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Biomedical subjects

D M Green

Publications and source records attributed to D M Green.

At least 37 records · Page 2Linked to original sources
PubMed2001

Intravascular extension of Wilms tumor.

OBJECTIVE: To define the incidence and manifestations of and optimal therapy for children with intravascular extension of Wilms tumor. METHODS: Children on a collaborative study of Wilms tumor who had intravascular extension into the inferior vena cava (IVC) or atrium were identified. Surgical checklists and surgical and pathology reports were reviewed. RESULTS: One hundred sixty-five of 2,731 patients had intravascular extension of Wilms tumor. The level of extension was IVC in 134 and atrium in 31. Sixty-nine had received preoperative therapy (55 with IVC extension and 14 with atrial extension) for a median of 8 weeks. Complications during preoperative chemotherapy were seen in five patients (tumor embolism and tumor progression in one each, and three with adult respiratory distress syndrome, one of which was fatal). The intravascular extension of the tumor regressed in 39 of 49 children with comparable pre- and posttherapy radiographic studies, including 7 of 12 in whom the tumor regressed from an atrial location, thus obviating the need for cardiopulmonary bypass. Surgical complications occurred in 36.7% of the children in the atrial group and 17.2% in the IVC group. The frequency of surgical complications was 26% in the primary resection group versus 13.2% in children with preoperative therapy. When all the complications of therapy were considered, including those that occurred during the interval of preoperative chemotherapy (one of the five also had a surgical complication), the incidence of complications among those receiving preoperative therapy was not statistically different from the incidence among those who underwent primary resection. The difference in 3-year relapse-free survival (76.9% for 165 patients with intravascular extension, 80.3% for 1,622 patients with no extension) was not statistically significant whether or not it was adjusted for stage and histology. CONCLUSIONS: Preoperative treatment of these children may facilitate resection by decreasing the extent of the tumor thrombus, but the overall frequency of complications is similar in both groups.

Child↗
PubMed2001

Clinical presentation of rhabdoid tumors of the kidney.

PURPOSE: We designed this study to differentiate the clinical presentation, particularly the incidence of hematuria, of a rhabdoid tumor of the kidney (RTK), a rare but highly malignant tumor, from a Wilms tumor. PATIENTS AND METHODS: We reviewed patient flow charts from the National Wilms Tumor Study Group and queried participating hospitals to obtain additional information regarding presenting symptoms and laboratory data for fifty patients. Patient ages ranged from 2 days to 3.5 years with a mean of 11 months. We documented the presence of gross and microscopic hematuria, fever, and hypercalcemia. RESULTS: Whereas 75% of children with rhabdoid tumor of the kidney (RTK) had stage III (44%), IV (27%), or V (4%) tumors, 67% of children with Wilms tumors had stage I (41%) or II (26%) tumors. Either gross or microscopic hematuria was present in 84.4% (27/32) of the patients with RTK. Gross hematuria was present in 59% (22/37) of children with RTK compared with 18% previously reported with Wilms tumor. Microscopic hematuria was present in 76% (22/29) of children with RTK compared with 24% previously reported with Wilms tumor. Fever was found in 44% (16/36) of children with RTK, compared with 22% of children previously reported with Wilms tumor. Hypercalcemia was seen 26% (6/23) of children with RTK. CONCLUSION: Although diagnosis of any renal mass still must be confirmed with histopathologic features, a distinct clinical presentation with fever, hematuria, a young age, and high-tumor stage at presentation suggests the diagnosis of RTK.

Age of Onset↗
PubMed2001

Secondary acute myelogenous leukemia in patients previously treated for childhood renal tumors: a report from the National Wilms Tumor Study Group.

