Comparison of asthma treatment given in addition to inhaled corticosteroids on airway inflammation and responsiveness.

There is increasing evidence that the assessment of eosinophilic airway inflammation using induced sputum and measurement of airway hyperresponsiveness provides additional, clinically important information concerning asthma control. The aim of this study was to directly compare the effects of different treatments on these markers in patients with asthma and persistent symptoms, despite the use of low-dose inhaled corticosteroids. A double-blind four-way crossover study was performed, which compared a 1-month treatment with budesonide 400 mug b.i.d., additional formoterol, additional montelukast and placebo in 49 patients with uncontrolled asthma despite budesonide 100 mug b.i.d., with each treatment separated by a 4-week washout period. The change in sputum eosinophil count with formoterol (2.4 to 3.8% change, 0.6-fold reduction, 95% confidence interval (CI) 0.5-0.9) differed significantly from placebo (2.8 to 2.5% change, 1.1-fold reduction, 95% CI 0.7-1.6) and high-dose budesonide (2.7 to 1.6% change, 1.6-fold reduction, 95% CI 1.2-2.2). The effects of montelukast did not differ from placebo. The changes in methacholine airway responsiveness were small and did not differ between treatments. High-dose budesonide had the broadest range of beneficial effects on other outcomes, including symptom scores, morning peak expiratory flow and forced expiratory volume in one second. In conclusion, treatment given in addition to low-dose inhaled corticosteroids results in modest benefits. Formoterol and high-dose budesonide have contrasting effects on eosinophilic airway inflammation.     

Negative symptoms in schizophrenia: considerations for clinical trials

There is little agreement about the methodology of clinical trials of antipsychotic drugs in patients with negative symptoms. A literature review revealed wide variation in experimental design, rating scales and study duration. This reflects differing views as to the definition and response to treatment of negative symptoms. Some degree of standardization would improve comparability of studies and aid the development of new compounds. Patients included in such studies should have displayed negative symptoms for at least 6 months. Depressive symptoms, positive schizophrenic symptoms and extrapyramidal signs may all influence or be confused with negative symptoms and may respond to treatment; they should be at a low level at baseline and should be measured during the study period. Studies should last at least 8 weeks. Several scales are available for measuring negative symptoms and are reviewed; a global impression score should be used additionally.     

Preliminary evidence for a role of apolipoprotein E alleles in identifying haemodialysis patients at high vascular risk

Conventional risk factors have very low predictive power in identifying haemodialysis patients at high risk of vascular accidents. A role for apolipoprotein E isotypes was looked for in a small, but rigorously defined, cohort of longterm haemodialysis patients. In individuals with high vascular risk, as identified by higher common carotid intima/media thickness, we found an excess of apolipoprotein E4 alleles. This preliminary result requires confirmation in large patient cohorts.      

Treatment approaches for clients with a stroke‐affected upper limb: Are we following evidence‐based practice?

Stroke rehabilitation is an area of practice that many occupational therapists encounter during their career. The literature promotes a wide range of management techniques and support devices for people who have a stroke-affected upper limb, but little is known about the validity of those that occupational therapists actually use in practice. A questionnaire was sent to occupational therapists working in Queensland and northern New South Wales facilities (n = 35), in which adults with a stroke were likely to be treated. Eighteen respondents answered questions about the management techniques and support devices used in their facility, and their perception of the benefit of these devices in the reduction of hemiplegic shoulder pain. Results are discussed with reference to evidence-based practice and indicate an urgent need for the collation and dissemination of the best current evidence available for the management techniques and support devices used in this area, as well as further research to extend this evidence.     

Binding potency of paroxetine analogues for the 5-hydroxytryptamine uptake complex.

The in-vitro inhibition constants (Ki) of 14 structural analogues of the potent 5-hydroxytryptamine (5-HT)-uptake inhibitor paroxetine were determined to assess the structure-affinity relationship of these derivatives. A goal of these studies was to determine those positions on paroxetine which could be derivatized without significantly decreasing the affinity of the drug for the binding site, so that radiolabels such as [18F]fluoroalkyl groups might be appended for future in-vivo imaging studies of the 5-HT uptake system. Using the methyl moiety as a steric probe for these studies, it was found that the rank order of potency of various methyl-substituted paroxetine analogues for inhibiting the binding of [3H]paroxetine to the 5-HT re-uptake site was: 4'-approximately equal to 3'-approximately equal to 2'- > 2'-approximately equal to 1- > 5'- > 6'-methyl. The in-vitro equipotent molar ratios (EPMR, Ki(analogue)/Ki(paroxetine)) of the analogues were determined, and the EPMRs of the 4'-, 3'-, and 2'-methyl derivatives were 1.9, 2.2 and 2.2, respectively. The 4'- and 2'-fluoromethyl and -fluoroethyl analogues were synthesized, and the EPMRs of the 4'- and 2'-fluoromethyl derivatives were determined to be 2.0 and 3.5, and those of the 4'- and 2'-fluoroethyl analogues were 5.2 and 6.2, respectively. The 2'-fluoromethyl analogue was unstable in aqueous solutions, and it is not a promising ligand for in-vivo studies.(ABSTRACT TRUNCATED AT 250 WORDS)     

Breast tumour thymidine kinase levels and disease recurrence.

Thymidine kinase (TK) exists in two forms, TK1 and TK2. TK levels and oestrogen receptor status (OR) were measured in tumours from 86 patients with operable breast cancer and the patients were monitored for recurrence over 24 months. During the monitored period, 13 patients showed recurrence. These patients also exhibited higher total TK levels per mg tumour (P < 0.01) and higher TK1 levels (P < 0.001) than those who did not show recurrence. TK1 levels relative to TK2 were significantly higher (P < 0.05) in OR-negative tumours (n = 29) than in OR-positive tumours (n = 57). OR-negative (n = 9) and OR-positive (n = 4) patients who recurred had significantly higher TK1 levels relative to TK2 than did those who not recur (n = 20 and n = 53, respectively). These preliminary results indicate that breast tumour TK levels may have value in determining prognosis.