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Biomedical subjects

M J Coppes

Publications and source records attributed to M J Coppes.

89 records · Page 5Linked to original sources
PubMed1992

Oxygen therapy in sickle cell disease.

The effect of oxygen therapy on the number of irreversibly (ISC) and reversibly (RSC) sickled cells was studied in patients with sickle cell anemia. Inhalation of 50% oxygen in patients who were not in crisis produced a significant fall in RSCs and a lesser fall in ISCs. Twenty-five subjects in sickle cell crisis were chosen at random to receive either oxygen (15 patients) or air (10 patients). Those who received oxygen showed a significant reduction in RSCs, but not in ISCs. No significant change in RSCs or ISCs occurred in the group who received air. Despite the reduction in RSCs in the oxygen-treated group, there was no significant difference between the air and oxygen groups in the duration of severe pain, opioid administration, and hospitalization. It was also observed that crisis was associated with arterial desaturation and a reduction in the number of RSCs. We conclude that, although RSCs may be involved in the pathophysiology of sickle cell crisis, reduction in RSCs by oxygen therapy in these studies did not result in any reduction in the duration of crisis.

Adolescent↗
PubMed1992

Acquired von Willebrand disease in Wilms' tumor patients.

PURPOSE: A prospective study was performed to determine the incidence of acquired von Willebrand disease (vWD) in children with newly diagnosed Wilms' tumor. PATIENTS AND METHODS: Fifty consecutive children with newly diagnosed Wilms' tumor were evaluated. Detailed family and bleeding histories were obtained in all cases. Laboratory evaluation included measurement of the circulating platelet count, bleeding time (BT), factor VIII (FVIII) and von Willebrand factor (vWF) levels, and ristocetin cofactor (RCoF) activity. A vWF multimer analysis was obtained in all cases in which vWD was suspected. RESULTS: Four of 50 (8%) consecutive children with a diagnosis of Wilms' tumor were found to have acquired vWD. Laboratory findings indicated type III vWD in two patients and type I vWD in the other two. CONCLUSIONS: The incidence of acquired vWD in association with Wilms' tumor merits further study through a large prospective trial. Such a trial should include careful family and clinical bleeding histories plus measurement of a platelet count, BT, coagulant FVIII and vWF levels, RCoF activity, and vWF multimer analysis. The response to 1-desamino-8-D-arginine vasopressin (DDAVP) should be tested in all patients with Wilms' tumor and acquired vWD, including patients with a type III profile, before an invasive procedure is performed. Successful use of DDAVP may avoid exposure of affected patients to blood products.

Blood Coagulation↗
PubMed1992

Coordinate expression of Wilms' tumor genes correlates with Wilms' tumor phenotypes.

The cloning and molecular characterization of two putative tumor genes, WT1 and WIT1, from the chromosome 11p13 region has provided a means of evaluating their role in the generation of Wilms' tumor heterogeneity. A series of 29 tumors were analyzed for WT1 and WIT1 expression by Northern blot or RNase protection analyses, and results were compared with tumor histopathology. Tumors were scored for the percentage of mesenchymal and epithelial derived tissue components. Homotypic tumors comprised blastema, tubular epithelium, and a fibroblast-like mesenchyme. In addition to these tissue components, the group of tumors designated as heterotypic also contained ectopic cell phenotypes such as muscle and squamous epithelium. The analyses suggest that heterotypic differentiation patterns occur when WT1 and WIT1 expression is low relative to normal fetal kidney. In situ hybridization using antisense RNA probes showed that WT1 and WIT1 were concordantly expressed in normal fetal kidney and in the blastema of tumors. The ratio of WT1:WIT1 expression remained relatively constant in homotypic tumors but deviated significantly in heterotypic tumors. These results suggest that expression patterns of the WT1 and WIT1 genes can be closely correlated to Wilms' tumor histopathology.

Blotting, Northern↗
PubMed1991

T-cell lymphoma and mature nephroblastoma after synchronous bilateral Wilms' tumor.

