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Biomedical subjects

M Sharland

Publications and source records attributed to M Sharland.

66 records · Page 4Linked to original sources
PubMed1992

Coagulation-factor deficiencies and abnormal bleeding in Noonan's syndrome.

Noonan's syndrome is characterised by a dysmorphic facies, congenital heart disease, and short stature, and is inherited as an autosomal dominant trait. Because abnormal bleeding has also been reported, we investigated a group of patients for coagulation-factor deficits. Of the 72 individuals studied (37 male, 35 female, mean age 11.4 years), 47 (65%) had a history of abnormal bruising or bleeding. 29 patients (40%) had a prolonged activated partial thromboplastin time. Specific abnormalities in the intrinsic pathway of coagulation (partial factor XI:C, XII:C, and VIII:C deficiencies) were found in 36 patients (50%). Multiple abnormalities among these 36 patients included combined factor XI:C and XII:C deficiencies (4 patients) and factor XI:C and VIII:C deficiencies (4), and 1 patient had combined factor VIII:C, XI:C, and XII:C deficiency. There was poor correlation between a history of abnormal bleeding and coagulation-factor deficit. In five families, similar coagulation-factor deficiencies were present in first-degree relatives with the syndrome. The pattern of inherited bleeding abnormalities seen in Noonan's syndrome suggests autosomal regulation of the intrinsic coagulation pathway.

Adolescent↗
PubMed1992

Ocular manifestations of Noonan syndrome.

Noonan syndrome is a genetic condition inherited in an autosomally dominant manner, characterised by congenital heart disease, short stature, abnormal facies and the somatic features of Turner's syndrome, but a normal Karyotype. The ophthalmological and orthoptic findings on 58 patients with Noonan syndrome are reported. External features were hypertelorism (74%), downward sloping palpebral apertures (38%), epicanthic folds (39%) and ptosis (48%). The orthoptic examination revealed strabismus in 48%, refractive errors in 61%, amblyopia in 33%, and nystagmus in 9% of cases. Sixty-three per cent of cases had anterior segment changes consisting of: Prominent corneal nerves (46%), anterior stromal dystrophy (4%), cataracts (8%) and panuveitis (2%). Fundal changes occurred in 20% of the study group, including optic nerve head drusen, optic disc hypoplasia, colobomas and myelinated nerves. Forty-seven per cent required non surgical treatment and a further 16% had undergone surgery for strabismus or ptosis. Only three patients had no visual defects. With such a high incidence of ophthalmic abnormalities it is clearly important that children with Noonan syndrome are screened by an ophthalmologist at an early age.

Adolescent↗
PubMed1992

Osteosarcoma: then and now. A fifty year review at Royal Prince Alfred Hospital.

The purpose of this study is to review survival, treatment methods and criteria for diagnosis of osteosarcoma at Royal Prince Alfred Hospital during two periods in the last 50 years. The records of 22 patients diagnosed with osteosarcoma and nine with osteosarcoma in Paget's disease (from 1939 to 1950) were reviewed. All but one had died within three years. One patient survived six years. The second series was taken from 1983 to 1990. Forty-nine patients, including three with Paget's sarcoma, were studied. Probability of survival was estimated by actuarial analysis using Kaplan-Meier curves. Overall survival was estimated at 45%. Those patients who were free of metastatic disease at the conclusion of their treatment were estimated to have a probability of survival of 85%.

Adolescent↗
PubMed1992

A clinical study of Noonan syndrome.

Clinical details are presented on 151 individuals with Noonan syndrome (83 males and 68 females, mean age 12.6 years). Polyhydramnios complicated 33% of affected pregnancies. The commonest cardiac lesions were pulmonary stenosis (62%), and hypertrophic cardiomyopathy (20%), with a normal echocardiogram present in only 12.5% of all cases. Significant feeding difficulties during infancy were present in 76% of the group. Although the children were short (50% with a height less than 3rd centile), and underweight (43% with a weight less than 3rd centile), the mean head circumference of the group was on the 50th centile. Motor milestone delay was usual, the cohort having a mean age of sitting unsupported of 10 months and walking of 21 months. Abnormal vision (94%) and hearing (40%) were frequent findings, but 89% of the group were attending normal primary or secondary schools. Other associations included undescended testicles (77%), hepatosplenomegaly (50%), and evidence of abnormal bleeding (56%). The mean age at diagnosis of Noonan syndrome in this group was 9.0 years. Earlier diagnosis of this common condition would aid both clinical management and genetic counselling.

