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Biomedical subjects

H McDowell

Publications and source records attributed to H McDowell.

29 records · Page 2Linked to original sources
PubMed1991

Long-term follow-up of ifosfamide renal toxicity in children treated for malignant mesenchymal tumors: an International Society of Pediatric Oncology report.

The renal function of 74 children with malignant mesenchymal tumors in complete remission and who have received the same ifosfamide chemotherapy protocol (International Society of Pediatric Oncology Malignant Mesenchymal Tumor Study 84 [SIOP MMT 84]) were studied 1 year after the completion of treatment. Total cumulative doses were 36 or 60 g/m2 of ifosfamide (six or 10 cycles of ifosfamide, vincristine, and dactinomycin [IVA]). None of them had received cisplatin chemotherapy. Ages ranged from 4 months to 17 years; 58 patients were males and 42 females. The most common primary tumor site was the head and neck. Renal function was investigated by measuring plasma and urinary electrolytes, glucosuria, proteinuria, aminoaciduria, urinary pH, osmolarity, creatinine clearance, phosphate tubular reabsorption, beta 2 microglobulinuria, and lysozymuria. Fifty-eight patients (78%) had normal renal tests, whereas 16 patients (22%) had renal abnormalities. Two subsets of patients were identified from this latter group: the first included four patients (5% of the total population) who developed major toxicity resulting in Fanconi's syndrome (TDFS); and the second group included five patients with elevated beta 2 microglobulinuria and low phosphate reabsorption. The remaining seven patients had isolated beta 2 microglobulinuria. Severe toxicity was correlated with the higher cumulative dose of 60 g/m2 of ifosfamide, a younger age (less than 2 1/2 years old), and a predominance of vesicoprostatic tumor involvement. This low percentage (5%) of TDFS must be evaluated with respect to the efficacy of ifosfamide in the treatment of mesenchymal tumors in children.

Acute Kidney Injury↗
PubMed1991

N-myc genomic content and DNA ploidy in stage IVS neuroblastoma.

DNA ploidy and N-myc genomic content were analyzed in a series of stage IVS neuroblastomas by flow cytometry and Southern blot hybridization, respectively. Of the 12 stage IVS neuroblastomas studied, nine were aneuploid (DNA index [DI] greater than 1), two were diploid (DI = 1), and one was not assessable for DNA content due to insufficient tumor material. N-myc gene amplification was present in two of 12 tumors. None of the aneuploid tumors exhibited N-myc amplification. Among the aneuploid neuroblastomas, the DIs were between 1.27 and 1.60, ie, in the near-triploid range. The follow-up from diagnosis ranged from 1 to 41 months (mean, 20 months). The nine neuroblastomas with near-triploid DNA content were free of disease at the end of the follow-up period. In contrast, a rapid and fatal tumor progression was observed for the three neuroblastomas with N-myc amplification and/or diploidy. Although involving only a limited series, these results strongly suggest that the combined analysis of DNA ploidy and N-myc genomic content could predict clinical outcome in stage IVS neuroblastoma and should help to identify patients for whom a more aggressive therapy is required.

Aneuploidy↗
PubMed1991

High-dose chemotherapy containing busulfan followed by bone marrow transplantation in 24 children with refractory or relapsed non-Hodgkin's lymphoma.

Twenty-four children with relapsed or refractory non-Hodgkin's lymphoma underwent high-dose chemotherapy (HDC) with bone marrow transplantation (BMT). HDC comprised in all cases busulfan (16 mg/kg or 600 mg/m2), with either cyclophosphamide (200 mg/kg or 4.4 g/m2) and/or melphalan (140 mg/m2). Twenty-three of these children had received second-line therapy before receiving HDC. There were 16 B cell and eight T cell lymphomas. Twenty-three patients were evaluable at day 30 post-BMT; 19 were in complete remission, four did not respond. Eight patients are long-term survivors between 62 and 296 weeks after BMT. Among the seven children with resistant disease before HDC, only one is a long-term survivor. No toxic deaths occurred. The main adverse side effect was hepatic veno-occlusive disease which occurred in four patients, but resolved completely in all cases. Comparisons with other classic HDC regimens in relapsed childhood lymphomas show that HDC containing busulfan with BMT appears reasonably safe and is effective in refractory or relapsed lymphomas, even in these highly previously treated patients.

Adolescent↗
PubMed1989

Chromosome 1 studies in Wilms' tumor.

