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Biomedical subjects

M Bret

Publications and source records attributed to M Bret.

At least 37 records · Page 2Linked to original sources

Intravenous interleukin-2 in patients over 65 with metastatic renal carcinoma.

The present study was designed in order to evaluate the response rate and the toxicity of continuous infusion of Interleukin 2 (IL2) in patients over 65 with metastatic renal cell carcinoma. Twenty-five patients, median age 69 (range 65-77), without any prior systemic anticancer therapy received a continuous infusion of IL2 at a dose of 18 x 10(6) iu m-2 d-1 for 2 periods of 5 days separated by a 6 day break. Toxicity was not different compared with younger patients (e.g. fever, hypotension, rise in creatinine level), except for cardiac toxicity which was of great concern. Despite normal cardiac tests prior to inclusion into the study, abnormalities of the cardiac rhythm ranging from tachycardia to ventricular extrasystoles occurred in 44% of the patients and IL2 cardiac toxicity was responsible for one toxic death. Three objective responses, i.e. one partial and two complete persistent responses, were seen in 22 evaluable patients. Thus, if age does not seem to modify the potential for response to IL2 therapy, cardiac toxicity appears as a limiting factor for intravenous schedules of IL2.

Aged↗

Acute renal failure with preserved renal plasma flow induced by cancer immunotherapy.

Adoptive immunotherapy in patients with advanced cancer produces significant regression of metastatic disease in selected patients, but it is complicated by severe side effects. Prevention of these complications is still limited because their precise mechanisms remain unknown. For this reason we have investigated renal function and hemodynamic parameters in 16 patients with renal cell carcinoma before and during treatment with a combination of high doses of both recombinant interleukin-2 (rIL2) and recombinant alpha-interferon. After patients had received three injections of combined immunotherapy, there was a decrease in mean blood pressure (-20%), glomerular filtration rate (-25%), urine output (-50%), and fractional sodium excretion (-0.8%). This was associated with an increase in heart rate (+30%), plasma creatinine level (+30%), fractional potassium excretion (+14%) and microalbuminuria (+130%). However, renal plasma flow remained constant. The increment in microalbuminuria may reflect an alteration of glomerular capillary permeability. The reduction in GFR may be accounted either for a decrease in efferent to afferent arteriolar resistance ratio, leading to a decrease in glomerular capillary pressure, or for a decrease in ultrafiltration coefficient, or both. Nonsteroidal antiinflammatory drugs, such as ketoprofen, used to minimize side effects, could considerably worsen renal function and should be avoided in patients treated by rIL2. Our results bring new insights into the pathogenesis of functional acute renal failure and provide a rational basis for the use of vasopressors in the treatment of cytokine-induced acute renal failure.

Acute Kidney Injury↗

[Chronic hydrocephalus in adults].

