RESUMO
Drosophila suzukii (Spotted Wing Drosophila) has recently become a serious invasive pest of fruit crops in the USA, Canada, and Europe, leading to substantial economic losses. D. suzukii is a direct pest, ovipositing directly into ripe or ripening fruits; in contrast, other Drosophilids utilize decaying or blemished fruits and are nuisance pests at worst. Immature stages of D. suzukii are difficult to differentiate from other Drosophilids, posing problems for research and for meeting quarantine restrictions designed to prevent the spread of this pest in fruit exports. Here we used a combined phylogenetic and bioinformatic approach to discover genetic markers suitable for a species diagnostic protocol of this agricultural pest. We describe a molecular diagnostic for rapid identification of single D. suzukii larva using multiplex polymerase chain reaction. Our molecular diagnostic was validated using nine different species of Drosophila for specificity and 19 populations of D. suzukii from different geographical regions to ensure utility within species.
Assuntos
Drosophila/genética , Marcadores Genéticos/genética , Genômica/métodos , Controle de Insetos/métodos , Reação em Cadeia da Polimerase Multiplex/métodos , Filogenia , Animais , Biologia Computacional/métodos , Sequência Conservada/genética , Primers do DNA/genética , Geografia , Sensibilidade e Especificidade , Especificidade da EspécieRESUMO
Halyomorpha halys Stål, the brown marmorated stink bug (Hemiptera: Pentatomidae), is an invasive pest with established populations in Oregon. The generalist feeding habits of H. halys suggest it has the potential to be a pest of many specialty crops grown in Oregon, including hazelnuts, Corylus avellana L. The objectives of this study were to: 1) characterize the damage to developing hazelnut kernels resulting from feeding by H. halys adults, 2) determine how the timing of feeding during kernel development influences damage to kernels, and 3) determine if hazelnut shell thickness has an effect on feeding frequency on kernels. Adult brown marmorated stink bugs were allowed to feed on developing nuts for 1-wk periods from initial kernel development (spring) until harvest (fall). Developing nuts not exposed to feeding by H. halys served as a control treatment. The degree of damage and diagnostic symptoms corresponded with the hazelnut kernels' physiological development. Our results demonstrated that when H. halys fed on hazelnuts before kernel expansion, development of the kernels could cease, resulting in empty shells. When stink bugs fed during kernel expansion, kernels appeared malformed. When stink bugs fed on mature nuts the kernels exhibited corky, necrotic areas. Although significant differences in shell thickness were observed among the cultivars, no significant differences occurred in the proportions of damaged kernels based on field tests and laboratory choice tests. The results of these studies demonstrated that commercial hazelnuts are susceptible to damage caused by the feeding of H. halys throughout the entire period of kernel development.
Assuntos
Corylus/crescimento & desenvolvimento , Hemípteros/fisiologia , Herbivoria , Animais , Hemípteros/crescimento & desenvolvimento , Masculino , Ninfa/crescimento & desenvolvimento , Ninfa/fisiologia , Oregon , Sementes/crescimento & desenvolvimentoRESUMO
This study compared lethal and sublethal effects of five insecticides, chlorantraniliprole, cyantraniliprole, spinetoram, novaluron, and lambda-cyhalothrin, on adult and second instars of two green lacewing species, Chrysoperla carnea (Stephens) and Chrysoperla johnsoni Henry, Wells and Pupedis (Neuroptera: Chrysopidae) in the laboratory. Formulated pesticides were tested using concentrations equivalent to the high label rate dissolved in 378.5 liters of water. Novaluron and lambda-cyhalothrin were toxic to larvae and no treated larvae survived to the adult stage. Larva to adult survival was reduced in chlorantraniliprole, cyantraniliprole, and spinetoram treatments. Larva to adult developmental time and sex ratio were not different among the treatments within a species. Chlorantraniliprole, cyantraniliprole, spinetoram, and lambda-cyhalothrin treatments were highly toxic to adults of both species. C. johnsoni females had lower fecundity than C. carnea females in the control. Fecundity of females was similar in the control and novaluron treatment within each species. However, fertility and egg viability were negatively impacted for both species when females were treated with novaluron. C. carnea females had higher fertility and egg viability than C. johnsoni females in the control. Adults of both species had similar longevity in the control and novaluron treatment and adult longevity was not gender specific. All insecticides tested were toxic to C. johnsoni and C. carnea either at the immature or adult stage or both. Results of this study demonstrate a similarity between C. johnsoni and C. carnea for pesticide toxicity irrespective of their varied geographical distributions.
