Cerebral cavernous malformation (CCM) is a Mendelian model of stroke, characterized by focal abnormalities in small intracranial blood vessels leading to hemorrhage and consequent strokes and/or seizures. A significant fraction of cases is inherited as an autosomal dominant trait with incomplete penetrance. Among Hispanic Americans, virtually all CCM is attributable to a founder mutation localized to 7q ( CCM1 ). Recent analysis of non-Hispanic Caucasian kindreds, however, has excluded linkage to 7q in some, indicating at least one additional CCM locus. We now report analysis of linkage in 20 non-Hispanic Caucasian kindreds with familial CCM. In addition to linkage to CCM1, analysis of linkage demonstrates linkage to two new loci, CCM2 at 7p13-15 and CCM3 at 3q25.2-27. Multilocus analysis yields a maximum lod score of 14.11, with 40% of kindreds linked to CCM1, 20% linked to CCM2 and 40% linked to CCM3, with highly significant evidence for linkage to three loci (linkage to three loci supported with an odds ratio of 2.6 x 10(5):1 over linkage to two loci and 1.6 x 10(9):1 over linkage to one locus). Multipoint analysis among families with high posterior probabilities of linkage to each locus refines the locations of CCM2 and CCM3 to approximately 22 cM intervals. Linkage to these three loci can account for inheritance of CCM in all kindreds studied. Significant locus-specific differences in penetrance are identified. These findings have implications for genetic testing of this disorder and represent an important step toward identification of the molecular basis of this disease.

Seven of twelve autologous sera from patients with chronic idiopathic urticaria re-injected intradermally produced a weal at the site of injection. There was no response in 19 control subjects. Patients showing a positive response had a shorter duration of disease and shorter duration of spontaneous weals, and their urticaria was less likely to be exacerbated by pressure. There was some serological evidence of circulating immune complexes in both positive and negative responders to autologous serum, but only two showed complement abnormalities. When six of the serum-positive patients were re-tested after one year, five still showed a positive response with their original stored serum, but only two, whose disease remained active, were positive when challenged with freshly drawn serum, suggesting that a serum mediator is only present when the urticaria is active. A marked neutrophil infiltrate was seen within and around small dermal blood vessels at the injection site in the majority of urticaria patients but this appearance did not correlate with weal formation. In control subjects the cellular response was mild and mainly mononuclear.

Anecdotal evidence suggests that the prevalence of both scabies and head lice is increasing and also that both conditions are becoming refractory to pesticide treatment. Using information obtained from the Office of National Statistics, Royal College of General Practitioners Weekly Returns Service, Department of Health, local surveys of school children from Bristol and drug sales of insecticides, we have confirmed that there has been a rise in the prevalence of both conditions. We have shown that scabies is significantly more prevalent in urbanized areas (P < 0.00001), north of the country (P < 0.000001), in children and women (P < 0.000001) and commoner in the winter compared to the summer. Scabies was also shown to have a cyclical rise in incidence roughly every 20 years. Head lice were shown to be significantly more prevalent in children and mothers (P < 0.000001) though both conditions were seen in all age groups. Head lice were also less common during the summer. Host behaviour patterns, asymptomatic carriage, drug resistance and tourism from countries or districts with a higher incidence may be important factors in the currently high prevalence of both scabies and head lice.

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