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Biomedical subjects

J Pritchard

Publications and source records attributed to J Pritchard.

At least 217 records · Page 12Linked to original sources

A phase II study of ifosfamide in children with recurrent solid tumours.

Twenty children with recurrent or unresponsive tumours (10 Wilms', 3 rhabdomyosarcoma, 4 Ewings's, 1 osteosarcoma, 1 hepatoblastoma, 1 hepatoma) and one untreated patient with renal carcinoma were given ifosfamide as a 24-h infusion (5 mg/m2), with mesna as uroprotective. The number of courses ranged from 1 to 13 (median 3), and the interval between them was 2-3 weeks. Sixteen of these patients had previously received cyclophosphamide. Complete clinical responses were seen in 3 cases (2 Wilms' and 1 Ewing's) and lasted 5, 7, and 9 months. Partial responses were seen in 3 instances, mixed response or stable disease in 4, and progressive disease in 11. Treatment was well tolerated in most patients, with no cystitis or severe myelosuppression, but 2 children developed transient neurological symptoms and 1 became hypertensive. Nausea and vomiting were controlled by high-dose dexamethasone in most children. Plasma ifosfamide levels were estimated by means of gas-liquid chromatography in 10 patients. Peak concentrations ranged from 38 to 125 micrograms/ml (median 80). The elimination half-life, at 2.5-5.2 h (median 3.2) was shorter than previously reported in adults. Future studies should test the possibility that ifosfamide-containing combination chemotherapy may be more effective than the regimens, usually including cyclophosphamide, that are currently used as front-line treatment of embryonal and Ewing's sarcoma.

Adolescent↗

Renal toxicity of cisplatin in children.

We measured renal function in 22 children receiving cisplatin as initial treatment for neuroblastoma or malignant germ cell tumors. Glomerular filtration rates were estimated from the plasma clearance of 51Cr-EDTA and were compared with measurements of plasma creatinine concentration and creatinine clearance. The degree of cisplatin-induced renal damage varied widely, and plasma creatinine measurements and creatinine clearances were not reliable guides to glomerular filtration rate. Renal function in children receiving cisplatin should be monitored by measurement of glomerular filtration rate with an isotope clearance technique.

Albuminuria↗

Ovine hydatidosis: some immunological characteristics of the seronegative host.

The immune status of a group of sheep naturally infected with hydatid cysts was investigated. Low specific anti-hydatid antibody (Sab) titres and negative results in intradermal and leucocyte migration tests occurred in hosts with high hydatid antigen-stimulated lymphocyte transformation (LT). Total (non-specific) IgG was elevated in infected sheep and was positively correlated with LT. Circulating hydatid antigen (cAg) was detectable in some infected sheep, but not in all of those with low Sab. Relationships between cAg, Sab and immune complex levels suggest that most cAg is present in immune complexes.

Animals↗

Histiocytosis X: an ophthalmological review.

Of 76 children with histiocytosis X 18 had orbital involvement, and four developed additional neuro-ophthalmic complications. No instance of intraocular involvement was detected. Among those patients with ophthalmic involvement the main problems were bilateral or unilateral proptosis, ptosis, papilloedema, optic atrophy, and seventh nerve palsy. Only one patient developed a severe visual defect. Management of the ophthalmological complications depends not only on the extent of the orbital disease but also on the degree of systemic involvement. Overall management by a paediatric oncologist is mandatory.

Child↗

Albendazole treatment of pulmonary hydatid cysts in naturally infected sheep: a study with relevance to the treatment of hydatid cysts in man.

Albendazole was given orally to sheep with naturally occurring live pulmonary and hepatic cysts. The viability of pulmonary cysts was established before treatment by thoracotomy and needle puncture. Both 10 and 20 mg/kg/day doses were found effective in that no viable protoscoleces were found after six weeks' treatment in either group while untreated controls still had viable cysts. In addition, treated animals showed macroscopic and electron microscopic changes. Bone marrow toxicity probably occurred in two sheep.

Albendazole↗

Spontaneous remission of multi-system histiocytosis X.

Two infants presented with biopsy-proven histiocytosis X affecting multiple sites. Since neither showed evidence of organ failure or of constitutional upset, no specific therapy was given. In each case there was long-lasting spontaneous regression of disease. Analysis of blood mononuclear cells revealed a raised T4:T8 (helper:suppressor T lymphocyte) ratio at diagnosis but a normal ratio during remission. These observations support the argument that multi-system histiocytosis X, even in infants (Letterer-Siwe disease), is not a malignancy and that an "expectant" treatment policy may be indicated in selected patients.

Biopsy↗

Beta globin messenger RNA content of bone marrow erythroblasts in heterozygous beta-thalassemia.

RNA from bone marrow erythroblasts and peripheral blood reticulocytes of patients with heterozygous beta-thalassemia was analyzed for relative content of alpha and beta globin messenger RNA by molecular hybrization. Erythroblasts from nonthalassemic patients exhibited approximately the same alpha and beta globin mRNA content (beta/alpha mRNA ratio = 0.8-1.0) as circulating reticulocytes (beta/alpha mRNA ratio = 0.74-1.2). The mRNA ratios corresponded well to levels of globin synthesis observed in bone marrow and peripheral blood. Erythroblasts from four patients with heterozygous beta-thalassemia also exhibited approximately the same beta/alpha mRNA ratios in bone marrow erythroblasts (0.34-0.59) as in reticulocytes (0.34-0.4): beta globin mRNA was clearly deficient in bone marrow erythroblasts. Globin biosynthesis by erythroblasts of beta-thalassemia heterozygotes was balanced despite the mRNA deficiency (beta/alpha = 0.9-1.0), suggesting that post-translational phenoma (eg, proteolysis of free globin chains), rather than instability of beta mRNA, accounts for the balanced globin chain synthesis frequently observed in bone marrow erythroblasts of patients with beta-thalassemia trait.