PURPOSE: This review characterized cases of secondary acute myelogenous leukemia (AML) occurring after treatment of renal neoplasms on protocols of the National Wilms Tumor Study Group (NWTSG) between October 1969 and December 1991. PATIENTS AND METHODS: The NWTSG database was reviewed for cases of secondary AML and for WT1 status of the affected patients. Referring institutions were contacted by a confidential letter requesting pathology reports, results of immunophenotyping, cytogenetic, and molecular analyses, and details concerning treatment of AML. RESULTS: Of the 5,278 patients treated during the study period, 43 had second malignant neoplasms, and 7 of these 43 had AML. At the time of diagnosis of Wilms tumor, the median age of the seven patients (4 boys) was 3.2 years. Five of the seven renal neoplasms had favorable histologic characteristics. The most common French-American-British morphology was M5. One patient had bilateral tumors, and two were treated for recurrent Wilms tumor. All patients received chemotherapy regimens that included doxorubicin (6) or etoposide (1), and six were treated with infradiaphragmatic irradiation. The median latency period from initial diagnosis of the renal neoplasm to development of secondary AML was 3 years (range, 1.2-4 yrs). One patient had the translocation t(9:11)(p22;q23); WT1 status was not noted for any of the seven patients. CONCLUSIONS: The development of secondary AML in this subset of patients after treatment of renal neoplasms may reflect the interaction of the effects of treatment and possible genetic predisposition toward cancer.

Abnormalities, Multiple↗
PubMed2000

Renal failure in the Denys-Drash and Wilms' tumor-aniridia syndromes.

Nearly 6000 patients enrolled in four clinical trials of the National Wilms' Tumor Study Group during 1969-1995 were followed until death or for a median of 11.0 years of survival for the onset of renal failure (RF). Thirteen of 22 patients with Denys-Drash syndrome and 10 of 46 patients with the Wilms' tumor aniridia syndrome developed RF. The cumulative risks of RF at 20 years from Wilms' tumor diagnosis were 62% and 38%, respectively. Only 21 cases of RF were observed among 5358 patients with unilateral disease who did not have characteristic congenital genitourinary anomalies, and their risk was <1%. Although other explanations cannot be completely excluded, the high rate of RF in patients with the aniridia syndrome challenges the view that nephropathy is associated uniquely with missense mutations in the WT1 gene. It suggests the possibility of a further gradation in the spectrum of phenotypes associated with different WT1 mutations. Patients with Wilms' tumor and aniridia or genitourinary abnormalities should be followed closely throughout life for signs of nephropathy or RF.

Adolescent↗
PubMed2000

Ichthyophonus-like infection in wild amphibians from Québec, Canada.

Myositis associated with infection by Ichthyophonus-like organisms was diagnosed in 35 of 260 (13%) wild amphibians collected in Quebec, Canada, from 1959 to 1964 (n = 30), and 1992 to 1999 (n = 230). Infection was diagnosed in 17 green frogs Rana clamitans, 9 wood frogs R. sylvatica, 4 red-spotted newts Notophthalmus viridescens, 3 bullfrogs R. catesbeiana, 1 spring peeper Pseudacris crucifer, and 1 pickerel frog R. palustris. The spring peeper and one of the bullfrogs were collected in 1964 from the Mont Saint-Hilaire Biosphere Reserve, indicating long-term presence of the organism. Spores of the organisms invaded striated muscle fibers and were associated with variable degrees of granulomatous and eosinophilic inflammation. Infection was considered fatal in 2 green frogs, 1 wood frog, and 1 red-spotted newt. It was considered potentially significant in 3 additional green frogs in which up to 100% of the fibers of some muscles were replaced by spores associated with a severe granulomatous reaction. Ultrastructural features of Ichthyophonus-like spores included a thick trilaminated wall, a paramural cytoplasm, multiple nuclei, oval mitochondria with short tubulo-vesicular cristae and numerous ribosomes. This report represents 4 new host records and shows that ichthyophonosis is enzootic in amphibians from Quebec.

Amphibians↗
PubMed2000

Structure and evolution of supernumerary chromosomes in the Pacific giant salamander, Dicamptodon tenebrosus.

