A high-resolution genetic map of the familial Mediterranean fever candidate region allows identification of haplotype-sharing among ethnic groups.

Familial Mediterranean fever (FMF) is a recessive disorder of inflammation caused by mutations in a gene (designated MEFV) on chromosome 16p13.3. We have recently constructed a 1-Mb cosmid contig that includes the FMF critical region. Here we show genotype data for 12 markers from our physical map, including 5 newly identified microsatellites, in FMF families. Intrafamilial recombinations placed MEFV in the approximately 285 kb between D16S468/D16S3070 and D16S3376. We observed significant linkage disequilibrium in the North African Jewish population, and historical recombinants in the founder haplotype placed MEFV between D16S3082 and D16S3373 (approximately 200 kb). In smaller panels of Iraqi Jewish, Arab, and Armenian families, there were significant allelic associations only for D16S3370 and D16S2617 among the Armenians. A sizable minority of Iraqi Jewish and Armenian carrier chromosomes appeared to be derived from the North African Jewish ancestral haplotype. We observed a unique FMF haplotype common to Iraqi Jews, Arabs, and Armenians and two other haplotypes restricted to either the Iraqi Jewish or the Armenian population. These data support the view that a few major mutations account for a large percentage of the cases of FMF and suggest that some of these mutations arose before the affected Middle Eastern populations diverged from one another.

Linkage disequilibrium mapping places the gene causing familial Mediterranean fever close to D16S246.

This report presents refined genetic mapping data for the gene causing familial Mediterranean fever (FMF), a recessively inherited disorder of inflammation. We sampled 65 Jewish, Armenian, and Arab families and typed them for eight markers from chromosome 16p. Using a new algorithm that permits multipoint calculations for a dense map of markers in consanguineous families, we obtained a maximal LOD score of 49.2 at a location 1.6 cM centromeric to D16S246. A specific haplotype at D16S283-D16S94-D16S246 was found in 76% of Moroccan and 32% of non-Moroccan Jewish carrier chromosomes, but this haplotype was not overrepresented in Armenian or Arab FMF carriers. Moreover, the 2.5-kb allele at D16S246 was significantly associated with FMF in Moroccan and non-Moroccan Jews but not in Armenians or Arabs. Since the Moroccan Jewish community represents a relatively recently established and genetically isolated founder population, we analyzed the Moroccan linkage-disequilibrium data by using Luria-Delbrück formulas and simulations based on a Poisson branching process. These methods place the FMF susceptibility gene within 0.305 cM of D16S246 (2-LOD-unit range 0.02-0.64 cM).

Pediatric trauma care is cost effective: a comparison of pediatric and adult trauma care reimbursement.

Trauma causes staggering losses: in 1987, Hermann Hospital lost $8 million to uncompensated trauma care. To demonstrate the survivability of pediatric trauma care delivery we examined reimbursement profiles for adult and pediatric trauma patients. We retrospectively reviewed the records of 3445 patients with serious trauma from October 1987 through March 1992. The group was divided into adult (> or = 17 years) and pediatric patients (< 17 years). We compared reimbursement profiles based on hospital costs generated, reimbursement, financial class, demographics, discharge diagnostic codes, and outcome. Significance was assessed by t test and Chi-square. We found a decreased length of stay (LOS) and a lower association with under-reimbursement or zero reimbursement in pediatric patients. A significantly lower percentage of pediatric patients paid none of their bill (17.1%) compared with the adults (23.2%). Pediatric reimbursement exceeded hospital costs (110.0%) compared with adult reimbursement (90.3%). This suggests that pediatric trauma care can survive in an atmosphere of shrinking resources.

Adrenal insufficiency in two women with anticardiolipin antibodies. Cause and effect?

We describe 2 women with anticardiolipin antibodies and a lupus-like disorder who developed acute adrenal insufficiency. We also review 5 similar cases reported previously. Anticardiolipin antibodies appear to be a risk factor for this vascular complication.

Racial differences in ristocetin-induced platelet aggregation.

Several investigators have reported defective ristocetin-induced platelet aggregation (RIPA) in individuals whose red blood cells contain sickle haemoglobin, but the race of control subjects in these studies was not stated. Therefore, maximal amplitude of RIPA was examined in 75 normal whites and blacks, of 16 of whom had sickle trait defined by haemoglobin electrophoresis and sickle prep. Final ristocetin concentrations in platelet rich plasma were 1.1, 1.2 and 1.5 mg/ml. Mean aggregation at 1.1 mg/ml was significantly less in blacks (mean 31%) than in whites (mean 72%) (P less than 0.001). 60% of blacks but only 11% of whites had less than 50% RIPA at 1.1 mg/ml. RIPA was entirely absent in 19% of blacks. Differences in RIPA between black and white subjects were also present at ristocetin concentrations of 1.2 and 1.5 mg/ml but were less striking. RIPA in 25 children with homozygous sickle cell anaemia was similar to that in the normal AA and AS blacks. Differences in RIPA could not be explained by age, sex, presence of sickle haemoglobin, or medications. Addition of normal plasma or platelets did not correct reduced RIPA in seven blacks, and their plasma inhibited normal RIPA responses. Reduced platelet aggregation to low concentrations of ristocetin is a normal finding in many blacks, is not related to the presence of sickle haemoglobin, and appears to be due to a plasma inhibitor against RIPA.