Response to treatment with rosiglitazone in familial partial lipodystrophy due to a mutation in the LMNA gene

Background Familial partial lipodystrophy (FPLD) is a monogenic form of diabetes characterised by a dominantly inherited disorder of adipose tissue associated with the loss of subcutaneous fat from the limbs and trunk, with excess fat deposited around the face and neck. The lipodystrophy causes severe insulin resistance, resulting in acanthosis nigricans, diabetes, dyslipidaemia, and increased risk of cardiovascular disease. Preliminary results from animals and man suggest that increasing subcutaneous fat by treatment with thiazolidinediones should improve insulin resistance and the associated features of this syndrome. Case report We report a 24-year-old patient with FPLD caused by a mutation in the LMNA gene (R482W) treated with 12 months of rosiglitazone. Subcutaneous fat increased following rosiglitazone treatment as demonstrated by a 29% generalised increase in skin-fold thickness. Leptin levels increased from 5.8 to 11.2 ng/ml. Compared with treatment on Metformin, there was an increase in insulin sensitivity (HOMA S% 17.2–31.6) but no change in glycaemic control. The lipid profile worsened during the follow-up period. Conclusion This initial case suggests that, for modification of cardiovascular risk factors, there are no clear advantages in treating patients with FPLD with rosiglitazone despite increases in subcutaneous adipose tissue. Larger series will be needed to identify moderate beneficial effects and treatment may be more effective in patients with generalised forms of lipodystrophy.     

Effects of acute administration of d-amphetamine and haloperidol on procedural learning in man

The effects of an indirect dopamine-agonist, d-amphetamine, and a non-selective dopamine receptor antagonist, haloperidol, were investigated in normal male volunteers using a between-subjects double-blind design in a procedural learning task, thought mainly to involve unconscious/automatic learning. The results showed: (1) d-amphetamine facilitated response speed, whereas haloperidol inhibited it, in comparison to placebo; (2) the linear increase in procedural learning corresponded with pharmacological manipulation of degree of dopaminergic activity, i.e. subjects given haloperidol showed the least, and subjects given d-amphetamine the greatest, procedural learning. The implications of these findings are discussed in relation to investigation of abnormalities of procedural learning processes in schizophrenia. Received: 28 June 1996/Final version: 2 October 1996     

Laterality of cross-modal spatial processing

This study examined the laterality of spatial-form perception in normal adults using a cross-modal matching paradigm involving visual and tactile processing. Randomly generated eight-point and 12-point Vanderplas and Garvin (1959) patterns were used as the stimuli. In a visual-to-tactile task, a lateralized visual pattern was followed immediately by a haptic task requiring subjects to discriminate which of two simultaneously felt shapes matched the visual pattern. In a tactile-to-visual task, subjects decided which of two simultaneously felt shapes matched a lateralized visual pattern presented after haptic manipulation. There were no main effects for laterality or for sex differences. Matching accuracy was better in the visual-to-tactile task and for less complex stimuli. A visual field by feeling hand interaction showed best recognition accuracy when visual-feeling hand combinations on the same side of the body were used in the two matching tasks. These data reflect a stimulus-response compatibility explanation of spatial-form perception that is consistent with a behavioral and not a cerebral asymmetry model.