Assuntos
Insetos/efeitos dos fármacos , Inseticidas/toxicidade , Animais , Agentes de Controle Biológico , Feminino , Insetos/crescimento & desenvolvimento , Larva/efeitos dos fármacos , Masculino , Óvulo/efeitos dos fármacos , Especificidade da EspécieRESUMO
This laboratory bioassay focused on lethal and sublethal effects of five insecticides (chlorantraniliprole, cyantraniliprole, spinetoram, novaluron, and lambda-cyhalothrin) and two fungicide treatments (sulfur and a mixture of copper hydroxide and mancozeb) on the predatory mired bug, Deraeocoris brevis (Uhler) (Hemiptera: Miridae) using second instars and adult males and females. Formulated pesticides were tested using concentrations that were equivalent to the high label rate (1x) (high rate) and 1/10th of that amount (0.1x) (low rate) dissolved in 378.5 liters of water. Lambda-cyhalothrin was highly toxic to D. brevis nymphs and adults at both rates, whereas both rates of novaluron were highly toxic to nymphs. Cyantraniliprole, chlorantraniliprole, and novaluron were less toxic to adults, and chlorantraniliprole and spinetoram were less toxic to nymphs. Both rates of spinetoram caused significant mortality to adults. Fecundity of adult females was affected negatively by the high rates of either novaluron or spinetoram, whereas the fertility was affected only by the high rate of novaluron. The high rate of spinetoram reduced survival of nymphs. Adults treated with spinetoram had reduced longevity. Cyantraniliprole caused some mortality to nymphs and affected their survival. Both rates of sulfur were toxic to nymphs and affected emergence to adults. The mixture of copper hydroxide and mancozeb was less toxic to D. brevis. Neither adult longevity nor sex ratio was affected by the fungicides. The r values for D. brecis treated with lambda-cyhalothrin, novaluron, spinetoram, and sulfur were low, indicating that these products may have negative impact on population growth.
Assuntos
Fungicidas Industriais/toxicidade , Hemípteros/efeitos dos fármacos , Inseticidas/toxicidade , Animais , Agentes de Controle Biológico , Feminino , Humanos , Masculino , Ninfa/efeitos dos fármacosRESUMO
A 6 year old pluriparous Merino ewe was presented for investigation of a large intra-abdominal mass. Post-mortem examination revealed a 360° clockwise uterine torsion was present with a mummifying fetus. The torsion involved the left ureter resulting in a severe hydroureteronephrosis. Uterine torsion is uncommon in the ewe, occurring in less than 0.1% of pregnancies in one report (Mahmoud et al. Livest Res Rural Dev 2018;30), but cases are likely to be undiagnosed, particularly under the extensive management conditions typical of Australia. The chronicity of the condition in this ewe would support this statement. To the authors' knowledge this is the first reported case of hydroureteronephrosis secondary to uterine torsion in any species.
Assuntos
Doenças dos Ovinos , Ureter , Animais , Austrália , Feminino , Morte Fetal , Feto , Gravidez , Ovinos , Doenças dos Ovinos/diagnóstico por imagem , Anormalidade Torcional/diagnóstico por imagem , Anormalidade Torcional/veterinária , Útero/diagnóstico por imagemRESUMO
Ultrasonography, radiography and exploratory coeliotomy were used to diagnose and treat a large intracoelomic neoplasm from a female koi carp (Cyprinus carpio) presented for abdominal enlargement of several months duration. Feed was withheld for 1 week immediately prior to surgery and the fish was sedated with isoeugenol (AQUI-S) at a dose rate of 10 mL/L to facilitate diagnostic imaging techniques. Surgical anaesthesia was induced by adding tricaine (MS-222) 50 mg/L to the water and an exploratory coeliotomy and tumour removal was performed. The fish was allowed to recover in fresh water at 18 degrees C and salt was added slowly to the water over a period of 1 hour to a concentration of 5 g/L This concentration was maintained in a recovery pond for 1 week postoperatively. Enrofloxacin was administered intramuscularly (10 mg/kg) immediately, 3 days and 1 week postoperatively. A diagnosis of undifferentiated ovarian carcinoma was made on the basis of the histological appearance of the neoplasm and immunohistochemical staining.
