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Biomedical subjects

A W Craft

Publications and source records attributed to A W Craft.

At least 127 records · Page 7Linked to original sources

Nephrotoxicity after ifosfamide.

Eleven children and adolescents with previously normal renal function who received ifosfamide for the treatment of extrarenal solid tumours underwent detailed investigation of glomerular and renal tubular function to assess the incidence and extent of renal damage. None had received cisplatin. Glomerular filtration rate (measured by plasma clearance of 51Cr labelled edetic acid) was reduced in six children. All 11 patients had evidence of proximal, and six of distal, tubular damage. Proximal tubular toxicity was indicated by phosphaturia and hypophosphataemia (n = 4), glycosuria (n = 5), increased urine beta 2 microglobulin excretion (n = 11), and generalised aminoaciduria (n = 10); distal tubular damage caused a reduction of the osmolality of the urine in an early morning sample. Two children developed clinical hypophosphataemic rickets, and one of these also had severe nephrogenic diabetes insipidus. Glomerular and tubular nephrotoxicity are common and potentially serious complications of ifosfamide treatment in children.

Adolescent↗

Virus infections in bone marrow transplant recipients: a three year prospective study.

Over three years 81 consecutive bone marrow transplant recipients (32 allogeneic and 49 autologous) who received prophylaxis with acyclovir, were studied for symptomatic virus infection. Thirty nine infections were documented in a total of 28 patients. Thirty two infections were mild, five were moderately severe, and two were severe. Cytomegalovirus infection occurred in only six allogeneic recipients. Herpes simplex virus and varicella zoster virus infections occurred infrequently. Seven patients who were considered at the time of death to have died due to an infectious cause were studied virologically at necropsy. In only one patient was a virus infection thought to have been the cause of death. Prophylaxis with acyclovir may have influenced the rate and clinical prominence of herpes virus infections. In this study viruses were considered to have had a relatively minor role in causing morbidity and mortality.

Acyclovir↗

Biochemical screening for neuroblastoma in infants: a feasibility study.

Neuroblastoma is the most common solid tumour of childhood with an incidence of about 1:10,000 births. Prognosis depends on age and stage at presentation and for disseminated disease presenting after the age of 1 year has scarcely altered at all in the past 20 years. In Japan a method has been pioneered of mass population screening of 6-month-old babies using a urine test for the catecholamine metabolites vanillylmandelic acid and homovanillic acid. They have been able to detect the majority of cases at 6 months and have improved the overall prognosis from 25% to 75% survival. A pilot study to assess the feasibility of such a study in the UK has been carried out in the north of England. Methodology has been established for the collection of urine by health visitors and biochemical analysis by gas chromatography with both flame ionisation and mass spectrometry detection; 4,897 samples have been collected, and reference ranges have been established.

Chromatography, Gas↗

Toxicity of high-dose ifosfamide in children.

Ifosfamide has been shown to be an active agent in the treatment of several childhood cancers. However, the optimal dose and method of administration remains to be established. The dose/response relationship of ifosfamide suggests that a maximum tolerable, fractionated dose be given, and to reduce hospitalisation this dose should be given in the shortest possible time. A total of 20 patients aged 1-23 years received 124 courses (mean, 6 courses/patient; range, 1-16); 9 subjects had either relapsed or resistant disease, and all of these had previously received cyclophosphamide. A dose of 3 g/m2 ifosfamide was given for 2 (five patients) or 3 (15 patients) successive days. In all, 9 patients received the drug twice daily as a bolus and 11 were given a continuous infusion. All patients received 3 g/m2 mesna per day with ifosfamide and for 12 h there after, and hydration was maintained with 3 l/m2 fluid daily. Myelosuppression occurred in all patients but was mild and reversible, with no toxic deaths. On four occasions in three patients treatment had to be delayed due to myelosuppression. Seven episodes of fever and neutropaenia were successfully treated with antibiotics. The mean glomerular filtration rate in 13 patients at the start of treatment was 104 ml/min per 1.73 m2 and at the end was 92 ml/min per 1.73 m2. In all, 19 patients had microscopic and 1 macroscopic haematuria, with no clinical sequelae. Two patients with grossly impaired renal function following previous cisplatin therapy may have been precipitated into terminal renal failure by the ifosfamide therapy. Only one person developed neurotoxicity, which recurred on further treatment with ifosfamide but was fully reversible. All patients had moderate to severe vomiting, which was controlled with anti-emetics. No abnormalities of liver or cardiac function were detected. We conclude that ifosfamide given by this schedule is safe in patients with normal renal function.

