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The results do not support linkage between the DRD2 locus and alcoholism in most of the families studied. It remains possible that this locus influences the predisposition to alcoholism in some families.

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SUMMARY. Calcium influx blockers reportedly suppress ventricular arrhythmias during acute ischemia. We therefore studied the effects of diltiazem and reduced serum ionized calcium on ventricular fibrillation (VF) in a reversible ligation model. VF was produced at 15-minute intervals by simultaneous occlusion of the left anterior descending and circumflex arteries of 31 dogs. Time from coronary occlusion to onset of VF showed no significant variation during 15 consecutive trials in six dogs that received saline alone. Intravenous infusion of diltiazem (0.02 mg/kg per min) markedly delayed the onset of VF in each of 10 dogs (P < 0.0001). Mean VF latency increased from 138 to 295 seconds during a 45-minute diltiazem infusion, declined exponentially when the infusion ceased, and was strongly correlated with serum diltiazem concentration (r = 0.96, P < 10~6). In five dogs, hemodynamic measurements, including coronary venous blood flow, were performed during each occlusion. The increase in VF latency by diltiazem was not due to increased coronary flow during occlusion or to reduction of left ventricular (LV) mechanical work. In six dogs, mean serum ionized calcium, [Ca ++ ], was reduced from 1.11 to 0.59 mM by infusion of sodium citrate. Citrate infusion increased mean VF latency from 155 to 243 seconds, and the increase observed in each dog was correlated (r = 0.84, P < 10~6) with the reduction in [Ca ++ ], VF latency was unaffected by lidocaine in nine dogs. The antifibrillatory effect of diltiazem during global LV ischemia may be an electrophysiological phenomenon related to reduction of cellular calcium influx. (Circ Res 50: 518-526, 1982) MORE than 10 years ago, Kaumann and Aramendia (1968) reported that the calcium influx blocker, verapamil, produces a dramatic reduction in the incidence of ventricular fibrillation following coronary artery ligation. This finding has been corroborated in several subsequent studies (Kaumann and Serur, 1975;Fondacaro et al., 1978, Brooks et al., 1980, but its physiological basis remains obscure. Calcium influx blockers are thought to improve myocardial metabolism during ischemia by alleviating intracellular calcium overload (Katz and Reuter, 1979), and they also suppress transmembrane currents that may mediate certain arrhythmias (Cranefield, 1975(Cranefield, , 1977. Furthermore, since calcium influx blockers are potent coronary vasodilators, they might prevent fibrillation by improving the distribution of coronary blood flow.The risk of VF following permanent coronary ligation is difficult to measure precisely in a manageable number of experimental animals. We have therefore developed a reversible ligation model in which the degree of ischemia is severe enough that VF occurs swiftly and predictably during successive trials (Clusin et al., 1979. The time between vessel occlusion and the development of VF-the VF latencycan be measured repeatedly before and after experimental interventions. Since the model involves the production of global left ventricular ischemia, changes...

Coeliac Disease (CD) is a gluten sensitive enteropathy characterised by villous atrophy and crypt cell hyperplasia. It has a very strong HLA class II association to the DQ locus. The nature of the involvement of the DQ locus in the susceptibility to CD has been examined by tissue culture experiments, association and peptide binding studies. We examined the role of the DQ molecules in the pathogenesis from the perspective of a genetic family study. Using flanking microsatellite markers to the class II region of the MHC to establish the parental origin of the susceptibility DQ alleles, we have evidence suggesting that the HLA association is probably due to the necessity to have these DQ alleles in order to express CD and there is no support for the presence of a rare mutation within the DQ alleles nor any rare HLA-linked gene nearby in linkage disequilibrium with the DQ locus. This approach is applicable to other diseases demonstrating strong association with common alleles, and can be used to predict whether screening the region for rare mutations is likely to be worthwhile. Coeliac disease (CD) is thought to represent an oligogenic disorder, one genetic locus being on the short arm of chromosome six in the major histocompatibility locus, that is at or very close to HLA-DQ2. The inherited susceptibility to the development of CD is demonstrated by a disease concordance among monozygotic twins of 70-100 % (Polanko et al. 1981 ; Salazar de Souza et al. 1987) and a disease prevalence among first degree family relatives of an affected individual of 10-15 % (Ellis, 1981) compared with a population prevalence in the UK of 0.08 % (Marsh,