A 15-year-old boy had lymphoblastic lymphoma of the left tonsil after being treated for bilateral Wilms' tumor (BWT) at 7 months of age. In addition, a fully differentiated Wilms' tumor was diagnosed in the remaining, partially nephrectomized left kidney. Development of second malignancies in patients with a history of BWT, as compared with those with unilateral Wilms' tumor, is discussed. A possible explanation for the concurrently diagnosed, fully differentiated Wilms' tumor in the remaining left kidney is suggested.

Humans↗
PubMed1991

Childhood malignant lymphoma of bone.

From 1974 to 1987, 450 children with non-Hodgkins' lymphoma (NHL) were seen at the Institut Gustave Roussy (IGR); 14 children had malignant lymphoma of bone (MLB). Eleven of the 14 were newly diagnosed, whereas three presented in relapse. Nine patients presented with multifocal bone involvement. The median age of these eight girls and six boys was 9.5 years (range 1.25-15 years). Bone pain was present in all patients as the initial symptom. Evaluation included physical examination, routine serum chemistries, complete blood count, chest roentgenography, skeletal survey, radionuclide bone scan, lumbar puncture, bone marrow aspiration, and intravenous pyelography, and/or abdominal ultrasonography. Hypercalcemia was found in six patients. Biopsy was performed in 12 patients, revealing high-grade lymphoblastic lymphomas in all. In two patients diagnosis was made on cytological examination of bone marrow aspirate. Immunophenotyping in four cases, demonstrated non-B, non-T cell origin in three and pre-B cell origin in one. Three patients were treated prior to 1982 with Cyclophosphamide/Oncovin/Prednisone/ADriamycin (COPAD) and seven patients, seen after 1982, were treated with a modified LSA2L2 protocol (LMT). None of the previously untreated patients received radiotherapy. All patients treated with COPAD have died, whereas four out of seven treated with LMT are alive with a median follow up of 51 months (range 36-82 months). One child treated on a pilot study died. One of the three children seen at relapse is disease-free with a follow-up of 98 months after high-dose chemotherapy followed by autologous bone marrow transplantation (ABMT). Five out of six patients presenting with hypercalcemia have died. Results with LMT are encouraging and together with published results suggest that sufficiently intensive chemotherapy can result in complete remission and cure in MLB. Radiotherapy does not seem to be necessary, avoiding possible serious long-term effects. Hypercalcemia is a bad prognostic feature.

Adolescent↗
PubMed1991

Neuroblastoma stage IV-S: a heterogeneous disease.

Eighteen patients were diagnosed and treated for Stage IV-S neuroblastoma at The Hospital for Sick Children, Toronto between January 1971 and December 1988. All patients were 6 months of age or younger at diagnosis. Nine patients (50%) have remained disease free with a mean follow-up of 9.3 years. Of the seven patients under 6 weeks of age at presentation, four presented in the early neonatal period and died, three due to mechanical complications related to progressive disease, and one due to late recurrence. The remaining three patients under 6 weeks of age, two of whom had skin involvement at diagnosis, are alive and disease free. Six of the 11 patients over 6 weeks of age at presentation survived, combined modality therapy (CMT) being more effective than single modality treatment. N-myc was studied from tumor tissue at diagnosis in four patients and was amplified in three (25x, 25x, 100x), all of whom had late disease progression and died. The patient with a single gene copy has no evidence of disease 24 months following diagnosis. Our study confirms the heterogeneity described in this clinically defined group of patients. Because of it, management of Stage IV-S neuroblastoma cannot be uniform and until further development of a subclassification, or a reclassification based on molecular biologic markers is developed, pediatric oncologists will regularly be confronted with a decision whether or not to treat a newly presenting patient that fits into the clinical classification IV-S.

Adrenal Gland Neoplasms↗
PubMed1991

Scrotal pneumatocele: a rare phenomenon.

In contrast to what would be expected in newborns with pneumoperitoneum, pneumoscrotum is a rare phenomenon. A newborn who presented with a pneumoscrotum as first, overt, sign of pneumoperitoneum is described. A perforated Meckel's diverticulum was responsible for the airleak.