The aim of this study is to sum up our current knowledge on the so-called "normal pressure hydrocephalus" syndrome, revisited by the authors as the "adult chronic hydrocephalus" syndrome (A.C.H.). It is based upon 1) a review of the literature dealing with the subject (518 references) and 2) an original series of 243 cases summarizing a 10 year experience of 2 french neurosurgical teams (Lyon: 123 cases, Clermont-Ferrand: 120 cases). Part I is devoted to the review of pathologic and pathophysiologic data. Both autopsy and microscopic findings clearly show 2 categories of anomalies in the brains of patients showing this condition: "non specific" lesions may be either causative (leptomeningeal thickening, villositar sclerosis) or secondary to hydrocephalus (ependymal wall disruption, sub-ependymal "edema"). Conversely, "specific lesions" are either degenerative (Alzheimer-type) or ischemic in origin. They seem unrelated to hydrocephalus, but may play a role in the ventricular enlargement by favoring changes in brain elastic properties. Data available from brain biopsies (13 cases) have confirmed the high incidence of such "specific lesions" of the parenchyma. Following the Hakim's initial hypothesis, several mechanisms have been proposed to explain the progressive ventricular dilation despite a fall in C.S.F. pressure. Experimental and clinical data (namely those referring to the pathogenesis of secondary A.C.H.) are reviewed. The sequence of events following acute ventricular obstruction is analysed. The ultimate state of chronic uncompensated hydrocephalus involve multiple factors among which a trans-cerebral mantle pressure gradient may play a major role. The intervention of compensatory mechanisms (reduction of C.S.F. production, establishment of alternative pathways of C.S.F. absorption) is also discussed. Part II is devoted to the presentation of the clinical material. Series of the literature including more than 20 surgical cases are briefly reviewed together with the authors' material and methods. Criteria of selection of patients, methods of clinical evaluation and of statistical analysis of results are exposed. Of the 243 patients of the present series, 225 were managed by C.S.F. shunt (V.A.: 137, V.P.:60, L.P.:28). Results were as follows (mean follow-up:31 mths +/- 28): good results (including excellent results): 128 (52.6%), fair: 52 (21.3%), poor and aggravated: 49 (20%), early deaths: 14 (5.7%), 12 of those post-operatively. The rate of surgical complications was 35% (S.D.H.: 16.8%, sepsis: 4%, seizures: 4%, shunt malfunction: 10.6%) leading to reoperation in 25.7%. Long-term survival rate was 75% (172 alive patients and 57 late deaths).(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

[Staphylococcal toxic shock syndrome].

The case of a 31 year old woman with staphylococcal toxic shock syndrome is reported. The usual clinical characteristics were found: it began during a menstrual period, and she presented with a state of shock, a high fever and a cutaneous eruption. Its evolution was marked by pulmonary interstitial oedema and acute renal failure requiring dialysis; the patient recovered but residual renal failure was still present four months later. A Staphylococcus aureus was isolated from vaginal, nasal and tracheal cultures. It produced enterotoxins A and F, which were responsible for the symptoms.

Acute Kidney Injury↗

[Effects of a postpituitary extract and lysine vasopressin on portal and systemic hemodynamics in the cirrhotic patient].

The purpose of this work was to study the hemodynamic effects of a pituitary extract (Post-Hypophyse, Choay, EPH) and of lysine vasopressin (Diapid, Sandoz, VP). Cardiac, pulmonary and liver hemodynamics were measured in 50 cirrhotic patients before and during intravenous infusion (0.45 IU/kg/h) of EPH (24 patients) or VP (26 patients). EPH and VP did not have identical consequences in cardiac output and systemic resistances. EPH significantly increased cardiac output and significantly decreased systemic resistances while VP significantly and increased systemic resistances. Both vasoactive drugs similarly decreased myocardial performances. EPH and VP had a moderate influence on WHV/IVC pressure gradient. This was variable from one patient to another. The decrease of WHV/IVC pressure gradient observed during EPH infusion was mainly related to an increase of IVC pressure. Since the effects of both drugs on WHV/IVC pressure gradient are slight and unpredictable and they exert an important effect on cardiopulmonary hemodynamics, caution should be taken in administering EPH or VP to cirrhotic patients. The clinical use of EPH or VP should be undertaken only when cardiac and liver hemodynamics monitoring are available.

Cardiac Output↗

[Recurrent paroxysmal myoglobinuria with acute renal insufficiency caused by muscular carnitine (palmitoyltransferase deficiency. A case].

A 45-year-old man was hospitalized on 3 occasions for recurrent myalgias with paroxysmal myoglobinuria resulting in two episodes of acute renal failure. The second episode was fatal: the patient died of shock and hyperkaliaemia during haemodialysis. The predominant signs and symptoms were muscle pain with functional deficit, signs of renal failure and a rise in serum enzymes. All examinations were negative between attacks. Muscle biopsies showed a major degree of myolysis, and biochemical tests demonstrated severe muscle palmityl transferase deficiency associated with partial deficiency of muscle carnitine. The diagnostic features and physiopathology of the disease are reviewed.

