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Biomedical subjects

A W Craft

Publications and source records attributed to A W Craft.

At least 109 records · Page 6Linked to original sources
PubMed1992

Poor prognosis neuroblastoma: is screening the answer?

Neuroblastoma is one of the most common solid tumours of childhood and is unique amongst paediatric cancers in that it results in the urinary excretion of catecholamine metabolites which are easily measured in spot urine samples and so is a condition for which screening may be considered. The continuing poor prognosis associated with late stage disease has stimulated great interest in this proposition. The Japanese have been undertaking pioneering studies of such screening since 1974 and since 1985, all 6 months old babies have been offered screening. Preliminary data would appear to suggest that screening is effective in greatly improving the survival of children with neuroblastoma. However there are difficulties associated with the interpretation of survival data since screening undoubtedly results in the detection of cases which would otherwise have remained 'silent', and the well known problems of lead-time and length-time bias complicate matters still further. The time is not yet ready for universal implementation of screening and further investigation is required.

Adult↗
PubMed1991

p53 germline mutations in Li-Fraumeni syndrome.

Germline mutations within a defined region of the p53 gene have recently been found in families with the Li-Fraumeni syndrome (LFS). In the present study this region of p53 was sequenced in affected individuals from 8 families with LFS. In only 2 of them were such mutations detected. Our findings suggest that the p53 mutation could be the primary lesion in some but not all families with LFS, and confirm that there is a "hot spot" for these mutations at the CpG dinucleotide moiety of codon 248. Assigning risks and counselling families on the basis of presence of p53 mutations should be approached with caution.

Adolescent↗
PubMed1991

Assessment of chemotherapy-associated nephrotoxicity in children with cancer.

Assessment of the toxicity caused by chemotherapy in children with cancer has become more important as the number of long-term survivors has continued to increase. It is vital to monitor both acute life-threatening adverse effects and long-term toxicity that may impair the child's development and cause permanent morbidity. Renal damage may follow treatment with cytotoxic drugs, especially cisplatin or ifosfamide, and lead to glomerular, proximal tubular or distal tubular impairment or to any combination of these. Greater understanding of nephrotoxicity and of its prevention may enable the use of more intensive schedules or of higher doses of potentially nephrotoxic chemotherapy. However, the evaluation of cytotoxic drug-induced nephrotoxicity has frequently depended mainly on measurement of the plasma creatinine concentration, which may remain normal despite substantial glomerular impairment or severe tubular dysfunction. Detailed assessment of nephrotoxicity depends on an understanding of normal renal physiology and requires evaluation of all aspects of function. A comprehensive but simple investigatory protocol that enables assessment of the nature and severity of nephrotoxicity in children is described, which can be performed without admission to hospital. Glomerular function is assessed by measurement of the glomerular filtration rate from the plasma clearance of [51Cr]-ethylenediaminetetraacetic acid ([51Cr]-EDTA). Proximal nephron function is evaluated in three ways: by measurement of the concentration of calcium, magnesium, phosphate, glucose and urate in blood and urine along with calculations of their fractional excretion and of the renal threshold for phosphate; by determination of the excretion in urine of low-molecular-weight proteins (e.g. retinol-binding protein); and by investigation of urinary bicarbonate excretion in patients who are acidotic. Distal nephron function is initially investigated by examination of the concentration (osmolality) and acidification (pH) of an early morning sample of urine. Finally, a group of general investigations is performed, including quantitation of urinary excretion of renal tubular enzymes (e.g. N-acetylglucosaminidase) and measurement of blood pressure.

Acid-Base Equilibrium↗
PubMed1991

Cytogenetic analysis of a congenital fibrosarcoma.

Congenital (infantile) fibrosarcoma is a rare soft tissue sarcoma occurring in children aged less than 5 years. We performed cytogenetic analysis on such a tumor, which had an abnormal karyotype: 48,XY, +11, +20. Three other reports of karyotypes in congenital fibrosarcoma describe similar cytogenetic changes, and a specific pattern of trisomies that may prove diagnostic for this tumor is beginning to emerge.

Fibrosarcoma↗
PubMed1991

The influence of serum methotrexate concentrations and drug dosage on outcome in childhood acute lymphoblastic leukaemia.

Sequential methotrexate (Mtx) absorption studies were undertaken in 127 children undergoing treatment for childhood non-T acute lymphoblastic leukaemia (ALL) to determine whether serum drug concentration, clearance and dosage affect event free survival (EFS). Higher serum concentration and area under the plasma concentration curve (AUC) were not associated with an improved EFS. Methotrexate clearance was not found to be of prognostic significance. Patients who tolerated only low 6-mercaptopurine (6-MP) doses because of neutropaenia and those who randomly were prescribed higher doses of Mtx had a lower rate of leukaemia relapse after the completion of therapy. This suggests that the use of maintenance therapy in maximally tolerated doses may be associated with an increased survival in childhood ALL.

Administration, Oral↗
PubMed1991

Dental caries and dental anomalies in children treated by chemotherapy for malignant disease: a study in the north of England.

Fifty-two children in remission from childhood cancer and 41 siblings underwent a full clinical and radiographic dental examination. All the children had received chemotherapy. The leukaemic patients had received radiotherapy also, but not involving the jaws. There was no significant difference in dental caries experience between the treated children and the siblings, but significantly more dental anomalies were detected radiographically in the treated group.

Abnormalities, Drug-Induced↗
PubMed1991

Cognitive function after two doses of cranial irradiation for acute lymphoblastic leukaemia.

