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1.
Pediatr Blood Cancer ; 50(1): 145-7, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17009219

RESUMO

We report a case presenting with persistent pyrexia that led to the diagnosis of peripheral T-cell lymphoma, a rare malignancy in childhood. The case illustrates diagnostic conundrums in a patient who is not responding as expected to treatment.


Assuntos
Linfoma de Células T Periférico/diagnóstico , Pré-Escolar , Feminino , Humanos
2.
Eur J Cancer ; 43(17): 2537-44, 2007 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17962012

RESUMO

AIM: The activity of carboplatin was evaluated in a phase II window study in previously untreated children with metastatic soft tissue sarcoma. METHODS: Children with poor-risk metastatic disease (over 10 years and/or with bone/bone marrow involvement) treated in the SIOP MMT 98 study were scheduled to receive two courses of intravenous carboplatin (area under curve [AUC] of 10), 21 days apart. RESULTS: Sixteen eligible patients were entered into the rhabdomyosarcoma (RMS) group. Response (complete remission or partial remission) was seen in five children (31%, 95% confidence interval (CI) 14-56%). Ten eligible patients with other soft tissue sarcomas were recruited into the non-RMS group. Two responses (20%, 95% CI 6-51%) were seen. Toxicity in both groups was predictable nausea, vomiting and marrow suppression and there were no toxic deaths. CONCLUSION: Single-agent carboplatin at AUC of 10 has an acceptable toxicity profile but only moderate efficacy in poor-risk metastatic soft tissue sarcoma.


Assuntos
Antineoplásicos/administração & dosagem , Carboplatina/administração & dosagem , Rabdomiossarcoma/tratamento farmacológico , Neoplasias de Tecidos Moles/tratamento farmacológico , Adolescente , Antineoplásicos/efeitos adversos , Neoplasias da Medula Óssea/secundário , Carboplatina/efeitos adversos , Criança , Pré-Escolar , Humanos , Lactente , Infusões Intravenosas , Estudos Retrospectivos , Rabdomiossarcoma/secundário , Fatores de Risco , Análise de Sobrevida , Resultado do Tratamento
3.
J Clin Oncol ; 9(12): 2177-82, 1991 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-1720453

RESUMO

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


Assuntos
Ifosfamida/efeitos adversos , Nefropatias/induzido quimicamente , Sarcoma/tratamento farmacológico , Injúria Renal Aguda/induzido quimicamente , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Criança , Pré-Escolar , Dactinomicina/administração & dosagem , Síndrome de Fanconi/induzido quimicamente , Feminino , Seguimentos , Humanos , Ifosfamida/administração & dosagem , Lactente , Testes de Função Renal , Masculino , Vincristina/administração & dosagem
4.
J Clin Oncol ; 15(10): 3258-65, 1997 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-9336363

RESUMO

PURPOSE: To determine the maximum-tolerated dose (MTD) of cyclophosphamide (CTX) when administered over 2 consecutive days followed by hematopoetic stem-cell rescue given as two sequential courses to children with glioblastoma multiforme, poor-prognosis pontine gliomas, and other recurrent CNS tumors. PATIENTS AND METHODS: Two identical doses of CTX were administered 24 hours apart to 14 children and followed by hematopoetic stem-cell rescue. This treatment was repeated immediately following hematologic recovery. The starting dose of CTX was 2.5 g/m2/d with increments of 0.5 g/m2/d. CTX pharmacokinetics and metabolism were measured during 22 courses of treatment. Toxicity and tumor response were recorded. RESULTS: There were two toxic deaths at the dose level of 4 g/m2/d. These were not clearly related to cardiac toxicity and may have been due to generalized capillary leak syndrome. Thus, the MTD of CTX was 3.5 g/m2/ d. There were six complete responses (CRs) (46%; (95% confidence interval [CI], 19% to 73%) and four partial responses (PRs) (31%; 95% CI, 6% to 56%), and one patient achieved stable disease. All children with intracranial primitive neuroectodermal tumors (PNETs) improved following CTX. The median duration of tumor response was 6 months (range, 4 to 29) and only one patient remains disease-free following CTX alone. Overall survival is 21% (95% CI, 13% to 29%) at a median follow-up time of 27 months (range, 12 to 34). CONCLUSION: The MTD of CTX when followed by hematopoetic stem-cell rescue is 3.5 g/m2 administered on each of 2 consecutive days. This treatment was tolerable in children with poor-prognosis brain tumors and produced complete responses in children with recurrent PNETs.


