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Biomedical subjects

M Hauge

Publications and source records attributed to M Hauge.

At least 37 records · Page 2Linked to original sources

Congenital heart defects in live-born children of epileptic parents.

In a study of congenital heart defects (CHD) in 2,461 live-born children of an unselected group of 979 male and 1,093 female epileptics, 18 children with CHD were recorded; eight had epileptic fathers and 10 epileptic mothers. The prevalence of CHD does not differ significantly from that of the background population. Many different CHD types were recorded with no single defect being predominant. Likewise, no association with a specific type of anticonvulsant treatment was noted. The fact that the prevalence of CHD among children of male and female epileptics and of the background population was similar supports the view that antiepileptic treatment is no major factor in the etiology of CHD in the off-spring of epileptics.

Adult↗

An alternative sampling approach to the study of diabetes prevalence.

Sampling methods hitherto used in epidemiological surveys have generally faced two major sorts of potential bias: a latent period between listing and testing of listed individuals which can cause a misrepresentation of the population under study, compared with the population basis; population migration and death during the study period, which may result in a discrepancy between the population selected for study and the part of the population examined. A Central Population Register, found in all Scandinavian countries, permits an evaluation of the size of these problems of bias and makes it possible to use an alternative sampling method based on test samples successively drawn from the actual dynamic population. The feasibility of this new approach was tested in an epidemiological survey of diabetes mellitus among individuals in the age group 60-74 years living in a Danish municipality (Fredericia). It is concluded that this alternative dynamic method produces a more representative study population with less bias, thanks to the smaller number of deaths and migration among non-responders during the study, than do the methods previously used. Furthermore, the length of the study period, the size of the test samples, as well as the intervals between selecting samples may be adjusted to the capacity available, thus reducing the resources required. By using a correction in the computer program for selecting test sample size, the sex and age profile of the whole study population may be chosen in accordance with the incidence of the disease studied. In the Scandinavian countries a unique possibility exists to carry out prevalence studies on all kinds of diseases by the method described and evaluated here.

Aged↗

Genetic studies of insulin-dependent diabetes mellitus: segregation and linkage analyses.

The inclusion of HLA data in genetic studies of insulin-dependent diabetes mellitus (IDDM) has not led to conclusive segregation models for IDDM so far. As a new approach, we first applied complex segregation analysis, independently of HLA data, to two combined Danish family materials. Then the best fitting segregation model was entered into linkage analysis of a third material, including family as well as HLA data. The best solution obtained in the segregation analysis was a mixed model, including an intermediate gene, which on the penetrance scale acts as a recessive, together with a polygenic component. The linkage analysis showed an overall recombination fraction of 0.0417 with high coupling frequencies for the HLA-DR3 and HLA-DR4 alleles and the putative disease susceptibility gene. However, when the pedigrees were divided according to whether or not the proband had the heterozygous HLA-phenotype DR3/DR4, a maximum likelihood ratio test for heterogeneity was significant, with estimated recombination fractions of 0.0 and 0.0963 in HLA-DR3/DR4 pedigrees and the remaining pedigrees, respectively. In total, we found convincing evidence that two familial factors contribute to IDDM: a locus within HLA, which very well may be DR; and an unlinked mechanism which is unimportant for HLA-DR3/DR4 but simulates recombination. If confirmed, this conclusion has important implications for further genetic studies of IDDM and complex segregation analyses of family materials sampled according to criteria which include HLA data of the probands are highly needed.

Adolescent↗

HLA and diabetes.

HLA studies have conclusively demonstrated that IDDM and non-IDDM are separate disease entities. A considerable part of the genetic susceptibility to IDDM is due to one or more HLA genes. The HLA-DR3 and -DR4 factors showing the strongest association with IDDM belong to the so-called DR antigens, which are believed to be the immune response determinants of man. A dominant model for the HLA-controlled susceptibility to IDDM has been ruled out and a recessive model seems unlikely. A gene-dose model intermediate between dominance and recessivity is still possible, but there is also some evidence against this model, because DR3/4 heterozygotes seem to have a considerably higher risk of developing IDDM than has DR3/3 and DR4/4 homozygotes. It has been suggested that DR3 (or a DR3-associated factor) and DR4 (or a DR4-associated factor) confer susceptibility to IDDM each by a separate mechanism, and more recently that DR3/4 heterozygotes may carry combinatorial antigens which could contribute to the susceptibility to IDDM. Studies of HLA-associated clinical heterogeneity within IDDM are indicated to gain further insight in the genetics of IDDM.