The cognitive function of 23 children given cranial irradiation in a dose of 24 Gy was compared with that of 41 given 18 Gy. No significant differences were found in intellectual function or in mean number of intelligence quotient points lost between patients in the two treatment groups. A reduction in the dose of cranial irradiation does not seem to alleviate long term neuropsychological deficits.

Child, Preschool↗
PubMed1991

Choroidal involvement in lymphomatoid granulomatosis.

A 13-year-old boy with evidence of pulmonary lymphomatoid granulomatosis developed monocular diplopia. Fluorescein angiography revealed bilateral choroidal involvement. Following treatment with vincristine, cyclophosphamide, and prednisone his diplopia resolved and the angiographic appearances returned to normal.

Adolescent↗
PubMed1991

Urinary retention--an unusual dystonic reaction to continuous metoclopramide infusion.

Vomiting is one of the most distressing adverse effects of cancer chemotherapy. Metoclopramide by continuous infusion (400 micrograms/kg/h after a loading dose of 2.5 mg/kg) is a novel administration method for optimizing efficacy. A two-year-old boy developed urinary retention on three occasions, once accompanied by priapism and slurred speech, while receiving a continuous infusion. This was reversed by procyclidine, suggesting that it may have been a dystonic reaction.

Child, Preschool↗
PubMed1990

Lack of response of bone marrow, in vitro, to growth factors in congenital neutropenia.

Severe congenital neutropenia has a poor outlook. In vitro clonogenic assays using recombinant growth factors may improve understanding of the underlying pathogenetic mechanisms and identify those in whom growth factors might be clinically useful. Marrow from a boy with congenital neutropenia was cultured with a variety of recombinant growth factors. The results show that the neutropenia did not result from a lack of myeloid progenitors but that these progenitors could not produce mature neutrophils. Bone marrow transplantation is being considered as the most likely approach to correct neutropenia.

Agranulocytosis↗
PubMed1990

Local antibody production and respiratory syncytial virus infection in children with leukaemia.

Children undergoing therapy for acute lymphoblastic leukaemia (ALL) are at increased risk of severe viral respiratory infection, and some find it difficult to terminate virus secretion. This increased severity may result from a defect in the mucosal immune response. To test this hypothesis, nasal immunoglobulin secretion and specific antiviral antibody responses to infection with respiratory syncytial (RS) virus in children with ALL have been compared with those in a normal age-matched comparison group. Children with leukaemia secreted normal levels of IgA and slightly raised IgM levels. IgG levels were depressed. Following RS virus infection, the majority of children with leukaemia secreted normal amounts of IgA and IgG nasal antibody and successfully cleared the virus. However, three of the 13 children studied made poor or undetectable nasal antibody responses, which correlated with their inability to clear the virus.

Antibodies, Viral↗
PubMed1990

Gonadal function after 12-Gy testicular irradiation in childhood acute lymphoblastic leukaemia.

Gonadal function was assessed in 15 boys with acute lymphoblastic leukaemia (ALL) who had received testicular irradiation. The dose to the testes was 12 Gy in 12, 15 Gy in 1, and 24 Gy in 2 cases. All of those who had received 12 or 15 Gy had normal Leydig cell function, although high levels of gonadotropins suggest subclinical Leydig cell damage. The 2 who had 24 Gy had Leydig cell failure. All who were old enough to produce a semen specimen were azoospermic.

Adolescent↗
PubMed1990

Demonstration of Epstein-Barr viral DNA in formalin-fixed, paraffin-embedded samples of Hodgkin's disease.

The presence of Epstein-Barr virus (EBV) DNA in formalin-fixed, paraffin-embedded samples of Hodgkin's disease (HD) was investigated by Southern blot hybridization using a specific EBV Bam H1W fragment probe. DNA from 16 samples of HD in children and young adults was compared with that from ten samples in adults older than 45 years. A further eight cases of DNA extracted from fresh samples of HD were also studied, in order to compare the results obtained with fresh and fixed tissue samples. Hybridization was demonstrated in 15 of the 34 cases of HD studied in contrast to 3 or the 34 control specimens of non-Hodgkin's lymphoma, non-neoplastic lymph nodes, and carcinomas. No differences between the two age groups compared were found. The results of this study suggest that there is a definite association between EBV and HD, although the exact nature of this association remains to be established. It has also been shown that DNA of sufficient quality for the detection of EBV DNA can be extracted from formalin-fixed, paraffin-embedded material, and that comparable results can be obtained using DNA extracted from fresh and fixed tissue.

Adolescent↗
PubMed1990

Ototoxicity of cisplatinum in children and adolescents.

Twenty-two children and adolescents who had received cisplatinum for the treatment of solid tumours underwent audiometry to ascertain the extent of hearing damage. Five patients complained of hearing difficulties, causing difficulty at school in one child. Hearing loss greater than 20 decibels occurred in four patients at 1,000 Hz, seven at 2,000 Hz, 13 at 4,000 Hz and 21 at 8,000 Hz. Median hearing loss was greater at higher frequencies (P less than 0.0001), and with increasing cumulative dose of cisplatinum. However, a 'plateau' phenomenon was observed, with no apparent further deterioration in hearing loss at doses greater than 600 mg m-2. Two children who had received prior aural radiotherapy had severe hearing loss. Severe, mostly asymptomatic, ototoxicity is common in children given cisplatinum. However, there is considerable interpatient variability in the hearing loss suffered.

Adolescent↗