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Biomedical subjects

A W Craft

Publications and source records attributed to A W Craft.

At least 73 records · Page 4Linked to original sources
PubMed1995

Granisetron as antiemetic therapy in children with cancer.

The safety and efficacy of the new 5HT-3 antagonist granisetron as an antiemetic in children with cancer was evaluated in 40 children at a single dose of 40 micrograms/kg. No adverse affects attributable to the granisetron were noted. The overall major and complete response rate was 82.5% and this was highest in the younger children. Only 2 patients showed no response. Pharmacokinetic studies showed associations between some pharmacokinetic parameters and age which were no longer apparent after normalisation for body weight. Granisetron is an effective and very well-tolerated antiemetic and appears to be an important addition to the supportive care available for children with cancer.

Adolescent↗
PubMed1995

Osteogenic sarcoma of the neural arch.

Osteogenic sarcoma arising in the spine, and in particular the neural arch, is rare. We present the case of a 4-year-old girl with an osteogenic sarcoma arising in the left transverse process of the second lumbar vertebra. The child received chemotherapy and delayed surgical excision was performed following a favourable response. The radiological features and differential diagnosis are discussed.

Child, Preschool↗
PubMed1994

False positive results in a neuroblastoma screening programme.

Twenty thousand, eight hundred and twenty-nine babies were screened for neuroblastoma at 6 months of age by measuring homovanillic (HVA) and vanillylmandelic (VMA) acid in urine and rationing these to creatinine. Using a "cut off" of the mean + 3 SD, 10 were found to be positive. Two were found on evaluation to have neuroblastoma and in the remaining 8 the raised levels of HVA and/or VMA returned to normal. Only one of the 8 false positive babies was absolutely normal, most having a chronic disorder or illness. Utilising new centiles which relate HVA and VMA to creatinine, only 3 of the 8 would have remained positive, a false positive rate of 0.01%. The false negative rate would have remained unchanged.

Creatinine↗
PubMed1994

Cytogenetic abnormalities of small round cell tumours.

Between 1987 and 1991, cytogenetic studies were carried out on small round cell tumours of 68 patients from the Northern Health Region of England. Clonal chromosome abnormalities were found in 30, comprising 15 neuroblastomas, 7 Ewing's tumours, 7 rhabdomyosarcomas, and 1 granular cell tumour. Characteristic rearrangements were found in five cases of Ewing's tumour [all with translocation t(11;22) (q24;q12)] and in four cases of rhabdomyosarcoma [all with evidence of translocation t(2;13) (q35-37;q14)]. In one case of Ewing's tumour and three of rhabdomyosarcoma, the cytogenetic findings were important in diagnosis. Within the neuroblastomas, examples were found of hyperdiploidy, 1p rearrangements, double minute chromosomes, and homogeneously staining regions, but too few cases were available for prognostic associations to be assessed. Our findings confirm the diagnostic importance of chromosome abnormalities in small round cell tumours and indicate that cytogenetic analysis should be an intrinsic part of the initial investigations of all patients with such tumours.

Adolescent↗
PubMed1994

Changing causes of septicaemia in paediatric oncology patients: effect of imipenem use.

One hundred and fifty-four episodes of septicaemia occurred in 78 patients on a Paediatric Oncology Unit over 2 years. Septicaemias with Gram-positive bacteria were more common than with Gram-negative organisms, coagulase-negative staphylococci (CNS) being the commonest pathogens. The mortality rate in patients with septicaemia was 1.9%. Azlocillin and gentamicin comprised the first-line of empirical antibiotic therapy for suspected infection for the first 10 months of the study; imipenem with cilastatin, as monotherapy, was used subsequently. More isolates of enterococci, and fewer isolates of Enterobacter, were seen after the introduction of imipenem. The use of imipenem was associated with an increased frequency of resistance to flucloxacillin in CNS. Such strains have been shown to contain sub-populations of cells that are resistant to imipenem. A clinical response was achieved in 82.9% of septicaemic episodes treated with imipenem, compared with 62.7% for azlocillin and gentamicin. However, imipenem as monotherapy may not be appropriate in central venous catheter related infections, owing to the frequent occurrence of imipenem-resistant organisms, CNS and Pseudomonas spp., in this situation.

Bacteremia↗
PubMed1994

Inaccuracy of glomerular filtration rate estimation from height/plasma creatinine ratio.

