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Biomedical subjects

W A McGuire

Publications and source records attributed to W A McGuire.

16 recordsLinked to original sources

Single dose versus fractionated stereotactic radiotherapy for recurrent high-grade gliomas.

PURPOSE: To evaluate the efficacy of stereotactic radiotherapy (SRT) in patients with recurrent high-grade gliomas by comparing two different treatment regimens, single dose or fractionated radiotherapy. METHODS AND MATERIALS: Between April 1991 and January 1998, 71 patients with recurrent high-grade gliomas were treated with SRT. Forty-six patients (65%) were treated with single dose radiosurgery (SRS) and 25 patients (35 %) with fractionated stereotactic radiotherapy (FSRT). For the SRS group, the median radiosurgical dose of 17 Gy was delivered to the median of 50% isodose surface (IDS) encompassing the target. For the FSRT group, the median dose of 37.5 Gy in 15 fractions was delivered to the median of 85% IDS. RESULTS: Actuarial median survival time was 11 months for the SRS group and 12 months for the FSRT group (p = 0.3, log-rank test). Variables predicting longer survival were younger age (p = 0.006), lower grade (p = 0.0006), higher Karnofsky Performance Scale (KPS) (p = 0.0005), and smaller tumor volume (p = 0.02). Patients in the SRS group had more favorable prognostic factors, with median age of 48 years, KPS of 70, and tumor volume of 10 ml versus median age of 53 years, KPS of 60, and tumor volume of 25 ml in the FSRT group. Late complications developed in 14 patients in the SRS group and 2 patients in the FSRT group (p<0.05). CONCLUSION: Given that FSRT patients had comparable survival to SRS patients, despite having poorer pretreatment prognostic factors and a lower risk of late complications, FSRT may be a better option for patients with larger tumors or tumors in eloquent structures. Since this is a nonrandomized study, further investigation is needed to confirm this and to determine an optimal dose/fractionation scheme.

Adolescent↗

The use of tertiary collimation for spinal irradiation with extended SSD electron fields.

PURPOSE: The spine can be treated with an electron beam when its maximum posterior depth is within the therapeutic range of electrons. Electron fields treated at extended source-to-surface distances (SSDs), however, have larger penumbras and narrower therapeutic isodose widths relative to those at the standard SSD of 100 cm. We investigated the use of tertiary collimation close to the patient surface for these fields to sharpen the penumbra, minimizing dose to normal tissue and maximizing target coverage. METHODS AND MATERIALS: Using film dosimetry in a polystyrene phantom, we measured the dose distribution for electron fields at extended SSD under varying collimation conditions. Beam penumbra and therapeutic width as a function of depth, SSD, applicator insert size, and tertiary collimator opening were determined. We also measured the dose distributions in the junction region for various gaps between x-ray fields and an electron field as used for craniospinal irradiation. RESULTS: Measurements show that tertiary collimation close to the skin surface reduces penumbra width (lateral distance between the 90 and 20% isodose lines) by 56% and increases therapeutic isodose width (lateral width of the 90% isodose curve) by 25% at a depth of dmax relative to standard collimation. These numbers change to 23 and 13%, respectively, at an average depth of the spine. When lateral brain and posterior spine fields are used to irradiate the entire craniospinal axis, tertiary collimation aids in reducing the volume of the hot spot in the junction region by as much as 10% without compromising target coverage. CONCLUSIONS: Tertiary collimation for extended SSD electron fields is preferable to standard collimation in order to minimize dose to normal tissue and increase target coverage. This technique can be applied to both spinal and craniospinal irradiation. Support structures for the tertiary blocking are needed because the weight of the lead is usually too great for placement on the skin.

Electrons↗

Erythropoietin increases hemoglobin during radiation therapy for cervical cancer.