We examined the genetic make-up and plausible origins of the supernumerary (B) chromosomes of the Pacific giant salamander, Dicamptodon tenebrosus, from the Pacific Northwest of North America. These salamanders have variable numbers of B chromosomes, from 0 to 10 per individual. Salamanders from the most southerly and northerly regions of the species' range have lower average numbers of B chromosomes than salamanders in the middle of the range. To assess how the supernumerary chromosomes originated in D. tenebrosus, B chromosome DNA was isolated by microdissection and amplified by degenerate oligonucleotide-primed PCR. The B chromosome DNA hybridized similarly to genomic DNA from individuals of D. tenebrosus and the related species D. copei and D. ensatus, thus demonstrating that the supernumerary chromosomes were derived from the normal chromosome complement. Unique hybridization bands in both D. copei and D. tenebrosus suggest that the shared sequences have evolved independently.

Animals↗
PubMed2000

Evolutionary interactions between Drosophila melanogaster and its parasitoid Asobara tabida.

Drosophila melanogaster is attacked by parasitoids that develop internally in the larva. They can defend themselves by a cellular immune response (host resistance), although this can be disabled by parasitoid countermeasures (parasitoid virulence). D. melanogaster and its parasitoids are an excellent system in which to study coevolution experimentally. We designed an experiment to compare changes in resistance and virulence in replicate populations of flies and parasitoids maintained together for approximately 10 fly (five parasitoid) generations. The experiment had three treatments each with three replicates: (A) no parasitoids (B) outbred parasitoids (C) partially inbred parasitoids. Host resistance increased in treatments B and C but there was no difference between these treatments. Parasitoid virulence appeared not to change during the experiment. Host larvae in treatments B and C fed at lower rates than those in A, evidence of a trade-off between resistance and larval competitive ability. We found no evidence for local adaptation, as hosts from the different replicates of treatment C performed no differently against parasitoids from the same and other replicates. Also, we found no evidence for the evolution of behavioural traits in the host that could lead to lower probabilities of being attacked. Comparing the evolution of host resistance in these seminatural settings with that in artificial selection experiments provides insight into how the conflicting selection pressures on host resistance interact.

Animals↗
PubMed2000

Clear cell sarcoma of the kidney: a review of 351 cases from the National Wilms Tumor Study Group Pathology Center.

We reviewed 351 cases of clear cell sarcoma of the kidney (CCSK), including 182 cases entered on National Wilms Tumor Study Group (NWTSG) trials 1-4 for which clinical follow-up information was available. Tumors were restaged using NWTS 5 criteria. Mean age at diagnosis in the NWTS group was 36 months with a range of 2 months to 14 years. The male to female ratio was 2:1. Typical gross features included large size (mean diameter 11.3 cm), a mucoid texture, foci of necrosis, and prominent cyst formation. Nine major histologic patterns were identified (classic, myxoid, sclerosing, cellular, epithelioid, palisading, spindle, storiform, and anaplastic); virtually all tumors contained multiple patterns that blended with one another. Immunohistochemical stains were performed on 45 cases; only vimentin was consistently immunoreactive. Consistently negative results with other antibodies helped exclude other tumors in the differential diagnosis; all CCSKs were cytokeratin-negative, including epithelioid tumors that mimicked Wilms tumor, and MIC2-negative, including cellular tumors that mimicked primitive neuroectodermal tumor. The p53 gene product was rarely overexpressed in non-anaplastic CCSKs, but strikingly overexpressed in two of three anaplastic CCSKs. Overall survival was 69%. Multivariate analysis revealed four independent prognostic factors for survival: treatment with doxorubicin, stage, age at diagnosis, and tumor necrosis. Of note, stage 1 patients had a remarkable 98% survival rate. No other histologic or clinical variable independently correlated with survival.

Adolescent↗
PubMed2000

Characteristics and outcome of children with Beckwith-Wiedemann syndrome and Wilms' tumor: a report from the National Wilms Tumor Study Group.

