754 brain acetylcholinesterase undergoes circadian alterations, we suggest that the time of death may merit consideration in studies of necropsy brain tissue designed to investigate mental disorders. In addition, determination of the circadian fluctuation in putative neurotransmitter systems may be of value in the investigation of mental disorders. Thus, in depression, for example, the characteristic diurnal mood variation may be linked to fluctuations in one or more specific neurotransmitter activities. Department of Pathology, Newcastle General Hospital, Newcastle upon Tyne NE4 6BE
ELAINE K. PERRY ROBERT H. PERRY MICHAEL J. TAYLOR BERNARD E. TOMLINSON
SEASONALITY IN DOWN SYNDROME
SIR,-Dr Janerich and Professor Jacobson (March 5, p. 515) discuss seasonality of Down syndrome births, as pre-
study from Jerusalem,l and put forward an endocrinological explanation for seasonality and the aetiology of Down syndrome. Noting a similarity between monthly conception-rates of Down syndrome fetuses and monthly variation in restradiol-receptor levels in mammary tumours, they suggest that the endocrine factors which cause the changes in restradiol-receptor concentration also affect the meiotic process. While this hypothesis is interesting, it needs to be considered critically. First, seasonality in Down syndrome has not been consistently demonstrated .2 For example, McDonaldfound no association with month of birth in a study of 2398 Down syndromes cases in Quebec. Haynes et al. found no seasonal pattern for Down syndrome births in a 37-year period in Rochester, Minnesota. Robinson (cited by Smith and Berg2), sented in
a
on the other hand, found that there was no difference in incidence between the periods May to October and November to April for births to women over 35 but, for women under 35 there was a marked increase in incidence in the May-October period. The total number of cases was only 36. In the Jerusalem studyl seasonal peaks in incidence were demonstrated in the spring and autumn but the total number of cases was only 103. These data and others reviewed by Smith and Berg do not support a strong relationship between season of birth and the incidence of Down syndrome. A second point is the association between Down syndrome and advanced maternal age. This is by far the most consistent epidemiological finding in Down syndrome. Any hypothesis on the aetiology of Down syndrome must take this into account, and the endocrinological explanation proposed would be more convincing if an association between restradiol-receptor levels and age could be demonstrated. In Robinson’s studyz seasonality of Down syndrome births was restricted to younger mothers, supporting the suggestion that women who give birth to a Down syndrome child at a young age should be considered separately when aetiological factors are being sought.’ Since young mothers account for only a small proportion of Down syndrome births, a process possibly unique to them cannot entirely explain the aetiology, hence the importance of looking at age-related changes in the suggested endocrinological mechanism.
Division of Epidemiology, School of Public Health, University of California, Los Angeles, Los Angeles, California 90024, U.S.A.
SERUM-25-HYDROXYCHOLECALCIFEROL AND RENAL OSTEODYSTROPHY
reported low concentrations of serum-25-hydroxycholecalciferol (25-H.c.c.) in chronic renal SIR,—Eastwood
al.have
a relation between low concentration values and histomorphometric evidence of osteomalacia. The low serum-24-H.c.c. was thought to be caused by a disturbance in the hepatic transformation of vitamin D due to induction of hepatic microsomal enzymes. In a study of renal osteodystrophy in 26 patients with chronic renal failure (not on haemodialysis and not receiving vitamin-D supplements) we measured the serum concentrations of 25-H.c.c., calcium, immunoreactive parathyroid hormone (P.T.H.),2 alkaline phosphatase, and creatinine. Histomorphometric analysis of transiliac bone-biopsy specimens, obtained after double labelling with tetracycline, was done on undecalcified bone sections using the point-count principle.3 4 Serum-25-H.c.c. was measured by a competitive protein-binding assay’ with a minor modification in the chromatographic step. The coefficient of variation of repeated measurements at 35nmol/l was 13-5%. The sensitivity in the routine assay was 3.5 nmol/l.
failure and found
HISTOMORPHOMETRIC AND BIOCHEMICAL VALUES IN
26
(MEAN +- S.D.)
PATIENTS WITH CHRONIC RENAL FAILURE
* Data from 134 normal Danish
Data from 11 normal Danish
subjects. subjects.