Diabetes Mellitus↗

Facial clefts among epileptic patients.

Anticonvulsants have been suspected of teratogenicity, with facial clefts being the malformation most frequently associated with maternal anticonvulsant therapy. Paternal epilepsy has also been suggested as a factor in the genesis of birth defects, including facial clefts. An association between epilepsy per se and facial clefts would be reflected in a higher facial cleft prevalence among epileptics, and consequently result in an increase of such malformations among their children. The prevalence of facial clefts was determined in an unselected group of 3,203 epileptic probands: their personal data were cross-matched with a complete file of Danish facial cleft patients born between 1934 and 1977. Eleven epileptic probands had a facial cleft, which is twice the expected number. The increased prevalence of cleft defects among epileptics could partly explain why more of their children have facial clefts.

Adolescent↗

HLA-D and -DR antigens in genetic analysis of insulin dependent diabetes mellitus.

Three groups of patients with insulin-dependent diabetes mellitus, ascertained by different procedures, were investigated for HLA-A, B, C and D antigens (n = 164), and a subset (n = 93) for HLA-DR. Both HLA-D/DR3 and D/DR4 were strongly positively associated and D/DR2 was negatively associated with insulin-dependent diabetes. HLA-DR+ was found to be a better marker for insulin-dependent diabetes than Dw4. The HLA-B associations (B8, B15 and B18) were clearly secondary to the increases of HLA-D/DR3 and D/DR 4. The HLA associations did not differ between familial and isolated cases indicating that these two groups may well have a common genetic background. Based on analysis of HLA-haplotype sharing in affected sibling pairs, a simple dominant model of inheritance could be ruled out, and a simple recessive model was found unlikely. The relative risks for the HLA-Dw3,4 and HLA-DR3,4 phenotype were 21.2 and 44.4 respectively and exceeded those of both the HLA-Dw3 and HLA-DR3 (5.6 and 4.3) as well as the HLA-Dw4 and DR4 (10.1 and 10.5) phenotypes. This argues against an intermediate genetic model but further studies are needed to clarify whether there is more than one susceptibility gene for insulin-dependent diabetes mellitus within the HLA-system.

Diabetes Mellitus↗

Epidemiological studies of diabetes mellitus in Denmark. II. A prevalence study based on insulin prescriptions.

The study aimed at tracing the population of insulin-treated diabetics living in the Funen County, Denmark (approximately 450000 inhabitants) on 1 July 1973. It was based on a recording of insulin prescriptions among all prescriptions handled by the pharmacies in Funen County during a five-month period. Through information from medical records and public registries the verification of the diagnosis and the identity of the insulin prescription holders were checked, and it is estimated that the completeness of the study material was above 98%. Age- and sex-specific prevalence rates of insulin-treated diabetes mellitus were calculated. The overall prevalence rate for males was 3.6 per 1,000 and that for females 3.3 per 1,000.

Adolescent↗

Epidemiological studies of diabetes mellitus in Denmark. I. A case finding method based on the National Service Conscript Registry.

To provide unbiased material for epidemiological studies of diabetes mellitus a case finding method based on the Danish National Service Conscript Registry and death certificates is presented and discussed. Eight Danish total male birth cohorts, totalling 320 162 persons, have been observed as to the occurrence of diabetes mellitus during the first twenty years of life, and it is concluded that the conscript registry represents an ideal basis for case identification, if the individual cases are further elucidated. The material is estimated to be about 95% complete. The main source of error originates from omissions when the registries are scrutinized. The cumulative incidence rates for the birth cohorts range from 1.3 to 3.2 per thousand; in the total material 2.4 per thousand.

