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D M Green

Publications and source records attributed to D M Green.

At least 55 records · Page 3Linked to original sources
PubMed1999

Marriage in the survivors of childhood cancer: a preliminary description from the Childhood Cancer Survivor Study.

BACKGROUND: The goal of this paper is to provide a preliminary description of the marital status for a large number of childhood cancer survivors participating in the Childhood Cancer Survivor Study (CCSS). PROCEDURE: This report includes children and adolescents (< 21 years of age) diagnosed with cancer between 1970 and 1986 at 25 oncology centers in the United States and Canada who survived at least 5 years from diagnosis. Self-reported data from 10,425 survivors are used in this preliminary descriptive summary. The proportion of survivors ever married and divorced/separated is compared to the U.S. population according to age-specific groups. The median age of the survivor population at diagnosis was 7 years and 26 years at the time martial status was ascertained. Excluded from this assessment are children < 15 years of age at the time of study, those whose martial status was unknown, and those married prior to diagnosis. Data for marital status of the U.S. population, as tabulated in the Bureau of Census 1995 Update, is used as a general comparison to the survivor population. RESULTS: Overall, 32% of the survivors reported being married or living as married, 6% being divorced or separated, 0% being widowed, and 62% having never been married. In general, compared to the U.S. population, survivors were less likely to have ever married, particularly females and whites, but, once married, were less likely to divorce/separate, again particularly females and whites. Black survivors were generally found to be more likely to have married, with males and blacks more likely to divorce/separate once married. Comparison of childhood tumor types suggested that survivors of CNS tumors, particularly males, were less likely to have ever married and more likely to divorce/separate compared to those with other cancer diagnoses and the general U.S. population. CONCLUSIONS: This interim evaluation of the CCSS cohort provided preliminary data describing a suggested decreased likelihood of marriage, which may be influenced by gender and/or race. These patterns must be confirmed within the entire CCSS cohort and comparisons made with an appropriate sibling comparison group before making final conclusions.

Adolescent↗
PubMed1999

Hemizygous deletions of chromosome band 16q24 in Wilms tumor: detection by fluorescence in situ hybridization.

Loss of heterozygosity (LOH) for markers on chromosome arm 16q in Wilms tumor has been linked to an increased risk of treatment failure. We therefore postulated that fluorescence in situ hybridization (FISH) with probes from this region might enhance current strategies for identifying high-risk patients at diagnosis. In a blinded comparative pilot study of 19 Wilms tumor samples from 18 patients with favorable histology, FISH and DNA polymorphism analysis yielded concordant results in 14 cases, either retention (n = 6) or loss (n = 8) of chromosome arm 16q markers. Discordant findings in 4 of the 5 remaining cases resulted from detection of LOH, but no loss by FISH. Two of these cases, directly comparable at marker D16S422, appeared to have tumor-specific uniparental disomy, in that 2 copies of D16S422 and the 16 centromere were evident, despite LOH. In 2 other cases, the discrepancies could be explained by LOH confined to loci distal to the D16S422 locus. In the fifth case, FISH detected 2 distinct populations of tumor cells, one characterized by normal diploidy and the other by monosomy 16, whereas DNA polymorphism analysis failed to indicate LOH altogether. Thus, FISH confirmed the presence of allelic loss (hence, the possible location of biologically important tumor suppressor genes) on the distal long arm of chromosome 16 in cases of favorable-histology Wilms tumor, with the advantages of technical simplicity, successful analysis of samples that were otherwise uninformative by analysis of DNA polymorphisms, and the addition of internal controls for chromosomal aneusomy. We suggest that combined analysis of the chromosome 16q region in Wilms tumor by FISH and DNA polymorphism analysis would improve evaluations to identify high-risk patients who might benefit from alternative therapy.

Child↗
PubMed1999

Surgery-related factors and local recurrence of Wilms tumor in National Wilms Tumor Study 4.