Air↗
PubMed1991

Extrarenal Wilms' tumor: staging, treatment, and prognosis.

Extrarenal Wilms' tumors are rare and have mainly been the subject of isolated case reports. This retrospective evaluation of 34 patients suggests a clinical course very similar to that of renal Wilms' tumor. While clinical presentation varies according to the extrarenal localization, investigations to determine the size of the primary tumor (T), regional lymph node involvement (N), and the occurrence of distant metastasis (M) are very similar, ie, chest x-ray, abdominal ultrasound (US), and computed axial tomographic (CAT) scan of the abdomen and chest. Stage grouping according to the pathologic TNM classification showed stage I in 30%, stage II in 10%, stage IIIa in 34%, stage IIIb in 23%, and stage IVa in 3%; four patients could not be staged. Evaluation of therapy and survival indicate the need for postoperative chemotherapy (CT) to all patients, while the same data suggest that the drugs used for renal Wilms' tumor are equally effective for extrarenal Wilms' tumor. Radiotherapy (RT) probably should be reserved for those patients with unresectable gross residual disease and for metastatic disease. The radiation dose used in the reviewed cases varied from 2,000 to 5,000 cGy. However, recent experience suggests that high doses are not justified in renal Wilms' tumor. The estimated overall 2-year survival of the 34 patients is 82% (95% confidence interval, 63% to 92%).

Adolescent↗
PubMed1990

Tissue, developmental, and tumor-specific expression of divergent transcripts in Wilms tumor.

The Wilms tumor locus on chromosome 11p13 has been mapped to a region defined by overlapping, tumor-specific deletions. Complementary DNA clones representing transcripts of 2.5 (WIT-1) and 3.5 kb (WIT-2) mapping to this region were isolated from a kidney complementary DNA library. Expression of WIT-1 and WIT-2 was restricted to kidney and spleen. RNase protection revealed divergent transcription of WIT-1 and WIT-2, originating from a DNA region of less than 600 bp. Both transcripts were present at high concentrations in fetal kidney and at much reduced amounts in 5-year-old and adult kidneys. Eleven of 12 Wilms tumors classified as histopathologically heterogeneous exhibited absent or reduced expression of WIT-2, whereas only 4 of 14 histopathologically homogeneous tumors showed reduced expression. These data demonstrate a molecular basis for the pathogenetic heterogeneity in Wilms tumorigenesis.

Base Sequence↗
PubMed1990

Diagnostic and therapeutic problems of soft tissue tumors other than rhabdomyosarcoma in infants under 1 year of age: a clinicopathological study of 34 cases treated at the Institut Gustave-Roussy.

Thirty-four cases of soft tissue tumors (STT) other than rhabdomyosarcoma in infants under 1 year of age were seen in our institution between 1955 and 1985. All were diagnosed initially as malignant tumors except for three cases of fibromatosis, and, thus, they received therapy appropriate at that time. During a recent pathologic review, four were seen to have had hemangioma, six hemangiopericytoma, one hamartoma, seven fibromatosis, eight fibrosarcoma, and eight unclassified sarcomas. Of these 34 cases, the initial histological diagnosis was confirmed in only 17. Sixteen patients were believed to have received inappropriately aggressive therapy; indeed, four of these cases diagnosed prior to 1975 had been benign. Major long-term side effects were seen in 7/16 treated patients (six radiotherapy, one surgery), who, in retrospect, should have received less aggressive treatment. The reasons for these initial errors in diagnosis included doubtful histologic features associated in some cases with alarming clinical presentation. We believe that difficulties still remain in distinguishing benign from malignant STT in this age group by histological examination. Therefore, we urge extreme caution in using aggressive therapy before the diagnosis is certain.

Age Factors↗
PubMed1989

Magnetic resonance appearance of adrenal hemorrhage in a neonate.

The Magnetic Resonance (MR) appearance of adrenal hemorrhage in a neonate is described and compared with Ultrasound (US). The value of US studies in adrenal neonatal hemorrhage is well known. We present the MR appearance of this common condition.