Adolescent↗

Chromosome 22 abnormalities in Ewing's sarcoma.

A child with disseminated Ewing's sarcoma underwent cytogenetic investigations which showed different structural rearrangements of chromosome 22 at diagnosis (?ring22), and at relapse [t(10;22)], but the classic translocation t(11;22) was not detectable. This case provides further evidence of the importance of chromosome 22 in this disease, while raising some questions about the central importance of the translocation between chromosomes 11 and 22.

Bone Neoplasms↗

Three decades of chemotherapy for childhood cancer: from cure 'at any cost' to cure 'at least cost'.

The prognosis for childhood malignancy has improved substantially over the last 30 years. This has been principally due to the use of chemotherapy, centralization of care and treatment by standard protocols. With increasing numbers of children and adolescents cured of cancer there has been an increased awareness of the late effects of therapy. The recent recognition of disease-specific prognostic factors has permitted the subclassification of tumours into good and bad risk. The aim for those malignancies associated with a good outcome is the reduction of late adverse effects, eg intellectual impairment in children with acute lymphoblastic leukemia receiving central nervous system irradiation. In those diseases which have a poor prognosis with present therapy, new innovative and intensive regimens are being investigated in randomized trials. Neuroblastoma is a chemosensitive tumour but there has been little success in translating response into improvements in long-term cure. In poor prognosis neuroblastoma conventional combination chemotherapy, high dose therapy with autologous bone marrow rescue as consolidation and more recently high dose, or high dose rapid schedule, chemotherapy as initial treatment have been sequentially evaluated. In paediatric brain tumours only now are well designed phase II studies being undertaken and problems associated with the classification and evaluation of response to therapy are being addressed. In the past 30 years much of the success with childhood cancer has been largely empirical and the hope for the future is that there will be a more scientific approach to the chemotherapy of childhood malignancy.

Antineoplastic Agents↗

Intestinal permeability during chemotherapy for childhood tumours.

The intestinal permeability to mannitol and lactulose was measured in 29 children receiving treatment for solid tumours. At the time of study they had no gastrointestinal symptoms and appeared clinically well. However, there was a significant reduction in the absorption of mannitol when compared to normal children. This small bowel dysfunction may result in malabsorption of nutrients and drugs. There was a significant correlation between decreased mannitol absorption and low nutritional status.

Adolescent↗

Clostridium difficile in an oncology unit.

In one year 21 new cases of Clostridium difficile infection occurred on a paediatric oncology unit. Eleven cases were in a two month period. This infection should be regarded as a communicable disease. Investigations to detect C difficile should be carried out in children with malignant disease who have diarrhoea.

Adolescent↗

Cytogenetic investigations of solid tumours of children.

The association of non-random chromosome abnormalities with solid tumours of childhood may improve accuracy of diagnosis and prognosis and lead to a better understanding of their biology. In a pilot study in the Northern region of England fresh tumour biopsy specimens were obtained from 39 to 72 consecutive solid tumours in children who presented over a period of 21 months. Cytogenetic analysis was possible in 33 and clonal chromosomal abnormalities were detected in nine. In addition, seven of 10 tumours investigated after treatment were abnormal. Ten of these 16 abnormal karyotypes have not previously been described. This pilot study has shown that a concerted investigation of tumour cytogenetics is possible. A multicentre study is essential if our knowledge of basic tumour cytogenetics is to progress.

Biopsy↗

Globe luxation in histiocytosis X.

A boy with histiocytosis X, first diagnosed at the age of 9 months, presented at the age of 5 years with left globe luxation. Under general anaesthesia the globe was reduced and a temporary paracentral tarsorrhaphy carried out. He was started on a course of oral steroids. Two years later he had normal visual acuity, full ocular movements, and healthy fundi.

Child, Preschool↗