OBJECTIVE: To assess the prognostic factors for local recurrence in Wilms tumor. SUMMARY BACKGROUND DATA: Current therapy for Wilms tumor has evolved through four studies of the National Wilms Tumor Study Group. As adverse prognostic factors were identified, treatment of children with Wilms tumor has been tailored based on these factors. Two-year relapse-free survival of children in the fourth study (NWTS-4) exceeded 91%. Factors once of prognostic import for local recurrence may lose their significance as more effective therapeutic regimens are devised. METHODS: Children evaluated were drawn from the records of NWTS-4. A total of 2482 randomized or followed patients were identified. Local recurrence, defined as recurrence in the original tumor bed, retroperitoneum, or within the abdominal cavity or pelvis, occurred in 100 children. Using a nested case-control study design, 182 matched controls were selected. Factors were analyzed for their association with local failure. Relative risks and 95% confidence intervals were calculated, taking into account the matching. RESULTS: The largest relative risks for local recurrence were observed in patients with stage III disease, those with unfavorable histology (especially diffuse anaplasia), and those reported to have tumor spillage during surgery. Multiple regression analysis adjusting for the combined effects of histology, lymph node involvement, and age revealed that tumor spillage remained significant. The relative risk of local recurrence from spill was largest in children with stage II disease. The absence of lymph node biopsy was also associated with an increased relative risk of recurrence, which was largest in children with stage I disease. The survival of children after local recurrence is poor, with an average survival rate at 2 years after relapse of 43%. Survival was dependent on initial stage: those who received more therapy before relapse had a worse prognosis. CONCLUSIONS: This study has demonstrated that surgical rupture of the tumor must be prevented by the surgeon, because spills produce an increased risk of local relapse. Both local and diffuse spills produce this risk. Stage II children with local spill appear to require more aggressive therapy than that used in NWTS-4. The continued critical importance of lymph node sampling in conjunction with nephrectomy for Wilms tumor is also established. Absence of lymph node biopsy may result in understaging and inadequate treatment of the child and may produce an increased risk of local recurrence.

Child, Preschool↗
PubMed1999

Cancer and cardiac mortality among 15-year survivors of cancer diagnosed during childhood or adolescence.

PURPOSE: To evaluate the impact of cardiac disease and second malignant neoplasms on late mortality rate and to identify risk factors for late mortality among 15-year survivors of cancer diagnosed during childhood or adolescence. PATIENTS AND METHODS: Gender-specific all-cause and cause-specific (cardiac disease, cancer) standardized mortality ratios were calculated. Kaplan-Meier survival estimates and Cox regression analyses were performed to determine the relationship of several demographic and treatment variables to survival. RESULTS: Patients who survived for 15 years after diagnosis had excess subsequent all-cause, cancer (second malignant neoplasms only), and cardiac mortality rates. No decrease in the late mortality rate by treatment era (1960 to 1970, 1971 to 1984) was identified. Risk factors for males included disease recurrence during the first 15 years after diagnosis, treatment with doxorubicin, and the diagnosis of Hodgkin's disease. Those for females included treatment with radiation therapy, treatment with an alkylating agent, and disease recurrence during the first 15 years after diagnosis. Cox regression analysis demonstrated that only an initial duration of remission of less than 15 years (P <.01) and treatment with doxorubicin (P =.08) were significantly associated with shorter survival time for males. No variable was significantly associated with shorter survival time for females in Cox regression analysis. CONCLUSION: Fifteen-year survivors of childhood cancer have excess mortality. More effective treatments must be developed to reduce this excess risk. Fifteen-year relapse-free survivors did not have excess mortality. This group will require continued observation to determine whether excess mortality will become apparent as more events occur.

Adolescent↗
PubMed1999

American Society of Clinical Oncology clinical practice guidelines for the use of chemotherapy and radiotherapy protectants.