Assuntos
Carcinoma/veterinária , Carpas , Doenças dos Peixes/cirurgia , Neoplasias Ovarianas/veterinária , Animais , Carcinoma/diagnóstico , Carcinoma/patologia , Carcinoma/cirurgia , Feminino , Doenças dos Peixes/diagnóstico , Imuno-Histoquímica/veterinária , Laparoscopia/métodos , Laparoscopia/veterinária , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/cirurgia , Resultado do TratamentoRESUMO
This report describes the lesions seen in an extremely weak and emaciated adult male loggerhead turtle (Caretta caretta) found stranded near Perth, Western Australia. Blood collected from a dorsal cervical sinus immediately prior to euthanasia demonstrated severe anaemia, markedly elevated plasma concentrations of creatinine kinase (2263 U/L), alkaline phosphatase (58 U/L), urea (18.1 mmol/L) and hypoglycaemia (glucose 0.7 mmol/L). Necropsy examination demonstrated a severe chronic osteoarthritis of the right shoulder joint with marked remodelling of the glenoid fossa, coracoid, scapula and humerus. There was marked synovial effusion and periarticular fibrosis. Cytological examination and culture of synovial fluid failed to demonstrate an infectious agent. Other findings were low numbers of trypanorhynch cysts present on the surface of the liver and numerous spirorchid eggs in the attached mesentery. Several large and small spirorchid flukes were present in the heart and there was a localised endarteritis in the left aortic arch associated with this infection. Numerous nematode eggs and at least three species of spirorchid eggs were seen microscopically in faeces collected from the terminal colon. The pathogenesis and significance of these lesions is discussed.
Assuntos
Osteoartrite/veterinária , Articulação do Ombro/patologia , Tartarugas , Fosfatase Alcalina/sangue , Animais , Glicemia/análise , Doença Crônica , Creatina Quinase/sangue , Evolução Fatal , Masculino , Osteoartrite/diagnóstico , Osteoartrite/patologia , Radiografia , Articulação do Ombro/diagnóstico por imagem , Austrália OcidentalRESUMO
The clinical signs, radiographic and pathological findings of four histologically similar neoplasms that occurred as unilateral tumours projecting from the left axilla in three galahs (Eolophus roseicapillus) and one sulphur-crested cockatoo (Cacatua galerita) are described. In each case, the main reason for clinical presentation was respiratory distress. All cases were eventually fatal due to airway obstruction with evidence of extensive neoplastic invasion of the lungs, major airways and or humerus in all cases. A diagnosis of airsac cystadenocarcinoma was made in each bird on the basis of gross and histological appearance. The neoplasms were composed of fluid or air-filled sacs of proliferative cuboidal to squamous epithelial cells that stained positively with cytokeratin and negatively with vimentin. This was supported by a thin fibrovascular network although at least some areas in all four birds resembled airsac tissue. In some cases areas of haemorrhage, erythrophagocytosis, haemosiderosis and nodules of haemosiderophage infiltration with acicular cholesterol clefts were present in some parts of the sectioned tissue.
