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Biomedical subjects

N P Cavanagh

Publications and source records attributed to N P Cavanagh.

At least 19 recordsLinked to original sources
PubMed1990

Neurotoxicity in lymphoblastic leukaemia: comparison of oral and intramuscular methotrexate and two doses of radiation.

Serial cranial computed tomograms were carried out in 136 children with acute lymphoblastic leukaemia who were receiving 24 Gy or 18 Gy of cranial irradiation and continuing treatment with doses of methotrexate given weekly orally or intramuscularly. The findings were correlated with treatment variables, the development of fits, and the intelligence quotient (IQ). Reversible brain shrinkage, attributed to treatment with steroids, was found on 87 of 114 initial scans (76%); 14 showed changes in white matter during treatment (10%), and calcification was found in 13 either during or after treatment (10%). Eight children (6%) had fits, and in six of the eight there were changes in white matter or calcification on the scans. Comparison of the two radiotherapy dosages showed no difference in the incidence of abnormalities seen on computed tomography, fits, or serial IQ measurements, but children receiving intramuscular methotrexate had a higher incidence of calcification and a lower mean IQ at one year than those who received the drug orally, although this difference was not apparent later. Younger children were more likely to develop changes on computed tomograms and fits, and to have low IQs on completion of treatment, with changes most apparent in those less than 2 years of age. There were highly significant correlations between abnormalities on computed tomography, fits, and IQ. These findings confirm the neurological vulnerability of younger children with acute lymphoblastic leukaemia, show an association between abnormalities on computed tomography and intellectual deficit, and suggest that methotrexate is more toxic when given intramuscularly than orally. They provide no evidence that 18 Gy of cranial irradiation is less toxic than 24 Gy, and indicate the need for alternative treatment regimens.

Administration, Oral↗
PubMed1986

Neurological aspects of biopterin metabolism.

Plasma total biopterin concentration was measured by bioassay in 59 infants with hyperphenylalaninaemia and in 50 children with developmental regression and or movement disorder with normal plasma phenylalanine concentrations. In infants with raised phenylalanine concentrations plasma biopterin concentrations were significantly raised in proportion to the phenylalanine values. Five patients had plasma biopterin concentrations at the extremes of the range, and of these two had defective biopterin metabolism. One with low plasma biopterin concentration apparently had a partial defect of biopterin synthesis but died before investigations were complete. One with high plasma biopterin concentration, even when phenylalanine concentrations had fallen to the normal range, had dihydropteridine reductase deficiency. In this patient concentrations of homovanillic acid and 5-hydroxyindolacetic acid in the cerebrospinal fluid (CSF) were severely reduced. In children without hyperphenylalaninaemia plasma biopterin concentrations were normal. Twenty two patients were subjected to lumbar puncture, of whom six with developmental regression without movement disorder had normal CSF biopterin concentrations, and 11 with movement disorder other than torsion dystonia had significantly lower CSF biopterin concentrations. Five patients with torsion dystonia had normal biopterin concentrations.

Adolescent↗
PubMed1983

Possible manifestation of the dystrophic X chromosome in muscle cultures from carriers of Duchenne muscular dystrophy.

Multilayer cell clusters have been observed before confluence and before myotube formation in muscle cell cultures derived from open biopsies of 7 of 14 (50%) female carriers of Duchenne muscular dystrophy, and in a high percentage of other dystrophic cultures. By contrast, this abnormality was seen in only 12 of 204 (6%) muscle biopsies from patients with other neuromuscular disorders. It appears that cluster formation is independent of the amount of connective tissue present in vivo, because histopathological analysis of the carrier biopsies showed increased endomysial connective tissue in only two cases. These results suggest that cluster formation is an expression of a myogenic defect and that it may be a manifestation of the genetic abnormality in X-linked muscular dystrophy.

Adolescent↗
PubMed1981

Creatine kinase isoenzymes in cultured human muscle cells. I. Comparison of Duchenne muscular dystrophy with other myopathic and neurogenic disease.