Use of a height/plasma creatinine formula to estimate glomerular filtration rate (GFR) is simpler and less invasive than renal or plasma clearance methods. The aim of this study was to determine whether these formulas enabled accurate prediction of GFR measured from the plasma clearance of 51Cr labelled ethylenediaminetetra-acetic acid (51Cr-EDTA). Thirty nine patients underwent GFR measurement at least six months after potentially nephrotoxic chemotherapy. Altman-Bland analysis was performed on the measured GFR and that estimated simultaneously using the original and a modified Counahan-Barratt formula and the Schwartz formula. The limits of agreement of the estimated GFR with the measured GFR were unacceptably wide in each case, despite highly significant correlation coefficients. The bias was smallest for the modified Counahan-Barratt formula. Use of these formulas to estimate GFR in children is insufficiently accurate for research purposes and has limitations in clinical practice. Furthermore, use of correlation coefficients to evaluate different methods of measuring GFR is inappropriate.

Adolescent↗
PubMed1993

Geographical distribution of preconceptional radiation doses to fathers employed at the Sellafield nuclear installation, West Cumbria.

OBJECTIVE: To examine whether the geographical distribution of births associated with preconceptional exposure of fathers to radiation at the Sellafield nuclear installation is consistent with the suggestion that this exposure explains the excess of childhood lymphoid malignancy in the adjacent village of Seascale. DESIGN: Retrospective birth cohort study. SETTING: Cumbria, West Cumbria health district, and Seascale civil parish. SUBJECTS: The 10,363 children born in Cumbria during 1950-89 to fathers employed at Sellafield. MAIN OUTCOME MEASURES: The doses of external whole body ionising radiation received by fathers at Sellafield in the total time and in the six months before conception of their children; the proportions of the collective doses associated with Seascale and the rest of West Cumbria. RESULTS: 9256 children were born to fathers who had been exposed to radiation before the child's conception. Of these, 7318 had fathers who were exposed in the six months before conception. Overall 7% (38 person-Sv) of the collective total preconceptional dose and 7% (3 person-Sv) of the collective dose for the six months before conception were associated with children born in Seascale. Of all the children whose fathers worked at Sellafield, 842 (8%) were born in Seascale. The mean individual doses before conception were consistently lower in Seascale than in the rest of West Cumbria. CONCLUSIONS: The distribution of the paternal preconceptional radiation dose is statistically incompatible with this exposure providing a causal explanation for the cluster of childhood leukaemias in Seascale.

Adult↗
PubMed1993

Cancer in Cumbria and in the vicinity of the Sellafield nuclear installation, 1963-90.

OBJECTIVE: To reappraise the epidemiological findings reported by the Black Advisory Group concerning a possible excess of malignant disease, particularly of childhood acute lymphoid leukaemia and non-Hodgkin lymphomas, in the vicinity of the Sellafield nuclear installation, and to determine whether any excess of malignant disease had occurred among people aged 0-24 years in the area in the years after the Black report--that is, from 1984 to 1990. DESIGN: Calculation of incidence of cancer using data from population based cancer registries and special surveys. SETTING: England and Wales; county of Cumbria; county districts Allerdale and Copeland within Cumbria; Seascale ward within Copeland. SUBJECTS: All residents under the age of 75 years in the above areas, but with particular reference to those aged 0-24 years. MAIN OUTCOME MEASURES: Numbers of cases and incidence particularly of lymphoid leukaemia and non-Hodgkin lymphomas in those aged 0-24 years, but including other cancers and age groups. RESULTS: Previous reports of an increased incidence of cancer, especially of leukaemia, among those aged 0-24 years in Seascale during the period up to and including 1983 are confirmed. During 1984-90 there was an excess of total cancer among those aged 0-24 years. This was based on four cases including two cases of non-Hodgkin lymphoma but none of leukaemia. There was an increased, but nonsignificant, incidence of other cancers, based on two cases (one pinealoma and one Hodgkin's disease) occurring among those aged 15-24 years during 1984-90. This was not observed in the younger age group or in previous years. For the immediately surrounding area--that is, the county districts of Allerdale and Copeland excluding Seascale and in the remainder of Cumbria--there was no evidence of an increased incidence of cancer among those aged 0-24 years in either period. CONCLUSIONS: During 1963-83 and 1984-90 the incidence of malignant disease, particularly lymphoid leukaemia and non-Hodgkin lymphomas, in young people aged 0-24 in Seascale was higher than would be expected on the basis of either national rates or those for the surrounding areas. Although this increased risk is unlikely to be due to chance, the reasons for it are still unknown.

Adolescent↗
PubMed1993

Chemotherapy in the management of infantile fibrosarcoma.