Assuntos
Sacos Aéreos , Doenças das Aves/patologia , Cacatuas , Cistadenocarcinoma/veterinária , Neoplasias do Sistema Respiratório/veterinária , Sacos Aéreos/patologia , Animais , Cistadenocarcinoma/patologia , Evolução Fatal , Feminino , Imuno-Histoquímica/veterinária , Masculino , Metástase Neoplásica , Neoplasias do Sistema Respiratório/patologiaRESUMO
Wilms' tumor, an embryonic renal neoplasm diagnosed primarily in young children, can occur in either a noninheritable (sporadic) or a familial form, with the latter presenting earlier and more often at bilateral sites. Although familial Wilms' tumor is thought to develop through inherited and acquired mutational inactivation of the two alleles of predisposing tumor suppressor genes, only a small percentage of cases can be accounted for by mutations affecting the WT1 gene or linkage to the Beckwith-Weidemann syndrome of the BWS region on the short arm of chromosome 11. To find chromosomal regions that might contain genes important in the development of this disease, we used comparative genomic hybridization to analyze tumor specimens from familial cases for chromosomal regions that were consistently lost. Although inherited lesions of tumor suppressors are most often inactivating point mutations, accompanying somatic lesions in the malignant clones are often chromosomal deletions; therefore, consensus regions of loss in familial tumors are likely to harbor genes linked to familial predisposition. There were extensive genomic aberrations among the eight familial cases studied, with an average of 6.5 changes/tumor (range, 0-22). The most consistent findings with likely biological relevance were deletions of chromosomes 4 (consensus, 4q21-qter), 9 (consensus, 9p21-pter), 20p, and 3 (consensus, 3q12-q21). These regions have not been previously implicated in Wilms' tumor and may harbor novel genes that could aid attempts to understand the familial predisposition as well as the development and progression of these tumors.
Assuntos
Deleção Cromossômica , Neoplasias Renais/genética , Tumor de Wilms/genética , Cromossomos Humanos Par 20 , Cromossomos Humanos Par 3 , Cromossomos Humanos Par 4 , Cromossomos Humanos Par 9 , Genes Supressores de Tumor , Humanos , Hibridização de Ácido NucleicoRESUMO
BACKGROUND: Since its initial detection in Norway in 1998, atypical scrapie ('atypical/Nor98 scrapie') has been reported in sheep in the majority of European countries (including in regions free of classical scrapie) and in the Falkland Islands, the USA, Canada, New Zealand and Australia. CASE SERIES: The diagnosis in Australia of atypical scrapie in four Merino and one Merino-cross sheep showing clinical signs of neurological disease was based on the detection of grey matter neuropil vacuolation (spongiform change) in the brain (particularly in the molecular layer of the cerebellar cortex) and associated abnormal prion protein (PrPSc ) deposition in both grey and white matter. Changes were minimal in the caudal brainstem, the predilection site for lesions of classical scrapie. CONCLUSION: The distinctive lesion profile of atypical scrapie in these five sheep highlights the diagnostic importance of routine histological evaluation of the cerebellum for evidence of neuropil vacuolation and associated PrPSc deposition in adult sheep with suspected neurological disease.
Assuntos
Encéfalo/patologia , Scrapie/diagnóstico , Animais , Austrália , Feminino , Neurópilo/patologia , Proteínas PrPSc/análise , Scrapie/patologia , Ovinos , Vacúolos/patologiaRESUMO
PURPOSE: To investigate the incidence of and risk factors for late sequelae of treatment in patients who survived for more than 10 years after the diagnosis of childhood acute myeloid leukemia (AML). PATIENTS AND METHODS: Of 77 survivors (median follow-up duration, 16. 7 years), 44 (group A) had received chemotherapy, 18 (group B) had received chemotherapy and cranial irradiation, and 15 (group C) had received chemotherapy, total-body irradiation, and allogeneic bone marrow transplantation. Late complications, tobacco use, and health insurance status were assessed. RESULTS: Growth abnormalities were found in 51% of survivors, neurocognitive abnormalities in 30%, transfusion-acquired hepatitis in 28%, endocrine abnormalities in 16%, cataracts in 12%, and cardiac abnormalities in 8%. Younger age at the time of diagnosis or initiation of radiation therapy, higher dose of radiation, and treatment in groups B and C were risk factors for the development of academic difficulties and greater decrease in height Z: score. In addition, treatment in group C was a risk factor for a greater decrease in weight Z: score and the development of growth-hormone deficiency, hypothyroidism, hypogonadism, infertility, and cataracts. The estimated cumulative risk of a second malignancy at 20 years after diagnosis was 1.8% (95% confidence interval, 0.3% to 11.8%). Twenty-two patients (29%) were smokers, and 11 (14%) had no medical insurance at the time of last follow-up. CONCLUSION: Late sequelae are common in long-term survivors of childhood AML. Our findings should be useful in defining areas for surveillance of and intervention for late sequelae and in assessing the risk of individual late effects on the basis of age and history of treatment.