Adolescent↗
PubMed1992

Myocardial disarray in Noonan syndrome.

OBJECTIVE: To characterise the histopathology of the left ventricular hypertrophy commonly associated with Noonan syndrome by assessing the extent of myocyte disarray and therefore to define one aspect of the relation between this disease and idiopathic hypertrophic cardiomyopathy. DESIGN: Blinded histological analysis. SETTING: Hospital medical school. PATIENTS: Six hearts of children with the Noonan phenotype and isolated ventricular hypertrophy were compared with age and sex matched controls. METHODS: Histological analysis was performed with an image analyser under light microscopy. Representative sections from the entire left ventricular free wall were examined. Results were expressed as the percentage of fields showing disarray related to the number of fields evaluated: 100 fields were examined for each patient. RESULTS: In the patients with Noonan syndrome myocardial disarray was present in the ventricular septum in 24 (5.7)% (mean (SD)) of fields and in the free wall in 22.2 (6.8)%. In the controls disarray was present in the septum in 3.8 (2.3)% of fields and in the free wall in 2.4 (2.8)%. In both regions the extent of disarray was significantly greater in patients with Noonan syndrome (p < 0.0005; 95% confidence interval 14 to 26.3 for the septum: p < 0.005, 95% confidence interval 11.4 to 28.2 for the free wall). CONCLUSIONS: The ventricular hypertrophy associated with Noonan syndrome is histologically similar to hypertrophic cardiomyopathy but whether the two diseases are the expression of the same genetic defect remains to be determined.

Child↗
PubMed1992

Autosomal dominant palmoplantar hyperkeratosis and sensorineural deafness in three generations.

A family is presented with autosomal dominant progressive palmoplantar hyperkeratosis, which is invariably associated with a slowly progressive, bilateral, high frequency, sensorineural hearing loss. The family show no other ectodermal abnormality. The differential diagnosis and possible mechanisms are discussed. This family appears to represent a unique variant in the hyperkeratosis-deafness association.

Adult↗
PubMed1992

Absence of linkage of Noonan syndrome to the neurofibromatosis type 1 locus.

Eleven families with Noonan syndrome in either two or three generations have been identified. Following the reports of subjects with features of both Noonan syndrome and neurofibromatosis type 1, these pedigrees have been studied using a number of probes at the neurofibromatosis type 1 locus (17q11). A significantly negative lod score was obtained with the intragenic probe NF1-C2, suggesting that the genes for Noonan syndrome and neurofibromatosis type 1 are not contiguous.

Alleles↗
PubMed1992

Balanced translocation (14;20) in a mentally handicapped child with cystinuria.

A mentally handicapped 3 year old child with cystinuria is presented. Routine chromosomal analysis showed an apparently balanced de novo translocation in the child with breakpoints 14q22 and 20p13. Family studies suggested that the child is a type I/type II compound heterozygote for cystinuria. This translocation may indicate a possible locus for the gene for cystinuria.

Child, Preschool↗
PubMedDate not supplied

Pulmonary manifestations of pediatric HIV infection.

Vertically acquired HIV infection is becoming increasingly common in India. The main clinical manifestations of HIV in childhood are growth failure, lymphadenopathy, chronic cough and fever, recurrent pulmonary infections, and persistent diarrhoea. Pulmonary disease is the major cause of morbidity and mortality in pediatric AIDS, manifesting itself in more than 80% of cases. The most common causes are Pneumocystis carinii pneumonia (PCP), lymphocytic interstitial pneumonitis (LIP), recurrent bacterial infections which include bacterial pneumonia and tuberculosis. The commonest AIDS diagnosis in infancy is PCP, presenting in infancy with tachypnea, hypoxia, and bilateral opacification on chest-X-ray (CXR). Treatment is with cotrimoxazole. LIP presents with bilateral reticulonodular shadows on CXR. It may be asymptomatic in the earlier stages, but children develop recurrent bacterial super infections, and can progress to bronchiectasis. LIP is a good prognostic sign in children with HIV infection in comparison to PCP. HIV should be considered in children with recurrent bacterial pneumonia, particularly with a prolonged or atypical course, or a recurrence after standard treatment. Pulmonary TB is common in children with HIV, but little data is available to guide treatment decisions. Much can be done to prevent PCP and bacterial infections with cotrimoxazole prophylaxis and appropriate immunisations, which may reduce hospital admissions and health care costs.

Child↗