Adult↗

Immunolocalization of neuroblastoma using radiolabeled monoclonal antibody UJ13A.

The monoclonal antibody UJ13A, raised after immunization of mice with human fetal brain, recognized an antigen expressed on human neuroblastoma cell lines and fresh tumors. Antibody was purified and radiolabeled with iodine isotopes using chloramine-T. In preclinical studies, 125I-labeled UJ13A was injected intravenously into nude mice bearing xenografts of human neuroblastoma. Radiolabeled UJ13A uptake by the tumors was four to 23 times greater than that by blood. In control animals, injected with a similar quantity of a monoclonal antibody known not to bind to neuroblastoma cells in vitro (FD44), there was no selective tumor uptake. Nine patients with histologically confirmed neuroblastoma each received 100 to 300 micrograms UJ13A radiolabeled with 1 to 2.8 mCi 123I or 131I. Sixteen positive sites were visible on gamma scans 1 to 7 days after injection: 15 were primary or secondary tumor sites, and one was a false positive; there were two false negatives. In two of the 15 positive sites, tumor had not been demonstrated by other imaging techniques; these were later confirmed as areas of malignant infiltration. No toxicity was encountered.

Adolescent↗

Autologous bone marrow transplantation contributes to haemopoietic recovery in children with solid tumours treated with high dose melphalan.

During a 5 year period, 64 children with advanced stage malignant solid tumours have been treated with high dose melphalan (140-220 mg/m2) combined with non-cryopreserved autologous marrow transplantation. All children developed a profound neutropenia and thrombocytopenia following high dose melphalan. Both the duration of neutropenia (median 11 d) and the duration of thrombocytopenia (median 18 d) were related to the nucleated cell count of the reinfused marrow but neither appeared to be affected by the dose of melphalan. This suggests that the initial recovery of the peripheral blood count results from the engrafted autologous marrow. We conclude that autologous marrow transplantation accelerates haemopoietic recovery in children with solid tumours treated with high dose melphalan.

Adolescent↗

Advanced neuroblastoma: improved response rate using a multiagent regimen (OPEC) including sequential cisplatin and VM-26.

Forty-two children, all over one year of age, were given vincristine, cyclophosphamide, and sequentially timed cisplatin and VM-26 (OPEC) or OPEC and doxorubicin (OPEC-D) as initial treatment for newly diagnosed stage III or IV neuroblastoma. Good partial response was achieved in 31 patients (74%) overall and in 28 (78%) of 36 patients whose treatment adhered to the chemotherapy protocol, compared with a 65% response rate achieved in a previous series of children treated with pulsed cyclophosphamide and vincristine with or without doxorubicin. Only six patients, including two of the six children whose treatment did not adhere to protocol, failed to respond, but there were five early deaths from treatment-related complications. Tumor response to OPEC, which was the less toxic of the two regimens, was at least as good as tumor response to OPEC-D. Cisplatin-induced morbidity was clinically significant in only one patient and was avoided in others by careful monitoring of glomerular filtration rate and hearing. Other centers should test the efficacy of OPEC or equivalent regimens in the treatment of advanced neuroblastoma.

Adolescent↗

Spontaneous mesangiocapillary glomerulonephritis in Finn cross lambs from Alberta.

A spontaneous mesangiocapillary glomerulonephritis occurred in three, one to three month old Finnish Landrace cross lambs from a flock in northern Alberta. The ram was a purebred Finn sheep, and the ewes were Finn-Rambouillet and Finn-Suffolk-Rambouillet crosses. The lambs were found dead without previous clinical signs. Histologically there was marked thickening of glomerular capillary basement membranes, proliferation of mesangial cells, and peri-glomerular fibrosis. An interstitial infiltration of plasma cells and lymphocytes was present with occasional tubular degeneration and proteinaceous cast formation. Focal leukoencephalomalacia was present in one lamb. Electron microscopy demonstrated deposition of electron-dense deposits in a subendothelial location with occasional fusion of overlying foot processes in glomerular capillaries. Indirect immunofluorescence studies demonstrated positive staining material in glomerular capillary walls. These findings in Finnish Landrace cross lambs are characteristic of mesangiocapillary glomerulonephritis, a condition heretofore not reported in North America.

Animals↗

Combined measurement and significance of lipid-bound sialic acid and carcinoembryonic antigen in detection of human cancer.

We evaluated the clinical usefulness of lipid-bound sialic acid (LSA) as a "tumor marker" and assessed individual and carcinoembryonic antigen (CEA) in cancer patients. Serum LSA and CEA concentrations were measured by the resorcinol method after total lipid extraction and isolation of the sialolipid fraction, and by Abbott enzyme immunoassay procedures, respectively. Results indicate that the frequency of elevation and mean LSA values were highest in patients with lung cancer (318 mg/liter), intermediate in miscellaneous (210 mg/liter) and colorectal cancers (200 mg/liter), and lowest in breast cancer (175 mg/liter); while mean CEA values were highest in colorectal cancer (162.5 micrograms/liter), followed by lung (33.8 micrograms/liter), miscellaneous (30.3 micrograms/liter), and breast cancers (11.6 micrograms/liter). Statistically, LSA and CEA values for cancer patients were significantly (P less than 0.001) higher than for normal subjects. The combined measurement of LSA and CEA in serum provides better detection potential for cancer patients than either of the two markers alone.

Adult↗