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Biomedical subjects

D M Becroft

Publications and source records attributed to D M Becroft.

At least 73 records · Page 4Linked to original sources
PubMed1980

Purine and pyrimidine metabolism in hereditary orotic aciduria: some unexpected effects of allopurinol.

Purine and pyrimidine metabolism have been investigated in the longest surviving case of hereditary orotic aciduria after 15 years of chronic uridine therapy. Several unusual features were recorded: 1. Although the uridine dosage (0.5 mmol/kg) was adequate to control an otherwise normal clinical status, orotic acid excretion was still excessive (in congruent 7 mmol/24 h). Urinary drug metabolites (uracil and uridine), however, accounted for less than 7% of the daily uridine dose, and no orotidine, or any abnormal pyrimidines or purines, were identified at any time. 2. Urinary uric acid excretion was high and plasma uric acid low, resulting in a clearance up to 4 times normal. This was attributed to the uricosuric effect of orotic acid. 3. In direct contrast to previous findings in gouty subjects and healthy male controls we noted: (i) no increase in plasma or urinary uric acid levels, or uric acid clearance, following the change from a low to a high nucleoprotein regime (normally up to two-fold); (ii) allopurinol reduced both urinary uric acid and total oxypurine levels by more than 50% on the low (normally unaffected) as well as the high (normally reduced 20-50%) nucleoprotein regime; (iii) a substantial (up to 70%) reduction in orotic acid excretion during allopurinol therapy (normally mild orotic aciduria), of similar magnitude and in parallel with the reduction in uric acid levels. Uric acid and orotic acid excretion were closely related throughout. These findings differ from those of a similar study of hereditary orotic aciduria and suggest there is competitive transport between exogenous (dietary) purines and pyrimidines, as well as an important interdependence between endogenous purine and pyrimidine metabolism, by mechanisms as yet undefined.

Adolescent↗
PubMed1980

The lungs in fatal measles infection in childhood: pathological, radiological and immunological correlations.

Multinucleated inclusion-bearing giant cells diagnostic of measles infection were identified in the pulmonary alveoli of seven children post mortem. Two children with leukaemia and a third with thymic dysplasia had prolongaed illness without typical measles exanthemata. All showed a striking proliferation of the respiratory epithelia, with formation of peribronchiolar fibro-epithelial nodules and cystic transformation of tracheo-bronchial glands. The nodular lesions contained many giant cells and were seen radiologically as multiple slowly-enlarging pulmonary opacities, a pattern which appears to be highly characteristic of measles infection in the presence of cellular immune deficiency. Two other children showed similar proliferative lesions, but had shorter illness with exanthemata and few tissue giant cells; these differences are attributed to the late appearance of a cellular immune response in less severe immune deficiencies. Two children who had no evidence of immune deficiencies died of acute viral alveolitis, one in the pre-exanthematous phase. Acute alveolitis was characterized radiologically by the rapid development of diffuse pulmonary opacification and by variable cytological features which correlated with other evidence for the presence or absence of a cellular immune response against the virus.

Bronchi↗
PubMed1980

Fetal thyroid hyperplasia, rhesus isoimmunisation, and amniography.

Thyroid hyperplasia was identified at necropsy in 16 of 70 cases of haemolytic disease of the newborn due to rhesus isoimmunisation dying in the years 1959--76. No hyperplasia was found in the thyroids from 140 nonrhesus-affected infants matched for date of birth, bodyweight and length, and gestation, or in cases of haemolytic disease born before 1966. All 16 infants with thyroid hyperplasia had received intrauterine transfusions and the iodine-containing contrast media used for preliminary amniography were the only goitrogenic factors identified. Lipiodol, first used in 1966, was considered to have the greatest effect. The 16 infants with hyperplastic thyroids were less mature and smaller than 22 infants with normal thyroids who had been similarly exposed to contrast media. The high incidence of hyperplasia may be due to immaturity of the adaptive mechanisms which allow most normal individuals to escape the goitrogenic effects of iodine compounds.

Adult↗
PubMed1978

Absence of oroticaciduria in adenosine deaminase deficiency and purine nucleoside phosphorylase deficiency.

Orotic acid excretion was normal when tested by three methods in adenosine deaminase deficiency and purine nucleoside phosphorylase deficiency. These results do not support the speculation, based on the oroticaciduria observed by others, that the immunodeficiency in these disorders results from the inhibition of pyrimidine biosynthesis. An alternative hypothesis is discussed.

Adenosine Deaminase↗
PubMed1977

The Lesch-Nyhan syndrome: a family study.

Two brothers were found to have athetoid cerebral palsy, mental and growth retardation and evidence of self mutilation. One had passed a renal calculus and both had high serum uric acid levels. The diagnosis of Lesch-Nyhan syndrome was confirmed by the finding of low levels of hypoxanthine-guanine phosphoribosyl transferase in erythrocytes and by autoradiography of fibriblasts. The mother, maternal grandmother, a female sibling and a maternal aunt were identified as carriers of the X-linked mutation which was responsible for the enzyme deficiency in the two male siblings.

Allopurinol↗
PubMed1977

Drug reaction simulating malignant lymphoma: a case due to pyrimethamine.

A 9 1/2-year-old boy who had been treated with pyrimethamine and sulphadimidine presented with generalised lymphadenopathy, fever, and an unusual sun-tanning. He was found to have mild anaemia, severe leucopenia and thrombocytopenia. The bone marrow was megaloblastic. Lymph node biopsy was initially interpreted as showing malignant lymphoma. No treatment for neoplasia was given and he was well 4 1/2 years later. We consider that the seemingly malignant changes were due to pyrimethamine.