PURPOSE: Because toxicities associated with chemotherapy and radiotherapy can adversely affect short- and long-term patient quality of life, can limit the dose and duration of treatment, and may be life-threatening, specific agents designed to ameliorate or eliminate certain chemotherapy and radiotherapy toxicities have been developed. Variability in interpretation of the available data pertaining to the efficacy of the three United States Food and Drug Administration-approved agents that have potential chemotherapy- and radiotherapy-protectant activity-dexrazoxane, mesna, and amifostine-and questions about the role of these protectant agents in cancer care led to concern about the appropriate use of these agents. The American Society of Clinical Oncology sought to establish evidence-based, clinical practice guidelines for the use of dexrazoxane, mesna, and amifostine in patients who are not enrolled on clinical treatment trials. METHODS: A multidisciplinary Expert Panel reviewed the clinical data regarding the activity of dexrazoxane, mesna, and amifostine. A computerized literature search was performed using MEDLINE. In addition to reports collected by individual Panel members, all articles published in the English-speaking literature from June 1997 through December 1998 were collected for review by the Panel chairpersons, and appropriate articles were distributed to the entire Panel for review. Guidelines for use, levels of evidence, and grades of recommendation were reviewed and approved by the Panel. Outcomes considered in evaluating the benefit of a chemotherapy- or radiotherapy-protectant agent included amelioration of short- and long-term chemotherapy- or radiotherapy-related toxicities, risk of tumor protection by the agent, toxicity of the protectant agent itself, quality of life, and economic impact. To the extent that these data were available, the Panel placed the greatest value on lesser toxicity that did not carry a concomitant risk of tumor protection. RESULTS AND CONCLUSION: Mesna: (1) Mesna, dosed as detailed in these guidelines, is recommended to decrease the incidence of standard-dose ifosfamide-associated urothelial toxicity. (2) There is insufficient evidence on which to base a guideline for the use of mesna to prevent urothelial toxicity with ifosfamide doses that exceed 2.5 g/m(2)/d. (3) Either mesna or forced saline diuresis is recommended to decrease the incidence of urothelial toxicity associated with high-dose cyclophosphamide use in the stem-cell transplantation setting. Dexrazoxane: (1) The use of dexrazoxane is not routinely recommended for patients with metastatic breast cancer who receive initial doxorubicin-based chemotherapy. (2) The use of dexrazoxane may be considered for patients with metastatic breast cancer who have received a cumulative dosage of 300 mg/m(2) or greater of doxorubicin in the metastatic setting and who may benefit from continued doxorubicin-containing therapy. (3) The use of dexrazoxane in the adjuvant setting is not recommended outside of a clinical trial. (4) The use of dexrazoxane can be considered in adult patients who have received more than 300 mg/m(2) of doxorubicin-based therapy for tumors other than breast cancer, although caution should be used in settings in which doxorubicin-based therapy has been shown to improve survival because of concerns of tumor protection by dexrazoxane. (5) There is insufficient evidence to make a guideline for the use of dexrazoxane in the treatment of pediatric malignancies, with epirubicin-based regimens, or with high-dose anthracycline-containing regimens. Similarly, there is insufficient evidence on which to base a guideline for the use of dexrazoxane in patients with cardiac risk factors or underlying cardiac disease. (6) Patients receiving dexrazoxane should continue to be monitored for cardiac toxicity. Amifostine: (1) Amifostine may be considered for the reduction of nephrotoxicity in patients receiving cisplatin-based chemoth

Adult↗
PubMed1999

Nuclear morphometry and prognosis in favorable histology Wilms' tumor: A prospective reevaluation.

