Adenoma of bronchiolar rest--a new entity.
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Adenoma↗
Biomedical subjects
A W Craft
Publications and source records attributed to A W Craft.
Creatinine related reference ranges for urinary homovanillic acid and vanillylmandelic acid at 6 months of age.
The relationship between homovanillic acid (HVA), vanillylmandelic acid (VMA), and creatinine in the urine of 6 month old babies has been studied and reference ranges in the form of centiles constructed for HVA and VMA against creatinine. Over 10,000 urine samples were collected from babies in four health districts in the north of England. HVA and VMA concentration, either independently or when divided by creatinine concentration, were dependent upon the absolute concentration of creatinine in the sample. After adjustment for creatinine significant differences in the mean concentration of HVA were found between sexes. No such differences were found for VMA. HVA and VMA were also found to be age dependent. Centiles were constructed using a procedure which makes no distributional assumptions about the data. The net effect of utilising these centiles was to increase the predictive value of a positive screening test from 20% to 40% without any increase in the false negative rate.
Creatinine↗
p53 expression in three separate tumours from a patient with Li-Fraumeni's syndrome.
The Li-Fraumeni cancer syndrome is a rare autosomal dominant syndrome, characterised by the occurrence of diverse mesenchymal and epithelial neoplasms at multiple sites. It has recently been shown that some of these individuals have a germ line mutation of the p53 tumour suppressor gene. The case of one member of such a family who has now developed three separate primary malignant tumours is reported. All three tumours expressed mutant p53 protein.
Adult↗
Cancer in young people in the north of England, 1968-85: analysis by census wards.
OBJECTIVE: To determine whether the seeming excess of childhood leukaemia and lymphoma identified in Seascale, Cumbria, UK, remains unusual when put into a wider context. DESIGN: Analysis of cancer incidence by geographical area. SETTING: The north of England including the Northern and North Western Regional Health Authority regions and the Southport and South Sefton districts of the Mersey Regional Health Authority. SUBJECTS: Altogether 6686 cases of malignant disease in people under 25 years old. MEASUREMENTS AND MAIN RESULTS: Cases of cancer diagnosed before their 25th birthday between January 1968 and December 1985 identified from three regional cancer registries were allocated to a census ward on the basis of 'usual place of residence'. Population data were derived from the 1971 and 1981 censuses, and the cancer incidence was calculated for each ward. Of the 6686 cases, there were 1035 cases of acute lymphoblastic leukaemia and 361 of non-Hodgkins lymphoma. Wards were ranked by cancer incidence and Poisson probability, using different population bases. Seascale ward is the most highly ranked ward for acute lymphoblastic leukaemia for the time periods 1968-85 or 1968-76. It is not the most highly ranked for non-Hodgkins lymphoma. However, combining acute lymphoblastic leukaemia and non-Hodgkins lymphoma incidence gives an even more extreme position for Seascale. The most extreme Poisson probability for any of the analyses was that for brain tumours in the electoral ward of Ashton St Michael, Tameside (p = 0.000009). CONCLUSION: The incidence of acute lymphoblastic leukaemia and non-Hodgkins lymphoma in the Seascale ward remains high when put into a wider context. For other cancers there are wards with even more extreme Poisson probability values.
Adolescent↗
Ifosfamide, mesna, and nephrotoxicity in children.
PURPOSE: With the increasing use of ifosfamide in pediatric malignancies, nephrotoxicity has emerged as a potentially serious adverse effect, which may be dose-limiting or may cause severe chronic morbidity, including glomerular impairment and/or Fanconi's syndrome. The purpose of this review was (1) to improve the documentation of ifosfamide nephrotoxicity in children, and (2) to consider the possible causative role of ifosfamide metabolites. DESIGN: (1) A grading system was developed that allowed documentation of the nature and severity of published reports of ifosfamide-induced nephrotoxicity, and evaluation of patient and treatment-related risk factors. (2) The relationship between the pharmacology of ifosfamide/mesna and nephrotoxicity was investigated by examination of published data, especially that concerning the quantitative differences in the metabolism of ifosfamide and its nonnephrotoxic structural isomer, cyclophosphamide. RESULTS: (1) Examination of 16 published reports (with assessable data from 40 children) demonstrated that ifosfamide-induced nephrotoxicity was associated with a wide range of patient ages and ifosfamide cumulative doses given by different administration schedules. (2) Chloroacetaldehyde, a major metabolite of ifosfamide only, may be at least partly responsible for the renal toxicity of this drug. Although mesna may be capable of detoxifying the toxic metabolite(s), delivery to the renal tubule may not be sufficient to provide adequate protection of tubular glutathione from depletion by the metabolite(s), which results in a failure to prevent nephrotoxicity. CONCLUSION: Increased understanding of the interindividual variability in the extent and nature of ifosfamide metabolism, which may be a major determinant of susceptibility to renal damage, may lead to improved use of the drug with less nephrotoxicity.
