Tuberculous Pleurisy: an Unusual Complication During Treatment of Crohn Disease with Azathioprine

A patient is presented with Crohn disease who developed tuberculous pleurisy while treated with azathioprine. The prevalence of opportunistic infections is discussed in patients with inflammatory bowel disease and treated with immunosuppressive regimes.     

The GABA transporter and its inhibitors

GABA is the major inhibitory neurotransmitter in the brain and GABA re- uptake from the synaptic cleft is one important mechanism in the regulation of GABA activity. Inhibition of the re-uptake of GABA by potent and selective inhibitors of the GABA transporter enhances GABA activity. This property can be used therapeutically in for instance epilepsy or psychiatric disorders. In this paper putative structures of the GABA transporter, its mechanism of action, the progress made in the search for its amino acids involved in the binding of substrates and the SAR of inhibitors acting at the transporter will be discussed. To date only highly selective GAT-1 inhibitors are available. These compounds are lipophilic derivatives of (R)-nipecotic acid and guvacine. The most potent inhibitors of the cloned human GAT-1 are NNC-711 (IC50 = 0.04 mM) and tiagabine (IC50 = 0.07 mM). A diheteroarylvinyloxy analogue of tiagabine, 5 times more potent than tiagabine, has been reported recently. For the GAT-2, GAT-3 and BGT-1 subtypes only compounds with a small preference for one of the subtypes have been published.     

Dexetimide, a useful tool in acetylcholine-receptor localization

Binding of the anticholinergic agent ³H-dexetimide, the active isomer of (±)-benzetimide, to subcellular fractions of the caudate nucleus of the male Wistar rat was studied by equilibrium dialysis. The binding is stereospecific, reversible, appears to involve the muscarinic type of acetylcholine receptor (AchR) and correlates well with the physiological response of the AchR as can be concluded from displacement experiments using cholinergic and non-cholinergic ligands. The binding sites are located on membrane fragments probably originating from the post-synaptic membranes.     

A graphical method to evaluate exposure-response relationships in epidemiologic studies using standardized mortality or morbidity ratios

In occupational epidemiology, exposure-response analyses play an important role in the evaluation of the etiologic relevance of chemical and physical exposures. The standardized mortality or morbidity ratio (SMR) has been commonly used in occupational cohort studies. Statistical approaches to evaluate exposure-response patterns using SMRs have mostly been limited to analyses in which the exposure under investigation is categorized. Here, a graphical method for evaluating exposure-response patterns is presented based on SMR estimates across moving exposure windows. This method is demonstrated using the results of two hypothetical cohort studies. The proposed approach may be useful for graphical exploration of exposure-response trends in situations where the number of observed cases is small.     

Familial focal loss of cross striations

Summary Two patients, a brother and sister, both suffering from congenital generalized muscle weakness with a progressive course are reported. Muscle biopsy revealed areas with loss of cross striations in the muscle fibers, electronmicroscopically presenting complete disorganization of the myofibrils with streaming of the Z discs and absence of mitochondria. Vesicular nuclei with prominent nucleoli were present in these areas. There was a type I fiber prodominance in both cases. The mean diameter of the type I muscle fibers in one of the cases was too small. Motor endplate alterations in this patient gave no evidence of denervation but were suggestive of a delayed development of motor nerves.This study was supported by grants from the Prinses Beatrix Fonds, from the FRSM of Belgium and from the Free University of Brussels