Primary systemic therapy (PST) for operable breast cancer enables the identification of in vivo biological markers that predict response to treatment. A total of 118 patients with T2 -4 N0 -1 M0 primary breast cancer received six cycles of anthracycline-based PST. Clinical and radiological response was assessed before and after treatment using UICC criteria. A grading system to score pathological response was devised. Diagnostic biopsies and postchemotherapy surgical specimens were stained for oestrogen (ER) and progesterone (PgR) receptor, HER-2 and cell proliferation (Ki-67). Clinical, radiological and pathological response rates were 78, 72 and 38%, respectively. There was a strong correlation between ER and PgR staining (Po0.0001). Higher Ki-67 proliferation indices were associated with PgRÀ tumours (median 28.3%, PgR þ 22.9%; P ¼ 0.042). There was no relationship between HER-2 and other biological markers. No single pretreatment or postchemotherapy biological parameter predicted response by any modality of assessment. In all, 10 tumours changed hormone receptor classification after chemotherapy (three ER, seven PgR); HER-2 staining changed in nine cases. Median Ki-67 index was 24.9% before and 18.1% after treatment (P ¼ 0.02); the median reduction in Ki-67 index after treatment was 21.2%. Tumours displaying 475% reduction in Ki-67 after chemotherapy were more likely to achieve a pathological response (77.8 vs 26.7%, P ¼ 0.004).

Efavirenz is a non-nucleoside reverse transcriptase inhibitor (NNRTI) which shows good inhibitory activity against HIV-1. Reduced susceptibility to efavirenz has been reported with HIV-1 variants containing single and multiple mutations to the reverse transcriptase enzyme. In vitro and in vivo data suggest that the resistance profile of efavirenz overlaps with that of the NNRTIs nevirapine and delavirdine. Clinically significant drug interactions have been reported with efavirenz and indinavir and saquinavir. An increase in dosage of indinavir from 800 to 1000 mg 3 times daily is recommended during coadministration with efavirenz. Use of efavirenz in combination with saquinavir as the sole protease inhibitor is not recommended. Once-daily efavirenz in combination with zidovudine plus lamivudine or indinavir or nelfinavir increased CD4+ cell counts and reduced HIV RNA plasma levels to below quantifiable levels (< 400 copies/ml) in HIV-infected patients. A sustained reduction in viral load was maintained for at least 72 weeks in 1 study. Nervous system symptoms (including headache, dizziness, insomnia and fatigue) and dermatological effects (including maculopapular rash) appear to be the most common adverse events reported with efavirenz-containing antiretroviral regimens.

Meloxicam is a new nonsteroidal anti-inflammatory drug (NSAID) developed for the treatment of rheumatoid arthritis and osteoarthritis. It has greater in vitro and in vivo inhibitory action against the inducible isoform of cyclo-oxygenase (COX-2), which is implicated in the inflammatory response, than against the constitutive form of this enzyme (COX-1), inhibition of which is associated with gastric, renal and other adverse effects. It has anti-inflammatory effects similar to or better than those of other NSAIDs in animal models, and a greater therapeutic ratio (ulcerogenic potential:efficacy in adjuvant arthritis). In healthy volunteers meloxicam 7.5 or 15 mg caused less gastrointestinal mucosal damage on endoscopy than piroxicam 20 mg, with a significant difference between meloxicam 7.5 mg and piroxicam. In comparative clinical trials, meloxicam was at least as effective as piroxicam and naproxen in patients with rheumatoid arthritis, and diclofenac and piroxicam in patients with osteoarthritis. Meloxicam was at least as well tolerated as piroxicam, diclofenac or naproxen overall but had improved gastrointestinal tolerability compared with these agents.

Erdosteine is a thiol derivative developed for the treatment of chronic obstructive bronchitis, including acute infective exacerbation of chronic bronchitis. Erdosteine contains 2 blocked sulfhydryl groups which are released following first-pass metabolism. The 3 active metabolites exhibit mucolytic and free radical scavenging activity. Erdosteine modulates mucus production and viscosity and increases mucociliary transport, thereby improving expectoration. It also exhibits inhibitory activity against the effects of free radicals produced by cigarette smoke. Clinical studies in patients with chronic obstructive lung disease have demonstrated the efficacy and tolerability of erdosteine. Erdosteine 300mg twice daily reduced cough (both frequency and severity) and sputum viscosity more quickly and more effectively than placebo and reduced the adhesivity of sputum more effectively than ambroxol 30mg twice daily. Co-administration of erdosteine and amoxicillin in patients with acute infective exacerbation of chronic bronchitis resulted in higher concentrations of the antibiotic in the sputum, leading to earlier and more pronounced amelioration of clinical symptoms compared with placebo. Erdosteine is associated with a low incidence of adverse events, most of which are gastrointestinal and generally mild.