Like Eastwood et al.’ we divided our patients into three groups according to the severity of the mineralisation defect as expressed by calcification fronts which were normal (>62%) (6 patients) or 30-62% (10 patients) or
ELAINE K. PERRY ROBERT H. PERRY MICHAEL J. TAYLOR BERNARD E. TOMLINSON
SEASONALITY IN DOWN SYNDROME
SIR,-Dr Janerich and Professor Jacobson (March 5, p. 515) discuss seasonality of Down syndrome births, as pre-
study from Jerusalem,l and put forward an endocrinological explanation for seasonality and the aetiology of Down syndrome. Noting a similarity between monthly conception-rates of Down syndrome fetuses and monthly variation in restradiol-receptor levels in mammary tumours, they suggest that the endocrine factors which cause the changes in restradiol-receptor concentration also affect the meiotic process. While this hypothesis is interesting, it needs to be considered critically. First, seasonality in Down syndrome has not been consistently demonstrated .2 For example, McDonaldfound no association with month of birth in a study of 2398 Down syndromes cases in Quebec. Haynes et al. found no seasonal pattern for Down syndrome births in a 37-year period in Rochester, Minnesota. Robinson (cited by Smith and Berg2), sented in
a
on the other hand, found that there was no difference in incidence between the periods May to October and November to April for births to women over 35 but, for women under 35 there was a marked increase in incidence in the May-October period. The total number of cases was only 36. In the Jerusalem studyl seasonal peaks in incidence were demonstrated in the spring and autumn but the total number of cases was only 103. These data and others reviewed by Smith and Berg do not support a strong relationship between season of birth and the incidence of Down syndrome. A second point is the association between Down syndrome and advanced maternal age. This is by far the most consistent epidemiological finding in Down syndrome. Any hypothesis on the aetiology of Down syndrome must take this into account, and the endocrinological explanation proposed would be more convincing if an association between restradiol-receptor levels and age could be demonstrated. In Robinson’s studyz seasonality of Down syndrome births was restricted to younger mothers, supporting the suggestion that women who give birth to a Down syndrome child at a young age should be considered separately when aetiological factors are being sought.’ Since young mothers account for only a small proportion of Down syndrome births, a process possibly unique to them cannot entirely explain the aetiology, hence the importance of looking at age-related changes in the suggested endocrinological mechanism.
Division of Epidemiology, School of Public Health, University of California, Los Angeles, Los Angeles, California 90024, U.S.A.
SERUM-25-HYDROXYCHOLECALCIFEROL AND RENAL OSTEODYSTROPHY
reported low concentrations of serum-25-hydroxycholecalciferol (25-H.c.c.) in chronic renal SIR,—Eastwood
al.have
a relation between low concentration values and histomorphometric evidence of osteomalacia. The low serum-24-H.c.c. was thought to be caused by a disturbance in the hepatic transformation of vitamin D due to induction of hepatic microsomal enzymes. In a study of renal osteodystrophy in 26 patients with chronic renal failure (not on haemodialysis and not receiving vitamin-D supplements) we measured the serum concentrations of 25-H.c.c., calcium, immunoreactive parathyroid hormone (P.T.H.),2 alkaline phosphatase, and creatinine. Histomorphometric analysis of transiliac bone-biopsy specimens, obtained after double labelling with tetracycline, was done on undecalcified bone sections using the point-count principle.3 4 Serum-25-H.c.c. was measured by a competitive protein-binding assay’ with a minor modification in the chromatographic step. The coefficient of variation of repeated measurements at 35nmol/l was 13-5%. The sensitivity in the routine assay was 3.5 nmol/l.
failure and found
HISTOMORPHOMETRIC AND BIOCHEMICAL VALUES IN
26
(MEAN +- S.D.)
PATIENTS WITH CHRONIC RENAL FAILURE
* Data from 134 normal Danish
Data from 11 normal Danish
subjects. subjects.
Like Eastwood et al.’ we divided our patients into three groups according to the severity of the mineralisation defect as expressed by calcification fronts which were normal (>62%) (6 patients) or 30-62% (10 patients) or