PURPOSE: Children with Beckwith-Wiedemann syndrome (BWS) are at increased risk for developing Wilms' tumor (WT). We reviewed the National Wilms Tumor Study Group (NWTSG) records to assess clinical characteristics and outcome of patients with WT and BWS. METHODS: In the NWTSG, treating clinicians were asked to report, for each enrolled patient, whether the patient had BWS. Between 1980 and 1995, 4,669 patients were treated on two consecutive NWTSG protocols (NWTS 3 and NWTS 4). We retrospectively reviewed the clinical characteristics and treatment outcomes of BWS patients compared with patients with WT without BWS. RESULTS: Fifty-three children enrolled onto NWTS 3 and 4 were reported to have BWS. BWS patients were more likely to present with lower-stage tumors (P =.0001), with more than half (27 of 53) presenting with stage I disease. The overall treatment outcomes for the BWS patients were nearly identical to those without BWS, with overall survival at 4 years from diagnosis at 89% and 90%, respectively. Overall, 21% of the patients with BWS had bilateral disease, either at diagnosis (nine of 53) or as metachronous contralateral recurrence (two of 53). BWS patients enrolled onto NWTS 4 had smaller tumors than those enrolled onto NWTS 3 (P =.02), a trend not seen in the non-BWS patients. CONCLUSION: Like children without BWS, children with BWS and WT have an excellent prognosis with modern treatment regimens. There is a high risk of bilateral disease, and increasingly smaller tumors are being detected. This suggests that a national trial assessing the role of ultrasound screening followed by nephron-sparing surgery for some patients may be appropriate.

Beckwith-Wiedemann Syndrome↗
PubMed2000

Second malignant neoplasms after treatment for Hodgkin's disease in childhood or adolescence.

PURPOSE: To determine the frequency of and risk factors for second malignant neoplasms (SMNs) after treatment for Hodgkin's disease diagnosed in children and adolescents. PATIENTS AND METHODS: One hundred eighty-two consecutive, previously untreated patients with Hodgkin's disease who were younger than 20 years of age at diagnosis and who were referred to Roswell Park Cancer Institute (Buffalo, NY) for treatment between January 1, 1960, and December 31, 1989, were studied. Sex-specific standardized incidence ratios (SIRs) were calculated. Kaplan-Meier survival estimates and Cox regression analyses were performed to determine the relationship of several demographic and treatment variables to SMN incidence. RESULTS: Twenty-eight patients developed an SMN at a mean of 14.93 +/- 8.09 years (range, 2.65 to 29.88 years) after diagnosis of Hodgkin's disease. The cumulative percentage of patients who developed an SMN was 26.27 +/- 6.75% at 30 years after diagnosis. The SIR was 9.39 (95% confidence interval [CI], 4.05 to 18.49) for male patients and 10.16 (95% CI, 5.56 to 17.05) for female patients. The most frequent SMNs were thyroid cancer, breast cancer, nonmelanoma skin cancer, non-Hodgkin's lymphoma, and acute leukemia. Multivariate analysis of sex, treatment with any alkylating agent, treatment with doxorubicin, splenectomy, and relapse (as a time-dependent covariate) with time to SMN onset gave nonsignificant results. CONCLUSION: Successfully treated children and adolescents with Hodgkin's disease have a substantial risk for the occurrence of subsequent neoplasms. The most frequent SMNs (skin, thyroid, and breast) are readily detected by physical examination and available screening procedures.

Adolescent↗
PubMed2000

Recovery and enhancement of faded cleared and double stained specimens.

Cleared and stained specimens may become faded and/or opaque after long periods in preservative solutions. We developed a technique to revitalize faded and/or destained specimens regardless of their age. By adapting and revising Wassersug's procedure for differential staining of bone and cartilage, we successfully cleared and restained numerous small amphibian specimens of various ages. After rehydrating, specimens were bleached in potassium hydroxide and hydrogen peroxide, stained with alcian blue, and macerated with trypsin as needed. Alizarin red stain was applied or reapplied, although staining occasionally was unsuccessful in old formalin fixed specimens. After restaining, the specimens were dehydrated and placed in glycerol.

Animals↗
PubMed1999

Protamine-like sperm nuclear basic proteins in the primitive frog Ascaphus truei and histone reversions among more advanced frogs.

