Safety profile of 3 months' therapy with alfuzosin in 13,389 patients suffering from benign prostatic hypertrophy.

The safety profile of alfuzosin, a selective alpha 1-adrenergic antagonist, was assessed in a total of 13,389 patients (mean age 66.9 +/- 8.5 years) with symptomatic benign prostatic hypertrophy in two open, noncontrolled, multicentre, post-marketing surveillance studies, both conducted in France. Alfuzosin was prescribed at the recommended dose of 2.5 mg t.i.d., according to the current labelling recommendations, for a 3-month period. Clinical safety was assessed using spontaneous reporting of adverse events leading to discontinuation of treatment. Overall, 89.7% of the patients completed the treatment period. Drop outs were recorded in 10.3% of patients: 3.7% for intolerance; 1.5% for resolution of urinary symptoms; 2.1% for lack of efficacy, and 3.0% for loss to follow-up, noncompliance, and miscellaneous reasons. Two thirds of the adverse events leading to discontinuation were vasodilatory and occurred in 2.7% of the patients: vertigo/dizziness (1.4%); malaise (0.6%); hypotension (0.4%), and headache (0.4%). Other adverse events (predominantly gastrointestinal disorders) were recorded in < 1.2% of the patients. Three quarters of the adverse events occurred during the first week of therapy. As expected, adverse events were more frequent in the elderly (aged over 75 years) and in patients taking cardiovascular drugs or with concomitant cardiovascular disease. Overall, alfuzosin was very well tolerated and the adverse event profile was consistent with the cumulative experience of the drug. No unexpected or serious adverse events considered to be related to alfuzosin were recorded. Particular care must be taken when prescribing for very elderly patients and/or those with concomitant cardiovascular disease for which they are receiving therapy.

Combined oral lysine acetylsalicylate and metoclopramide in the acute treatment of migraine: a multicentre double-blind placebo-controlled study.

This multicentre, double-blind, randomized, placebo-controlled, parallel study was designed to evaluate the efficacy of combined oral lysine acetylsalicylate and metoclopramide (LAS-MCP) in the acute treatment of migraine attacks. A total of 266 patients, 18-65 years old, with two to six attacks of migraine with or without aura (IHS criteria) per month were included. The patients had to treat two migraine attacks with LAS-MCP (1620 mg lysine acetylsalicylate--the equivalent of 900 mg aspirin--combined with 10 mg metoclopramide) or placebo. The main outcome measure was headache relief (reduction in headache severity from grade 3 or 2--severe or moderate--to grade 1 or 0--mild or none) 2 h after treatment. LAS-MCP was superior to placebo for headache relief (56% vs 28%) and for the following secondary outcome measures: complete headache relief (18% vs 7%; p < 0.001), nausea (28% vs 44%; p < 0.001), vomiting (3% vs 11%; p = 0.001), use of rescue medication (47% vs 68%; p < 0.001), global efficacy judged as good or excellent (32% vs 14%; p < 0.001). The tolerability was considered as good in 94% of treated attacks in both groups. Combined oral lysine acetylsalicylate and metoclopramide is an effective and well-tolerated acute treatment of migraine attacks.

Cryoglobulinemia in chronic liver diseases: role of hepatitis C virus and liver damage.

BACKGROUND/AIMS: Mixed cryoglobulinemia is frequently associated with liver diseases. The respective role of hepatitis C virus (HCV) and liver damage in the pathogenesis of cryoglobulinemia is investigated in this study. METHODS: The prevalence of cryoglobulinemia in 226 consecutive patients with chronic liver diseases (hepatitis C, 127; hepatitis B, 40; other diseases, 59) was studied, and the epidemiological, biological, histological, and virological features in these three groups were analyzed. Anti-HCV antibodies, HCV proteins, and HCV RNA were searched in the cryoprecipitates. RESULTS: The prevalence of mixed cryoglobulinemia was high (41.5%) in patients with liver diseases and higher in patients with hepatitis C (54.3%) than in patients with hepatitis B (15%) or other causes of liver disease (32%). Patients with cryoglobulinemia had cirrhosis more frequently and had a longer history of hepatitis. In patients with hepatitis C, HCV RNA sequences and HCV proteins were detected in the cryoprecipitate. Cryoglobulins became undetectable in 21 of 43 patients treated with interferon. CONCLUSIONS: These findings suggest that HCV is a major cause of cryoglobulinemia. Besides viral infection itself, multiple factors appear to be responsible for the production of cryoglobulins, including cirrhosis and duration of liver disease.

