Prostaglandins and angioplasty. An experimental study in canine arteries

To prevent platelet aggregation following percutaneous transluminal angioplasty (PTA), cyclooxygenase inhibitors such as acetylsalicylic acid (ASA) and indomethacin are recommended. However, ASA blocks both the proaggregating effects of thromboxane (TXA2) and the antiaggregating and vasodilating effects of prostacyclin (PGI2). The authors measured the contractile response of dilated canine carotid arteries in situ and in vitro using an isometric force transducer. Following PTA, contraction of the arterial wall was significantly reduced (p less than 0.01). By blocking cyclooxygenase with indomethacin (3 micrograms/ml), contraction was greatly improved (p less than 0.001). These results suggest that PTA may result in marked release of prostacyclin by the damaged arterial wall, which could account for the decreased responsiveness of the artery to exogenous norepinephrine.     

The CTLA-4 gene region of chromosome 2q33 is linked to, and associated with, type 1 diabetes. Belgian Diabetes Registry

Susceptibility to autoimmune insulin-dependent (type 1) diabetes mellitus is determined by a combination of environmental and genetic factors, which include variation in MHC genes on chromosome 6p21 (IDDM1) and the insulin gene on chromosome 11p15 (IDDM2). However, linkage to IDDM1 and IDDM2 cannot explain the clustering of type 1 diabetes in families, and a role for other genes is inferred. In the present report we describe linkage and association of type 1 diabetes to the CTLA-4 gene (cytotoxic T lymphocyte associated-4) on chromosome 2q33 (designated IDDM12). CTLA-4 is a strong candidate gene for T cell- mediated autoimmune disease because it encodes a T cell receptor that mediates T cell apoptosis and is a vital negative regulator of T cell activation. In addition, we provide supporting evidence that CTLA-4 is associated with susceptibility to Graves' disease, another organ- specific autoimmune disease.      

Insomnia in the elderly : Prevalence,gender differences and relationships with morbidity and mortality

A sample of 1070 people aged 65 and over living in the Liverpool community was interviewed in 1982/3. Those traced were then reinterviewed 3 years later. Information was collected on the prevalence of perceived insomnia using a community version of the Geriatric Mental State (GMS), which also provided a diagnosis using AGECAT. Thirty-five per cent reported trouble sleeping, which was twice as common in women as men and was not wholly accounted for by the increased prevalence of mental illness in elderly women. There was no change in prevalence with age, but insomnia was more frequent in the depressed group (70%). Insomnia is more likely with increasing serverity of depression but was also common in the well group and hence is not a specific indicator. No relationship was found between mortality at year 3 and insomnia or hypnotic use at year 0. Use of hypnotics was related to the presence of sleep disturbance, but not to having a psychiatric diagnosis. Medical intervention may be much more successful in reducing the prevalence of benzodiazepine usage than may have been realized.     

Adalimumab for psoriasis patients who are non-responders to etanercept: open-label prospective evaluation

Background  Targeted biologic therapies have made a significant impact on the treatment for moderate to severe psoriasis. In the United Kingdom, the National Institute for Health and Clinical Excellence recommends etanercept, a human recombinant tumour necrosis factor (TNF) receptor fusion protein, for moderate to severe psoriasis patients who have failed conventional therapies. There is, however, no data available on the role of other TNF antagonists for patients who have failed etanercept. Adalimumab, a fully human, anti-TNF monoclonal antibody, is approved for treatment of moderate to severe psoriasis.
Objectives  To assess the efficacy and safety of adalimumab (40 mg weekly) in psoriasis patients who were non-responders to high-dosage etanercept (50 mg twice weekly).
Methods  All patients attending a tertiary referral service for severe psoriasis who were non-responders to high-dosage etanercept [i.e. failed to achieve ≥ 50% improvement in Psoriasis Area and Severity Index (PASI 50) after 12 weeks of treatment] were considered for open-label adalimumab therapy for 12 weeks. Details on clinical course, PASI, Dermatology Life Quality Index (DLQI) and adverse events were recorded at baseline and weeks 2, 4, 8, and 12.
Results  Four of five patients in this study had reached at least PASI 50 by week 12. Of these, two patients achieved a 75% improvement in PASI (PASI 75). No serious adverse events were reported.
Conclusions  Initial data from this open-label prospective evaluation suggests that weekly adalimumab therapy is an effective treatment for patients with severe psoriasis who had failed to respond to at least 3 months of high-dosage etanercept.     

Guidelines for international collaborative research

OBJECTIVE: As the global village becomes a reality, there is an increasing need to conduct international collaborative studies in family practice. A workshop at the WONCA meeting in Hong Kong used international attendees to produce a set of guidelines for international research. METHODS: At the workshop four completed international projects, each using a different strategy, were presented so that common themes might become apparent. The themes were then discussed and guidelines emerged from the process. RESULTS: Seven guidelines emerged for consideration before embarking on an international collaborative research project in family medicine. The guidelines deal with the characteristics of the research question and the importance of communication. The need for simple, brief methods of data collection, funding and pilot testing were identified. CONCLUSION: The question must be relevant to all participants to maintain interest and measurement tools must be validated to understand the impact of cultural differences in understanding.