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Biomedical subjects

P Attali

Publications and source records attributed to P Attali.

At least 19 recordsLinked to original sources

Urinary flow rates in patients with benign prostatic hypertrophy following treatment with alfuzosin. DUALF Group.

In order to document further the onset of action of alfuzosin, a selective alpha-1 blocker, 93 symptomatic patients with benign prostatic hypertrophy were randomly allocated to a single oral dose of either alfuzosin 1.25 mg or 2.5 mg, or placebo, after a 1-week placebo lead-in period. The effects on flow rates were assessed 1 h 30 min after administration. Peak and mean flow rates were significantly increased in the alfuzosin groups, as compared with placebo, in a dose-dependent manner. After a single intake of placebo, the mean values of these 2 parameters showed little change. The effect on the cardiovascular system (heart rate and blood pressure) was mild. This study indicates that the action of alfuzosin is already present 1 h 30 min after administration.

Adrenergic alpha-Antagonists

The safety and efficacy of zolpidem in insomniac patients: a long-term open study in general practice.

The safety and efficacy of 10 or 20 mg/day zolpidem, a new hypnotic belonging to the imidazopyridine class, were studied over a 180-day period in 96 patients with sleep disorders. The treatment was continued for a further 180 days by 49 of these patients. Follow-up information from 21 patients who discontinued treatment after 180 days showed no rebound insomnia or withdrawal signs. Efficacy of treatment with respect to reduction of sleep onset latency and number of nocturnal wakenings, and improvement in duration of sleep, quality of sleep and morning wakenings was found in nearly 90% of patients and was maintained in those patients who continued treatment for 360 days. This efficacy was achieved with a stable percentage of patients receiving 10 mg/day and 20 mg/day zolpidem from day 30 to the final visit. Zolpidem, therefore, has been shown to be an effective and safe hypnotic, and to be devoid of rebound and withdrawal effects.

Family Practice

Effects of zolpidem versus diazepam and placebo on breathing control parameters in healthy human subjects.

The following study explores the possibility that zolpidem, a new hypnotic agent derived from imidopyridine, may induce changes in ventilatory function in normal subjects. The study, conducted double-blind on 16 subjects (eight men and eight women, aged 21 to 33 years) was undertaken in two successive phases: phase A with a cross-over, intended to compare the ventilatory effects of 10 mg oral dose of diazepam with a placebo, and then phase B, with a Latin square design, intended to compare the effects of 10 and 20 mg oral doses of zolpidem with 10 mg oral doses of diazepam and a placebo. Central inspiratory drive was assessed by occlusion pressure (P0.1) and breathing pattern in air and during carbon dioxide rebreathing. Measurements were performed one and three hours after each drug or placebo administration. Zolpidem did not affect tidal volume (Vt), slopes S1, S2 or P0.1, but decreased the duration of the phases of the respiratory cycle ti by 14% (p less than 0.01) and ttot by 15% (p = 0.03) after three hours post dosing without any change in ventilation, Vt/ti or ti/ttot. Nevertheless, these timing changes, although statistically significant, seem to have no clinical relevance to overall ventilation regulation in normal subjects. On the other hand, diazepam slightly changed S2 at three hours post dosing (0.14 +/- 0.07 versus 0.17 +/- 0.10 after the placebo; p = 0.06) without modifying the other parameters.

Administration, Oral

Alfuzosin for treatment of benign prostatic hypertrophy. The BPH-ALF Group.

To assess the long-term efficacy and safety of alfuzosin, a selective alpha 1-adrenergic antagonist, 518 symptomatic patients with benign prostatic hypertrophy (BPH) were randomised to received either alfuzosin (daily dose 7.5-10 mg) or placebo for 6 months. Obstructive and irritative symptoms, assessed according to the Boyarsky scale, significantly improved in the alfuzosin group compared with the placebo group (p = 0.0004). Fewer patients in the alfuzosin group than in the placebo group dropped out due to lack of efficacy (6.8% vs 14.6%, p = 0.004) and the prevalence of spontaneous acute urine retention was lower in the alfuzosin group (0.4% vs 2.6%, p = 0.04). By 6 months, mean urinary flow rates had increased (p less than 0.05) and residual volume had decreased (p = 0.017) in the alfuzosin group, although the two groups were broadly similar with respect to increase in peak flow rate. The overall incidence of adverse events was similar in the two groups, which led to the withdrawal of 10.8% and 9.0% of patients, respectively. The findings emphasise the magnitude of the placebo response in symptomatic patients with BPH and show that treatment with alpha 1 adrenergic antagonist drugs provides long-lasting improvement in such patients.