Child↗
The European Osteosarcoma Intergroup (E.O.I.) studies 1980-1991.
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Adolescent↗
Screening for neuroblastoma in the north of England.
OBJECTIVE: To determine the feasibility of establishing a system of screening for neuroblastoma. DESIGN: Prospective study of mass screening in four clearly defined geographical areas. SETTING: Four health districts of the Northern region of England. SUBJECTS: 20,829 babies aged 6 months, 92% of target population. INTERVENTIONS: Collection of urine on filter paper for analysis of content of homovanillic and vanillylmandelic acid in relation to urinary creatinine concentrations. MAIN OUTCOME MEASURES: Derivation of reference range. Identification of babies with homovanillic or vanillylmandelic acid > 3 SD above the mean (positive cases). Investigation of positive cases for evidence of neuroblastoma. RESULTS: The upper limit of normal (3 SD above the mean) for vanillylmandelic acid was 15 mumol/mmol creatinine and for homovanillic acid 24 mumol/mmol creatinine. Of the 20,829 babies screened, 2537 (12.2%) required a second sample to be taken because the first sample was inadequate. Of these, 527 (2.5%) provided a liquid urine specimen and 10 (0.04%) had positive results for neuroblastoma. Two of them had neuroblastoma (true positives) and eight did not (false positives). A further three children from the cohort were subsequently found to have neuroblastoma; they had raised homovanillic acid or vanillylmandelic acid values, or both, but screened negative at 6 months. CONCLUSIONS: Screening for neuroblastoma is possible in the health care system of the United Kingdom. Evaluation of the efficacy of screening in reducing the mortality from neuroblastoma requires a controlled trial.
Creatinine↗
Poisoning and child resistant containers.
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Child↗
Enterococcal superinfection in paediatric oncology patients treated with imipenem.
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Bacteremia↗
Comparison of saphenous versus jugular veins for central venous access in children with malignancy.
A retrospective analysis was carried out to compare the performance and complications of central catheters inserted into either the saphenous (27) or jugular (52) veins. The saphenous route may be preferred in certain circumstances including extensive mediastinal pathology, prior neck surgery, previous catheter(s), and cosmetic reasons. There was no difference in complications (local or systemic catheter-related infections, catheter occlusions, or venous thrombosis). The incidence of catheter removal due to complications was also not different between sites. Hence, the saphenous route can provide an additional portal of vascular access in selected patients.
Adolescent↗
High-dose rapid schedule chemotherapy for disseminated neuroblastoma.
In a high-dose schedule for disseminated neuroblastoma, eight courses of chemotherapy were administered every 10 days, regardless of myelosuppression, to eradicate tumour cells rapidly and reduce emergence of drug-resistant clones. Relatively non-myelotoxic vincristine and cisplatin were alternated with high-dose cisplatin-etoposide and cyclophosphamide-etoposide. Of 12 evaluable patients, there were 1 complete (CR), 3 very good partial (VGPR), 5 partial (PR) and 3 mixed responses (MR) 100 days after starting treatment. 6 out of 9 achieved a bone marrow CR at 40 days. 9 of 11 primary tumours were completely resected, after which 4 patients had CR, 3 VGPR (bone scan alone being abnormal), 4 PR and 1 mixed response (MR). Myelotoxicity was the major adverse effect. The only death was due to fungal infection. Clinically important renal dysfunction occurred in 3 patients. 4 had convulsions and 4 temporary hypertension. This schedule produced a rapid response and its toxicity, though serious, was manageable. Further evaluation is warranted.