Child↗
PubMed1977

46, X,X-X terminal rearrangement/45, X mosaicism in a child with short stature.

A phenotypically female child, investigated because of short stature, had abnormally large, often bipartite Barr bodies and a mosaicism of 45, X cells and cells with 46 chromosomes which included an exceptionally large metacentric chromosome (Xp+). G- and C-banding established that the chromosome was derived from two substantially entire X chromosomes joined short arm-to-short arm, and was likely to be an isodicentric X with functional inactivation of one centromere.

Body Height↗
PubMed1977

Intramuscular iron-dextran and susceptibility of neonates to bacterial infections. In vitro studies.

An increased incidence of E. coli sepsis has been observed in neonates given intramuscular iron-dextran for prevention of iron deficiency. Mechanisms for this apparent effect on susceptibility to infection were investigated by comparing phagocytic and antibacterial functions in paired samples of venous blood from 7 infants, median age 5 days, before and after iron-dextran. Post-treatment sera had increased inhibitory effects on leucocyte chemotaxis and markedly reduced bacteriostatic effects agaainst E. coli. The clinical relevance of the effects on chemotaxis is uncertain. The reduction in serum bacteriostasis is similar to that observed in other forms of hyperferraemia not associated with saturation of transferrin, and is a likely cause of the increased susceptibility to infection in vivo. We consider that prophylactic treatment with parenteral iron-dextran is contraindicated in early infancy.

Anemia, Hypochromic↗
PubMed1977

Histiocytoid cardiomyopathy of infancy: an unexplained myofibre degeneration.

An unusual multifocal degeneration of the myofibres of all chambers and the conducting system of the heart was found in a 4-month-old female in whom ventricular pre-excitation (Wolff-Parkinson-White syndrome) had been demonstrated. There was a complex malformation of the brain with hydrocephalus and bilateral corneal opacities and microphthalmos. The affected myofibres had a swollen vacuolated or granular cytoplasm and rounded nuclei giving a histiocytoid appearance. Disruption of myofibrils and gross dilation and disorganization of mitochondria were the major fine structural features. Reports of similar lesions in 8 other young female children are reviewed. 'Histiocytoid cardiomyopathy' is the term preferred over others which refer to an increased lipid content. The aetiology is unknown.

Autopsy↗
PubMed1976

Perinatal infections by group B beta-haemolytic streptococci.

Since 1970 there has been an increase in isolations of Group B beta-haemolytic streptococci from infants and mothers at the National Women's Hospital and the organism has become the major cause of fatal perinatal infection. Forty-three of 60 stillborn and liveborn infants with postmortem isolations of Group B streptococci had pneumonia and of these a minority also had meningitis and/or septicaemia. Amnionitis was found in 15 of 20 placentae examined from these patients and an ascending infection from the maternal genital tract, often through intact membranes, was considered likely in the majority. However, a review of the prenatal histories of 33 infants showed that only a minority had premonitory features such as prolonged rupture of membranes, prolonged labour or maternal fever. Thirteen of 26 liveborn infants had a birth weight less than 2500 g. The majority presented within one hour of birth with respiratory distress or apnoea and died within 48 hours of birth. Early diagnosis of Group B infection is possible if bacteriological and radiological evidence is sought in infants of low birth weight, with low Apgar scores and with early onset of respiratory distress syndrome or apnoea in addition to those having the more usual indications of intrauterine infection. Group B streptococci were carried vaginally in 9 per cent of women attending an antenatal clinic and this high carrier rate is considered to preclude prophylactic treatment.

Female↗
PubMed1976

Supravalvular aortic stenosis-infantile hypercalcaemia syndrome: in vitro hypersensitivity to vitamin D2 and calcium.

The incidence of cytoplasmic metachromasia has been studied in cultures of skin fibroblasts derived from 6 cases of the syndrome of supravalvular aortic stenosis, characteristic facies, and mental retardation which in many instances represents the late normocalcaemic stage of the severe form of infantile hypercalcaemia. The percentage of metachromatic cells (mean positivity 7.3%) was significantly higher than in control cultures. The addition of vitamin D2 and calcium to culture media caused a highly significant increase in metachromatic cells (mean positivity in supplemented media 16.1%) compared with a lesser increase in controls. These findings strengthen previous suggestions that there is a genetically determined hypersensitivity to vitamin D in some cases of the syndrome. A multifactorial aetiology is proposed, dependent on a variable genetic susceptibility of fetal connective tissues to a non-physiological effect of D vitamins and a variable level of maternal vitamin D nutrition.

Adolescent↗
PubMed1975

Chronic granulomatous disease: an inherited disorder of phagocytosis in a Maori ancestry.

Chronic granulomatous disease, in which abnormal susceptibility to infection is caused by an inherited defect in phagocytic cells, has been diagnosed in three brothers. Two brothers had repeated bacterial infections of the skin, superficial lymph nodes and lungs from infancy and died aged 27 months and 13 months. Characteristic suppurating granulomata were found in many organs. The diagnosis was established in both during life, and in the third asymptomatic brother shortly after birth, by studies of phagocytic function which included tests for nitroblue-tetrazolium reduction, hexose monophosphate shunt activity and bactericidal capacity. Their mother and a maternal aunt, both Maoris with no known Caucasian ancestry, were identified as carriers of the presumed sex-linked recessive gene. The clinical features of the disease and the laboratory methods for diagnosis are described.

Child, Preschool↗