PURPOSE: This study was designed to evaluate the ability of a previously published nuclear morphometry discriminant function to predict disease-free survival in patients with Wilms' tumor. PATIENTS AND METHODS: We identified 218 patients with stage I-IV Wilms' tumor of favorable histology who were entered onto the National Wilms' Tumor Study (NWTS) between January 1, 1990 and April 15, 1994. The nuclear morphometry score was calculated for each patient as follows: MV(f) = (0.02 x AGE) + (1.17 x SNRF) + (90.6 x LEFD) - 94, with AGE denoting age at diagnosis in months, SNRF the skewness of the nuclear roundness factor, and LEFD the lowest value of nuclear ellipticity as measured by the feret diameter method. Relative risks of relapse were estimated for the total score and for each of its components. Sensitivity and specificity were determined for the criterion of "MV(f) is greater than -0.35" as a predictor of relapse. RESULTS: By contrast with previously published results, neither the SNRF nor the LEFD made any contribution to the prediction of disease-free survival. Sensitivity and specificity of the criterion of "MV(f) is greater than -0.35" were 71% and 56%, respectively. CONCLUSION: Re-evaluation of a published nuclear morphometry score showed that it did not predict disease-free survival in patients with Wilms' tumor. The earlier study very likely overestimated the predictive power of nuclear morphometry by using the same data set both to develop the score and to evaluate its properties. Because of the huge number of combinations of nuclear morphometry measurements that may enter into the multivariate discriminant function, use of appropriate statistical methods is essential to estimate accurately the sensitivity and specificity.

Child↗
PubMed1998

TNF-alpha released by comigrating monocytes promotes transendothelial migration of activated lymphocytes.

We investigated mechanisms that increase motility and transendothelial trafficking of activated lymphocytes. Freshly isolated lymphocytes stimulated with immobilized anti-CD3 for 2 h migrate into polymerized collagen in 1.99+/-0.25-fold greater numbers and across confluent endothelial monolayers in 4.8+/-0.5-fold greater numbers compared with leukocytes incubated with non-specific IgG. Activated lymphocytes form clusters with monocytes, and their increased motility was dependent on the presence of comigrating monocytes. Five lines of evidence support the idea that monocytes modulate lymphocyte motility through the release of TNF-alpha: 1) flow-cytometric analyses, using highly specific and avid mAbs to probe permeabilized whole blood leukocytes, showed that >80% of circulating monocytes contain intracellular TNF-alpha, whereas <5% contain IL-1 and none contain IL-6; 2) stimulation with immobilized anti-CD3 that was intended to activate lymphocytes also induced monocytes to release increased quantities of TNF-alpha; 3) rTNF-alpha, added in doses of 1 to 20 pg/ml to purified anti-CD3-stimulated lymphocytes, reproduced, in a dose-dependent manner, the motility-enhancing effect of adding monocytes; 4) the transient increase in the expression of TNF R-I on CD3-activated T lymphocytes parallels their transiently increased motility; and 5) addition of anti-TNF-alpha, anti-TNF R-I, anti-TNF R-II, or soluble TNF R-I decreased the motility of stimulated lymphocytes. These results suggest that T lymphocyte stimulation via the CD3-TCR complex signals nearby monocytes to release TNF-alpha, which feeds back on the lymphocytes to increase their locomotor activity.

Antigens, CD↗
PubMed1998

Comparison of the transdermal delivery of estradiol from two gel formulations.

OBJECTIVE: Conventional oral oestrogen replacement therapy can relieve postmenopausal symptoms but is associated with undesirable side-effects which can be minimised by avoiding the fluctuating hormonal blood levels resulting from oral therapy and eliminating hepatic first-pass metabolism by the use of the transdermal route. The two commercially available transdermal gel formulations differ in composition and application recommendations. Sandrena Gel contains 0.1% (w/w) and Oestrogel 0.06% (w/w) estradiol and recommended dosages are 0.5-1.5 g over 200-400 cm2 (Sandrena Gel) and 2.5 g gel over 720 cm2 (Oestrogel). In transdermal therapy the formulation composition may have a significant effect on drug delivery and we have therefore compared the permeation of estradiol from these formulations across human skin in vitro. METHODS: The in vitro percutaneous penetration of estradiol from the formulations through epidermal membranes prepared from excised female human thing skin was assessed over a 24 h period using static type Franz diffusion cells. RESULTS: Permeation of the active was similar from each formulation representing (at 24 h) 18.2 +/- 3.5% of the applied dose from Sandrena Gel and 17.4 +/- 4.8% of the applied dose from Oestrogel. These percentages equate to cumulative skin permeations of 0.65 +/- 0.15 microgram/cm2 and 0.45 +/- 0.15 microgram/cm2 respectively. CONCLUSION: The results suggest that the two formulations are bioequivalent at the recommended dose levels.