Adrenal Gland Diseases↗
PubMed1989

Bilateral Wilms' tumor: long-term survival and some epidemiological features.

Sixty-seven children with a bilateral Wilms' tumor (BWT) who were registered to the International Society of Pediatric Oncology (SIOP) nephroblastoma trial and studies 1, 2, and 5, conducted between 1971 and 1980, were analyzed. The overall 10-year survival was 64%. While most deaths due to tumor occurred within 3 years after diagnosis of bilateral disease, five patients died after 3 years (20%), three with synchronous and two with metachronous BWT. The survival rates for the 42 children with synchronous BWT (follow-up time, 6 1/2 to 14 years) and the 25 children with metachronous BWT (follow-up time, 5 to 13 years) were 69% and 56%, respectively. Due to an improvement in the synchronous group, overall survival improved over the years: 47%, 72%, and 70%, in SIOP 1, 2, and 5, respectively. Age at diagnosis and most advanced tumor stage affected prognosis. Children presenting a tumor manifestation before the age of 2 years had better prognosis than older children. This difference is significant in synchronous BWT. Prognosis for children with local stage 1 or 2 was better than for those with local stage 3. Median age at initial presentation in BWT was lower than in unilateral nephroblastoma and lower in metachronous BWT than in synchronous BWT. Young children presenting with unilateral nephroblastoma should have a careful follow-up of the contralateral kidney for at least the next 3 1/2 years, as most contralateral tumors will develop during this period.

Age Factors↗
PubMedDate not supplied

Safety, tolerability, antiemetic efficacy, and pharmacokinetics of oral dolasetron mesylate in pediatric cancer patients receiving moderately to highly emetogenic chemotherapy.

PURPOSE: The safety, antiemetic efficacy, and pharmacokinetics of single oral doses of dolasetron, a new highly selective 5-HT3 receptor antagonist, were evaluated in children with cancer undergoing treatment with moderately to highly emetogenic chemotherapy. PATIENTS AND METHODS: A total of 32 children, ages 3 to 18 years, were enrolled in a nonrandomized, multicenter, open-label, dose-escalation study. Three oral dose levels (0.6, 1.2, or 1.8 mg/kg) were studied. Safety, efficacy, and pharmacokinetic parameters were assessed over 24 hours at each dosage level. RESULTS: The most effective dose was 1.8 mg/kg; 60% of the patients achieved a complete or major response (< or =2 emetic episodes in 24 hours). A complete response was achieved in 3 of 9 patients (33%) who received 0.6 mg/kg, 4 of 13 (31%) patients who received 1.2 mg/kg, and 5 of 10 (50%) patients who received 1.8 mg/kg of dolasetron. Overall, dolasetron was well tolerated. Adverse events were mild and similar to those reported in adults. Peak plasma concentrations (Cmax) of dolasetron's active reduced metabolite, MDL 74,156, were dose proportional and occurred, on the average, within 1 hour of oral administration. The half-life (t1/2) in plasma was approximately 6 hours for all dose levels, and the mean clearance (CLapp) was unrelated to dose. CONCLUSIONS: Oral dolasetron is safe and effective in reducing chemotherapy-induced nausea and vomiting, particularly at the 1.8-mg/kg dose level. These results support further evaluation of oral dolasetron in larger randomized clinical trials in the pediatric cancer population.

Administration, Oral↗
PubMedDate not supplied

Wilms tumour: diagnosis and treatment.