Assuntos
Leucemia Mieloide/complicações , Leucemia Mieloide/terapia , Doença Aguda , Adolescente , Adulto , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Transplante de Medula Óssea/efeitos adversos , Criança , Pré-Escolar , Transtornos Cognitivos/induzido quimicamente , Transtornos Cognitivos/etiologia , Irradiação Craniana/efeitos adversos , Doenças do Sistema Endócrino/induzido quimicamente , Doenças do Sistema Endócrino/etiologia , Feminino , Fertilidade/efeitos dos fármacos , Fertilidade/efeitos da radiação , Seguimentos , Transtornos do Crescimento/induzido quimicamente , Transtornos do Crescimento/etiologia , Cardiopatias/induzido quimicamente , Hepatite B/etiologia , Hepatite C/etiologia , Humanos , Lactente , Masculino , Recidiva Local de Neoplasia , Segunda Neoplasia Primária/induzido quimicamente , Segunda Neoplasia Primária/etiologia , Lesões por Radiação/etiologia , Fatores de Risco , Fumar , Fatores de Tempo , Irradiação Corporal Total/efeitos adversosRESUMO
PURPOSE: Children younger than 24 months with small (< 550 g), favorable histology (FH) Wilms tumors (WTs) were shown in a pilot study to have an excellent prognosis when treated with nephrectomy only. PATIENTS AND METHODS: A study of nephrectomy only for the treatment of selected children with FH WT was undertaken. Stringent stopping rules were designed to insure closure of the study if the true 2-year relapse-free survival rate was 90% or lower. RESULTS: Seventy-five previously untreated children younger than 24 months with stage I/FH WTs for which the surgical specimen weighed less than 550 g were treated with nephrectomy only. Three patients developed metachronous, contralateral WT 1.1, 1.4, and 2.3 years after nephrectomy, and eight patients relapsed 0.3 to 1.05 years after diagnosis (median, 0.4 years; mean, 0.51 years). The sites of relapse were lung (n = 5) and operative bed (n = 3). The 2-year disease-free (relapse and metachronous contralateral WT) survival rate was 86.5%. The 2-year survival rate is 100% with a median follow-up of 2.84 years. The 2-year disease-free survival rate (excluding metachronous contralateral WT) was 89.2%, and the 2-year cumulative risk of metachronous contralateral WT was 3.1%. CONCLUSION: Children younger than 24 months treated with nephrectomy only for a stage I/FH WT that weighed less than 550 g had a risk of relapse, including the development of metachronous contralateral WT, of 13.5% 2 years after diagnosis. All patients who experienced relapse on this trial are alive at this time. This approach will be re-evaluated in a clinical trial using a less conservative stopping rule.