Ten newly diagnosed patients with Wilms' tumor had blood and tumor samples taken for cytogenetic analysis. DNA was also extracted from these samples, along with blood obtained from both parents and an age- and sex-matched control. Molecular biological techniques were employed to study changes present in these samples with respect to chromosome 1. Two DNA probes, PIB 174 and PFBl, mapping to 1q12-qter and 1p12-pter, respectively, were examined for the presence of restriction fragment length polymorphisms (RFLPs) and to detect copy numbers of sequences homologous to the probes. These were normalized with respect to themselves and with regard to a control probe P30. No RFLPs were found with the restriction enzymes used. However, seven patients showed a marked alteration in hybridization signal in tumor and/or blood samples compared to control samples and the control probe. This was apparent using probe PFBl, but just failed to reach statistical significance using nonparametric testing. This would suggest that submicroscopic chromosome 1 changes are present more often in Wilms' tumor than previously recognized, and they may play a leading role in the genesis of this tumor.

Blotting, Southern↗
PubMed1988

The reason for cardiac output reduction after aortic cross-clamping.

The hypothesis that a decrease in cardiac output during infrarenal aortic cross-clamping is related to a decrease in oxygen consumption in the perfused tissues (cross-clamp-adapted oxygen consumption) rather than to deterioration of myocardial performance has been tested. Twenty-two patients undergoing excision of an aortic abdominal aneurysm were randomly divided into two groups of equal number. During aortic cross-clamping, Group 1 patients received nitroglycerin infusion, 1 to 2 micrograms.kg-1.min-1, whereas Group 2 patients did not receive a nitroglycerin infusion. During aortic cross-clamping, cross-clamp-adapted body oxygen consumption decreased equally in both groups by 40 to 42 percent of baseline values, whereas cardiac output decreased by 17 percent in Group 2 but did not change significantly in Group 1. Mixed venous oxygen content increased significantly after induction of anesthesia and prior to aortic cross-clamping in both groups. During cross-clamping, the values of mixed venous oxygen content remained increased in Group 2 and increased further in Group 1. The data support our hypothesis since a decrease in cardiac output was not associated with an increase in filling pressures during aortic cross-clamping, but was instead associated with an increase in mixed venous oxygen content and a decrease in the arteriovenous oxygen content difference. Nitroglycerin infusion was associated with a further increase in mixed venous oxygen content during aortic cross-clamping and a decrease in the arteriovenous oxygen content difference, without a concomitant increase in oxygen utilization.

Aorta, Abdominal↗
PubMed1980

Hemodynamic response to infrarenal aortic cross-clamping in patients with and without coronary artery disease.

The effect of coronary artery disease (CAD) on hemodynamic response to infrarenal aortic cross-clamping was studied in 25 patients undergoing either aortofemoral bypass or abdominal aortic aneurysmectomy. Ten patients had evidence of CAD and 15 did not. Systemic, pulmonary artery (PAP), and pulmonary capillary wedge pressures (PCWP), thermodilution cardiac output, and heart rate were measured immediately before, and 2 and 5 min after infrarenal aortic cross-clamping. Heart rate decreased and arterial pressures and pulmonary and systemic vascular resistances increased in both CAD and non CAD groups after aortic clamping. Cardiac index decreased after clamping in both groups and was significantly lower in the patients with CAD. However, PCWP decreased after clamping in patients without CAD as compared to a significant increase in the patients with CAD. The significantly lower cardiac index (1.8-1.9 L/min x M2) and increased PCWP (13-15 torr) in patients with preexisting CAD scheduled for aortofemoral surgery may suggest that this subgroup is at greater risk for myocardial dysfunction immediately after aortic cross-clamping.

Aged↗
PubMedDate not supplied

Flow cytometric and molecular analysis of proliferative activity and DNA content in neuroblastoma: presence of stationary cells in S-phase.

Twenty-nine previously untreated neuroblastomas were analyzed for DNA content and percentage of cells in S-phase, both determined by flow cytometry, and N-myc oncogene copy number. Twelve of them were also tested for histone H3 transcript levels as a marker of actual proliferative activity. A significantly higher S-phase fraction was associated with advanced stages of disease, unfavorable (i.e., near-diploid and near-tetraploid) DNA content, and N-myc amplification. The occurrence of six tumors with a remarkable (greater than or equal to 10%) S-phase fraction but lacking histone H3 transcripts suggests the presence of stationary S-phase cells in neuroblastoma.

Cell Division↗
PubMedDate not supplied

Multidrug resistance gene transcript level, and P-glycoprotein expression in paediatric malignant mesenchymal tumours.

Twenty-four malignant mesenchymal tumour specimens were analysed for human multidrug resistance (MDRI) gene transcript levels using Northern and slot blot techniques. The presence of P-glycoprotein was assessed in 12 of the 24 samples by immunohistochemistry using the monoclonal antibody (MAb) C219. Increased MDRI transcript levels were found in 2 (8.3%), while, using immunohistochemistry, 2 samples were positive and 3 faintly positive (41.6%). Overall, elevated P-glycoprotein or MDRI transcript levels were found in tumours of 6 patients, 3 of whom are dead. The relationship to MDRI expression and subsequent resistance to chemotherapy has to be established.

ATP Binding Cassette Transporter, Subfamily B, Mem↗