We report the results of the Ticlopidine Aspirin Stroke Study, a blinded trial at 56 North American centers that compared the effects of ticlopidine hydrochloride (500 mg daily) with those of aspirin (1300 mg daily) on the risk of stroke or death. The medications were randomly assigned to 3069 patients with recent transient or mild persistent focal cerebral or retinal ischemia. Follow-up lasted for two to six years. The three-year event rate for nonfatal stroke or death from any cause was 17 percent for ticlopidine and 19 percent for aspirin--a 12 percent risk reduction (95 percent confidence interval, -2 to 26 percent) with ticlopidine (P = 0.048 for cumulative Kaplan-Meier estimates). The rates of fatal and nonfatal stroke at three years were 10 percent for ticlopidine and 13 percent for aspirin--a 21 percent risk reduction (95 percent confidence interval, 4 to 38 percent) with ticlopidine (P = 0.024 for cumulative Kaplan-Meier estimates). Ticlopidine was more effective than aspirin in both sexes. The adverse effects of aspirin included diarrhea (10 percent), rash (5.5 percent), peptic ulceration (3 percent), gastritis (2 percent), and gastrointestinal bleeding (1 percent). With ticlopidine, diarrhea (20 percent), skin rash (14 percent), and severe but reversible neutropenia (less than 1 percent) were noted. The mean increase in total cholesterol level was 9 percent with ticlopidine and 2 percent with aspirin (P less than 0.01). The ratios of high-density lipoprotein and low-density lipoprotein to total cholesterol were similar in both treatment groups. We conclude that ticlopidine was somewhat more effective than aspirin in preventing strokes in this population, although the risks of side effects were greater.

To identify single-nucleotide polymorphisms (SNPs) associated with risk and age at onset of Alzheimer disease (AD) in a genomewide association study of 469 438 SNPs.

A large sample of Canadian adults was surveyed by telephone to determine the prevalence and characterization of headache, and the effects of headache on life-style, consulting behaviours and medication use. We reported prevalence and characterization in a previous issue; here, we detail the effects of headaches on sufferers. Sixteen and one-half percent of adult Canadians experience migraine and 29% tension-type headaches. In over 70% of headache sufferers interpersonal relationships are impaired. Regular activities are limited in 78% of migraine attacks and 38% of tension-type headaches. Despite this, only 64% of migraine and 45% of tension-type headache sufferers had ever sought medical attention, and of these only 32% returned for ongoing care. Fourteen percent of migraine and 8% of tension-type headache sufferers had used emergency departments. Most headache sufferers take medication, primarily over-the-counter varieties. Measures to reach the headache population are needed, as are safe effective treatment options that will encourage them to participate in their medical care. RESUME: Impact de la migraine et de la cephalee de tension sur le mode de vie, les habitudes de consultation et I'utilisation de medicaments: une etude canadienne de population. Nous avons effectue une enquete tel6-phonique aupres d'un echantillon important d'adultes canadiens pour determiner la prevalence et le type de cephalee, ainsi que les effets de ces cephalees sur le mode de vie, les habitudes de consultation et la medication utilisee. Nous avons rapporte la premiere partie de cette etude dans une publication anterieure; nous rapportons ici les effets des cephalees chez ceux qui en souffrent. Seize et demi pourcent des adultes canadiens souffrent de migraine et 29% de cephalee de tension. Chez plus de 70% des individus qui souffrent de cephalee, les relations interpersonnelles en sont affectees. Les activites courantes sont limitees lors de 78% des acces de migraine et de 38% des acces de cephal6e de tension. Malgre cela, seulement 64% des individus qui souffrent de migraine et 45% de ceux qui souffrent de cephalee de tension ont deja consulte un medecin a ce sujet et parmi ceux-ci, seulement 32% ont maintenu le suivi. Quatorze pourcent de ceux qui souffrent de migraine et 8% de ceux qui souffrent de cephalee de tension ont consulte un departement d'urgence. La plupart de ceux qui souffrent de cephalee utilisent une medication, surtout une medication sans ordonnance. II est necessaire de mettre en place des mesures visant a informer la population qui souffre de c6pha!6e et de lui fournir des options therapeutiques securitaires pour l'encourager a participer a ses propres soins medicaux.