Wilms tumour is the most common intra-abdominal solid tumour of childhood. Treatment includes surgical resection and chemotherapy for virtually all affected children and additional radiotherapy for those with advanced disease or adverse prognostic features. This approach leads to cure rates exceeding 80%. During the last decade there have been a number of advances which have increased our understanding of the biology of Wilms tumour. The development of Wilms tumour, for example, involves several genes, including WT1, the Wilms tumour suppressor gene at 11p13, and WT2, the putative Wilms tumour suppressor gene at 11p15. In addition, certain chromosomal regions, most notably 16q and 1p, might predict outcome and hence serve as a prognostic factor, useful for determining the intensity of therapy. This novel information is now being incorporated into current therapeutic protocols. We reviewed the medical literature and present a summary of the advances made, outlining the current treatment of Wilms tumour. Future protocols will continue incorporating biological markers. The goal is to identify patients at low risk for relapse, which will allow a reduction in treatment intensity and subsequent toxicity. Children at an increased risk for relapse can be selected for more intensive treatment.

Abdominal Neoplasms↗
PubMedDate not supplied

Analgesia in children with sickle cell crisis: comparison of intermittent opioids vs. continuous intravenous infusion of morphine and placebo-controlled study of oxygen inhalation.

The objectives of the study were to compare the efficacy and safety of a continuous infusion (CIV) of morphine and intermittent parenteral opioids (IPO) in children with sickle cell vaso-occlusive crises (VOCs); to determine whether 50% oxygen administration through a face mask can reduce the duration of severe pain in patients receiving CIV morphine; and to measure morphine concentration at steady state for pharmacokinetic and pharmacodynamic analysis in patients receiving CIV morphine. The study was designed as a prospective, controlled, "before-and-after" evaluation of two different analgesic regimens. For patients receiving CIV morphine, there was a randomized, double-blind, placebo-controlled study of O2 vs. air. The patients were 66 children with sickle cell disease, 3-18 years old, requiring opioid therapy for severe VOC (32 patients in phase A, 34 in phase B). The analgesic regimens were as follows: phase A: meperidine, morphine, or codeine IM or IV bolus every 3 or 4 hours; phase B: morphine sulfate, loading dose 0.15 mg followed by CIV 0.04 mg/kg/hr. The infusion rate was adjusted every 8 hours according to pain and/or symptoms of opioid toxicity. Pain assessment was by behavioral observation (BPS). In terms of results, the mean opioid dose (morphine equivalent) was similar in both groups (0.032 +/- 0.020 mg/kg/hr in phase A and 0.035 +/- 0.011 in phase B). However, the duration of severe pain was significantly shorter in phase B (0.9 +/- 1.0 days) than in phase A (2.0 +/- 1.8 days). No severe opioid toxicity was observed in either group. Oxygen did not shorten the duration of severe pain compared to the placebo group (0.94 +/- 1.08 and 0.95 +/- 1.19 days, respectively) nor did it prevent the appearance of new pain sites. Pharmacokinetic analysis was performed in 24 patients of phase B. Total body clearance (TBC) of morphine was greater in children before puberty than after (40.4 +/- 10 vs. 28 +/- 11 mL/kg/min; p < 0.05). In conclusion, in children with severe VOCs, continuous infusion of morphine provides better analgesia than intermittent opioid therapy. Fifty percent oxygen inhalation had no effect on the duration of pain.

Adolescent↗
PubMedDate not supplied

Mesna inactivates platinum agents in vitro.

BACKGROUND: Platinum agents are frequently combined with ifosfamide. Mesna, originally coadministered to protect from ifosfamide side effects, might also react with the platinum agents in these combinations. METHODS: Malignant glioma cells were incubated with cisplatin, carboplatin and mesna. Cell numbers were measured by counting and by MTT-tests. RESULTS: In cell free solution mesna turned MTT to its blue farmazan product. Mesna's effect on cells were cell-line specific: It penetrated U87 cells without effect on growth, reduced cell numbers in C6 and T98G cells and did not alter U251 cells. The concentration of cisplatin killing 50% of the cells were 7 x 10(-7) in C6, 9.7 x 10(-6) in T98G, 1.2 x 10(-5) in U251 and 2.4 x 10(-4) in U87 cells. For the same effect, carboplatin required 3-10 times higher concentrations. Mesna protected all cell lines from the cytotoxicity of the platinum agents. CONCLUSION: Clinical studies should specify in detail, infusion schedules of mesna and platinum agents.

Antineoplastic Agents↗