Effect of an inhaled antihistamine (clemastine) as a bronchodilator and as a maintenance treatment in asthma.

Although intravenous chlorpheniramine can cause bronchodilatation, oral and parenteral antihistamines have not proved useful in treating asthma. Inhaled antihistamines may cause throat irritation, but a recent study of the antihistamine, clemastine, showed it to be an effective bronchodilator without irritant effects. We have extended these studies to determine the site of action of inhaled clemastine and to assess its potential usefulness both as a bronchodilator and as a maintenance treatment. Eleven stable asthmatic patients received inhaled clemastine and placebo and the effect was assessed by serial maximum expiratory flow volume (MEFV) curves breathing air and a helium/oxygen (He/O2) mixture. There was no significant improvement in peak flow rates during air breathing after clemastine and no significant difference between the responses to drug and placebo. Minor but significant changes were seen in some flow measurements on the downslope of the MEFV curve during air and He/O2 breathing, and these are tentatively ascribed to a dilating effect of clemastine on peripheral airways where flow is laminar. Subsequent administration of inhaled isoprenaline showed the patients to be still capable of significant bronchodilatation. The addition of clemastine, from a pressurised aerosol, to the patients' therapeutic regimen for two weeks was no more effective than placebo in controlling airflow obstruction, and did not reduce the need for standard bronchodilators. In our patients clemastine was not a clinically useful bronchodilator either acutely or as a maintenance treatment for asthma.     

Stress lesions of the lower leg and foot.

Technetium 99 methylene diphosphonate scans were performed on 32 patients with suspected stress fractures. Twenty-six patients had abnormal scans, 13 had abnormal X-rays and on these only nine had either fresh periosteal new bone and/or a fracture line. A logical approach of the use of X-ray and radionuclide techniques in patient management is suggested.     

An investigation of operating theatre staff exposed to humidifier fever antigens.

Sixty staff working in a hospital operating theatre, where a case of humidifier fever had been identified, were studied together with 49 subjects working in other parts of the hospital. They each had a blood test for serology, a skin test, and a chest radiograph and completed a questionnaire. The theatre staff also had pulmonary function tests. The theatre humidifier was found to contain several organisms including amoebae and antigens cross-reacting highly with those implicated in previous outbreaks of humidifier fever. Of the 60 exposed subjects, 25 had developed antibodies, nine had probable symptoms of humidifier fever, and six possible symptoms. There was a strong association between symptoms and antibodies (p = 6 x 10(-5) by Fisher's exact test). The development of antibodies was also related to duration of exposure in the theatre (p less than 0.01 by X2 test for trend) and inversely to smoking (p = 0.0073 by Fisher's exact test) but not to history of atopy. Because of the presence of antigens and because certain biocides added were ineffective in controlling antigenic build-up the humidifier was switched off. Eight months later specific IgG levels in the theatre staff sera, estimated by an enzyme-linked immunosorbent assay technique, had fallen on average by 25%. Inhalation challenge with humidifier water was performed in eight subjects. Four subjects reacted to the challenge, including both those with antibodies and previous symptoms.     

Management of advanced colorectal cancer: state of the art

Colorectal cancer (CRC) caused over 500 000 deaths worldwide in 2002. Recent advances in the treatment of advanced disease include the incorporation of two new cytotoxic agents, irinotecan and oxaliplatin, into first-line regimens. The concept of planned sequential therapy involving three active agents during the course of a patient's treatment is evolving. Coupled with the integrated use of targeted monoclonal antibodies, we can now expect overall survival rates for advanced disease to exceed 20 months. This review considers current treatments and suggests where future progress may occur.     

A measure of the performance of biomarkers for disease

The statistical properties required for effective biomarkers for disease are examined. It is shown that an "effectiveness parameter" D can be calculated that summarises the performance of a given biomarker and can distinguish between effective and ineffective biomarkers. D can be readily calculated from published summaries of biomarker levels and provides a simpler alternative to the commonly used "Area under the Curve" statistic. The impact of within-individual and between-individual variation in biomarker levels is also evaluated. An approach to the choice of sample size for experiments to estimate D is described.     

Multiple papillomas of the breast: Is current management adequate?

Multiple papillomas (MP) are subject to debate in terms of their clinical and pathological significance and management. To date the ideal management is still not well established. The Royal Perth Hospital Multidisciplinary Breast Service has prospectively accrued clinical and pathological data on over 9000 patients since 1994. The database was interrogated and all pathology reports retrospectively reviewed. A total of 23 cases with the diagnosis of MP were retrieved from the database between 1994 and 2004. Of these 23 cases, 13 (56.5%) were diagnosed by core biopsy, nine (39.1%) on excision biopsy, and one (4.4%) on a mastectomy specimen. The average age of patients was 56.4 years (range 44-74 years). The average duration of follow up is 4.1 years (range 1-10 years). In our series a close association with malignancy was noted for MP, which was also associated with a spectrum of proliferative breast disease. Contemporary guidelines should be developed for this controversial condition. We recommend that all patients with MP, especially when associated with atypia, undergo wide excision of the lesion with clear margins of at least 10mm and that these patients be monitored closely with annual imaging.