To determine the interfamilial and intrafamilial variation in the expression of the Bardet-Biedl syndrome (a form of Laurence-Moon-Biedl syndrome), we looked for the five recognized features of the disorder (retinal dystrophy, obesity, polydactyly, mental retardation, and hypogonadism), plus possible renal manifestations, in some or all of 32 patients with this disorder. All 28 patients examined had severe retinal dystrophy, but only 2 had typical retinitis pigmentosa. Polydactyly was present in 18 of 31 patients, but syndactyly, brachydactyly, or both were present in all. Obesity was present in all but 1 of 25 patients. Only 13 of 32 patients were considered mentally retarded. Scores on verbal subtests of intelligence were usually lower than scores on performance tasks. Seven of eight men had small testes and genitalia, which was not due to hypogonadotropism. All 12 women studied had menstrual irregularities, and 3 had low serum estrogen levels (1 of these had hypogonadotropism, and 2 had primary gonadal failure). The remaining women who were of reproductive age had endocrinologic evidence of reproductive dysfunction. Diabetes mellitus was present in 9 of 20 patients. Renal structural or functional abnormalities were universal (n = 21), and three patients had end-stage renal failure. We conclude that the characteristic features of Bardet-Biedl syndrome are severe retinal dystrophy, dysmorphic extremities, obesity, renal abnormalities, and (in male patients only) hypogenitalism. Mental retardation, polydactyly, and hypogonadism in female patients are not necessarily present.

The aetiology of multiple sclerosis (MS) is uncertain. There is strong circumstantial evidence to indicate it is an autoimmune complex trait. Risks for first degree relatives are increased some 20 fold over the general population. Twin studies have shown monozygotic concordance rates of 25-30% compared to 4% for dizygotic twins and siblings. Studies of adoptees and half sibs show that familial risk is determined by genes, but environmental factors strongly influence observed geographic differences. Studies of candidate genes have been largely unrewarding. We report a genome search using 257 microsatellite markers with average spacing of 15.2 cM in 100 sibling pairs (Table 1, data set 1 - DS1). A locus of lambda>3 was excluded from 88% of the genome. Five loci with maximum lod scores (MLS) of >1 were identified on chromosomes 2, 3, 5, 11 and X. Two additional data sets containing 44 (Table 1, DS2) and 78 sib pairs (Table 1, DS3) respectively, were used to further evaluate the HLA region on 6p21 and a locus on chromosome 5 with an MLS of 4.24. Markers within 6p21 gave MLS of 0.65 (non-significant, NS). However, D6S461, just outside the HLA region, showed significant evidence for linkage disequilibrium by the transmission disequilibrium test (TDT), in all three data sets (for DS1 chi2 = 10.8, adjusted P < 0.01)(DS2 and DS3 chi2 = 10.9, P < 0.0005), suggesting a modest susceptibility locus in this region. On chromosome 5p results from all three data sets (222 sib pairs) yielded a multipoint MLS of 1.6. The results support genetic epidemiological evidence that several genes interact epistatically to determine heritable susceptibility.

ABSTRACT:Trained telephone interviewers contacted 1,573 adults across Canada about the nature and frequency of headaches suffered by them or by others in their households. Using a table of pain symptoms and other characteristics abstracted from the International Headache Society (IHS) classification, the headaches were assigned to migraine headache, tension-type headache or other diagnostic groups. Of the households sampled, 59% had at least one headache sufferer in residence. The proportion of headache sufferers with migraine was 14%; with tension-type, 36%; and with both, 14%. Migraine headache caused more disability than tension-type headache, with nearly 20% of migraine sufferers taking time off work and disability lasting for a mean of 1 day. It is concluded that the current prevalences of migraine and tension-type headache in Canada fall around the mean of previous studies, that the IHS criteria can form a basis for diagnostic classification and that the functional impact of migraine has been seriously underestimated in the past.

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