Assuntos
Nefrectomia , Tumor de Wilms/cirurgia , Intervalo Livre de Doença , Feminino , Humanos , Lactente , Masculino , Projetos Piloto , Prognóstico , Tumor de Wilms/mortalidade , Tumor de Wilms/patologiaRESUMO
Our purpose was to evaluate frequency and severity of bone mineral decrements and frequency of osteonecrosis in survivors of pediatric allogeneic bone marrow transplantation (alloBMT). We retrospectively reviewed demographic information, treatment, magnetic resonance (MR) imaging studies (hips and knees), and bone mineral density (BMD) studies of 48 patients as measured by quantitative computed tomography (QCT). In all, 24 patients were male; 37 were Caucasian. Median age at alloBMT was 10.3 years (1.6-20.4 years). Of the 48 patients, 43 underwent QCT. Median time between alloBMT and imaging was 5.1 years (1.0-10.2 years). Median BMD Z-score was -0.89 (-4.06 to 3.05). BMD Z-score tended to be associated with female sex (P=0.0559) but not with age at BMT, race, primary diagnosis, time from alloBMT, T-cell depletion of graft, total-body irradiation, or acute/chronic graft-versus-host disease (GVHD). MR showed osteonecrosis in 19 of 43 (44%). We found no associations between osteonecrosis and sex, race, diagnosis, age at BMT, history of GVHD, time from BMT, or T-cell depletion. Seven patients (15%) had MR changes of osteonecrosis and BMD Z-scores of less than -1 s.d. We conclude that pediatric alloBMT survivors have decreased BMD and are at risk of osteonecrosis. They should be monitored to assure early intervention that may ameliorate adverse outcomes.
Assuntos
Densidade Óssea , Transplante de Medula Óssea/efeitos adversos , Osteonecrose/etiologia , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Seguimentos , Doenças Hematológicas/complicações , Doenças Hematológicas/terapia , Humanos , Lactente , Imageamento por Ressonância Magnética , Masculino , Estudos Retrospectivos , Fatores de Risco , Sobreviventes , Transplante HomólogoRESUMO
Twenty-three children with de novo acute myelogenous leukemia (AML) (n = 20), secondary AML (n = 1), or non-Hodgkin's lymphoma (NHL) (n = 2) underwent allogeneic bone marrow transplantation (alloBMT) for graft failure (n = 1) or recurrent malignancy (n = 22) between February 1992 and August 1999 following autologous BMT (ABMT). Induction chemotherapy was given to 14 patients and nine patients went directly to alloBMT. Five received marrow from matched siblings, 14 from matched unrelated donors and four from mismatched family members. Conditioning regimens included cyclophosphamide, cytarabine, and total body irradiation. Nine patients are alive disease-free between 627 and 2433 days (1.7-6.7 years) post BMT resulting in a 4-year DFS of 39%. Eight patients relapsed at a median of 206 days (range, 35-669 days) post alloBMT and all eventually died. Eight patients (two of whom also relapsed) died of RRT. Although RRT and relapse remain significant problems, a significant percentage of pediatric patients failing ABMT may be cured with alloBMT.
Assuntos
Transplante de Medula Óssea , Leucemia Mieloide Aguda/terapia , Linfoma não Hodgkin/terapia , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Leucemia Mieloide Aguda/patologia , Linfoma não Hodgkin/patologia , Masculino , Recidiva , Estudos Retrospectivos , Terapia de Salvação , Transplante Autólogo , Transplante Homólogo , Resultado do TratamentoRESUMO
The histiocytoses are rare disorders of antigen-processing phagocytic or antigen-presenting cells. Allogeneic bone marrow transplantation (BMT) can be curative of these disorders. We report a series of five children with Langerhans cell histiocytosis (n=2) or hemophagocytic lymphohistiocytosis (n=3), who received allogeneic BMT with a total body irradiation (TBI)-containing regimen (TBI, cytarabine, and cyclophosphamide) at our institution between 1995 and 2000. One of these patients received busulfan, cyclophosphamide, and etoposide for the first of two BMTs. All grafts except one (a matched sibling-donor graft) were T-cell-depleted grafts from unrelated donors. All received cyclosporine graft-versus-host disease (GvHD) prophylaxis; the recipient of the matched sibling graft also received methotrexate. Three patients engrafted at a median of 24 days after transplantation. The patient who did not receive TBI experienced primary graft failure and recurrent disease. After the TBI-containing conditioning regimen was given, a second transplant engrafted on day +17. One patient with concurrent myelodysplastic syndrome died of toxicity on day +33 without evidence of engraftment. No acute or chronic GvHD was observed. Four patients survive disease-free, a median of 63 months after transplantation, all with Lansky performance scores of 100. We conclude that a conditioning regimen containing TBI but not etoposide is effective in allogeneic BMT for children with histiocytic diseases.