[Thoraco-cervicofacial purpura caused by thoracic compression: a new Perthes syndrome?]. / Purpura thoracocervicofacial par compression thoracique: un nouveau syndrome de Perthes?

A case of a major thoracocervicofacial purpura in a 16-year-old patient following a prolonged thoracic compression by his motor car is reported. The causative mechanism, equivalent to a Valsalva manoeuvre is discussed. As the first case has been described and analyzed by Perthes, the authors suggest to call it "Perthes syndrome".

Chronic administration of cyclosporin A induces a decrease in hepatic excretory function in man.

Chronic administration of cyclosporin A may induce cholestasis in a few patients. The purpose of this study was to examine the effect of chronic administration of cyclosporin A on serum bile acid levels, serum bilirubin concentration, and bromosulfophthalein plasmatic fractional clearance. Twenty heart-transplanted patients with normal serum alanine aminotransferase activity receiving cyclosporine A during a mean duration of 33 months (range 7-54) were compared to 20 matched kidney-transplanted patients with normal serum alanine aminotransferase receiving azathioprine for a mean duration of 34 months (range 6-72). As compared to azathioprine-treated patients, patients treated with cyclosporin A had an increase in serum bile acid levels of 32% (P < 0.01), an increase in serum bilirubin concentration of 100% (P < 0.001), and a decrease in bromosulfophthalein plasmatic fractional clearance of 60% (P < 0.001). These results suggest that cyclosporin A induces a decrease in hepatic excretory function in man.

Liver/kidney microsome antibody type 1 and hepatitis C virus infection.

Recent studies have shown that hepatitis C virus antibodies are present in a large proportion of patients with autoimmune hepatitis type 2. We have studied 83 patients with liver/kidney microsome antibody-positive type 1 hepatitis. Hepatitis C virus antibodies were sought in every case by second-generation tests (hepatitis C virus enzyme-linked immunosorbent assay and recombinant immunoblot assay). Hepatitis C virus RNA sequences were sought in 22 patients (12 with recombinant immunoblot assay-positive results and 10 with recombinant immunoblot assay-negative results) by means of polymerase chain reaction and by use of primers located in the 5' noncoding region. Sixty-four patients (77%) had positive results for hepatitis C virus antibodies in the enzyme-linked immunosorbent assay test, and 41 (49.3%) were confirmed by recombinant immunoblot assay. Hepatitis C virus RNA sequences were found in all the recombinant immunoblot assay-positive patients but in none of the 10 who were recombinant immunoblot assay-negative. The recombinant immunoblot assay-negative patients were younger than those who were positive (13 +/- 11 vs. 50 +/- 11 years) and had higher gamma-globulin levels and liver/kidney microsome antibody-positive type 1 titers (61% had a titer of 1:1,000 or more, vs. only 17% of the recombinant immunoblot assay-positive patients).(ABSTRACT TRUNCATED AT 250 WORDS)

Spontaneous dialytic ultrafiltration with intraperitoneal reinfusion of the concentrate versus large paracentesis in cirrhotic patients with intractable ascites: a randomized study.

Dialytic ultrafiltration of ascites through a hemofilter associated with peritoneal reinfusion (DUF) of the concentrate has been proposed for the treatment of refractory ascites. In five cirrhotic patients, 18 ascites evacuation procedures were randomized either to DUF (n = 8) or to large paracenteses (LP) (n = 10). The effects of these two methods on hemodynamic and renal function were assessed. After DUF, the protein concentration in ascites increased transiently from 28 +/- 7 g/l to 64.8 +/- 8 g/l (p less than 0.04); urinary output increased from day 1 to day 4 (1000 +/- 100) VS 1430 +/- 140 ml/24h; p less than 0.02). After LP, ascitic protein concentration and urinary output were unchanged. No side effects were observed with the two methods. The mean amount of albumin infused was 20 +/- 15 g after DUF and 15 +/- 5 after LP (ns).

Spontaneous dialytic ultrafiltration with intraperitoneal reinfusion of the concentrate in 15 cirrhotic patients with intractable ascites.

The clinical efficacy and tolerance of dialytic ultrafiltration of ascites through a hemofilter (DUF) with peritoneal reinfusion of the concentrate was evaluated in 15 cirrhotic patients with intractable ascites. All together, 51 DUF procedures were carried out. An average of 8.6 was ultrafiltered during 12 h with no significant change in blood pressure, hemoglobin, coagulation parameters or plasma creatinine. A significant increase in ascitic protein concentration was observed immediately after the procedure and a slight but significant increase in 24 h urinary output. A controlled evaluation of DUF compared to large paracenteses seems to be justified by these preliminary results.

