Phorbol diester-inducible, cyclosporine-suppressible transcription from a novel promoter within the mouse mammary tumor virus env gene.

The mouse T-cell lymphoma cell line EL4.E1 constitutively synthesizes mouse mammary tumor virus (MMTV) transcripts encoding either the entire proviral genome or segments of it. In addition to these conventional mRNAs, however, an mRNA of about 1 kilobase accumulates after induction of these cells with phorbol myristate acetate (PMA). The accumulation of this transcript is strongly inhibited by the immunosuppressive agent cyclosporin A. Its pattern of induction by PMA and suppression by cyclosporin A is thus the same as seen for several lymphokine mRNAs in these cells, including interleukin-2 and granulocyte-macrophage colony-stimulating factor. The short MMTV transcript is the most abundant PMA-induced transcript in EL4.E1 cells, but was not found in a series of other leukocyte tumor cell lines. It is initiated from a novel promoter within the env gene, and a segment of 1,161 nucleotides is then spliced out. The major part of the transcript is a copy of the long terminal repeat (LTR) of MMTV. The MMTV proviral genomes in these cells, and the short transcript, contain a 491-nucleotide deletion in the LTR compared with the normal MMTV provirus. The resulting open reading frame could encode a protein of molecular weight 22,800, which is a likely candidate for an LTR-related protein with a similar molecular weight recently described in this system (J. Racevskis, J. Virol. 58:441-449, 1986).

A comparison of pivmecillinam/pivampicillin and amoxycillin in acute exacerbations of chronic bronchitis.

Courses of 7 days on either 200 mg pivmecillinam/250 mg pivampicillin given twice daily or 250 mg amoxycillin given three times daily were compared in 3783 general practice patients with acute exacerbations of chronic bronchitis in a single-blind parallel group study. Patients on pivmecillinam/pivampicillin had significantly more 'excellent' responses, although there was no difference in overall response between treatments. Post-treatment sputum colour and consistency and peak expiratory flow rates were significantly better with pivmecillinam/pivampicillin. The incidence of side-effects was the same for both groups (approximately 10%), although significantly more patients reported lower gastro-intestinal problems with amoxycillin. Treatment was withdrawn due to side-effects in 47 (2.5%) patients on pivmecillinam/pivampicillin and 51 (2.7%) patients on amoxycillin. Amoxycillin is a standard therapy in the treatment of patients with acute exacerbations of chronic bronchitis. In this study, however, it was shown that pivmecillinam/pivampicillin offers benefits over amoxycillin in these patients.

A post-marketing acceptability study in 11,685 patients of the efficacy of timolol/bendrofluazide in the management of hypertension in general practice.

A post-marketing acceptability study was performed in 11,685 patients to assess the efficacy and acceptability of 10 mg timolol/2.5 mg bendrofluazide in patients with mild to moderate hypertension in general practice. The initial dose was 1 tablet/day. This was adjusted at weekly intervals up to a maximum of 4 tablets/day or until blood pressures of less than or equal to 95 mmHg diastolic or, in patients of greater than or equal to 60 years, less than or equal to 100 mmHg plus the patient's age (in years) systolic, were achieved. Stabilized patients were followed-up after 12, 24 and 48 weeks. Of the patients enrolled, 69% (8039) were successfully treated for at least 8 weeks, 26% (3033) were withdrawn and 5% (613) defaulted. One tablet/day was required by 61% of patients and 29% required 2 tablets/day to achieve stabilization. The mean reductions in systolic and diastolic blood pressures and pulse rate were 31 and 19 mmHg, and 11 beats/min, respectively. Over 60% of the patients enrolled were still taking timolol/bendrofluazide after 12 months' continuous therapy. The most frequently reported reason for withdrawal was an 'adverse event' which occurred in 15.4% (1805) of patients. Only 1.9% (217) failed to achieve target blood pressure on 4 tablets/day. This large study has shown timolol/bendrofluazide to be a highly effective and acceptable once daily therapy for mild to moderate hypertension in general practice.

A comparative study of Miraxid (pivmecillinam plus pivampicillin) and Augmentin (amoxycillin plus clavulanic acid) in the treatment of lower respiratory tract infections in general practice.

Two treatments, pivmecillinam 200 mg plus pivampicillin 250 mg (Miraxid) given twice-daily and amoxycillin 250 mg plus clavulanic acid 125 mg (Augmentin) given three times daily were compared in two parallel groups of 388 general practice patients with acute bronchitis or acute exacerbations of chronic bronchitis. Patients with acute bronchitis (140 on Miraxid, 144 on Augmentin) received a 7-day course of treatment and those with acute exacerbations of chronic bronchitis (55 on Miraxid, 49 on Augmentin) a 10-day course of treatment. Both treatments were equally effective, with 99 (71%) patients with acute bronchitis being successfully treated with Miraxid and 107 (74%) with Augmentin. In acute exacerbations of chronic bronchitis, Miraxid was successful in 29 (53%) patients and Augmentin in 24 (49%) patients. Side-effects were reported by 26 (12%) of patients in both treatment groups. This single blind multicentre general practice study comparing twice-daily Miraxid with 3 times daily Augmentin demonstrated that both treatments were equally effective clinically and equally well tolerated.

