Therapeutic benefit of benfluorex in type II diabetic patients treated with sulfonylureas.

The objective of this study was to evaluate the effect of benfluorex in type II diabetic patients already treated with sulfonylureas (SU) in a randomized placebo-controlled trial. After a 4-week placebo run-in, 68 patients (49 men and 19 women; age range 40-70 years; known duration of diabetes 0.5-19 years) were randomized to double-blind 12-week treatment with benfluorex (B) or placebo (P). Primary end points were HbA1c and fasting blood glucose (FBG). Secondary end points were glucose tolerance (meal test over 120 min), plasma insulin, C-peptide, and lipid profile. Results were analyzed using both intention-to-treat analysis (ITT) in patients completing at least one treatment visit and per protocol analysis in those completing the whole study. There were no baseline differences between the two groups in any study parameter. Fifty-eight patients completed the study (28 B, 30 P), and 66 patients (33 B, 33 P) were eligible for ITT analysis. Over the 12-week treatment period, FBG decreased by 14.9% in the B group (-1.39 mmol/L, p < 0.001), and 3.2% in the P group (-0.28 mmol/L, NS) according to the ITT analysis and by 17.4% (p < 0.001) and 3.8% (NS), respectively, in the per protocol analysis. The difference in FBG outcome between the two groups was significant (p = 0.009 and p = 0.004, respectively). In patients completing the study, mean HbA1c decreased in the B group (-0.66%, p = 0.005) and remained stable in the P group (+0.14%, NS). HbA1c outcome differed between the two groups (p = 0.007). The decrease in AUCglucose was greater in the B group than in the P group (-210 +/- 220 versus -60 +/- 270 mmol/L x 120 min, p = 0.026). Plasma insulin and C-peptide changes did not differ between the two groups. Low-density lipoprotein (LDL) cholesterol decreased in B patients and was stable in P patients (-0.43 versus -0.05 mmol/L, p = 0.026). Of the 68 randomized patients, six on B and four on P reported at least one adverse event, causing dropout in five and two patients, respectively. In conclusion, benfluorex is an effective agent for combination therapy in type II diabetic patients poorly controlled on SUs alone.

Laser Doppler and transcutaneous oximetry: modern investigations to assess drug efficacy in chronic venous insufficiency.

During chronic venous insufficiency (CVI), microcirculatory changes, e.g. a decrease in transcutaneous oxygen pressure (tcpO2) and an increase in transcutaneous carbon dioxide pressure (tcpCO2), are implicated in the pathophysiology of trophic disorders leading ultimately to venous ulcers. Daflon 500 mg1, a micronized purified flavonoid fraction, has been shown to improve venous tone, capillary permeability and resistance, and lymphagogue activity at a daily dose of 2 tablets. To assess the effects of Daflon 500 mg on microcirculatory parameters by means of laser Doppler fluxmetry and transcutaneous oxiketry, a 3-month, double-blind, randomized, parallel-group study was carried out in 104 patients divided into 3 groups according to the daily dose: 1 tablet (group 1, n = 34), 2 tablets (group 2, n = 33), on 4 tablets (group 3, n = 37). All patients (mean age 43.7 +/- 13.1 years; 100 females, 4 males) included in the study were affected by mild CVI. They were followed for 90 days with visits at 1 month (day 28) and 3 months (day 90). At inclusion, there were no significant differences between groups as regards biometric data, mean tcpO2 (group 1, 62.7 +/- 4.5 mm Hg; group 2, 64.0 +/- 3.3 mm Hg; group 3, 64.1 +/- 3.5 mm Hg), mean tcpCO2 (group 1, 40.7 +/- 2.5 mm Hg; group 2, 39.3 +/- 2.9 mm Hg; group 3, 40.0 +/- 2.5 mm Hg) and laser Doppler parameters. Fourteen patients withdrew from the study (group 1, n = 4; group 2, n = 3; group 3, n = 7): 9 for reasons not related to treatment, 3 for adverse events, 2 because they were lost to follow-up. From day 0 to day 90, mean tcpO2 significantly increased (p < 0.001) in each group (group 1, 3.0 +/- 2.1 mm Hg; group 2, 2.9 +/- 2.1 mm Hg; group 3, 2.5 +/- 1.6 mm Hg), mean tcpCO2 significantly decreased (p < 0.001) in each group (group 1, 2.6 +/- 2.0 mm Hg; group 2, 1.7 +/- 1.9 mm Hg; group 3, 2.2 +/- 1.5 mm Hg). No significant differences were observed between groups. Laser Doppler parameters remained unchanged from day 0 to day 90 in the 3 groups. Symptoms (discomfort, pain, heaviness, burning sensation) and signs (oedema) of CVI as well as perimetric measurements of calf and supramalleolar area were significantly improved in the 3 groups. In conclusion, during this 3-month study, Daflon 500 mg improved oximetric measurements and did not alter laser Doppler parameters. These data suggest that Daflon 500 mg, at the early stages of CVI, acts favourably on the microcirculatory disturbances also involved in the pathophysiology of more severe stages of CVI.