Administration, Cutaneous↗
PubMed1998

Guidelines for a therapeutic alliance between families and staff: a report of the SIOP Working Committee on Psychosocial Issues in Pediatric Oncology.

This, the fifth official document of the SIOP Working Committee on Psychosocial Issues in Pediatric Oncology, develops another important topic: the Therapeutic Alliance between families and staff. This is addressed to the Pediatric Oncology Community as Guidelines that could be followed. Every parent, medical staff member, and psychosocial professional involved in the care of the child should be responsible for cooperating in the child's best interest. Everyone must work together toward the common goal of curing the cancer and minimizing its medical and psychosocial side-effects.

Family↗
PubMed1998

B-chromosome origin in the endemic New Zealand frog Leiopelma hochstetteri through sex chromosome devolution.

The endemic New Zealand frog Leiopelma hochstetteri has variable numbers of mitotically stable B chromosomes. To assess whether the B chromosomes were derived from the autosome complement, they were isolated by micromanipulation and their DNA amplified by degenerate oligonucleotide primed PCR. Southern hybridizations of B chromosome DNA probes to genomic DNA from males and females characterized by differing numbers of B chromosomes demonstrated that the B chromosomes were derived from the univalent W sex chromosome characteristic of North Island populations. The presence of homologous B chromosome specific sequences from geographically distinct populations indicates a single origin of the B chromosomes. Furthermore, a primitive homology shared by B chromosomes and the W sex chromosome from an ancestral WZ/ZZ karyotype, which is still present in frogs from Great Barrier Island, shows that the B chromosomes originated soon after the univalent W sex chromosome had originated. Sequence analysis revealed that B chromosome DNA is composed of repeat sequences and has the potential to form stable hairpin structures. The molecular dynamics of these structures may reflect an inherent propensity to undergo rapid change in nucleotide sequence and chromosome structure.

Animals↗
PubMed1998

Codes for sound-source location in nontonotopic auditory cortex.

We evaluated two hypothetical codes for sound-source location in the auditory cortex. The topographical code assumed that single neurons are selective for particular locations and that sound-source locations are coded by the cortical location of small populations of maximally activated neurons. The distributed code assumed that the responses of individual neurons can carry information about locations throughout 360 degrees of azimuth and that accurate sound localization derives from information that is distributed across large populations of such panoramic neurons. We recorded from single units in the anterior ectosylvian sulcus area (area AES) and in area A2 of alpha-chloralose-anesthetized cats. Results obtained in the two areas were essentially equivalent. Noise bursts were presented from loudspeakers spaced in 20 degrees intervals of azimuth throughout 360 degrees of the horizontal plane. Spike counts of the majority of units were modulated >50% by changes in sound-source azimuth. Nevertheless, sound-source locations that produced greater than half-maximal spike counts often spanned >180 degrees of azimuth. The spatial selectivity of units tended to broaden and, often, to shift in azimuth as sound pressure levels (SPLs) were increased to a moderate level. We sometimes saw systematic changes in spatial tuning along segments of electrode tracks as long as 1.5 mm but such progressions were not evident at higher sound levels. Moderate-level sounds presented anywhere in the contralateral hemifield produced greater than half-maximal activation of nearly all units. These results are not consistent with the hypothesis of a topographic code. We used an artificial-neural-network algorithm to recognize spike patterns and, thereby, infer the locations of sound sources. Network input consisted of spike density functions formed by averages of responses to eight stimulus repetitions. Information carried in the responses of single units permitted reasonable estimates of sound-source locations throughout 360 degrees of azimuth. The most accurate units exhibited median errors in localization of <25 degrees, meaning that the network output fell within 25 degrees of the correct location on half of the trials. Spike patterns tended to vary with stimulus SPL, but level-invariant features of patterns permitted estimates of locations of sound sources that varied through 20-dB ranges. Sound localization based on spike patterns that preserved details of spike timing consistently was more accurate than localization based on spike counts alone. These results support the hypothesis that sound-source locations are represented by a distributed code and that individual neurons are, in effect, panoramic localizers.