The amounts of creatine kinase (CK) and the proportions of isoenzymes have been investigated in human primary cultures. There were increases in total CK activity and the transitions in the isoenzyme profiles showed initial patterns in which only the brain form is present, and later in culture showed patterns in which the muscle or hybrid forms are also present. These changes are similar to those found in muscle cultures grown from other species. These parameters have been compared in cultures derived from boys with Duchenne muscular dystrophy and from patients with various neurological diseases. The dystrophic CK activities were significantly lower and the amounts of brain-type isoenzyme were significantly higher than in the cultures from patients with neurogenic disorders, but the values were similar to the cultures from the myopathic group of diseases. The dystrophic CK isoenzyme profiles resembled those produced by cultures examined at time points, early in their growth period when they were less differentiated.

Cells, Cultured↗
PubMed1981

Creatine kinase isoenzymes in cultured human muscle cells. II. A study of carrier females for Duchenne muscular dystrophy by needle and open biopsy.

Creatine kinase (CK) isoenzymes, total and specific CK activities and protein concentrations were measured in the cultured cells from muscle biopsies of 18 carriers of Duchenne muscular dystrophy (DMD) and the results compared with those in the cultures of patients with DMD and other neuromuscular disorders. The proportion of MB and BB isoenzyme in the carriers was similar to that in boys with DMD and in patients with other myogenic disorders, and significantly different from neurogenic patients. CK isoenzyme analysis appears to be a more sensitive index of in vitro differentiation than estimation of CK activities. Cell differentiation is reduced and the incidence of cell death increased in cultures derived from needle rather than open biopsies.

Biopsy↗
PubMed1981

The possible adjuvant role of bordetella pertussis and pertussis vaccine in causing severe encephalopathic illness: a presentation of three case histories.

The clinical and some laboratory details of three children who had severe neurological sequelae after either infection with Bordetella pertussis or immunisation with diphtheria, tetanus and pertussis vaccine and oral polio vaccine are reported. Each of these patients had had a recent or concurrent viral illness. The severity of their encephalopathic illness may have been due to an adjuvant role of B. pertussis or a component of the vaccines they received.

Adjuvants, Immunologic↗
PubMed1981

Calf hypertrophy and asymmetry in female carriers of X-linked Duchenne muscular dystrophy: an over-diagnosed clinical manifestation.

The height, weight and calf sizes of 19 carriers of X-linked Duchenne muscular dystrophy were compared with 32 normal female controls of comparable age. Whereas the regression of the sum of right and left calf sizes on weight was highly significant in both groups, the difference between right and left calf size showed no significant association with weight, height or age. There was no significant difference between carriers and controls in the sum of calf sizes either before or after correction for weight by Analysis of Covariance and no significant difference between the two groups in the degree of asymmetry of right and left calf size.

Adolescent↗
PubMed1980

Shwachman's syndrome. A review of 21 cases.

21 patients (10 male, 11 female) aged between 11 months and 29 years with Shwachman's syndrome are reviewed. All patients had exocrine pancreatic insufficiency. Haematological features included neutropenia in 19 (95%), anaemia in 10 (50%), and thrombocytopenia in 14 (70%); one patient developed erythroleukaemia. Severe infections occurred in 17 (85%) from which 3 (15%) died. Only one child exceeded the 3rd centile for height, and growth retardation was particularly evident in the older patients. All had skeletal abnormalities or delayed skeletal maturation, or both. Metaphyseal dyschondroplasia affected 13 of the older patients and was associated with skeletal deformities. Eight of 9 children under 2 1/2 years had rib abnormalities. Respiratory function tests in children under 2 years demonstrated reduced thoracic gas volume and chest wall compliance. Older patients had reduced forced expiratory volume and forced vital capacity. Neurological assessment showed developmental retardation or reduced IQ assessments, or both, in 85% of patients studied. Other neurological abnormalities included hypotonia, deafness, and retinitis pigmentosa. Neonatal problems had been present in 16 (80%) of the patients and 5 were of low birthweights. Hepatomegaly with biochemical evidence of liver involvement occurred in the younger patients and resolved with age. Other associated features included dental abnormalities, renal dysfunction, an icthyotic maculopapular rash in 13 (65%), delayed puberty, diabetes mellitus, and various dysmorphic features. These findings stress the diverse manifestations of the syndrome and extend knowledge on a number of aspects. Sibship segregation ratios support an autosomal mode of inheritance and an hypothesis for the pathophysiological basis of this syndrome is advanced.

