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P Grattan-Smith

Publications and source records attributed to P Grattan-Smith.

17 recordsLinked to original sources
PubMed2007

A subgroup of spinocerebellar ataxias defective in DNA damage responses.

A subgroup of human autosomal recessive ataxias is also characterized by disturbances of eye movement or oculomotor apraxia. These include ataxia telangiectasia (A-T); ataxia telangiectasia like disorder (ATLD); ataxia oculomotor apraxia type 1 (AOA1) and ataxia oculomotor apraxia type 2 (AOA2). What appears to be emerging is that all of these have in common some form of defect in DNA damage response which could account for the neurodegenerative changes seen in these disorders. We describe here sensitivity to DNA damaging agents in AOA1 and evidence that these cells have a defect in single strand break repair. Comparison is made with what appears to be a novel form of AOA (AOA3) which also shows sensitivity to agents that lead to single strand breaks in DNA as well as a reduced capacity to repair these breaks. AOA3 cells are defective in the DNA damage-induced p53 response. This defect can be overcome by incubation with the mdm2 antagonists, nutlins, but combined treatment with nutlins and DNA damage does not enhance the response. We also show that AOA3 cells are deficient in p73 activation after DNA damage. These data provide further evidence that different forms of AOA have in common a reduced capacity to cope with damage to DNA, which may account for the neurodegeneration observed in these syndromes.

Brain Chemistry↗
PubMed2003

PEHO and PEHO-like syndromes: report of five Australian cases.

PEHO syndrome is a rare progressive infantile encephalopathy with onset within the first few months of life. Few patients fulfilling the diagnostic criteria for PEHO syndrome have been reported outside Finland. Affected infants have facial dysmorphism and suffer from severe hypotonia, profound mental retardation, convulsions (often with a hypsarrhythmic EEG pattern), transient or persistent peripheral oedema, and optic atrophy. Cerebellar and brainstem atrophy are usually present on neuroimaging. A PEHO-like syndrome has been described, in which the affected individuals have neither optic atrophy nor the typical neuroradiological findings. We report five Australian patients, the first with classical features of PEHO syndrome, and four who have a PEHO-like disorder. We compare their features with other published cases. We suggest that PEHO or a PEHO-like syndrome may affect more patients than are currently identified, based on the original diagnostic criteria for this disorder.

Brain Diseases, Metabolic, Inborn↗
PubMed2001

Congenital fibrosis of the extraocular muscles associated with cortical dysplasia and maldevelopment of the basal ganglia.

BACKGROUND: Congenital fibrosis of the extraocular muscles (CFEOM) is a rare condition that has been traditionally regarded as a primary eye muscle disease. Recent studies, however, suggest that CFEOM may be the result of a primary neuropathy with secondary myopathic changes. PURPOSE: To describe a previously unrecognized association between congenital fibrosis of the extraocular muscles and structural abnormalities of the brain. DESIGN: Small case series. METHODS: Detailed clinical examinations and neuroradiologic studies were performed on the three affected family members. In addition, genetic analysis of the family was performed. RESULTS: The three affected family members, mother and two children, have the ocular features of 'classic' congenital fibrosis of the extraocular muscles. All showed dilation of the left lateral ventricle secondary to hypoplasia of the body and tail of the ipsilateral caudate nucleus. There was fusion of an enlarged caudate nucleus head with the underlying putamen. Both children showed widespread bilateral cortical dysplasia. Genetic analysis of the family was inconclusive but consistent with linkage to the CFEOM1 locus on chromosome 12. Chromosomal analysis of the affected individuals did not show evidence of a deletion of chromosome 12 and haplotype analysis was not suggestive of a microdeletion. CONCLUSIONS: Cerebral cortical and basal ganglia maldevelopment can be found in individuals with CFEOM. This suggests that neuroimaging should be considered in the initial diagnostic evaluation of these patients, particularly if there is developmental delay.

Abnormalities, Multiple↗
PubMed2000

The value of partial sleep deprivation as a routine measure in pediatric electroencephalography.

For more than 50 years it has been known that in patients with epilepsy, sleep markedly increases the diagnostic yield of the electroencephalogram (EEG). Sleep deprivation could have an additional activating role. Many laboratories do not use these methods routinely but reserve them for a second EEG if equivocal or negative findings are present in the initial EEG. We studied a regime of routine partial sleep deprivation without the use of hypnotic agents in 396 children younger than age 17 years who were referred for EEG with a diagnosis of epilepsy or suspected epilepsy. Sleep was achieved for the EEG in 77% (96% in the 1 month to 2 year age group, 78% in the 2 to 8 year age group, and in 64% of those more than 8 years old). In a comparison group of 72 children who had not been sleep-deprived, sleep was achieved in 44% (69% of those less than 2 years old, 27% of those between 2 and 8 years of age, and 33% of those older than 8 years). The differences were highly significant. The regime was well tolerated. Routine partial sleep deprivation is a practical and effective method of obtaining sleep and thus maximizing the information obtained from a single EEG.

