Daily variation and other factors affecting the occurrence of cerebrovascular accidents.

A study was made of 1,630 Melbourne patients, mostly elderly, who had suffered a cerebral vascular accident in the community or while in hospital for another illness. There was a significant increase in age over the period of investigation (1970 to 1977) and the sex of the subjects was found to varying marginally with the side affected and the location of occurrence; a more important difference was observed in relation to ethnicity. There were significant tendencies for strokes to occur in winter and, for patients already hospitalized, in the middle of the week. The latter finding was largely confined to the spring. It is suggested that this may be due to the transition from weekend rest to the activity associated with ward routines at the beginning of the week.

Factors influencing dementia and epilepsy in Huntington's disease of early onset.

A sample of young patients with Huntington's disease, ascertained from case material reported in the literature, was examined to determine whether muscular rigidity or age at onset of the disorder is the major factor in giving rise to early dementia and epilepsy. Because of correlation between explanatory variables, adjustment for their effects was made in calculating the strength of associations. The risk of incurring dementia early was found to be over twice as great for rigid patients than for those without the sign. Onset age was independently involved with rigidity in this relationship. When the effect of muscular rigidity was adjusted for sex and onset age, virtually no influence on the occurrence of epilepsy was detected. Onset age, on the other hand, was strongly associated with the likelihood of epileptic attack.

Parental factors associated with rigidity in Huntington's disease.

The discriminatory power of ten factors has been explored in relation to the presence or absence of muscular rigidity in patients with Huntington's disease. The sex and neurological sign of an affected parent were the only two significant determinants of rigidity or choreoathetosis in offspring. It was shown, using the Mantel-Haenszel method of adjusting for confounding variables that the risk of a patient displaying rigidity (and thereby having a graver prognosis) is five times as great for those with rigid parents as it is for those with non-rigid parents. Additionally, the risk of a patient displaying rigidity is more than three times as great for those with affected fathers as it is for those with affected mothers. Some implications of these findings are discussed.

Characteristics of births in each cycle of the bimodal monthly distribution in cystic fibrosis.

The bimodal monthly birth distribution of patients with cystic fibrosis (CF) in Victoria, Australia, is shown to be similar within and among sibships, so that intrafamilial concentration of births around March (mode 1) or September (mode 2) cannot explain the observed periodic pattern. Mode 2 children are subject to a higher stillbirth rate and have younger maternal ages than mode 1 children. A sample of persons dying with CF in England and Wales displaying a similar bimodal birth pattern is shown to have a reduced infant survival rate for males of mode 2. These findings suggest that two annual cycles are a more appropriate model than a six-monthly cycle. An attempt is made to equate mode 1 in the northern hemisphere with mode 2 in the southern hemisphere by pointing out the high perinatal death rate in the former and the high stillbirth rate in the latter.

Bimodal month of birth distribution in cystic fibrosis.

The month of birth of 923 patients in England and Wales dying with cystic fibrosis as an underlying cause was found to be distributed independently of sex and year of birth during 1954-1976. When adjusted for the monthly variations in births in the national population, birth frequencies were bimodally distributed. This confirmed results obtained previously in the Netherlands and Australia. Peak births occurred in late February and August, regardless of whether a single six-monthly cycle or two annual cycles were assumed. It was not possible to choose the better of these models, each yielding similar parametric estimates.

A statistical study of sarcoma complicating Paget's disease of bone in three countries.

Details of sex, age at presentation and anatomical site of sarcoma complicating Paget's disease of bone were recorded from the literature for white patients in Australia, the United Kingdom and the United States over the period 1978--77. Evidence is presented to suggest that sex and tumour-site distributions are free from bias, except possibly for the skull. There was a male predominance for all sites except the skull, where the odds ratio of sarcoma compared with other locations is more than twice as high for females as for males. No national differences emerged in the sex ratio of patients. In Australia a latitudinal effect was observed. Whereas the percentage of males with uncomplicated Paget's disease was essentially constant, those with sarcoma showed a decrease with increase in latitude from Queensland to Victoria. This was attributable to tumours of the skull. Patients with bone involvement above the waist were significantly younger than those with affected feet, legs or pelvic girdle.

Relation of occupational stress to the age at onset of Huntington's disease.

