patients had both anti-DNA and anti-Sm antibodies (Group I) and 22 had anti-DNA antibodies only (Group II). The disease patterns were comparable, except for (1) cutaneous vasculitis, which was observed in six of 12 patients in Group I and one of 22 in Group II (p less than 0.01); (2) pulmonary manifestations, nine of 12 in Group I and two of 22 in Group II (p less than 0.001); (3) cardiac manifestations, eight of 12 in Group I and four of 22 in Group II (p less than 0.01); and (4) renal biopsy, which showed milder lesions in Group I than in Group II (p less than 0.05). Evolution was fatal in four patients in Group I and in none in Group II. It is suggested that in SLE, the presence of anti-Sm antibody is associated with a much higher incidence of vasculitis, resulting in peculiar visceral manifestations, which can be poorly responsive to therapy. Whether there is a direct association between anti-Sm antibody and vasculitis or whether the common denominator is a genetic selection remains to be determined.

Renal transplantation and immunological abnormalities in thrombotic microangiopathy of adults: report of 5 cases.

Renal transplantation was performed in five adult patients with thrombotic microangiopathy, three of whom had had a bilateral nephrectomy prior to transplantation. The graft remained functional in three patients 72, 18, and 12 months after transplantation. One patient developed a thrombosis of the renal artery and one patient died from infection. There was no clinical or histological evidence of recurrence of thrombotic microangiopathy in the five patients after transplantation. Immunological investigations were performed in four of five patients before transplantation: C3 and C1q levels were low in two patients; serum C3-splitting activity and circulating immune complexes were present in all four patients and remained unchanged on haemodialysis and/or after bilateral nephrectomy. Complement abnormalities and immune complexes were not detected in the three patients with successful renal transplantation.

Unusual aspects of the dialysis disequilibrium syndrome.

In five patients with chronic renal failure, rapid correction by dialysis of hypertension and/or high blood urea levels provoked acute neurological disorders, followed by slowly reversible neuropsychiatric disturbances. Focal EEG alterations were noted in three patients with normal carotid angiograms. Our cases differed from those usually described as suffering from the dialysis disequilibrium syndrome because of their duration, the severity of mental disturbances, and the asymmetrical pattern of EEG abnormalities. We propose that the symptoms observed could be due to cerebral ischemia. This possibility emphasizes the importance of limiting the duration and efficiency of the first dialyses in patients with severe hypertension and high nitrogen retention, especially if high performance dialyzers are used.

Renal failure in myeloma: relationship with isoelectric point of immunoglobulin light chains.

Renal failure is a frequent but inconstant complication of myeloma related to light chain excretion. Since it has been suggested that cationic light chains (lc) are most likely to induce renal damage, we have studied the isoelectric point (pI) of light chains produced by 17 patients with myeloma and related the results to the type and severity of renal damage assessed clinically and pathologically. In order to do so, we have applied immunoenzymatic techniques which allow identification of light chain types as well as measurement of pI without prior purification. Ten of fifteen patients with renal failure produced lambda light chains. There was no simple relationship between the isoelectric point and nephrotoxicity. However, light chains with the lowest pI observed in this series were associated with normal renal function in two cases and with acute reversible but severe renal failure requiring dialysis in five cases. By contrast, pI values above 6.0 observed in the remaining patients were associated with moderate renal failure in six patients with recently diagnosed myeloma and with irreversible renal failure, and in two patients in whom myeloma had been evolutive for several years. We thus suggest that further pI measurements may help to identify light chains with different nephrotoxic potentials.

[Epidemiologic aspects of hypertension in pregnancy. Study of 442 cases]. / Aspects épidémiologiques de l'hypertension gravidique. Etude sur 442 cas.

We studied retrospectively the case records of 442 women who were followed because of hypertension during a pregnancy. Pregnancy hypertension was more frequent in white european than in black or arabic women. It occurred more frequently in women with an important professional activity than it did in housewives. 58% of patients had a familial history of high blood pressure, 35% were obese, 12% had glucose intolerance and 18% had hypercholesterolemia. Those frequencies were out of proportion with those in the control population. Finally, 32% of patients remained hypertensive after pregnancy. It is concluded that pregnancy hypertension occurs mainly in women whose genetic and metabolic background is that of essential hypertension.

[Evaluation of medical faculties in France]. / Evaluation des facultés de médecine en France.

A "comité national d'évaluation" founded in 1985 scrutinizes the french universities, autonomous but still partly run by the government. So far 17 medical faculties have been examined. Here are presented some remarks on the following points: the selection of the students and the end of the first year and the fate of those who failed; the reinforcement of science teaching for the students eager to go into research or academic medicine; the links binding teaching and research; the international relationships; the impulse of the evaluation on the Faculté.

[Medicine in the Cuvier Report on Natural Sciences (1810)]. / La medecine dans le Rapport Historique sur les Progres des Sciences Naturelles de Georges Cuvier (1810).

Through that many sided Report to Napoleon, Cuvier delivers a plain view upon European medicine in 1800. That document remained somewhat ignored as biochemical and physiological information are scattered throughout the text, with no clear link with the "Medicine, an applied science" chapter. Chemistry and physiology of animal beings include most of the recent true data about digestion, metabolism, respiration and nervous system added to the classic irritability. Proved data, still very few, are completed by logical and well organized but theoretical concepts forshadowing future physiology, "milieu interieur" and thermal regulation among everything. But the anatomist Cuvier did not link chemistry to physiology. Clinical practice fascinate Cuvier. Nosology, thoroughly studied, disappointed the naturalist for its incapability of establishing a classification of diseases. Morbid anatomy and physical investigation, the just appearing percussion, are welcome with hope as well as experimental pharmacology and hygiene. But normal and pathological chemistry and biology are not integrated to clinical medicine leading to neglect Bichat's works and those on experimental asphyxiation ...etc. Cuvier, who was not a physician, deliberately adopted this attitude : didn't he change the effect of an expert memoir he had asked J.N. Halle, a famous physician and scientist ? But nevertheless he stated that progress in medicine is experimental! This statement report, written by a critic scientist, is an important reference mark of time, when medicine shifted, ceasing to be only empirical.

[Pierre Rayer and the foundation in 1858 of the AGMF: an underrated social-political event]. / Pierre Rayer et la Fondation en 1858 de l'Association Générale des Médecins de France, un événement socio-politique méconnu.

The founding by Rayer in 1858 of the Association Générale des Médecins de France (AGMF), which gathered academic, hospital, and rural or urban doctors, was an act of professional solidarity. This action had a major social and political impact, making obsolete the Le Chapelier law of 1791, which limited to local communities the activity of provident societies. The AGMF also fought against illegal medical acts and for the dignity of medical care. It organized social health care, free for the poor and negotiated for local mutualists, helped establish relations between health care and government, and prepared the 1868 law on industrial injuries. Rayer financed the AGMF from the beginning, and devoted himself to it as a renowned clinician fully aware of the medical applications of science and as the founding President of the Société de Biologie and of Napoléon III's private physician, who fully supported the AGMF.