Early cytotoxic events were studied on B77 fibroblasts. Cells were treated with sulphur mustard (SM) in short-term experiments in which cell viability was unchanged, as evaluated by the neutral red cytotoxicity test. This treatment was correlated to two early signs of cytotoxicity. The intracellular Ca2+ concentration [Ca2+]i level in SM-treated Fura-2-loaded fibroblasts showed a significant dose-dependent increase. This observed rise was sustained, in contrast to the Ca2+ signal induced by serum, and was already visible 5-10 min after the addition of SM to cell suspensions in vitro. Modification of the extracellular Ca2+ concentration in the medium had no effect on the cytosolic calcium rise caused by SM, suggesting release from intracellular Ca2+ pools. Furthermore, a time-dependent inhibition of the [Ca2+]i transient increase induced by growth-factors (as evaluated by the fetal calf serum (FCS) response) was observed within the first hour of exposure. These latter results suggest that early alterations of calcium distribution induced by SM could be one of the earliest markers of SM intoxication.

Animals↗

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Retroviral transfer of antisense sequences results in reduction of C-Abl and induction of apoptosis in hemopoietic cells.

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Animals↗

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Methylation analysis of the fragile X syndrome by PCR.

The fragile X syndrome is predominantly caused by a large expansion of a CGG trinucleotide repeat in the promoter region of the FMR1 gene, which is associated with methylation and downregulation of transcription. The molecular diagnosis of this disorder is based on repeat size and methylation analysis of the FMR1 gene usually by Southern blot analysis. We describe a PCR-based method for the analysis of methylation of the FMR1 gene, which involves bisulfite treatment of DNA prior to amplification. Fifty-two normal and 48 affected, premutation, or mosaic males were analyzed in a blinded study by this method. A prospective study of 30 males suspected of fragile X was also performed. Amplification specific for the methylated FMR1 sequence was readily observed in all individuals with a full mutation, whereas all normal and premutation individuals showed only amplification-specific for the unmethylated sequence, thus, allowing affected and unaffected males to be distinguished. A full mutation in the presence of mosaicism was also detectable by this method. Methylation-specific PCR appears to be a rapid and reliable tool for the diagnosis of fragile X males.

Base Sequence↗

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Short-course treatment of sinusitis and other upper respiratory tract infections with azithromycin: a comparison with erythromycin and amoxycillin. European Azithromycin Study Group.

In two randomized, multicentre studies patients with upper respiratory tract infections treated with 1.5 g azithromycin in five or six doses over 5 days were compared with patients treated with 10 g erythromycin in 40 doses over 10 days or 15 g amoxycillin in 30 doses over 10 days. The majority of azithromycin- (65%) and erythromycin- (67%) treated patients in the azithromycin/erythromycin study and all patients in the azithromycin/amoxycillin study had sinusitis. Clinical cure was recorded in 83% of azithromycin- and 79% of erythromycin-treated patients, and in 81% and 87%, respectively, of azithromycin- and amoxycillin-treated patients. There was no significant difference in bacteriological eradication between the treatments. Adverse events, predominantly mild or moderate gastro-intestinal complaints, occurred in 17% and 15%, respectively, of azithromycin- and erythromycin-treated patients, and in 5% and 11%, respectively, of azithromycin- and amoxycillin-treated patients but there were no serious laboratory safety abnormalities. Azithromycin appeared to be an effective, simplified treatment for upper respiratory tract infections and may improve patient compliance compared with standard therapies.

Adolescent↗

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Simplified treatment of acute lower respiratory tract infection with azithromycin: a comparison with erythromycin and amoxycillin. European Azithromycin Study Group.

In two randomized, multicentre studies azithromycin treatment (1.5 g in five or six doses over 5 days) was compared with erythromycin treatment (14 or 20 g in 28 or 40 doses over 7 or 10 days) and amoxycillin treatment (10.5 g in 21 doses over 7 days) in patients with acute respiratory tract infection. In the two separate studies, azithromycin gave complete clinical cure in 70% and 51%, respectively, of patients compared with in 60% of erythromycin- and 45% of amoxycillin-treated patients. Eradication of the main pathogens isolated at baseline (Haemophilus influenzae, Streptococcus pneumoniae and Staphylococcus aureus) was comparable in the azithromycin, erythromycin and amoxycillin treatment groups. Efficacy was not affected by the presence or absence of underlying pulmonary disease. There were no major abnormalities in laboratory safety parameters and adverse events, principally mild/moderate gastro-intestinal symptoms occurred in 5% or 15%, respectively, of azithromycin-treated patients compared with in 18% or 17%, respectively, of those receiving erythromycin or amoxycillin. It is concluded that azithromycin was as effective and better tolerated than erythromycin or amoxycillin.

Acute Disease↗

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Azithromycin, erythromycin and cloxacillin in the treatment of infections of skin and associated soft tissues. European Azithromycin Study Group.

Azithromycin (total dose 1.5 g) given orally in five or six doses over 5 days was compared with erythromycin and cloxacillin both given orally as 500 mg four times daily for 7 days in two multicentre studies of patients with skin and associated soft-tissue infections. Azithromycin eradicated baseline pathogen(s), mainly Staphylococcus aureus, in 89% compared with in 78%, of erythromycin-treated patients (P = 0.501) and in 78% compared with in 59% of cloxacillin-treated patients (P = 0.421). No statistically significant difference in clinical cure was reported between azithromycin (74%) and erythromycin (75%, P = 1.00) and between azithromycin (60%) and cloxacillin (47%, P = 0.301) treatment groups. The side-effects reported for azithromycin were mainly mild or moderate gastro-intestinal complaints and there were no major abnormalities in laboratory parameters. It is concluded that azithromycin was as effective as, but better tolerated than, either erythromycin or cloxacillin and short-course therapy may improve patient compliance.

Abscess↗

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