Adrenergic alpha-Antagonists

Asymptomatic bacterascites: is it spontaneous bacterial peritonitis?

Asymptomatic bacterascites is defined as the presence of bacteria in ascitic fluid without clinical features of peritonitis or increased ascitic fluid polymorphonuclear cells. Asymptomatic bacterascites is a controversial entity, and little information is available regarding its spontaneous evolution. Clinical features, bacteriological data and outcome in 22 cirrhotic patients with asymptomatic bacterascites are reported and are compared with those of a group of 36 cirrhotic patients with spontaneous bacterial peritonitis. Eleven patients had gram-negative bacteria and 11 had one gram-positive bacteria. Only in three patients (13.6%) did peritonitis develop. Twelve patients received no antibiotic therapy, and in none did peritonitis develop. At 1 month, 27% of patients with asymptomatic bacterascites had died. Patients with asymptomatic bacterascites had less-severe liver disease; they more frequently had gram-positive bacteria in ascitic fluid and had a lower 1-mo mortality rate than did patients with spontaneous bacterial peritonitis. We conclude that asymptomatic bacterascites is usually the transient residence of bacteria in ascitic fluid. Peritonitis rarely develops in patients with asymptomatic bacterascites and, in most of them, antibiotic therapy is not required.

Adult

Sulindac causes regression of rectal polyps in familial adenomatous polyposis.

In familial adenomatous polyposis, sulindac-induced polyp regression has been reported by several authors. In this study, the goal was to confirm these results by a randomized, placebo-controlled, double-blind crossover study in 10 patients with rectal polyps that had been previously treated by colectomy and ileorectal anastomosis. Patients received sulindac, 300 mg/day, or placebo during two 4-month periods separated by a 1-month wash-out phase. One patient was not compliant and was excluded. With sulindac, the authors observed a complete (6 patients) or almost complete (3 patients) regression of the polyps. With placebo, the authors observed an increase (5 patients), no change (2 patients), and a relative decrease (2 patients) in the number of polyps. The difference between sulindac and placebo was statistically significant (P less than 0.01). In biopsy specimens of polyps and normal rectal mucosa of 6 patients, the authors conducted an immunohistochemical study of the cellular proliferation index using the Ki 67 monoclonal antibody (Ki 67 index), at the beginning and at the end of each treatment period. They were not able to show a sulindac-induced modification of the Ki 67 index. The authors conclude that sulindac is effective in inducing the regression of rectal polyps in familial adenomatous polyposis.

Adenomatous Polyposis Coli

Pharmacokinetics of metoclopramide in patients with liver cirrhosis.

The pharmacokinetics of metoclopramide were investigated after intravenous and oral administration in eight patients with severe alcoholic cirrhosis and in eight healthy volunteers. As a consequence of a 50% lower clearance (0.16 +/- 0.07 vs 0.34 +/- 0.09 l h-1 kg-1, plasma drug concentrations and the half-life of metoclopramide were greater in patients following both routes of drug administration. Volume of distribution (3.1 +/- 0.8 vs 3.4 +/- 1.2 l kg-1) and absolute bioavailability (79 +/- 19 vs 84 +/- 15%) were similar in the two groups. The adverse effects of metoclopramide observed in patients with marked hepatic impairment are likely to result from increased accumulation of the drug as a result of impaired clearance. Consequently a reduction in dose of 50% is recommended in patients with severe liver cirrhosis.

Administration, Oral

A randomized trial of hepatic arterial chemoembolization in patients with unresectable hepatocellular carcinoma.