Adolescent↗
PubMed1997

Gillespie syndrome: a report of two further cases.

We describe two unrelated patients with Gillespie syndrome (partial aniridia, cerebellar ataxia, and mental retardation). The typical presentation is the discovery of fixed dilated pupils in a hypotonic infant. The iris abnormality is specific and seems pathognomonic of Gillespie syndrome. It can be distinguished clinically from other forms of aniridia and a presumptive diagnosis of Gillespie syndrome can be made in the first months of life on the basis of the ocular findings. Neurological involvement includes marked motor delay, hypotonia, disabling ataxia, and usually mental retardation. Cerebral and cerebellar atrophy with white matter changes on MRI scan were present in our second patient suggesting that patients with Gillespie syndrome may have more extensive CNS involvement than previously described. The parents of this child were first cousins; thus Gillespie syndrome may be heterogeneous with autosomal recessive and autosomal dominant forms.

Aniridia↗
PubMed1994

Very long chain fatty acids in X-linked adrenoleukodystrophy brain after treatment with Lorenzo's oil.

The fatty acid composition of postmortem brain and liver from an adrenoleukodystrophy patient whose diet was supplemented with Lorenzo's oil (glycerol trioleate and glycerol trierucate) for 9 months was determined. The diet depressed plasma and liver saturated very long chain fatty acids (24:0 and 26:0) and increased plasma and liver erucic (22:1) and nervonic (24:1) acids. The levels of plasma linoleic (18:2 n-6), eicosopentaenoic (20:5 n-3), and docosahexaenoic (22:6 n-3) acids were also reduced, while the biochemical marker for essential fatty acid deficiency (20:3 n-9) was markedly increased in liver. However, we were unable to detect any corresponding changes in brain indicating that little erucic acid crossed the blood-brain barrier. Our findings suggest that dietary supplementation with Lorenzo's oil is of limited value in correcting the accumulation of saturated very long chain fatty acids in the brain of patients with adrenoleukodystrophy.

Adolescent↗
PubMed1994

Delayed cerebral radiation necrosis.

The clinical features and long-term outcome of seven patients with delayed cerebral radiation necrosis (DCRN) are described. Radiotherapy had been given for pituitary tumour (1), astrocytoma (2), pinealoma (2), craniopharyngioma (1) and parotid carcinoma (1). The mean latency to onset of the first neurological symptoms was 22 months (range 6-40 months), and mean duration of follow-up was 86 months (range 60-126). Three patients died at a mean of 84 months after radiotherapy (range 62-98). A fourth patient probably died from metastatic disease. Three patients remain alive, albeit severely disabled, after 5-10 years. The illness typically ran a stepwise course, with fits and stroke-like episodes occurring against a background of progressive dementia and somnolence. CT and MRI scans showed progressive ventricular dilatation associated with cerebral atrophy and diffuse or focal changes in the white matter. Four patients had had two or more neurosurgical procedures after the radiotherapy. In only one of the seven patients was the diagnosis made at presentation. DCRN produces a distinctive clinical picture, yet remains a poorly recognized complication of cranial irradiation.

Adolescent↗
PubMed1990

Roseola infantum and other syndromes associated with acute HHV6 infection.

Eight cases of acute human herpesvirus type 6 (HHV6) infection in infants were diagnosed serologically by the demonstration of IgM anti-HHV6 (8/8) and a significant change in total anti-HHV6 antibody titre (6/8). Four infants were sufficiently ill to require admission to hospital and further investigations: one with encephalitis and three with gross hepatosplenomegaly, two of whom had evidence of simultaneous infection with another herpes-virus. The remaining four infants had an illness compatible with roseola infantum, although this diagnosis had not been made clinically. Sera from two of those infants with rash had been sent for analysis to exclude rubella because the infants' mothers were pregnant. The other two had received antibiotics when febrile, and the subsequent appearance of the roseola rash had raised the possibility of antibiotic allergy. The data suggest that there are clinical syndromes in addition to roseola infantum associated with the presence of IgM anti-HHV6, in which serological screening for evidence of acute HHV6 infection may be useful.

Antibodies, Viral↗
PubMed1989

A 15-year survey of chronic lung disease of prematurity.