Sevoflurane is a preferred anaesthetic agent for induction and maintenance of paediatric anaesthesia because of its rapid induction and recovery characteristics, lack of pungency and agreeable odour, and acceptable cardiovascular profile. Although the issue of postoperative excitement requires clarification, sevoflurane anaesthesia can be considered a rational choice for ambulatory and nonambulatory surgery in children.

Gemcitabine [2'-deoxy-2',2'-difluorocytidine monohydrochloride (beta isomer); dFdC] is a novel deoxycytidine analogue which was originally investigated for its antiviral effects but has since been developed as an anticancer therapy. Gemcitabine monotherapy produced an objective tumour response in 18 to 26% of patients with advanced non-small cell lung cancer (NSCLC) and appears to have similar efficacy to cisplatin plus etoposide. Objective response rates ranging from 26 to 54% were recorded when gemcitabine was combined with cisplatin, and 1-year survival duration after such treatment ranged from 35 to 61%. Improvements in a range of NSCLC disease symptoms and/or in general performance status occurred in many patients who received gemcitabine, with or without cisplatin, in 3 clinical trials. Gemcitabine appears to be cost effective compared with best supportive care for NSCLC. In addition, direct costs associated with administration of gemcitabine monotherapy may be lower than those for some other NSCLC chemotherapy options, according to retrospective cost-minimisation analyses. The combination of gemcitabine plus cisplatin was associated with a lower cost per tumour response than cisplatin plus etoposide or cisplatin plus vinorelbine, according to a retrospective cost-effectiveness analysis. In a single comparative study in patients with advanced pancreatic cancer, gemcitabine was more effective than fluorouracil with respect to survival duration and general clinical status. It also showed modest antitumour and palliative efficacy in patients refractory to fluorouracil. Gemcitabine appears to be well tolerated, although further comparisons with other chemotherapy regimens are required. The available data indicate that gemcitabine monotherapy is better tolerated than cisplatin plus etoposide in patients with NSCLC. Data from noncomparative studies suggest that the combination of gemcitabine and cisplatin has an acceptable tolerabilty profile. In a single trial in patients with pancreatic cancer, fluorouracil was better tolerated than gemcitabine; however, gemcitabine was generally well tolerated overall in this study. Thus, gemcitabine (with or without cisplatin) may prove attractive to patients with advanced NSCLC, given their limited life expectancy and the toxicity associated with many other chemotherapy regimens. More detailed characterisation of its risk-benefit profile compared with those of current and developing regimens for NSCLC should be possible once results from several ongoing studies are available. Gemcitabine is a valuable new chemotherapy option for patients with advanced pancreatic cancer, a disease considered incurable at present. Its apparent survival and palliative benefits over fluorouracil require confirmation, but are encouraging, as the need to improve both the duration and quality of survival in these patients is well recognised.

Intravenous recombinant tissue plasminogen activator (rt-PA) and urokinase in acute myocardial infarction: results of the German activator urokinase study (GAUS).

Racecadotril is an oral enkephalinase inhibitor used in the treatment of acute diarrhoea. It prevents the degradation of endogenous opioids (enkephalins), thereby reducing hypersecretion of water and electrolytes into the intestinal lumen. In a randomised double-blind study in 6 adult volunteers with castor oil-induced diarrhoea, racecadotril significantly reduced stool weight and stool number in comparison with placebo. Similar results have been obtained in treating castor oil-induced diarrhoea in rats. Racecadotril was significantly more effective than placebo in randomised double-blind studies in adults or children with diarrhoea (of infectious origin or in adults with HIV infection). In well controlled trials, racecadotril had efficacy similar to that of loperamide and was generally as effective as loperamide-oxide. Racecadotril had a similar tolerability profile to placebo, and was better tolerated than loperamide, in adults and children with diarrhoea. It caused significantly less constipation after resolution of diarrhoea than loperamide.