PURPOSE: Anemia during radiation therapy independently predicts poor outcome in patients with cervical cancer. Despite a randomized trial demonstrating red cell transfusions improve local control and survival, many patients are not transfused due to toxicity concerns. This study evaluates the efficacy of recombinant human erythropoietin (r-HuEPO) in reversing anemia in patients undergoing radiation therapy. METHODS AND MATERIALS: Twenty patients with criteria of anemia (Hgb < 12.5 g/dL) and surgically staged cervical cancer FIGO stages IB (n = 7), IIA (n = 1), IIB (n = 9), and IIIB (n = 3), ranging in ages from 23-75 years (median 43), were included in this Phase I/II study. Fifteen were treated with r-HuEPO (200 U/kg/day) and ferrous sulfate 5-10 days prior to initiation of external beam radiation therapy, continuing until Hgb was < or = 14 g/dL or completion of radiation therapy. Five patients were treated with ferrous sulfate alone. An additional 61 historical controls meeting eligibility criteria were analyzed. All received external beam radiation therapy and two intracavitary cesium applications. Cisplatinum chemotherapy (20 mg/m2/week) was given as a radiosensitizer in 14 r-HuEPO patients, 4 concurrent controls, and 17 historical controls. RESULTS: A marked reticulocytosis was seen in the r-HuEPO group, but not the study controls. In the r-HuEPO group, the mean +/- SD serum Hgb rose + 30% over the course of radiation therapy from a baseline of 10.3 +/- 1.04 g/dL to 13.2 +/- 1.7 g/dL. Average increase in Hgb was 0.5 g/dL per week. Average Hgb during RT was 13.4 g/dL. In study and historical controls, mean initial Hgb levels were 10.7 +/- 1.04 g/dL and 11.1 +/- 1.3g/dL, respectively, remaining unchanged over the course of radiation therapy. Average Hgb levels during radiation therapy were 11.1 g/dL in study controls and 11.4 g/dL in historical controls, significantly lower than r-HuEPO patients (p = 0.0001). Erythropoietin was well tolerated. There were no significant differences in white blood counts (p = 0.6) or platelet counts (p = 0.4) between r-HuEPO patients and both control groups. No patients had blood pressure changes during r-HuEPO therapy. The only possible side effect was deep venous thrombosis, occurring in two patients who were withdrawn from r-HuEPO therapy. Two additional patients developed deep venous thrombosis 9 and 10 days after radiation therapy and r-HuEPO were completed. CONCLUSION: Erythropoietin appears to be both safe and effective at raising Hgb levels in anemic cervical cancer patients receiving radiation therapy and chemotherapy.

Adult↗

Platelet apheresis for extreme thrombocytosis in an 11-year-old girl with CML.

This report describes the dramatic reduction in the platelet count and ablation of symptoms by consecutive platelet apheresis in a young girl with CML who presented with an extremely high platelet count of 10,320 x 10(9)/l. Extreme thrombocytosis, although quite rare, can be symptomatic and life-threatening in paediatric patients and should be considered an emergency. The mechanical removal of platelets by apheresis is effective therapy and should begin as soon as possible.

Child↗

Qualitative functional deficiency of affinity-purified lactoferrin from neutrophils of patients with chronic myelogenous leukemia, and lactoferrin/H-ferritin-cell interactions in a patient with lactoferrin-deficiency with normal numbers of circulating leukocytes.

The iron-binding proteins lactoferrin (LF) and H-ferritin have been implicated in the negative regulation of myelopoiesis in vitro and in vivo. The present studies evaluated the functional activity of affinity-purified LF from polymorphonuclear neutrophils (PMN) of patients with chronic myelogenous leukemia (CML) and LF/H-ferritin-cell interactions in a nonleukemic patient with LF deficiency with normal levels of circulating blood leukocytes. Affinity-purified CML-PMN-LF was found to be qualitatively deficient as a suppressor of the release of colony-stimulating factors from mononuclear blood cells, adding to previous information from our group documenting defective LF-cell interactions in CML. LF was detected by immunoradiometric assay in PMN of the patient with LF deficiency, but at a much lower level than normal. This LF was found, however, to be active as a suppressor molecular against the patient's cells and normal donor cells. Patient cells were as responsive as normal cells to effects of purified milk LF. Decreased LF levels in this patient were associated with increased levels of monocyte H-ferritin inhibitory activity, consistent with the known suppressive effects in vitro of LF on H-ferritin release from monocytes. Patient marrow hematopoietic progenitor cells were as responsive as progenitors from normal donors to suppression by purified H-ferritin and prostaglandin E1. These results are consistent with a role of LF and H-ferritin in the control of myelopoiesis in this patient.

Alprostadil↗

Purine excretion during tumor lysis in children with acute lymphocytic leukemia receiving allopurinol: relationship to acute renal failure.