Antineoplastic Combined Chemotherapy Protocols↗
Toxicity of single-day high-dose vincristine, melphalan, etoposide and carboplatin consolidation with autologous bone marrow rescue in advanced neuroblastoma.
16 unselected patients with advanced neuroblastoma were given high-dose consolidation chemotherapy with vincristine, melphalan, etoposide and carboplatin over 5 h followed by autologous bone marrow rescue. 3 patients died from treatment-related toxicity, 2 from disease, 1 is alive with disease and 10 are alive and disease-free a median of 12.5 months (range 2-38 months) after bone marrow rescue. All had bone marrow toxicity, most mucositis and 6 had seizures. Renal failure was unexpectedly severe. In the last 3 patients, administration of carboplatin was delayed by 18 h in an attempt to reduce renal damage. The results show that this regimen produces significant morbidity and has a high mortality. Although the overall outcome is encouraging, too few patients have been studied to gauge its efficacy. Whether such aggressive consolidation is necessary in heavily pretreated children with neuroblastoma remains unknown.
Adolescent↗
Memory after treatment for acute lymphoblastic leukaemia.
Long term survivors of acute lymphoblastic leukaemia (ALL) often experience cognitive difficulties, which may be related to impairment of memory function. Memory ability has been studied in a group of survivors of ALL along with sibling controls and in children who have received treatment for other forms of cancer. Children in the ALL group were found to have significant deficits in memory function in tasks which required the application of strategic planning behaviour. These deficits are potentially remediable by educational strategies.
Adolescent↗
Alveolar rhabdomyosarcoma infiltrating bone marrow at presentation: the value to diagnosis of bone marrow trephine biopsy specimens.
AIMS: To describe the histological appearances of bone marrow infiltrated with rhabdomyosarcoma at presentation and to determine their value in establishing the diagnosis. METHODS: Patients presenting over seven years in the northern health region of England with rhabdomyosarcoma were studied. Bone marrow aspirates and trephine biopsy specimens taken at presentation were examined. RESULTS: Seven of 32 patients with rhabdomyosarcoma had bone marrow infiltration, resulting in marrow failure in all cases, at diagnosis. The diagnosis was established in these seven by the typical cytological appearances and immunophenotype of the infiltrating cells (all seven patients) and cytogenetic abnormalities (three patients). Histological examination of the bone marrow showed a pseudoalveolar pattern with fibrous septal bands, enlarged vascular channels, and lack of cohesion of the tumour cells within the subdivided aggregates in all seven. In four cases multinucleate giant cells, often with peripherally sited nuclei, were found. CONCLUSIONS: These histological features of infiltrated marrow are so characteristic that the diagnosis of alveolar rhabdomyosarcoma can be made, or at least suspected, in many cases even without recourse to technically difficult and expensive further investigations. Bone marrow biopsy should be a routine part of the investigation of patients with bone marrow failure and will be of particular value in the diagnosis of those with disseminated alveolar rhabdomyosarcoma.
Adolescent↗
A comparison of two short intensive adjuvant chemotherapy regimens in operable osteosarcoma of limbs in children and young adults: the first study of the European Osteosarcoma Intergroup.
PURPOSE: A randomized pilot study was undertaken to assess the acute and chronic toxicities of two short intensive chemotherapy regimens, and to evaluate the feasibility of conservative surgery in this setting. Additional aims were to determine the clinical and radiologic response and the degree of histologic necrosis after chemotherapy. With extension of the study, eventual accrual was sufficient to compare disease-free survival (DFS) and overall survival (OS). PATIENTS AND METHODS: Between July 1983 and December 1986, the European Osteosarcoma Intergroup (EOI) entered 198 eligible patients with classic high-grade extremity osteosarcoma onto a randomized trial that compared doxorubicin (DOX) 25 mg/m2/d times three, intravenous (IV) bolus plus cisplatin (CDDP) 100 mg/m2, 24 hour infusion, every 3 weeks times six; the same combination was preceded 10 days earlier by high-dose methotrexate (HDMTX) 8 g/m2, 6-hour infusion, every 4.5 weeks times four. In the majority of patients (179), chemotherapy was commenced after biopsy; definitive surgery was scheduled at 9 weeks in both groups. RESULTS: Toxicities for both regimens did not differ substantially from those that occurred in other trials of adjuvant chemotherapy in osteosarcoma. Local recurrence (9%) and surgical complications (18%) after conservative surgery were acceptable. With a median follow-up of 53 months, DFS at 5 years is superior (P = .02) for DOX/CDDP, 57% versus 41%, although OS, 64% versus 50%, is not different significantly (P = .10). In a subset of 66 patients for whom pathologic data on the resected specimen were available, DFS (P = .003) and OS (P = .008) were better for those who demonstrated > or = 90% necrosis. CONCLUSION: A brief intensive chemotherapy regimen of DOX/CDDP has produced excellent long-term results, which are similar to those that have been achieved in cooperative group studies of longer, more complex multiagent chemotherapy, and provide the basis for a direct comparison in the next EOI study.
