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M W Thompson

Publications and source records attributed to M W Thompson.

At least 73 records · Page 4Linked to original sources
PubMed1983

Complex segregation analysis and computer-assisted genetic risk assessment for Duchenne muscular dystrophy.

Two hundred forty-four Toronto pedigrees of Duchenne muscular dystrophy patients have been partitioned into nuclear families with pointers for complex segregation analysis under a mixed model. The model takes into account the major X-linked locus and a multifactorial transmissible component for creatine kinase activity in females. The incidence in the province of Ontario is estimated to be 292 per million male births. The proportion of sporadic cases is 1/3, demonstrating equal mutation rates in males and females. A multifactorial component (H = 0.379) contributes to family resemblance for creatine kinase measurements. Examples are presented of the application of a computer program, COUNSEL, to derive genetic risks for genetic counseling with consideration of the multifactorial component.

Computers↗
PubMed1982

Duchenne muscular dystrophy carrier detection using logistic discrimination: serum creatine kinase, hemopexin, pyruvate kinase, and lactate dehydrogenase in combination.

In the absence of an unambiguous test for identifying Duchenne muscular dystrophy (DMD) heterozygotes, methods are needed for combination of the results of individually equivocal tests as effectively and rationally as possible. Tw used logistic discrimination to assess the effectiveness of measurements of serum creatine kinase, hemopexin, pyruvate kinase, and lactate dehydrogenase alone and in various combinations in identifying DMD carriers. We analyzed 127 serum samples from 63 normal female controls (20-40 years old) and 67 from 38 obligate DMD carriers. The best two tests to use in combination were creatine kinase and hemopexin, and these two, with lactate dehydrogenase, were the best three. t the 95% level (with 5% of controls misclassified), 54% of the carriers were identified by CK alone, whereas 88% were identified by means of the four tests. Although a small proportion of known carriers still cannot be identified, application of the four tests to a group of 45 possible carrier mothers of isolated cases of DMD resolves the population into fairly discrete "normal" and "abnormal" subgroups. Thus, if bias of selection can be eliminated, application of logistic discrimination may permit a direct estimate of the proportion of mothers of affected boys who are homozygous normal.

Adult↗
PubMed1982

Serum creatine kinase in the detection of Duchenne muscular dystrophy carriers: effects of season and multiple testing.

The usefulness of serum creatine kinase (CK) activity in the detection of Duchenne muscular dystrophy (DMD) carriers is dependent upon a reliable control distribution. In controls there is a small but reproducible seasonal variation in CK activity, with a statistically significant variation in the upper 95th percentile (78 IU/liter in May, 53 IU/liter in November, as compared with 67 IU/liter for the whole calendar year). Because CK values in DMD heterozygotes are higher in November than in May, the carrier detection rate may be highest in November. Failure to consider this seasonal variation in controls may cause misclassification of too many normal subjects. If tests are conducted throughout the year, however, the seasonal influence can be reduced by serial testing at intervals of several months. In this case, use of the highest of the results obtained in 3 tests compared with the normal range of single measurements misclassifies too many normal subjects. Use of the mean of 3 determinations provides more accurate classification.

Adult↗
PubMed1981

Duchenne muscular dystrophy carrier detection using logistic discrimination: serum creatine kinase and hemopexin in combination.

Creatine kinase (CK) activity and hemopexin concentration were measured in 208 serum samples from 104 normal females and 22 obligate carriers of Duchenne muscular dystrophy (DMD) 20-40 years old. Logistic discrimination was used to assess the effectiveness of the parameters alone or in combination in identifying DMD carriers. In this approach, a serum sample with particular CK, hemopexin, or a combination of CK and hemopexin values is given a probability that if drawn at random from a defined mixture of controls and carriers, it comes from a carrier. The carrier probability based on the biochemical tests can be directly combined with the carrier probability determined from a woman's pedigree to yield a final posterior probability that she is a carrier. When CK and hemopexin were considered individually, 65 and 27% of the carriers, respectively, could be distinguished from 95% of the controls. When the two tests were used in combination, 82% of the carriers could be distinguished from 95% of the controls. When the two-test method was applied to 93 possible carriers, 35 women were classified as carriers, whereas only 29 were identified using CK alone. This method can be extended to include other variables in order to further improve the identification of DMD carriers. It can also be applied to carrier detection in other genetic disorders.

Adolescent↗
PubMed1980

Investigation of the secretion and metabolism of cortisol during a 100 km race using [4-14C] and [11 alpha-3H] cortisol.

A mixture of [11 alpha-3H] and [4-14C] cortisol was administered orally to healthy men, following which urine was collected for 24 h. Four subjects acted as basal controls, going about their normal (sedentary) work; a further 3 resting subjects also received 100 mg cortisol orally (high cortisol controls) and 6 subjects competed in a 100 km race. Decreases in the carbon-14 specific activity of the cortisol metabolite excreted by the runners suggested that they secreted cortisol at 2-4 times the rate of the basal controls. This change was mirrored by the excretion of urine free cortisol but not by that of 17-hydroxycorticosteroids. The isotope ratio (3H:14C) of 11-hydroxy metabolites of cortisol from the runners was intermediate between those of the basal and high cortisol controls, from which we conclude that though the fractional oxidation of cortisol to cortisone is reduced by increasing the cortisol pool, it is not affected by exercise per se. This and other results show that although continuous running for 6-8 h, involving energy expenditure in excess of 25 megajoules, leads to a moderate increase in the rate of cortisol secretion, running per se does not appear to markedly affect the metabolism of cortisol.

17-Hydroxycorticosteroids↗
PubMed1979

Specific cellular defects in patients with Fanconi anemia.