In vitro activity of zidovudine alone and in combination with ciprofloxacin against Salmonella and Escherichia coli.

The in vitro antibacterial activity of zidovudine alone and in combination with ciprofloxacin was investigated. Zidovudine showed a good activity against Escherichia coli and Salmonella (MIC range 0.5-8 micrograms/ml and 1.5-62 micrograms/ml respectively) isolated from biological samples of HIV-infected patients. These strains proved to be extremely susceptible to ciprofloxacin alone. The interaction between zidovudine and ciprofloxacin ranged from additive activity to indifference. No antagonism was observed: the FIC index for every combination resulted < or = 1.5. The addition of AZT 1 mg/l (clinically achievable plasma concentration after therapeutic doses of 1200 mg/day) did not affect the bactericidal activity of ciprofloxacin; on the contrary, in some cases we observed an increase of bactericidal effect of the quinolone. These data have to be considered in patients with AIDS who can be treated concomitantly with zidovudine and ciprofloxacin.

In vitro activity of clarithromycin alone or in combination with other antimicrobial agents against Mycobacterium avium-intracellulare. Complex strains isolated from AIDS patients.

The activity of clarithromycin and five other antimicrobial agents, namely amikacin, rifampicin, rifabutin, clofazimine and ciprofloxacin, was assessed both by an agar dilution and a radiometric method in broth on 11 Mycobacterium avium-intracellulare complex (MAC) strains, recently isolated from AIDS patients. Minimum inhibitory concentrations (MICs) radiometrically determined were, in general, several times lower than MICs assessed in agar, probably because of a partial degradation of antimicrobials during the long incubation period needed for tests in solid medium. When tested in broth, rifabutin and clofazimine showed very low MICs 90 (0.24 and 0.78 microgram/ml, respectively). Ciprofloxacin and clarithromycin also had MICs90 in the range of peak serum levels (1.93 and 3.76 micrograms/ml, respectively). Moreover, all these antimicrobials are known to concentrate several times in macrophages. MICs90 were higher for amikacin (11 micrograms/ml) and for rifampicin (8 micrograms/ml). When clarithromycin was tested against three MAC strains in combination with another drug, it showed a synergistic effect only when combined with rifampicin. Some synergistic effect was observed also when combining clarithromycin with rifampicin and amikacin, whereas in combination with rifabutin and clofazimine there was only an additive effect.

[Monitoring of plasma concentrations of aminoglycosides]. / Monitoraggio della concentrazione plasmatica degli aminoglucosidi.

Aminoglycosides are antibiotics commonly used in the management of a large number of gram- and gram+ infections but their use is limited by their potential nephrotoxicity and ototoxicity. At present, monitoring of plasma concentrations is the most reliable method for assuring adequate therapy with these antibiotics. The above paper was intended to show the importance of pharmacokinetic monitoring in order to guarantee therapeutic efficacy and control potential toxicity of aminoglycosides in a series of 90 patients.

[Significant bacteriological findings in HIV-positive patients]. / Dati batteriologici significativi in soggetti HIV positivi.

Twenty-four episodes of bacterial infections were identified over a 18 month period in 11 patients (8 with acquired immunodeficiency syndrome and 3 with AIDS related complex). Eight of the 11 infected patients were drug abusers and 3 homosexual people. Nosocomial bacterial infections were common in patients with AIDS and had high fatality rates. Gram-negative bacteria resulted the most common micro-organisms (E.coli, Proteus, Enterobacter, Serratia, Klebsiella). The Aztreonam treatment was very useful in providing bacteria eradication. Gram-positive bacteria as Staphylococcus from a sepsis and Enterococcus from a cystopyelitis were eradicated by B-lactam antibiotics. Common micro-organism are frequent in patients affected by LAS/ARC or AIDS and they negatively interfere with the disease outcome.

[Epidemiologic surveillance of influenza in Rome 1982-1984]. / Sorveglianza epidemiologica dell'influenza in Roma nel periodo 1982-1984.

In the periods from July 1982 to June 1983 and July 1983 to June 1984, 31 strains of influenza virus, of which 19 A/H3N2 6 A/H1N1 and 6 type B, were isolated from 242 throat cultures obtained from patients with acute febrile respiratory disease. A seroepidemiological survey on 520 serum samples confirms significant activity of influenza viruses during the winterly period of 1983-1984. In the period July-August 1983 the evaluation of mortality from respiratory diseases presents an excess in respect of epidemic threshold probably ascribable to heat stroke.