The in-hospital findings for infants of 500-1,500 g birthweight admitted for intensive care over the years 1971-87 were reviewed at four intervals. Survival rate improved substantially. The incidence of chronic lung disease (CLD) in survivors at 28 days of age was unchanged though severity diminished in terms of both mortality and degree of radiographic change. Mean conceptual age for ceasing supplemental oxygen was 32 weeks for those with normal X-rays and 37 weeks for abnormal X-rays regardless of initial degree of immaturity. CLD was diagnosed twice as often when supplemental oxygen beyond 28 days was used as an indicator as against an abnormal X-ray and was hence unreliable for this purpose. Since candidates for CLD are a heterogeneous group care is needed in analysis or selection of material in forming conclusions which concern etiology or management.

Age Factors↗
PubMed1988

Clinical features of conversion disorder.

This study reviewed the case notes of 52 children diagnosed as suffering from hysterical conversion during admission to a paediatric teaching hospital over a 10 year period. The disorder was rare below 8 years of age and girls outnumbered boys three to one. Altogether 75% of the children presented during spring and summer; at the time of end of year exams and the beginning of the new school year. The presentation was usually polysymptomatic with gait disturbance being the main complaint in 36 children. Sensory abnormality, predominantly pain, was present in 40 children; this indicates a strong association between psychogenic pain and conversion disorder in children. At discharge 32 were completely recovered or had appreciably improved. There was a core group that presented particular difficulties with diagnosis and showed little positive response to treatment.

Adolescent↗
PubMed1987

Perinatal factors and the development of chronic lung disease in preterm infants: a case control study.

A case control study of neonates was performed to determine those factors contributing to the development of chronic lung disease (CLD). During the 5 years 1981-84 there were 487 neonatal survivors at gestations of 25-32 weeks; 391 of these developed respiratory failure (oxygen therapy required for more than 6 h). Fifty-six of the latter developed CLD (oxygen therapy required for more than 28 days and a coarse reticular pattern on chest X-ray). These neonates were predominantly of the shortest gestational ages, regardless of the initial chest X-ray diagnosis. Forty-three of these infants with CLD were matched for gestation and initial chest X-ray appearance (respiratory distress syndrome, n = 20; normal, n = 15; non-specific, n = 8) with 42 control infants. The mean duration of oxygen therapy (P less than 0.001), maximum FiO2 (P less than 0.001), incidence (P less than 0.01) and duration of intermittent positive pressure respiration (IPPR; P less than 0.05) and peak IPPR (P less than 0.05) were significantly greater in the CLD group. Mean birthweight (P less than 0.001), arterial cord pH (P less than 0.05) and base excess (P less than 0.05) were significantly lower in the CLD group. Factors that were not statistically significant in the development of CLD included antenatal fetal heart rate abnormality, hypertensive disease of pregnancy, acute intrauterine infection (chorioamnionitis or umbilical vasculitis), administration of antenatal steroids, sex, patent ductus arteriosus and pneumothorax. The association between CLD and ventilator/oxygen therapy is confirmed. Contrary to other reports, male sex, clinical patent ductus arteriosus and pneumothorax were not associated with CLD.

Birth Weight↗
PubMed1976

Neurofibromatosis involving the lower urinary tract in children. A report of three cases and a review of the literature.

Three children with neurofibromatosis involving the lower urinary tract are reported and their clinical, radiological and pathological findings are described. Lower urinary tract involvement in neurofibromatosis has previously been reported in 17 children, 12 of whom had other stigmata of von Recklinghausens disease. Lower urinary tract involvement may be asymptomatic and can be found incidentally. Every case with neurofibromatosis presenting with what may appear to be even only insignificant urinary symptoms should be thoroughly investigated urologically. Symptoms are usually related to urinary tract obstruction or neurogenic bladder dysfunction due to the involvement of the nerves supplying the bladder. Urinary diversion is the treatment of choice as surgical removal of the extensive tumour is seldom feasible. Following treatment the prognosis for survival appears to be good.

Child, Preschool↗
PubMed1966

The baby who vomits.

Explore the source record for details and available documents.

Duodenal Obstruction↗
PubMedDate not supplied

Status dystonicus and Hallervorden-Spatz disease: treatment with intrathecal baclofen and pallidotomy.

Severe dystonia or status dystonicus is a life threatening disorder that develops in patients with both primary and secondary dystonia. We present the case of a 9-year-old boy with Hallervorden-Spatz disease (HVS) who developed status dystonicus, failing to respond to high dose oral therapy with multiple antidystonic agents. High dose intravenous sedating agents combined with endotracheal intubation and mechanical ventilation were required to control the spasms. Alleviation of the spasms was achieved by a combination of temporary intrathecal baclofen infusions and bilateral pallidotomy. Although it could be argued this is a situation where only palliative measures should be used, we believe a relatively aggressive approach was justified. It relieved the intense pain associated with the spasms and allowed the child to be discharged home without the prolonged stay in intensive care, morbidity and mortality, which characterize status dystonicus.

Baclofen↗