Measurements of plating efficiency, accumulation of metaphases and generation times have shown that fibroblast from patients with Fanconi anemia (FA) have decreased probability of completing a further division after successful mitosis. Thus FA cells show decreased growth rates and increased generation times. We have also measured the survival of FA fibroblasts and lymphoblasts after treatment with a variety of mutagens. All FA cells show an increased sensitivity to drugs such as MMC and psoralen plus long wave length UV which cause DNA interstrand crosslinks. FA strains show varying degrees of sensitivity to these drugs and the extent of this sensitivity seems to be characteristic of each patient. FA cells are equal to controls in their sensitivity to other alkylating agents such as ethyl methane sulfonate, N-methyl-N1-nitro-N-nitrosoguanidine and actinomycin D. Both the decreased growth and increased drug sensitivity may result from defect in DNA replication or repair.

Adolescent↗
PubMed1979

Aerobic performance of female marathon and male ultramarathon athletes.

The aerobic performance of thirteen male ultramarathon and nine female marathon runners were studied in the laboratory and their results were related to their times in events ranging in distance from 5 km to 84.64 km. The mean maximal aerobic power output (VO2 max) of the men was 72.5 ml/kg . min compared with 58.2 ml/kg . min (p less than 0.001) in the women but the O2 cost (VO2) for a given speed or distance of running was the same in both sexes. The 5 km time of the male athletes was closely related to their VO2 max (r = -0.85) during uphill running but was independent of relative power output (%VO2 max). However, with increasing distance the association of VO2 max with male athletic performance diminished (but nevertheless remained significant even at 84.64 km), and the relationship between %VO2 max and time increased. Thus, using multiple regression analysis of the form: 42.2 km (marathon) time (h) = 7.445 - 0.0338 VO2 max (ml/kg . min) - 0.0303% VO2 max (r = 0.993) and 84.64 km (London-Brighton) time (h) = 16.998 - 0.0735 VO2 max (ml/kg . min) - 0.0844% VO2 max (r = 0.996) approximately 98% of the total variance of performance times could be accounted for in the marathon and ultramarathon events. This suggests that other factors such as footwear, clothing, and running technique (Costill, 1972) play a relatively minor role in this group of male distance runners. In the female athletes the intermediate times were not available and they did not compete beyond 42.2 km (marathon) distance but for this event a similar association though less in magnitude was found with VO2 max (r = -0.43) and %VO2 max (= -0.49). The male athletes were able to sustain 82% VO2 max (range 80--87%) in 42.2 km and 67% VO2 max (range 53--76%) in 84.64 km event. The comparable figure for the firls in the marathon was 79% VO2 max (ranges 68--86%). Our data suggests that success at the marathon and ultramarathon distances is crucially and (possibly) solely dependent on the development and utilisation of a large VO2 max.

Adult↗
PubMed1978

Clinical, pathological and genetic aspects of a form of cystic disease of the renal medulla: familial juvenile nephronophthisis (FJN).

A combined clinical, pathological and genetic study of 13 cases of FJN is reported. The clinical features are conistent with those described in the literature, except that short stature is not a feature in this group. Hyperplasia of the juxtaglomerular apparatus has been seen in 5 of 9 cases where histology was done. The genetic studies support the view that FJN is an autosomal recessive hereditary disease. Because their patterns of inheritance differ, FJN and medullary cystic disease (MCD) are separate entities. We suggest simplification of the nomenclature to: medullary cystic disease of childhood type, formerly FJN and medullary cystic disease of adult type, formerly MCD.

Adolescent↗
PubMed1976

Carrier detection and genetic counselling in Duchenne muscular dystrophy: a follow-up study.

Assay of serum creatine kinase activity is useful in the detection of carriers of the X-linked gene for Duchenne muscular dystrophy (DMD). For genetic counselling this assay has been used in conjunction with pedigree analysis to improve estimates of the risk that a female relative of a DMD patient is a carrier. To measure the impact of the program, follow-up information was obtained from women who had received genetic counselling for DMD. Their responses showed that the risk of producing an affected son had been a major factor in their attitude toward family planning, and their reproductive performance correlated inversely with their genetic risk. The decision by the majority of proven carriers to prevent the birth of further male offspring was reflected in a recent decline in the frequency of a known family history of DMD among newly ascertained cases.

Abortion, Therapeutic↗
PubMed1976

Acromesomelic dwarfism: description of a patient and comparison with previously reported cases.

A woman is described who has a severe bone dysplasia confined to the limbs. The degree of involvement is more marked in the distal bones. Her forearms and legs are short; the fibulae are represented by distal triangular remnants; the metacarpals are short, several phalanges in the fingers are absent; and the toes are represented by "ball-like" remnants containing a single bone. The findings in our patient are compared to previously reported cases of acromesomelic dwarfism.

Adult↗
PubMed1974

Sex-linked hereditary ataxic deplegia, the borderland between cerebral palsy and Pelizaeus-Merzbacher disease.

After a review of the literature concerning hereditary cases of cerebral palsy, a family is reported in which ataxic diplegia appears to be inherited as a sex-linked and probably recessive condition occurring in 3 males in successive generations. This ataxic diplegia, occurring after an unremarkable perinatal course, is associated with mild to moderate mental retardation, congenitial nystagmus and significantly small stature and prevents the acquisition of free walking. Associated extrapyramidal features may gradually become more marked, while the nystagmus may subside. The condition is similar to that described in three previous reports in the literature. No evidence of linkage with other sex-linked disorders has been found, Xga typing showed that recombination between the Xg locus and the locus for hereditary ataxic deplegia has occurred once out of three possible opportunities. In the absence of neuropathological findings or specific biochemical tests, the differential diagnosis from Pelizaeus-Merzbacher disease cannot be made with certainty. The differentiation from other progressive sex-linked neurological disorders is discussed.

Ataxia↗