A double blind, randomised, multicentre comparison of two doses of intravenous iloprost in the treatment of Raynaud''s phenomenon secondary to connective tissue diseases.

OBJECTIVE--To compare low (0.5 ng/kg/min) and standard dose (2 ng/kg/min) iloprost (a stable carbacyclin analogue of prostacyclin) in patients with Raynaud''s phenomenon secondary to connective tissue disorders. DESIGN--Double blind, random allocation, three six hour infusions on consecutive days. Follow up period eight weeks. SETTING--Rheumatology units, five teaching hospitals. PATIENTS--55 Patients with Raynaud''s phenomenon (greater than seven attacks per week), 32 secondary to well documented classical progressive systemic sclerosis (American Rheumatism Association criteria), 11 CREST syndrome, 5 mixed connective tissue disease, 1 rheumatoid arthritis, 1 Sjögren''s syndrome, 1 childhood dermatomyositis, and 4 abnormal nailfold capillaroscopy and antibody profiles but no definite diagnosis. INTERVENTIONS--All other treatment for Raynaud''s phenomenon was discontinued two weeks before entry. 28 Patients were randomly allocated to receive the low dose, 27 the standard dose. Differing dilutions allowed infusion rates to be started at 10 ml/h with increments of 10 ml/h every 15 minutes until infusion rates reached 0.5 ng/kg/min and 2 ng/kg/min respectively. MAIN OUTCOME MEASURE(s)--Reduction in frequency, duration, and severity of attacks of Raynaud''s phenomenon. Assessment of ulcer and ischaemic lesion healing. RESULTS--Both dosage regimens were equally effective in reducing severity, frequency, and duration of Raynaud''s attacks. Ulcer healing occurred to similar degree in both treatment groups (standard dose 44%, low dose 39%). Low dose was associated with significantly fewer side effects. CONCLUSIONS--Both dosage regimens reduce severity of Raynaud''s phenomenon and encourage ulcer healing. Low dose was associated with fewer side effects and was better tolerated by the patients.     

The prospective pioglitazone clinical trial in macrovascular events (PROactive): can pioglitazone reduce cardiovascular events in diabetes? Study design and baseline characteristics of 5238 patients

OBJECTIVE: The PROspective pioglitAzone Clinical Trial In macroVascular Events (PROactive) assesses the effect of pioglitazone, a peroxisome proliferator-activated receptor agonist, with anti-inflammatory and vascular properties, on the secondary prevention of macrovascular events in type 2 diabetes. RESEARCH DESIGN AND METHODS: PROactive is an on-going randomized, double-blind outcome study in patients with type 2 diabetes managed with diet and/or oral blood glucose-lowering drugs (combination of oral agents with insulin is permitted) who have a history of macrovascular disease. Patients are randomized to receive pioglitazone (forced titration from 15 to 30 to 45 mg, depending on tolerability) or placebo in addition to existing therapy. The primary end point is the time from randomization to occurrence of a new macrovascular event or death. Follow-up is estimated to span 4 years. RESULTS: A total of 5238 patients have been randomized from 19 countries. At entry into the study, patients enrolled are a mean age of 61.8 years, with type 2 diabetes for a mean of 9.5 years; 60.9 and 61.5% are taking metformin or a sulfonylurea, respectively; and 33.6% are using insulin in addition to oral glucose-lowering drugs. The majority of patients are men (66.1%). Patients are required to meet one or more of entry criteria, as follows: >6 months' history of myocardial infarction (46.7%); coronary artery revascularization (30.8%), stroke (18.8%), or acute coronary syndrome for >3 months (13.7%); other evidence of coronary artery disease (48.1%); or peripheral arterial occlusive disease (19.9%). One-half (48.5%) of the patients have two or more of these risk factors. Three-quarters (75.4%) have hypertension, and 58.8% are current or previous smokers. CONCLUSIONS: The cohort of patients enrolled in PROactive is a typical type 2 diabetic population at high risk of further macrovascular events. The characteristics of this population are ideal for assessing the ability of pioglitazone to reduce the cardiovascular risk of patients with type 2 diabetes.     

The multi-dimensional measure of informed choice: a validation study

The aim of this prospective study is to assess the reliability and validity of a multi-dimensional measure of informed choice (MMIC). Participants were 225 pregnant women in two general hospitals in the UK, women receiving low-risk results following serum screening for Down syndrome. The MMIC was administered before testing and the Ottawa Decisional Conflict Scale was administered 6 weeks later. The component scales of the MMIC, knowledge and attitude, were internally consistent (alpha values of 0.68 and 0.78, respectively). Those who made a choice categorised as informed using the MMIC rated their decision 6 weeks later as being more informed, better supported and of higher quality than women whose choice was categorised as uninformed. This provides evidence of predictive validity, whilst the lack of association between the MMIC and anxiety shows construct (discriminant) validity. Thus, the MMIC has been shown to be psychometrically robust in pregnant women offered the choice to undergo prenatal screening for Down syndrome and receiving a low-risk result. Replication of this finding in other groups, facing other decisions, with other outcomes, should be assessed in future research.     

In vivo microscopic study of microcirculatory perfusion of the skin of the foot in peripheral vascular disease.

OBJECTIVES: the aim of this study was to determine the proportion of perfused capillaries in the skin of the foot in patients with peripheral vascular disease, and compare it with that in normal subjects. DESIGN: experimental study comparing capillary perfusion in nine patients with severe peripheral vascular disease (group 2) with seven age- and sex-matched control subjects (group 1). MATERIALS AND METHODS: using in vivo video microscopy, a method was developed to measure the ratio of perfused to total capillaries, by comparing the numbers of corresponding capillaries before and after intravenous injection of sodium fluorescein. RESULTS: the mean percentage ratio of perfused to total capillaries was 54.7% (range 41-87%, standard deviation 16.5) in group 1, and 86.0% (range 62-100%, standard deviation 13.2) in group 2 (p<0.001, t-test). CONCLUSION: a significantly higher proportion of capillaries is perfused in the skin of the foot of patients with severe peripheral vascular disease than in that of normal subjects. This is of important pathophysiological significance and may have clinical implications with regard to the role of pharmacological intervention in severe limb ischaemia.     

Macrocytic anaemia due to copper deficiency in a patient with late onset hypogammaglobulinaemia

Very few cases of acquired severe copper deficiency have been described. The principal effects are haematological, but the precise abnormalities are uncertain due to the possible association of other deficiencies. A case of isolated severe copper deficiency associated with late onset hypogammaglobulinaemia is reported in which the chief findings were macrocytic anaemia, neutropenia and a decrease in mean platelet volume. All these abnormalities resolved when copper therapy was instituted and recurred when the medication was stopped.