Infantile fibrosarcoma (IF) has traditionally been treated with surgery, which may have considerable morbidity. Chemotherapy has been suggested in order to reduce the need for extensive surgery. Nine children with histologically confirmed IF who received chemotherapy are described. Six children were treated with chemotherapy initially, two following conservative surgery, and one following recurrence after surgery. All received vincristine (V) and actinomycin D (A), and six received additional drugs including ifosfamide (I), cyclophosphamide (C), adriamycin (Ad), etoposide (E), and cisplatinum (CDDP). Objective responses were achieved in eight: three responded completely (CR), two responded partially (PR), which allowed conservative surgery, one had stable disease, one had an initial PR, but subsequently had tumour recurrence 1 month after cessation of treatment, necessitating further surgery and chemotherapy, and one had an initial PR but died following local and regional metastases. One child had no response to chemotherapy but is alive with stable residual disease. Thus, five of nine children achieved a CR--three with chemotherapy alone. With the inclusion of chemotherapy as part of their treatment, five children, for whom curative surgery may have resulted in amputation, remain alive with limbs intact. Chemotherapy including V and A should be given to infants with fibrosarcoma in whom curative surgery would be mutilating.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

Low dose continuous infusion doxorubicin in children and young adults.

Ten patients (age range 3.2-26.3 yrs) with relapsed or resistant malignancies received a total of 20 courses of low dose continuous infusion doxorubicin (3 mg/m2/day for 28 days) delivered by portable Graseby infusion pumps via central venous catheters. Each patient received a median dose of 144 mg/m2 (range 87-261). Four patients responded to treatment (1 complete response (CR) and 3 partial response (PR)) and performance status improved in seven patients. Overall toxicity was minimal: WHO Grade 4 anaemia in 2/18 courses, Grade 4 neutropenia in 1/18, Grade 3-4 thrombocytopenia in 3/18, nausea and vomiting of Grades 2 and 4 in 4/20 and 1/20 respectively, and mucositis of Grades 2 and 4 in 2/20 courses each. Cardiac toxicity was assessed using echocardiography, and fractional shortening remained within normal limits in all patients. Low dose continuous infusion doxorubicin is a feasible, well tolerated, ambulatory therapy in children and may be an effective way of delivering doxorubicin with less toxicity, thus enabling the development of more dose intensive regimens.

Adolescent↗
PubMed1993

Prohibitive toxicity of a dose-intense regime for metastatic neuroblastoma containing ifosfamide, doxorubicin and cisplatin.

Three patients with stage 4 neuroblastoma were treated with a schedule comprising alternating modules of myelosuppressive (ifosfamide, etoposide, doxorubicin) and less myelosuppressive (vincristine, cisplatin) drugs given every 10 days regardless of the neutrophil count. A partial response was seen in two patients, and a very good partial response, in one patient. Extensive blood-component support was required. Non-haemopoietic toxicity was severe and led to treatment delays in two patients. Ifosfamide-related encephalopathy was seen in one patient and nephrotoxicity, in two patients. Mucositis was severe in two patients, may have contributed to the high rate of sepsis observed, and precluded the use of doxorubicin in one patient. As ifosfamide and doxorubicin were felt to be responsible for much of the toxicity, a subsequent schedule did not include these agents.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

Myxoid liposarcoma of the porta hepatis in childhood.

Liposarcoma in childhood is rare. A case of a myxoid liposarcoma arising at the porta hepatis is reported in a 3-year-old boy with initial favourable response to surgery combined with radio- and chemotherapy. Fatal recurrence occurred at age 15 years. The radiological and sonographic findings of liposarcomas are reviewed.

Child, Preschool↗
PubMed1993

T cell function in children with acute lymphoblastic leukaemia.

Modern intensive chemotherapy has dramatically improved the prognosis of acute lymphoblastic leukaemia (ALL) in children. However, once remission has been established, quality of life and even survival may be threatened by exacerbation of viral infections in the prolonged period of continuation therapy necessary to prevent relapse. Often the viruses involved in the most severe infections are from the herpesvirus and paramyxovirus groups, suggesting that patients suffer from a defect in the cellular immunity thought essential to control such cell-associated infections. This may result from a T cell defect and, in this study, T cell responsiveness of patients under therapy for leukaemia has been investigated. In vitro proliferative responses of peripheral blood leucocytes (PBL) to the T cell mitogen phytohaemagglutinin (PHA) were impaired in children with ALL before treatment and in the induction of remission. Impairment was attributable to reduced T cell numbers, the presence of inhibitors in the patient's serum and direct damage to lymphocytes. On achieving remission, proliferative responses to PHA of both CD4+ and CD8+ T cell subsets quickly returned to normal levels with the switch to continuation chemotherapy. Proliferative responses to Herpes simplex virus antigens were also apparently normal in the majority of patients tested in remission. Further investigations, however, have suggested a persisting defect in CD8+ lymphocyte function. Gamma interferon secretion by PHA-stimulated PBLs was severely reduced for children with ALL in remission when compared with control children of similar age. Further, cytotoxic T lymphocyte responses to allogeneic cells could only be induced in PBL isolated from two of 13 children in remission from ALL whilst all control children of similar age and adults produced anti-allogeneic responses.

Adolescent↗