Acute Kidney Injury↗

[Evaluation of nutritional status in hospital surgical patients (author's transl)].

The nutritional status of 90 hospital surgical patients was evaluated on admission by simple, easily measured anthropometric and biological indexes. The results indicated that many patients were admitted with malnutrition, the degree of which varied according to the indices utilized. Anthropometric measurements showed that 29 to 35% of the patients had moderate malnutrition and 0 to 18% severe malnutrition, while biological indexes revealed moderate or severe malnutrition in over 50% of the subjects. Changes in indices were assessed in 51 patients during their stay in hospital. There was a significant decrease in all anthropometric indexes (p less than 0.01) and in blood albumin (p less than 1.10(-6)) though not in other biological indexes. Differences in sensitivity between indexes may be due to the fact that they reflect activities in different tissues. Several indexes must therefore be utilized in hospital patients to make detection and monitoring of malnutrition more reliable and to evaluate its various aspects.

Adult↗

[Prazosine: a new vasodilator used for treatment of hypertension (author's transl)].

Prazosine, a derivative of quinazoline, acts by relaxing the smooth vascular muscles and blocking postsynaptic alpha-adrenoreceptors. A special protocol was used to treat arterial hypertension in 21 subjects. A small dose (0.5 mg) was given the first day to avoid orthostatic hypotension, then 0.5 mg x 3 on days 2, 3 and 4, followed by 1 mg x 3 on subsequent days. Dosage can be progressively increased up to 30 mg/day. During the first 36 days of treatment, prazosine was given alone. A significant drop in systolic and diastolic arterial pressure was observed in the reclining subject. The effect on orthostatic pressures were nevertheless significantly lower than before initiating treatment. Prazosine induces only a slight increase plasma renin activity. In 9 patients the use of prazosine alone at 3 to 6 mg per day produced not only a drop in arterial pressure but its normalization. In 5 other patients, the administration of prazosine associated with a beta-blocker, acebutolol, induced normalization of arterial pressure. The association of prazosine with a thiazide diuretic was not considered successful. In 5 patients, treatment was interrupted with the appearance of coronary insufficiency, orthostatic hypotension and frequent headaches. Minor side-effects observed in 8 others patients did not require interruption of treatment. Based on the above results, it can be stated that prazosine is an efficient new peripheral vasodilator with good patient tolerance for the treatment of arterial hypertension.

Acebutolol↗

[Pregnancy and severe pancreatitis (author's transl)].

We studied the relationship between pregnancy and pancreatitis together with reviewing the bibliography after having had 4 cases. As far as the aetiology is concerned there does not seem to be a mechanical factor associated with the pregnant uterus but a vesicular factor (gall bladder) of stasis and hypersecretion, with hyperlipidaemia of pregnancy and pancreatic oversecretion in pregnancy, all of which are finally associated with a neuro-vegetative lack of tone and with the part played by certain drugs that are often prescribed in pregnancy. The fetal prognosis is relatively good except for the risks of premature delivery. Management of a case of acute severe pancreatitis is difficult to work out. All the same, the treatment should be above all conservative, which means medical. Surgery should be reserved for those cases with definite indications such as progressive deterioration in spite of medical treatment with the knowledge beforehand that it will not make much difference to the final prognosis.

Adolescent↗

[Treatment of cancer of the kidney with interleukin 2 in adults, the Lyon experience].

Like interferon-alpha, interleukin 2 (IL2) is active on metastatic kidney cancers, which are regarded as chemoresistant tumors. Out of 20 to 30% objective responses, 5 to 10% complete remissions are reported with various IL2 delivery schedules. The considerable toxicity is well mastered at present, thus allowing treatment in non-intensive care departments, or even in an ambulatory mode for subcutaneous administration. Even though Interleukin 2 has been authorized for sale in France, optimal mode of administration, the role of the IL2-interferon-alpha combination or the predictive factors of response to treatment still raise many questions.

Drug Therapy, Combination↗