Action Potentials↗
PubMed1998

Comparison between single-dose and divided-dose administration of dactinomycin and doxorubicin for patients with Wilms' tumor: a report from the National Wilms' Tumor Study Group.

PURPOSE: The National Wilms' Tumor Study (NWTS)-4 was designed to evaluate the efficacy, toxicity, and cost of administration of different regimens for the treatment of Wilms' tumor (WT). PATIENTS AND METHODS: Between August 6, 1986 and September 1, 1994, 1,687 previously untreated children less than 16 years of age with stages I to II/favorable histology (FH) or stage I/anaplastic histology WT (low-risk [LR] group) or stages III to IV/FH WT or stages I to IV/clear cell sarcoma of the kidney (high-risk [HR] group) were randomized to treatment that included vincristine and either divided-dose (standard [STD]) courses (5 days) or single-dose (pulse-intensive [PI]) treatment with dactinomycin. HR patients also received either STD courses (3 days) or PI treatment with doxorubicin. RESULTS: The 2-year relapse-free survival (RFS) rates for LR patients were 91.3% for 544 randomized to treatment with PI and 91.4% for 556 randomized to treatment with STD chemotherapy (P = .988). The 2-year RFS rates for HR patients were 87.3% for 299 randomized to treatment with PI and 90.0% for 288 randomized to treatment with STD chemotherapy (P = .865). CONCLUSION: We conclude that patients treated with PI combination chemotherapy for LR or HR WT or clear cell sarcoma of the kidney have equivalent 2-year RFS to those treated with STD regimens. PI drug administration is recommended as the new standard based on demonstrated efficacy, greater administered dose-intensity, less severe hematologic toxicity, and the requirement for fewer physician and hospital encounters.

Adolescent↗
PubMed1998

Effect of duration of treatment on treatment outcome and cost of treatment for Wilms' tumor: a report from the National Wilms' Tumor Study Group.

PURPOSE: National Wilms' Tumor Study (NWTS)-4 was designed to evaluate the efficacy, toxicity, and cost of the administration of different regimens for the treatment of Wilms' tumor (WT). PATIENTS AND METHODS: Between August 6, 1986 and September 1, 1994, 905 previously untreated children aged younger than 16 years with stage II favorable histology (FH) WT (low-risk [LR]), stages III to IV FH WT, or stages I to IV clear-cell sarcoma of the kidney (high-risk[HR]) were randomized after the completion of 6 months of chemotherapy to discontinue (short) or continue for 9 additional months (long) treatment with chemotherapy regimens that included vincristine and either divided-dose (standard [STD]) courses (5 days) or single-dose (pulse-intensive [PI]) treatment with dactinomycin. HR patients also received either divided-dose (STD) courses (3 days) or single-dose (PI) treatment with doxorubicin. RESULTS: The 4-year relapse-free survival (RFS) rates after the second randomization for LR patients were 83.7% for the 190 patients treated with short and 88.2% for the 187 patients treated with long chemotherapy (P = .11). The 4-year RFS rates after the second randomization for HR FH patients were 89.7% for the 256 patients treated with short and 88.8% for the 246 patients treated with long chemotherapy (P = .87). The charge for treatment with the short PI treatment regimens for all children with stages I through IV FH WT was approximately one half of that with the long STD treatment regimens. CONCLUSION: The short administration schedule for the treatment of children with WT is no less effective than the long administration schedule and can be administered at a substantially lower total treatment cost.

Adolescent↗