The action of Clofazimine on the level of lysosomal enzymes of cultured macrophages.

Mouse peritoneal and calf alveolar macrophage cultures were exposed to various concentrations of Clofazimine, 3 (p-chloroanilino)-10-p-Chlorophenyl 2, 10-dihydro-2-isopropylimino, for 120 hr and an increase of four lysosomal enzymes were found with 0 . 3 micrograms/ml of the drug. In mouse peritoneal macrophage cultures, higher concentrations were toxic. Cycloheximide inhibited the lysosomal enzyme activity increase found. No change in enzymatic activity was observed when a lysosomal enriched granular fraction was incubated with various drug concentrations. Our results strongly suggest that Clofazimine at concentrations close to therapeutic serum levels induces de novo synthesis of lysosomal enzymes in macrophage cultures.     

Amino acids in retinitis pigmentosa.

A survey of fasting whole blood amino acids in 65 patients with various subtypes of retinitis pigmentosa performed. Eight X-linked recessive patients showed decreased taurine and aspartate. Nineteen autosomal recessive patients, and to lesser extent 10 autosomal dominant patients, showed reduced levels of whole blood threonine and histidine. Branched-chain amino acids and arginine were present in increased amounts in 2 patients with Laurence-Moon-Bardet-Biedl syndrome. These findings in LMBB patients are probably related in part to their obesity and emphasise that appropriate controls are required, and other factors (including age) known to affect amino acid levels must be accounted for. The biochemical implications of our findings are not yet apparent.     

Does chronic illness place constraints on positive constructions of identity? Temporal comparisons and self-evaluations in people with schizophrenia

It is often suggested that people in potentially threatening situations might engage in self-enhancing temporal comparisons that allow them to view themselves and their experience in a more positive light. Data from semi-structured interviews with 12 individuals in the UK diagnosed as having schizophrenia were content analyzed to explore patterns of temporal comparison. The study found that the onset of schizophrenic symptoms created a new baseline in participants' representations of their past, with different types of temporal comparisons occurring before and after this point. Although comparisons with past selves after onset supported the suggestion that people may select and construct their past in such a manner that permits them to see their present circumstances more positively and envisage a better future, comparisons with past selves before onset were more negative. The findings suggest that the Theory of Temporal Self-Appraisals (Ross & Wilson, 2000) needs to be elaborated to include people who have experienced major life changes.     

Screening for colorectal cancer: virtually there

A national rollout of faecal occult-blood screening, federally funded, is the best approach.     

A systematic review of drug therapy to delay or prevent type 2 diabetes

OBJECTIVE: To systematically review the evidence for the prevention of type 2 diabetes by pharmacological therapies. RESEARCH DESIGN AND METHODS: Randomized controlled trials and cohort studies examining the effect of oral hypoglycemic agents, antiobesity agents, antihypertensive agents, statins, fibrates, and estrogen on the incidence of type 2 diabetes were identified from MEDLINE, EMBASE, the Cochrane Controlled Trials Registry, and searches of reference lists. Two reviewers independently assessed studies for inclusion and performed data extraction. RESULTS: Ten studies of oral hypoglycemic agents and 15 studies of nonoral hypoglycemic agents were found. Oral hypoglycemic agents and orlistat are the only drugs that have been studied in randomized controlled trials with diabetes incidence as the primary end point. In the largest studies of 2.5-4.0 years' duration, metformin (relative risk [RR] 0.69, 95% CI 0.57-0.83), acarbose (0.75, 0.63-0.90), troglitazone (0.45, 0.25-0.83), and orlistat (hazard ratio [HR] 0.63, 95% CI 0.46-0.86) have all been shown to decrease diabetes incidence compared with placebo; however, follow-up rates varied from 43 to 96%. Current evidence for statins, fibrates, antihypertensive agents, and estrogen is inconclusive. In addition, the critical question of whether drugs are preventing, or simply delaying, onset of diabetes remains unresolved. CONCLUSIONS: Currently, no single agent can be definitively recommended for diabetes prevention. Future studies should be designed with diabetes incidence as the primary outcome and should be of sufficient duration to differentiate between genuine diabetes prevention as opposed to simple delay or masking of this condition.     

Milrinone and Low Cardiac Output Following Cardiac Surgery in Infants: Is There a Direct Myocardial Effect?

We assessed the effect of milrinone on myocardial function in pediatric patients with postoperative low cardiac output syndrome by index of myocardial performance in a prospective, open-label, nonrandomized, consecutive study. Fifteen patients with low cardiac output syndrome following cardiac surgical treatment were studied in the tertiary cardiothoracic pediatric intensive care unit between April 2001 and November 2003 (age range, 0.2–16 months; median, 7; weight, 2.7–11.8 kg; median, 5). Echocardiographic, Doppler-derived, time interval-based index of myocardial performance (Tei index) was used to study cardiac function prior to and while on intravenous milrinone treatment for 18–24 hours. Treatment with milrinone led to improvement in biventricular myocardial function [mean right ventricular index from 0.521 (SD-0.213) to 0.385 (SD-0.215), p = 0.003; mean left ventricular index from 0.636 (SD-0.209) to 0.5 (SD-0.171), p = 0.012). No difference was found in the values of heart rate corrected right or left ventricular ejection time prior to and while on treatment with milrinone (right ventricle: mean, 1.23 (SD-0.42) and 1.14 (SD-0.48), p = 0.29; left ventricles: mean, 1.17 (SD-0.51) and 1.13 (SD-0.48), p = 0.66) Our data support the direct myocardial effect of milrinone as part of the mechanism behind its already proven benefit in children with low cardiac output syndrome following cardiac surgery.     

Two decades experience of the Psoriasis Disability Index

The Psoriasis Disability Index (PDI) was formed 20 years ago. Since its introduction it has been used widely as a tool for assessment of quality of life in psoriasis. This paper reviews its use in 23 peer-reviewed articles and over 35 published abstracts, and describes its use in conjunction with other general and psoriasis-specific quality of life assessments, and with a range of physical and psychological measures. The PDI is effective in demonstrating the effects of interventions, both of treatments and in health service research. The PDI has been translated into at least 16 languages and has been used in published research in 20 countries.