Chronic liver dysfunction in heart transplant recipients, with special reference to viral B, C, and non-A, non-B, non-C hepatitis. A retrospective study in 80 patients with follow-up of 60 months.

In order to assess the prevalence, causes, and severity of chronic liver dysfunction (LD) in heart transplant patients, 80 transplanted patients followed for 60 months (median; range, 1.5-98 months) were reviewed. Sustained liver dysfunction was found in 50 patients, occurring during the first year after heart transplantation in 42 (84%) of them. Most patients were asymptomatic (80%). Causes for the liver dysfunction included non-A, non-B hepatitis in 16 cases (32%), viral B hepatitis in 13 (26%), delta hepatitis in one (2%), drug-induced hepatitis in six (12%), and cardiac failure in seven (14%). Anti-HCV antibodies were found in 56.2% of patients with non-A, non-B hepatitis and in 22% of patients with HBV hepatitis. It was found neither in patients with drug-induced hepatitis cardiac failure nor in patients with normal liver tests. This study outlines a high prevalence of LD (62.5%) in heart transplant patients, the high frequency of viral-related chronic LD (usually of moderate severity), and high incidence of HCV and HBV hepatitis.

Demographic factors and the antihypertensive effect of diltiazem.

The maximum blood pressure (BP) decrease obtained after dose titration with calcium antagonists is said to be greater in older patients. Because the dose necessary to achieve this maximum effect may also vary, it is not clear whether the sensitivity to treatment is actually increased in older patients. We evaluated the possible influence of pretreatment BP, age, and weight on the BP and heart rate (HR) response to 14-day treatment with a fixed dose of 120 mg diltiazem twice daily (b.i.d.) in 231 hypertensive patients aged 24-82 years (44 +/- 27). Diltiazem decreased BP from 171 +/- 1/103 +/- 7 to 156 +/- 1/91 +/- 1 mm Hg. Decreases in both systolic and diastolic BP (SBP, DBP) were related to their pretreatment values (p less than 0.0001 for both). Although pretreatment SBP was related to age (p less than 0.0001), its decrease with diltiazem was not. Neither pretreatment DBP nor its decrease with diltiazem was related to age; BP decrease was not superior in elderly patients (aged greater than 60 years) as compared with that in younger patients (SBP -16 +/- 2 vs. -15 +/- 1 mm Hg, NS; DBP -13 +/- 1 vs. -12 +/- 1 mm Hg, NS). In conclusion, the response to this average dose of diltiazem is related to pretreatment BP and is not affected by patient's age. Because this result is at variance with the concept that calcium antagonists are more effective in the elderly, this concept should not be used as a general therapeutic guideline.

Predictive value of whole blood chemiluminescence in patients with alcoholic hepatitis.

Recent reports suggest that ethanol metabolism leads to reactive oxygen intermediates that may be responsible for the lesions observed in alcoholic hepatitis. This study investigated the production of reactive oxygen intermediates in peripheral blood phagocytes of patients with alcoholic hepatitis and attempts to evaluate its predictive value. Using a luminol-dependent chemiluminescence method, reactive oxygen intermediate production was measured directly within microamounts of whole blood, both in the absence (basal chemiluminescence production) and in the presence of phagocyte-stimulating agents including latex, zymosan, phorbol myristate acetate and N-formyl-methionyl-leucyl-phenylalanine. Thirty patients with well-documented and histologically proven alcoholic hepatitis were studied. Pugh's and Child's classification, Orrego's composite clinical and laboratory index and Maddrey's discriminant function were used to assess the prognosis of the liver disease. Patients were followed up monthly for 6 mo. Results were compared with those obtained in 17 patients with nonalcoholic liver disease and in 78 normal control subjects. Basal chemiluminescence production was significantly higher in patients with alcoholic hepatitis than in those with nonalcoholic liver disease and in normal subjects (p less than 0.001). Chemiluminescence responses to latex, zymosan and phorbol myristate acetate were significantly lower in alcoholic hepatitis patients than in normal subjects (p less than 0.001); however, when compared with nonalcoholic liver disease patients, these responses were significantly decreased only in the presence of zymosan (p less than 0.05). Both basal chemiluminescence production (p less than 0.001) and zymosan-induced chemiluminescence responses (p less than 0.02) were closely related to alcoholic hepatitis prognosis indices (i.e., Pugh's and Child's classification, Orrego's composite clinical and laboratory index and Maddrey's discriminant function.(ABSTRACT TRUNCATED AT 250 WORDS)