Sperm nuclear basic proteins (SNBPs) that condense chromatin are very diverse. In animals, evolution of SNBPs has proceeded from lysine-rich histone H type in sponges to more arginine-rich protamine-like PL and protamine P types. Yet sporadic PL/P to H reversions are known to occur in both protostomes and deuterostomes. To determine why this is the case, we have examined SNBPs in eleven anuran species. We find that sperm of the primitive, internally fertilizing archeobatrachian frog A. truei (family Ascaphidae) has PL/P type (42 mol % arginine), with an electrophoretic profile similar to SNBPs in another archeobatrachian, externally fertilizing Leiopelma hochstetteri (family Leiopelmatidae). Cytochemistry of sperm nuclei in the advanced, externally fertilizing neobatrachian frogs Crinia signifera and C. deserticola (family Myobatrachidae) indicates that they have reverted to H type SNBPs. This is also known to be the case in externally fertilizing Rana (family Ranidae) and Silurana, a subgenus of Xenopus (family Pipidae). Such a trend, from PL/P type SNBPs in two archeobatrachians to sporadic reversions to H type in more advanced frogs, parallels the ultrastructural simplification from complex A. truei introsperm to neobatrachian aquasperm that Jamieson et al. (1993. Herpetologica 49:52-65) attribute as a secondary reversion to external fertilization.

Animals↗
PubMed1999

Sulfonamidopyrrolidinone factor Xa inhibitors: potency and selectivity enhancements via P-1 and P-4 optimization.

Sulfonamidopyrrolidinones were previously disclosed as a selective class of factor Xa (fXa) inhibitors, culminating in the identification of RPR120844 as a potent member with efficacy in vivo. Recognizing the usefulness of the central pyrrolidinone template for the presentation of ligands to the S-1 and S-4 subsites of fXa, studies to optimize the P-1 and P-4 groups were initiated. Sulfonamidopyrrolidinones containing 4-hydroxy- and 4-aminobenzamidines were discovered to be effective inhibitors of fXa. X-ray crystallographic experiments in trypsin and molecular modeling studies suggest that our inhibitors bind by insertion of the 4-hydroxybenzamidine moiety into the S-1 subsite of the fXa active site. Of the P-4 groups examined, the pyridylthienyl sulfonamides were found to confer excellent potency and selectivity especially in combination with 4-hydroxybenzamidine. Compound 20b (RPR130737) was shown to be a potent fXa inhibitor (K(i) = 2 nM) with selectivity against structurally related serine proteinases (>1000 times). Preliminary biological evaluation demonstrates the effectiveness of this inhibitor in common assays of thrombosis in vitro (e.g. activated partial thromboplastin time) and in vivo (e.g. rat FeCl(2)-induced carotid artery thrombosis model).

Amidines↗
PubMed1999

Aminoisoquinolines: design and synthesis of an orally active benzamidine isostere for the inhibition of factor XA.

The design, synthesis and SAR of sulfonamidopyrrolidinone fXa inhibitors incorporating a new benzamidine isostere, namely aminoisoquinolines, is described. These inhibitors have higher Caco-2 cell permeability than comparable benzamidines and attain higher levels of exposure upon oral dosing. The most potent member 14b (fXa Ki=6 nM) is selective against other serine proteases of interest (>600 fold).

Administration, Oral↗
PubMed1999

Significance and management of computed tomography detected pulmonary nodules: a report from the National Wilms Tumor Study Group.

PURPOSE: To define the optimal treatment for children with Wilms tumor who have pulmonary nodules identified on chest computed tomography (CT) scan, but have a negative chest radiograph, we evaluated the outcome of all such patients randomized or followed on National Wilms Tumor Study (NWTS)-3 and -4. PATIENTS AND METHODS: We estimated the event-free and overall survival percentages of 53 patients with favorable histology tumors and pulmonary densities identified only by CT scan (CT-only) who were treated as Stage IV with intensive doxorubicin-containing chemotherapy and whole-lung irradiation, and compared these to the event-free and overall survival percentages of 37 CT-only patients who were treated less aggressively based on the extent of locoregional disease with 2 or 3 drugs, and without whole-lung irradiation. RESULTS: The 4-year event-free and overall survival percentages of the 53 patients with CT-only nodules and favorable histology Wilms tumor who were treated as Stage IV were 89% and 91%, respectively. The 4-year event-free and overall survival percentages for the 37 patients with CT-only nodules and favorable histology who were treated according to the extent of locoregional disease were 80% and 85%, respectively. The differences observed between the 2 groups were not statistically significant. Among the patients who received whole-lung irradiation, there were fewer pulmonary relapses, but more deaths attributable to lung toxicity. CONCLUSIONS: The current data raise the possibility that children with Wilms tumor and CT-only pulmonary nodules who receive whole lung irradiation have fewer pulmonary relapses, but a greater number of deaths due to treatment toxicity. The role of whole lung irradiation in the treatment of this group of patients cannot be definitively determined based on the present data. Prolonged follow-up of this group of patients is necessary to accurately estimate the frequency of late, treatment-related mortality.