Adolescent↗
Screening for neuroblastoma in the northern region of England. Laboratory aspects.
Our pilot study for neuroblastoma screening started in 1986. The study has progressed through several phases, with use of several analytical methods to a procedure based primarily on the use of automated gas chromatography mass spectrometry. The northern region of England has a relatively static population of approximately 3.5 million, with an annual birth rate of 41,000. The region consists of 16 administrative health districts. In 4 years, we have screened 20,829 infants from four health districts. In this program, we screen all children at 6 months of age. A urine sample is collected on filter paper by a health visitor, either at the time of the infant's routine clinic visit or during the health visitor's follow-up visit at home. In the laboratory, the sample is dried and processed for analysis of homovanillic acid (HVA) and vanillylmandelic acid (VMA), using a benchtop Hewlett Packard gas chromatograph mass spectrometer. The results are related to the creatinine content of the urine. Using cut-off limits of 39 micrograms/mg of creatinine for HVA and 25 micrograms/mg of creatinine for VMA, 2,537 infants (12.2%) required a second paper sample and 527 infants (2.5%) were observed with a liquid urine collection. Of these, the conditions of nine infants with elevated levels of HVA or VMA were investigated clinically for the possible presence of neuroblastoma. Two infants were found to have neuroblastoma; the other seven showed no evidence of tumor. In addition, there were three children who, when screened at 6 months of age, had normal levels of HVA and VMA but in whom neuroblastoma subsequently developed.
Biomarkers, Tumor↗
A pilot study of screening for neuroblastoma in the north of England.
A pilot study has been carried out to assess the feasibility of screening for neuroblastoma in 6-month-old infants in the north of England. A total of 20,829 infants were screened. Two true-positive cases were found, along with eight false-positive and three false-negative cases. It was shown that the concentrations of catecholamine metabolites in the urine are dependent on the creatinine content; centiles have been established to allow this relationship to be taken into account. Five of the eight false-positive cases would have been correctly assessed as normal if the new centiles had been used. Preliminary results lend support to the need for a well-designed study of neuroblastoma screening to be carried out, with death from this disease as the only end point.
England↗
The influence of age on nephrotoxicity following chemotherapy in children.
Nephrotoxicity is an important adverse effect of chemotherapy in children. Renal function after treatment with either ifosfamide or cisplatinum in children aged 5 years or less ('younger children') was compared with that in those over 5 years ('older children'). Eighteen children (six younger, 12 older) given ifosfamide were studied after completion of chemotherapy, and 28 patients (16 younger, 12 older) were evaluated after cisplatinum. Glomerular filtration rate was measured from the plasma clearance of 51chromium-labelled edetic acid. Proximal tubular function was assessed by determination of plasma and urine calcium, phosphate, magnesium and glucose concentration; calculations of their fractional excretions, and of the renal threshold for phosphate; and measurement of urinary excretion of beta 2-microglobulin. Distal tubular function was evaluated by measurement of the early morning urine osmolality. Younger children had more severe proximal tubular toxicity than older children treated with ifosfamide, with significantly lower plasma phosphate concentrations and higher fractional excretions of glucose. However, there was no evidence of any such difference in glomerular or distal tubular damage after ifosfamide, and no difference in any aspect of renal function between younger and older children treated with cisplatinum. Increased proximal tubular toxicity after ifosfamide in younger children may have serious implications for future growth and development.
Age Factors↗