A multi-centre general practice clinical evaluation of pivmecillinam plus pivampicillin ('Miraxid') and co-trimoxazole ('Septrin') in respiratory tract infections.

Seven-day courses of either 200 mg pivmecillinam plus 250 mg pivampicillin or co-trimoxazole (800 mg sulphamethoxazole plus 160 mg trimethoprim) given twice daily were compared in a multi-centre general practice study in 318 patients with signs and symptoms of upper or lower respiratory tract infection. Patients were stratified into four diagnostic groups (sinusitis, otitis media, throat infections, and acute bronchitis) and randomly allocated to treatment within these groups. Assessments at Day 7 showed that both treatments were equally effective clinically, 154 (91%) patients in the pivmecillinam plus pivampicillin group showing clinical cure or improvement and 142 (88%) patients in the co-trimoxazole group. Side-effects were reported by 19 (11.9%) patients in the pivmecillinam plus pivampicillin group and by 24 (15.8%) patients in the co-trimoxazole group. Two patients in the pivmecillinam plus pivampicillin group and 4 patients in the co-trimoxazole group stopped treatment.

A clinical comparison of pivmecillinam plus pivampicillin (Miraxid) and a triple tetracycline combination (Deteclo) in respiratory infections treated in general practice.

Seven-day courses of either pivmecillinam 200 mg plus pivampicillin 250 mg (Miraxid) or a combination of tetracycline hydrochloride, chlortetracycline hydrochloride and demeclocycline hydrochloride (Deteclo) 300 mg, both given twice daily, were compared in a multicentre general practice study in 408 patients with symptoms of upper or lower respiratory tract infection. Patients were stratified into four diagnostic groups: sinusitis, otitis media, throat infections, and acute bronchitis and randomly allocated to treatment within these groups. Assessment at 7 days showed no difference in clinical efficacy between the two treatments where 193 of the 208 infections receiving Miraxid (93%) were rated as either cured or improved compared with 181 of the 201 infections treated with Deteclo (90%). At 7 days, the percentage of patients completely free of symptoms was the same for both groups (66%). The mean time for symptoms to clear was 3.9 days in the Miraxid group and 4.0 days in the Deteclo group. Side-effects were reported by significantly fewer patients in the Miraxid group (9.3%) than the Deteclo group (17.5%) (p less than 0.05) and six patients in the latter group failed to complete the course of treatment. Miraxid given twice daily for respiratory tract infections is as effective as Deteclo but causes significantly fewer side-effects.

A multi-centre general practice comparison of a fixed-dose combination of pivmecillinam plus pivampicillin with amoxycillin in respiratory tract infections.

Seven-day courses of either 200 mg pivmecillinam plus 250 mg pivampicillin given twice daily or 250 mg amoxycillin given 3-times daily were compared in a multi-centre general practice study in 350 patients with symptoms of upper or lower respiratory tract infection. Patients were stratified into four diagnostic groups: sinusitis, otitis media, throat infections, and acute bronchitis, and randomly allocated to treatment within these groups. Assessments at 7 days showed no difference in overall clinical efficacy between the two treatments; however, patients with acute bronchitis showed a better response to pivmecillinam plus pivampicillin. After treatment, signs of infection were absent in 139 (79%) patients in the pivmecillinam plus pivampicillin group and in 143 (80%) patients in the amoxycillin group. Both treatments were well tolerated, adverse effects being reported in only 17 (9.8%) patients after pivmecillinam plus pivampicillin and 15 (8.6%) patients after amoxycillin. These were mainly associated with disturbances of the gastro-intestinal tract where reports of diarrhoea were twice as common after amoxycillin.

Nasal carriage and antibiotic susceptibility of Staphylococcus aureus in general practice.

The incidence of nasal carriage of Staphylococcus aureus and the in vitro susceptibility of isolates to fusidic acid, penicillin, erythromycin, methicillin and tetracycline was determined in 204 patients who had been treated previously with a short course of a topical preparation of Fucidin for acute skin sepsis, and in an equal number of control subjects. Staphylococcus aureus was isolated from 36 per cent and 34 per cent of patients in the Fucidin and control groups respectively. Only one of the 144 isolates was resistant to fusidic acid. Short, single courses of topical therapy in general practice are unlikely to be epidemiologically hazardous in the long term. Evidence of possible cross-infection in general practice was obtained.