A randomized trial of hepatic arterial chemoembolization was conducted in 42 patients with unresectable hepatocellular carcinoma. These patients represented 41% of patients with hepatocellular carcinoma seen during the inclusion period. In the remaining 59%, 9% had resectable tumours and 50% had unresectable tumours with contraindication for chemoembolization. Patients received either repeated chemoembolization with gelfoam powder and doxorubicin (group 1) or symptomatic treatment (group 2). There was no difference in age, prevalence of cirrhosis or staging according to Okuda between the two groups of patients. A complete tumour response (assessed by arteriography, ultrasonography and serum alphafetoprotein) was observed in four patients, and a partial response in three other patients from group 1. Actuarial survival rates were 33 and 24% in group 1 and 52 and 31% in group 2 at 6 and 12 months, respectively (differences were not significant--logrank test). With the treatment used in our study, chemoembolization did not prolong the survival time of patients with unresectable hepatocellular carcinoma. There were, however, some complete or partial responses. The high spontaneous 1-year survival rate of untreated patients was probably due to the exclusion of the most severely ill patients. Our results do not support the use of this method of chemoembolization in the treatment of hepatocellular carcinoma.

Adult

Culture-negative neutrocytic ascites: a less severe variant of spontaneous bacterial peritonitis.

The clinical signs and symptoms, the biological data and the prognosis of 38 cirrhotic patients with culture-positive spontaneous bacterial peritonitis and 15 cirrhotic patients with culture-negative neutrocytic ascites were compared. The diagnosis of culture-negative neutrocytic ascites was based on the following criteria: an ascitic fluid polymorphonuclear count greater than 250/mm3, a negative ascitic fluid culture and the absence of previous antibiotic therapy and intraabdominal source of infection. All patients were treated by antibiotic therapy. There were no differences in clinical signs and symptoms and Pugh grading between the two groups of patients. Serum creatinine and prevalence of positive-blood culture were higher in spontaneous bacterial peritonitis. Patients with culture-positive spontaneous bacterial peritonitis had a higher ascitic fluid polymorphonuclear count and a lower ascitic fluid pH. Mortality was higher in patients with culture-positive spontaneous bacterial peritonitis than in patients with culture-negative neutrocytic ascites (relative risk: 2.6, p less than 0.01): cumulative mortality was, respectively, 50% and 20% at 1 months, 61% and 33% at 6 months, 75% and 41% at 1 year. The higher mortality observed in patients with culture-positive spontaneous bacterial peritonitis persisted after hospitalization (relative risk: 3, p less than 0.03). Our results suggest that culture-negative neutrocytic ascites is a less severe variant of spontaneous bacterial peritonitis.

Adult

Mechanocardiographic evaluation of left ventricular diastolic function in hypertrophic cardiomyopathy and hypertensive cardiomyopathy.

Usefulness of computerized mechanocardiography and echocardiography in the diagnosis of impaired left ventricular diastolic function is shown in a study comparing 17 hypertrophic obstructive cardiomyopathy and 17 hypertensive cardiomyopathy patients to 20 normal subjects. Mechanocardiography allows the evaluation of three different parameters of diastolic function: isovolumic relaxation evaluated by S2a-O or better by t-dr/dt and dr/dt/A2 ratio, left ventricular compliance by the A/H ratio and time of rapid filling. All the parameters are impaired in both pathological populations. Isovolumic relaxation being more depressed in hypertensive cardiomyopathy and duration of rapid filling being prolonged especially in the hypertrophic obstructive cardiomyopathy patients. Although the differences are small indicating only trends computerized mechanocardiography gives some evidence for difference in the alteration of diastolic function in hypertrophic obstructive cardiomyopathy and hypertensive cardiomyopathy.

Cardiomyopathy, Hypertrophic

Pharmacokinetics of ornidazole in patients with acute viral hepatitis, alcoholic cirrhosis, and extrahepatic cholestasis.

Pharmacokinetics of ornidazole, a nitroimidazole derivative, was investigated after intravenous injection in 3 groups of 10 patients with different hepatic diseases: hepatitis, noncholestatic cirrhosis and extrahepatic cholestasis. Plasma concentrations of ornidazole and its two major hydroxylated metabolites, M1 [alpha-(chloromethyl)-2-hydroxymethyl-5-nitroimidazole-1-ethanol] and M4 [3-(2-methyl-5-nitroimidazole 1-yl)-1,2-propane diol] were measured by HPLC assay. As a consequence of a decreased clearance (26% to 48%), the half-life and MRT are increased in all patients by 19% to 38% when compared with healthy volunteers. No clear difference could be established between the different groups. The volume of distribution remains the same in all patients and controls except those suffering from cancer. As previously shown in patients with severe liver cirrhosis, both metabolites accumulate in plasma as a result of decreased elimination; formation is no longer the rate-limiting step of their kinetics. This metabolite accumulation is in part due to decreased biliary excretion and to hepatocellular failure.