Adolescent↗

Etiologic factors of breast cancer elucidated by a study of unselected twins.

The Danish Twin Register consists of the total population of twin pairs born in Denmark during a certain period. Within this population were found 50 monozygotic (MZ) female twins belonging to 45 MZ pairs and 81 dizygotic (DZ) twins belonging to 77 DZ female pairs, of which at least 1 twin had breast cancer (BC) and both twins were alive at the time of the first BC diagnosis. In 5 MZ and 4 DZ pairs, both partners had BC. Pairwise concordance rates were not significantly different between the 2 groups of twins but were of the same magnitude as in a previous study. The heritability, evaluated by genetic determination, was estimated to be 0.30-0.40. The observed number of BC cases developing in the co-twins after the first BC diagnosis in the twin pairs was increased by a factor of nearly 6 in MZ co-twins and by a factor of about 2 in DZ co-twins. For cancer of other sites, the observed and expected numbers were nearly identical in both MZ and DZ co-twins. In 8 of 9 pairs concordant for BC, the lesion was found on the same side. The mean age at diagnosis showed no significant difference between the concordant and discordant pairs. In the 40 MZ pairs with only 1 twin affected, she was more often unmarried and/or nulliparous than her unaffected, genetically identical co-twin, but this finding was not significant. A general tendency for the twin with BC to have the first child at a later age than her unaffected twin sister could not be demonstrated.

Adult↗

Renal transplantation and cancer in the Scandiatransplant material.

Scandinavian material is presented, consisting of 3,875 transplanted patients and containing 128 patients in whom cancer was diagnosed. In a subgroup of 566 first-time transplanted Danish patients, there was a significantly increased incidence of tumours compared with the Danish population, a correlation between tumour frequency and mismatch in HLA-A and in HLA-B, a correlation to chronic interstitial nephritis, but no correlation to the occurrence of lymphocytotoxic antibodies or to sex difference between donor and recipient. In this material there is evidence indicating that the presence of constant stimulation by alloantigens leading to chronic immunostimulation, with possible loss of the suppressor function of lymphocytes towards the development of malignant tumours, is an important factor in the development of tumours in transplanted patients.

ABO Blood-Group System↗

Prenatal diagnosis of polycystic kidneys and encephalocele (Meckel syndrome).

Two unrelated families are presented with repeated occurrences of a congenital syndrome of which the main stigmata were polycystic kidneys and occipital encephalocele (Meckel syndrome). Prenatal diagnosis, followed by interruption of pregnancy, was performed in one case. The diagnosis was based on an increase of amniotic alpha-fetoprotein (AFP), and on the mode of growth and cell types of cultured amniotic cells. In another similarly examined case the diagnosis was suspected, but the parents did not wish the pregnancy to be interrupted. The child was stillborn and malformed. AFP values are presented and discussed in relation to the observed malformations. Neural tube defects are associated with an increase of AFP in amniotic fluid, but, as in normal pregnancies, the values decrease with increasing gestational age. On the other hand, kidney malformations seem to be associated with AFP values which remain high or even increase with increasing gestational age.

Amniotic Fluid↗

Metacarpal morphometry in monozygotic dizygotic elderly twins.

The relative importance of genetic factors in the pathogenesis of age related bone loss has been investigated in a study involving 17 monozygotic (MZ) and 8 dizygotic (DZ) pairs of twins aged 64 to 75 years. Radiographic morphometry was performed at the midpoints of the 2nd, 3rd and 4th metacarpals of both hands and the mean total and cortical widths were evaluated. The heritability, h2, was calculated as the difference between the intrapair variances in same sexed DZ and MZ pairs divided by the intrapair variance in DZ pairs. The mean intrapair variance of both total and cortical width was found to be four to five times higher in DZ than in MZ pairs. The differences are highly significant with an h2 value between 0.7 and 0.8, indicating a predominant genetic influence. It is stressed that this result applies only to the population from which the twin sample was drawn.

Aged↗