Two hypotheses were tested to determine whether occupational stress was related to the age at onset of Huntington's disease. Using case material drawn from four kindreds in southern Norway, occupations of affected persons were graded into three categories according to their degree of physical stress. Adjusting for the effects of related factors, grade of stress was found to be a significant contributor to the variation in onset age. Minor and severe stress were associated with earlier onset ages than moderate stress; the difference between minor and moderate grades was 9 years. The results are interpreted as conforming to the psychosocial concept of Levi, whereby both under- and overstimulation of sensory functions are more stressful and more potent precipitants of illness than intermediate levels of stimulation.

The seasonal variation of births of offspring from couples heterozygous for cystic fibrosis.

To test whether the month of birth of patients with cystic fibrosis (CF) is seasonally distributed as reported in a Dutch survey, published Australian data were examined and no difference in the monthly variation was found between births of CF patients and their unaffected sibs. When the two groups were combined and analysed by periodic regression using successively higher Fourier terms, a significant fit to the observed frequencies was obtained with a bimodal curve. Possession of a single CF gene seems therefore sufficient for expression of the cyclic variation. In substantial agreement with the Dutch series, maximum frequencies were found to occur in March or April and in September. It is suggested that one or both parents may be subject to variable fertility mediated by a temperature-dependent mechanism. The relevance of a periodic fertility pattern in preserving the CF gene in the population by selective heterozygote advantage is discussed.

A linkage study of the loci for Huntington's disease and some common polymorphic markers.

The phenotypic frequencies of 24 polymorphic blood markers in a sample of patients with Huntington's disease (HD) have been compared with those in a sample of healthy Australian volunteers in an effort to detect any associations between HD and the markers concerned. The Rh factor, c, has a significantly lower frequency in the HD sample while ACP1c and Gm1,2 have a significantly higher frequency. The linkage relations of the HD locus have been analysed with respect to the various marker loci concerned. This analysis involved the development of methods to overcome the general lack of genetic data concerning the affected parent and the possibility that presently unaffected offspring may be asymptomatic carriers of the HD gene. The results suggest that close linkage between the HD locus and Fy, ADA, ACP1, Gc or Bg is highly unlikely. They also suggest a low probability of close linkage to ABO, Rh, Jk, Lu, AK1, PGM1 or C3. Positive linkage scores were obtained for P, Hp and Gm. The results are inconclusive for MNSs, K, Le, Se, GPT and Inv. The available data were uninformative for linkage between the HD locus and Co, 6-PGD or E1.

A study of phenotypic arrays derived from seven genetic systems in an Australian population sample.

The phenotypic arrays for seven erythrocyte antigenic systems of a sample of the Melbourne population were found to be distributed according to Zipf's Law. A simple model of heterozygote selective advantage was unable to account for the excess of observed frequencies of arrays over those expected under the random-mating hypothesis. Persons with (ccDEe, MMss) were over-represented and those with (A1, MNSs P1--) were under-represented in the sample.

Validation and aplication of an interval factor in estimating age at onset of Huntington's disease.

The time interval between the first appearance of signs in the transmitting parent and the birth of the subsequently affected child has been shown by Brackenridge and Telscher (1975) to influence the age at onset of Huntington's disease. The cirticism by Burke (1976) that the interval factor offers no predictive advantage over parental onset age is refuted. The advantage of small sibship sizes in familial correlation studies is noted and an equation to estimate onset age is derived to control for ascertainment bias. The interval factor is shown to surpass parental onset age as a determinant of offspring onset age. When applied to Queensland material, reasonable agreement is obtained between predicted and reported onset ages. Evidence for the desirability for parents at risk who intend to have families to plan them early is discussed.

The secular variation of Australian twin births over fifty years.

Twins born during the fifty years 1920-69 in Australia were analysed statistically and their sex composition was found to be homogeneously distributed in a geographical but not a secular manner. The twinning rate reached a maximum in 1953 after which it fell to pre-war levels. This behaviour was due to dizygotic twins, and the role of intermediate maternal age at parturition as a contributing factor is discussed. Considered in relation to all twin maternities, however, the dizygotic rate declined significantly and linearly with time. This could be attributed to the gradual secular decline in maternal age.