Adolescent↗
PubMed1979

Hereditary sensory neuropathy with spastic paraplegia.

Five cases of spastic paraplegia with a progressive symmetrical sensory neuropathy producing ulceration and osteomyelitis of the hands and feet are reported. The pathology in one patient, who died of secondary amyloidosis, was similar to that found by Denny-Brown in hereditary sensory radicular neuropathy with severe loss of posterior root ganglion cells and loss of myelinated fibres in both peripheral nerves and posterior columns of the spinal cord. A sural nerve biopsy in another case showed a striking loss of both myelinated and unmyelinated fibres, with some evidence of degeneration and regeneration. The inheritance is probably by an autosomal recessive gene. The prognosis in the more severe form of the disorder is poor.

Adolescent↗
PubMed1979

Congenital fibre type disproportion myopathy. A histological diagnosis with an uncertain clinical outlook.

Nine children with congenital fibre type disproportion (CFTD) are described. Their muscle biopsies contained type 1 fibres which were smaller than the largest type 2 fibres by at least 13.5%. Attention is drawn to the variable natural history of this disorder which generally carries a good prognosis but may sometimes be associated with fatal respiratory problems. For important therapeutic, genetic, and prognostic reasons CFTD must be distinguished from other conditions with similar histochemical or clinical features.

Biopsy↗
PubMed1978

Early-juvenile Batten's disease--a recognisable sub-group distinct from other forms of Batten's disease. Analysis of 5 patients.

In most cases where rectal biopsy is performed to diagnose Batten's disease, there is good correlation between biopsy appearance, age of onset, clinical course and electrophysiological parameters. As a result 3 forms of the disease have been recognised; infantile, late infantile and juvenile. In a review of rectal biopsy in Batten's disease at the Hospital for Sick Children, Great Ormond Street, we have studied the few cases in which no such correlation appeared to exist. In 5 the features are sufficiently similar to suggest a further recognisable sub-group which could be descriptively called "early juvenile". The clinical course, electrophysiological features and the absence of vacuolated lymphocytes in this subgroup are as found in the late infantile form, whereas the biopsy findings are identical to those of the juvenile form. By analogy with some of the mucopolysaccharidoses we speculate that the genes of the late infantile and juvenile forms of Batten's disease are allelic and that the "early juvenile" sub-group is a genetic compound presenting as an intermediate phenotype.

Child↗
PubMed1978

Alternating hemiplegia: complicated migraine of infancy.

Alternating hemiplegia in children is a rare form of "complicated" migraine. There are a number of similarities to seizure disorders and correct diagnosis may prove difficult. The clinical features of 6 patients with alternating hemiplegia are presented together with the results of electrophysiological, radiological, and biochemical studies. While there were a number of clinical similarities between the patients, extensive investigations failed to demonstrate significant abnormalities. Although a diagnosis of a seizure disorder was suggested at some time in all of the patients, in only 2 was it certain there was a fit. Headaches occurred in the eldest patient (although not always with a hemiplegic attach) while in the younger patients misery often accompanied their attacks. Intellectual status was impaired in 5 patients, although in 2 of these the cause was most likely to be perinatal difficulties. Response to various forms of treatment was generally not encouraging and concern is expressed that this alternating hemiplegia of childhood may carry an unfavourable prognosis.

Adolescent↗