We measured serial urine levels of hypoxanthine, xanthine, and uric acid in 19 children with acute lymphocytic leukemia (ALL) receiving allopurinol therapy during tumor lysis; four of these children developed acute renal failure. The urinary excretion of uric acid rose moderately from 447 +/- 251 micrograms/dl glomerular filtrate before chemotherapy to 778 +/- 463 micrograms/dl glomerular filtrate during tumor lysis (P less than 0.05) whereas the urinary excretion of hypoxanthine (17.9 +/- 15 to 292 +/- 213 micrograms/dl glomerular filtrate) and xanthine (74 +/- 62 to 1091 +/- 1085 micrograms/dl glomerular filtrate) rose dramatically (P less than 0.001). The urinary excretion of uric acid, hypoxanthine, and xanthine per deciliter of filtrate was significantly higher (P less than 0.001) in those who developed acute renal failure than in those who did not, but the highest urine concentration of these purine metabolites did not differ in the two groups. In all 19 children, the highest urine concentration of uric acid and hypoxanthine during tumor lysis did not exceed the solubility limit of each in an alkaline urine specimen. In contrast, the peak urine concentration of xanthine exceeded its solubility limit in an alkaline urine specimen in 16 of 19 children. The urine sediment during the period of tumor lysis was examined by diffuse reflectance infrared spectroscopy; precipitated xanthine was found in sediment from eight of the 19 children, was significantly (P less than 0.001) associated with a urine xanthine level greater than 350 mg/dL, and occurred with equal frequency in those who did or did not develop acute renal failure. We conclude that urinary excretion of hypoxanthine and xanthine increases dramatically whereas uric acid excretion rises moderately in children undergoing tumor lysis while receiving allopurinol, that acute renal failure occurs in children with a higher purine load per deciliter of glomerular filtrate, but that factors other than tubular precipitation of purine metabolites are likely to be involved in the pathogenesis of renal failure during tumor lysis.

Acute Kidney Injury↗

Congenital monoblastic leukemia cutis. A case report with chromosomal abnormality: del (10p).

Congenital monoblastic leukemia cutis is a rare disorder. We report an infant who developed infiltrative skin lesions by 2 weeks of age, which, when biopsied at 4 1/2 months of age revealed a monoblastic infiltrate. Blasts in the peripheral blood were not seen until 1 week before her death at 8 months of age. Chromosomal analyses of her bone marrow showed an abnormal clone of cells with a 46,XX,del(10)(p12) karyotype. Although chromosome 10 is rarely involved in hematologic malignancies, abnormalities of this chromosome within the region 10p11-10p13 have now been shown in four of 10 reported cases of congenital monoblastic leukemia.

Bone Marrow↗

Stage II neuroblastoma--does adjuvant irradiation contribute to cure?

Twenty-one children with Stage II neuroblastoma diagnosed between 1973 and 1983 were analyzed retrospectively. Median age at diagnosis was eleven months (1 week to 153 months). Primary tumor was above the diaphragm in 67% and below the diaphragm in 33%. All patients underwent surgical resection and pathologic diagnosis was neuroblastoma in 76% and ganglioneuroblastoma in 24%. Regional lymph nodes were positive in three of eleven patients sampled. Sixty-seven percent had gross residual disease, and thirty-three percent had microscopic residual disease. Seventeen patients received postoperative irradiation and none has relapsed (median follow-up 57 months). Four patients received surgery alone (median follow-up 24 months); one local relapse occurred in this group and was subsequently treated with irradiation. All patients are alive and disease free, with a median length of follow-up of 55 months. Radiation dosage was 1000-1800 rad in patients less than 12 months of age, and 1800-3000 rad in those greater than 12 months of age at diagnosis. The high disease-free survival rate in both groups of patients, but especially in the group receiving adjuvant irradiation, emphasizes the need for a controlled, prospective study to determine which Stage II neuroblastoma patients, if any, would be benefitted by postoperative irradiation.

Age Factors↗

Chemotherapy-associated Raynaud's phenomenon in a two-year-old girl.

Raynaud's phenomenon occurred in a 2-year-old girl 17 months after starting multiagent chemotherapy for an endodermal sinus tumor of the vagina. Symptoms began 2 months after receiving her final dose of bleomycin, and gradually resolved over a 6-month period despite continuing vinblastine. Chemotherapy-associated Raynaud's phenomenon appears to be unusual in young children, although mild episodes of vasospasm may not be reported by children or their parents. Specific questions regarding symptoms of Raynaud's phenomenon should be asked of all children receiving vinblastine and bleomycin therapy.