Assuntos
Transplante de Medula Óssea/estatística & dados numéricos , Histiocitose de Células de Langerhans/cirurgia , Condicionamento Pré-Transplante/métodos , Irradiação Corporal Total/métodos , Transplante de Medula Óssea/efeitos adversos , Criança , Seguimentos , Doença Enxerto-Hospedeiro/epidemiologia , Humanos , Depleção Linfocítica/métodos , Estudos Retrospectivos , Linfócitos T/imunologia , Fatores de Tempo , Resultado do TratamentoRESUMO
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.
Assuntos
Deleção Cromossômica , Cromossomos Humanos Par 16 , Hibridização in Situ Fluorescente , Neoplasias Renais/genética , Tumor de Wilms/genética , Criança , Pré-Escolar , DNA de Neoplasias/análise , Feminino , Homozigoto , Humanos , Lactente , Perda de Heterozigosidade , Masculino , Polimorfismo GenéticoRESUMO
PURPOSE: To assess the pharmacokinetics of paclitaxel for recurrent Wilms' tumor in an anephric pediatric patient receiving hemodialysis. METHODS: Paclitaxel was administered at a dose of 250 mg/m2 and 350 mg/m2 by 24-h continuous intravenous (IV) infusion as two consecutive courses, respectively, separated by approximately 3 weeks. Paclitaxel plasma concentrations were measured by high-performance liquid chromatography (HPLC). RESULTS: Paclitaxel disposition was comparable to that reported in similarly treated children with normal renal function. For the first course (250 mg/ m2), paclitaxel concentrations were best fit by a two-compartment, first-order model. The calculated pharmacokinetic parameters were 0.312 h(-1) for the first-order rate constant of elimination (Ke), 52.4 l/m2 for the apparent volume of distribution (Vc), 0.170 h(-1) and 0.105 h(-1) for the first-order rate constants for transit from central to peripheral compartments (Kcp) and peripheral to central compartments (Kpc), respectively, 16.9 microM x h for the area under the plasma concentration-versus-time curve (AUC), and 273 ml/min per m2 for average clearance (Cl). The concentration-versus-time data with the second course (at the higher dosage of 350 mg/m2) were better described by a two-compartment model with saturable elimination. The calculated pharmacokinetic parameters were 12.0 micromol x h(-1) for the maximal rate of elimination (Vm1-0), 0.158 microM for the concentration at which the rate of elimination is 50% of maximal (Km1-0), 0.809 h(-1) for Kcp, 0.0792 h(-1) for Kpc, 23.5 l/m2 for Vc, 20.9 microM x h for AUC, and 327 ml/min per m2 for Cl. Paclitaxel was undetectable in the dialysate. CONCLUSIONS: The level of systemic exposure in our anephric patient was comparable to or lower than that achieved in patients with normal renal function at similar dosages. The patient tolerated therapy without problems. It appears that pediatric patients in renal failure can be treated with paclitaxel as a 24-h continuous infusion at doses similar to those used in patients with normal renal function.