Adult

[Retinopathy in pancreatitis].

Three patients with retinopathy associated with acute pancreatitis were observed. Each of them had a long history of alcohol abuse. The first patient was asymptomatic. Second one developed moderate visual loss in one eye (visual acuity 20/40), with a fascicular defect on Goldmann visual field registration. Third patient complained with bilateral and severe visual loss, with a large central scotoma. Cotton-wool patches and hemorrhages were present in the mild types of retinopathy. These cases had a good prognosis. An ischemic edema of posterior pole was associated in severe type of retinopathy. In this case, fluorescein angiography showed occluded macular retinal arterioles. Visual prognosis was poor. Pathogenesis of the lesions is still discussed. The main hypothesis are fat emboli or activated complement-induced granulocyte embolus formation. Efficacity of corticosteroids is not known.

Acute Disease

[Prognosis of spontaneous ascitic infection in cirrhotic patients].

The aim of this retrospective study was to define prognostic factors for cure and survival after spontaneous bacterial peritonitis. In a 4-year period from 1982 to 1986, spontaneous bacterial peritonitis was diagnosed in 38 consecutive hospitalized cirrhotic patients (positive ascites culture and polymorphonuclear cell concentration greater than 250 cells per mm3). Twenty-five patients recovered from their infection (69 p. 100) in a mean time of 9 +/- 7 days. The cumulative survival was 68 p. 100 at one week, 50 p. 100 at one month, and 25 p. 100 at one year. The best independent prognostic factors for lack of cure from peritonitis were a low ascitic pH value (p less than 0.001), an elevated serum creatinine level (p = 0.01) and the presence of hepatocellular carcinoma (p less than 0.05). The best prognostic factors for death were low ascitic pH value (p = 0.001) and gastrointestinal hemorrhage (p = 0.005). A low ascitic pH value was correlated with other signs of severe infection (signs of generalized infection, ongoing infection during the first week after diagnosis), with signs of severe liver disease (encephalopathy, hepatocellular carcinoma) or severe renal dysfunction (high serum creatinine level, low arterial pH value). Because of the late high-death rate associated with spontaneous bacterial peritonitis, liver transplantation should be considered in these patients.

Bacterial Infections

[Prevention of hemorrhagic recurrence in cirrhotic patients. Is sclerotherapy better than propranolol?].

The effectiveness of oral propranolol and sclerotherapy in preventing recurrent bleeding after an endoscopically proven haemorrhage from oesophageal varices was compared in Pugh's grade B and C patients divided into two successive therapeutic groups. Group I patients (n = 32) were given oral propranolol, while sclerotherapy was performed in group II patients (n = 32), 23 of whom simultaneously received propranolol. There was no difference between groups I and II in the severity of the initial bleeding and liver failure (Groups I/II, B 19/18, C 13/14), in the withdrawal of alcohol (group I 25, group II 17) and in compliance with either treatment (group I 25, group II 27). Obliteration of the oesophageal varices was achieved in 69 p. 100 of group II patients within a median number of 4 courses and 46 days, and in 84 p. 100 of the patients of this group who survived for more than 3 months. One year after the beginning of treatment rebleeding had occurred in 43 p. 100 of either group I or group II patients. The 1-year survival rate was 72 p. 100 in group I and 62 p. 100 in group II (non significant). The causes of death were the same in both groups. Irrespective of the treatment assigned, death was 2.1 times more frequent (P = 0.02) and rebleeding was 1.2 time more frequent (P = 0.08) in grade C than in grade B patients.

Esophageal and Gastric Varices

Light chain deposition disease presenting with hepatomegaly: an association with amyloid-like fibrils.

We report an unusual case of lambda light chain deposits without overt plasma cell dyscrasia. The clinical presentation was hepatomegaly without biochemical sign of renal involvement. Portal hypertension, spontaneous rupture of the spleen and fracture of the 12th thoracic vertebra occurred during the course of the disease. Ultrastructural studies showed that lambda light chain deposits were associated with amyloid-like deposits. This case suggests that light chain deposition disease and amyloidosis could be two expressions of the same disease.

Amyloidosis