Antineoplastic Combined Chemotherapy Protocols↗

A microcomputer-based program for video analysis of chemotaxis under agarose.

We have developed a computerized system for the quantification of video images of cell migration patterns obtained in the chemotaxis under agarose assay. This system allows either manual or automatic measurement of standard parameters of chemotaxis, as well as quantification of three new parameters which reflect mean cell movement and chemokinesis. The parameters of mean cell population movement are not obtainable by the traditional analysis of the chemotaxis under agarose assay. Our system operates on an inexpensive microcomputer, is easy to use and provides data output in a format that is directly transferable to standard statistical packages.

Chemotaxis, Leukocyte↗

Glycoprotein-180 deficiency: genetics and abnormal neutrophil activation.

Neutrophil function was studied in a patient with polymorphonuclear leukocyte (PMN) glycoprotein-180 deficiency and in her parents. PMNs of the patient had abnormal chemotaxis, phagocytosis, adherence, surface charge, and membrane-associated events of activation. Selective defects to C3b, immunoglobulin G (IgG), phorbol myristate acetate (PMA) and N-formyl-methionyl-leucyl-phenylalanine (FMLP) are described, although C3b receptor density was normal. The parents were found to have abnormal adherence to nylon-wool fibers, abnormal transmembrane potential depolarization with PMA, and reduced amounts of glycoprotein-180 in their PMNs. These studies provide further evidence that the oxidative burst has several different pathways for activation. They demonstrate that the absence of a single PMN surface glycoprotein is associated with a broad spectrum of PMN functional abnormalities. Finally, the observations made in the parents support an autosomal recessive mode of inheritance.

Blood Protein Disorders↗

Case report of an allergic reaction to parenteral nutrition in a pediatric patient.

We report a 34-month-old girl with stage IV neuroblastoma who developed hives when parenteral nutrition (PN) containing amino acids, dextrose, electrolytes, minerals, vitamins, and trace elements was infused. Administration of diphenhydramine resulted in disappearance of the rash. Infusion of the PN solution without intravenous fat emulsion produced a similar rash with itching. The pediatric multiple vitamin (PMV) preparation was removed from the PN formula and the formula was infused without incident. The patient was maintained on PN and an oral vitamin supplement with no further complaints. Inadvertent administration of a PN solution containing PMV resulted in a recurrence of hives. Absence of any adverse reactions when the PMV preparation was removed from the PN solution and an allergic reaction when the multivitamin was added to the PN solution support the possibility that the allergic reaction was related to the infusion of the multiple vitamin preparation.

Child, Preschool↗

Oncogene RNA expression in three human lymphoblastic leukemia cell lines lymphocytes.

We have explored the RNA oncogene expression by three human acute lymphoblastic leukemia lines, NALM-6, MOLT-3, and REH. We compared such expression with that of normal human lymphocytes. Marked differences in the RNA expression of the third exon of c-myc, v-myb, v-Hras, N-ras, v-fes, and v-fos were found. We noted minimal or no differences in the RNA expression of v-abl, B-lym, v-erb-B, c-ets, v-fms, v-kras, v-mos, v-raf, and v-sis.

Cell Line↗

H-ras and c-myc RNA expression in human T-cell ALL and in normal human lymphocytes.

We have compared the RNA expression of two oncogenes, H-ras and c-myc, with normal human lymphocytes, normal human T-cells, and human T-cell acute lymphoblastic leukemia (ALL). T-cell ALL RNA was derived from two human T-cell lines (MOLT-3 and CEM) and from five children with T-cell ALL. The RNA expression of H-ras and the third exon of c-myc was determined by northern hybridization. RNA from both MOLT-3 and CEM overexpressed both H-ras and the third exon of c-myc compared to normal lymphocytes and normal T-cells. T-cell ALL samples from four of five children overexpressed H-ras, while three of five patient samples overexpressed the third exon of c-myc when compared to normal lymphocytes and normal T-cells. Additional information on the oncogene expression of T-cell ALL may prove to be useful in the diagnosis and treatment of T-cell ALL.

Blotting, Northern↗