Assuntos
Antineoplásicos Fitogênicos/farmacocinética , Paclitaxel/farmacocinética , Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos Fitogênicos/uso terapêutico , Área Sob a Curva , Criança , Feminino , Humanos , Infusões Intravenosas , Neoplasias Renais/metabolismo , Neoplasias Renais/patologia , Recidiva Local de Neoplasia , Nefrectomia , Paclitaxel/administração & dosagem , Paclitaxel/uso terapêutico , Diálise Renal , Tumor de Wilms/metabolismo , Tumor de Wilms/patologiaRESUMO
Relapse in acute myeloid leukemia (AML) following intensive chemotherapy bears a bad prognosis. We treated 18 children with relapsed AML on two separate protocols that included continuous infusion (CI) of cytosine arabinoside (ara-C) (total dose 4gr-6gr/m2) over 96-120 hours. In an attempt to increase the fraction of blasts in S-phase and render them more sensitive to cell-cycle specific agents such as ara-C, 10 patients received 5mcg/kg rhG-CSF twice daily beginning 48 hours before and continuing through the duration of the CI ara-C (POG #9192 study). The percentage of cells is S phase before and after G-CSF administration was determined. In a second group of patients (n = 8) who received ara-C alone, endogenous concentrations of G-CSF and serial blood counts were measured (St Jude's R4 study). The rationale of the St Jude's R4 was to optimize the schedule of the second course of ara-C at a time when the patient's endogenous G-CSF concentration was increased and thus maximize the percent of cells captured in S phase. Four out of 8 patients receiving CI ara-C alone and 4 out of 10 patients receiving CI ara-C with rhG-CSF achieved a complete remission (CR) after 1 cycle of therapy. Four patients in CR underwent marrow transplantation (2 allogeneic and 2 autologous). Cell cycle analysis of blast cells cultured in vitro with or without G-CSF showed a two fold increase in the percentage of cells in S phase (P = 0.03) whereas cells obtained from patients before and after G-CSF administration showed no difference in cell cycling. Correlation between G-CSF concentrations and ANC showed a negative association indicating that the regulatory mechanisms for G-CSF production remained intact. In our relatively small series, CI ara-C achieved a CR rate of 44% with rhG-CSF having no effect on the remission rate. Although in vitro rhG-CSF increased the percentage of blasts in S phase significantly, in vivo effects were not observed. Larger studies with combinations of different hematopoietic growth factors and cell-cycle active drugs are needed to evaluate the role of these cytokines in the therapy of recurrent AML.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia Mieloide/tratamento farmacológico , Doença Aguda , Adolescente , Criança , Pré-Escolar , Citarabina/administração & dosagem , Feminino , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Humanos , Infusões Intravenosas , Leucemia Mieloide/patologia , Masculino , Projetos Piloto , Proteínas Recombinantes/administração & dosagem , Fase S/efeitos dos fármacosRESUMO
Treatment for cancer too often adversely affects the very patients it is meant to help, especially children. Long-term damage can be found in the skeleton and soft tissues, in cardiopulmonary and renal function, and endocrine and neurologic function. The authors survey these late effects, including generalized growth suppression, dental and maxillofacial deficits, and pulmonary disorders, and suggest ways to prevent or alleviate them.
Assuntos
Antineoplásicos/efeitos adversos , Neoplasias/terapia , Radioterapia/efeitos adversos , Adolescente , Adulto , Idoso , Encefalopatias/etiologia , Sistema Nervoso Central/efeitos dos fármacos , Criança , Doenças do Sistema Endócrino/etiologia , Feminino , Transtornos do Crescimento/diagnóstico , Transtornos do Crescimento/etiologia , Transtornos do Crescimento/terapia , Hormônio do Crescimento/metabolismo , Coração/efeitos dos fármacos , Coração/fisiopatologia , Cardiopatias/etiologia , Humanos , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Rim/efeitos dos fármacos , Rim/fisiopatologia , Pulmão/efeitos dos fármacos , Pulmão/fisiopatologia , Masculino , Ovário/efeitos dos fármacos , Ovário/fisiopatologia , Testículo/efeitos dos fármacos , Testículo/fisiopatologia , Glândula Tireoide/efeitos dos fármacos , Glândula Tireoide/fisiopatologiaRESUMO
Literature regarding the natural history and prognosis of epithelioid sarcoma in the pediatric population is sparse. During the past 11 years, eight patients with epithelioid sarcoma were treated at St Jude Children's Research Hospital. Of the eight children, six of whom were male, seven presented with localized disease and one with metastatic disease. The primary tumor was located in the upper extremity in four patients; the other sites were the scalp, external ear, back, and mediastinum. The mean duration of symptoms before diagnosis was 8.3 months (range, 1 to 12 months). Surgical treatment comprising amputation or wide local excision was performed in six patients, three of whom had additional lymph node dissection. Three patients received multiagent chemotherapy, and four patients were treated with supplementary radiation. Two patients died of progressive local and distant disease within 9 months of diagnosis. The other six patients are alive and have no evidence of disease 12 months to 10 years 6 months after the completion of treatment.