Adolescent↗
PubMed1999

Factors affecting the risk of contralateral Wilms tumor development: a report from the National Wilms Tumor Study Group.

BACKGROUND: Approximately 1% of children with unilateral Wilms tumor develop contralateral disease. The authors assessed the demographic and histologic features associated with metachronous bilateral Wilms tumor (BWT). METHODS: Characteristics of all children registered on the first four National Wilms Tumor Studies (NWTS) were recorded. The primary endpoint for evaluation was the first appearance of Wilms tumor in the remaining kidney. The cumulative risk of contralateral disease as a function of time since initial presentation was calculated as 1 minus the Kaplan-Meier estimate of remaining free of contralateral disease. A matched case control study was conducted to determine whether the presence and type of nephrogenic rests (NRs) were associated with metachronous BWT. RESULTS: Fifty-eight of 4669 registered children developed metachronous BWT; 38 of 2445 females (expected, 30.2) versus 20 of 2224 males (expected, 27.8) (P = 0.04) developed BWT. The cumulative incidence of contralateral disease 6 years after initial diagnosis decreased from greater than 3% in the first NWTS to approximately 1.5% in the three subsequent studies (P = 0.08). Patients with NRs had a significantly increased risk of metachronous BWT. This was particularly true for young children (20 of 206 age < 12 months compared with 0 of 304 age > 12 months). Data from the matched case control study confirmed the increased relative risk associated with young age and the presence of NRs. CONCLUSIONS: Children younger than 12 months diagnosed with Wilms tumor who also have NRs, in particular perilobar NRs, have a markedly increased risk of developing contralateral disease and require frequent and regular surveillance for several years. Surveillance is also recommended for those with NRs who are diagnosed after the age of 12 months.

Age Factors↗
PubMed1999

Screening for Wilms tumor in children with Beckwith-Wiedemann syndrome or idiopathic hemihypertrophy.

BACKGROUND: Children with Beckwith-Wiedemann syndrome and idiopathic hemihypertrophy (BWS/HH) are at increased risk for developing Wilms tumor and screening with abdominal sonography is frequently recommended. However, there is a paucity of published data supporting this strategy. The purpose of this study was to determine whether sonographic screening at intervals of 4 months or less reduced the proportion of late-stage Wilms Tumor (WT) in children with BWS/HH. PROCEDURE: A case series analysis was employed to compare the proportion of late-stage (stage III or IV) Wilms tumor in patients with BWS/HH who were screened with sonography (n = 15) to the proportion of late-stage Wilms tumor in unscreened patients with BWS/HH (n = 59). Patients were identified from the BWS Registry and from previously published studies. Screened patients had sonograms at intervals of 4 months or less. RESULTS: None of the 12 screened children with Wilms tumor had late-stage disease, whereas 25 of 59 (42%) of unscreened children had late-stage Wilms tumor, a difference that was statistically significant (P < 0.003). Three children had false positive screening studies. They were operated on for suspected Wilms tumor but the lesions proved to be complicated renal cysts (n = 2) or nephroblastomatosis (n = 1). CONCLUSIONS: This study suggests that children with BWS/HH may benefit from screening sonograms at intervals of 4 months or less. However, false positive screening exams may result in unnecessary surgery. Given the rarity of BWS/HH, a larger, prospective international screening study is necessary to determine if the benefits of screening outweigh the risks.

Adolescent↗