Assuntos
Antineoplásicos Alquilantes/administração & dosagem , Neoplasias Encefálicas/tratamento farmacológico , Ciclofosfamida/administração & dosagem , Adolescente , Antineoplásicos Alquilantes/efeitos adversos , Antineoplásicos Alquilantes/farmacocinética , Neoplasias Encefálicas/mortalidade , Criança , Pré-Escolar , Terapia Combinada , Ciclofosfamida/efeitos adversos , Ciclofosfamida/farmacocinética , Feminino , Transplante de Células-Tronco Hematopoéticas , Humanos , Lactente , Masculino , Recidiva Local de Neoplasia/tratamento farmacológico , Prognóstico , Taxa de Sobrevida
5.
J Clin Oncol ; 9(8): 1371-5, 1991 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-2072140

RESUMO

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


Assuntos
DNA de Neoplasias/genética , Genes myc , Neuroblastoma/genética , Ploidias , Aneuploidia , Southern Blotting , DNA de Neoplasias/análise , Citometria de Fluxo , Seguimentos , Amplificação de Genes , Humanos , Lactente , Recém-Nascido , Estadiamento de Neoplasias , Neuroblastoma/mortalidade , Neuroblastoma/patologia , Prognóstico
6.
Endocrinology ; 136(10): 4315-22, 1995 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-7664650

RESUMO

Phosphatidylinositol 3-kinase (PI3k) activity is required for the insulin stimulation of glucose transport in adipocytes and Chinese hamster ovary cells. Wortmannin (WM), an inhibitor of PI3k, inhibits the stimulation of glucose transport by insulin and the gain of glucose transporters at the cell surface. However, the effect of inhibition of PI3k on the maintenance of the basal and the insulin-stimulated glucose transport and on the intracellular donor pool of glucose transporters has not been clarified. Here we show that in L6 skeletal muscle cells in culture WM significantly inhibits the basal PI3k activity (by 40%), decreases the levels of phosphatidylinositol 3,4-phosphate and 3,4,5-phosphate (by about 50%) and abolishes the activation of the enzyme by insulin. WM inhibited the basal rate of transport of glucose (by 45%) and of amino acids through system A (by 25%) and abolished their stimulation by insulin. Insulin caused a transient increase in PI3k activity and PI3k products that returned to basal levels within 40 min, whereas glucose and amino acid transport remained elevated. Under these conditions, WM reduced the rate of glucose and amino acid transport back to basal levels. In unstimulated cells, WM decreased significantly the GLUT4 glucose transporter content at the plasma membrane and prevented the ability of insulin to recruit transporters to this membrane. Interestingly, the intracellular pools of the GLUT3 and GLUT4 glucose transporters were significantly reduced in response to WM treatment alone. We conclude that in muscle cells PI3k activity is required to maintain basal and insulin-stimulated glucose and amino acid transport, as well as to develop the stimulation of the two transport processes in response to the hormone. We hypothesize that PI3k, likely through production of phosphatidylinositol 3,4-phosphate and 3,4,5-phosphate, regulates the basal plasma membrane glucose transporter recycling and the organization of the transporter intracellular pool, in addition to being an insulin signal.


Assuntos
Aminoácidos/metabolismo , Glucose/metabolismo , Proteínas de Transporte de Monossacarídeos/análise , Proteínas Musculares , Músculo Esquelético/metabolismo , Proteínas do Tecido Nervoso , Fosfotransferases (Aceptor do Grupo Álcool)/fisiologia , Androstadienos/farmacologia , Transporte Biológico , Células Cultivadas , Transportador de Glucose Tipo 1 , Transportador de Glucose Tipo 3 , Transportador de Glucose Tipo 4 , Insulina/farmacologia , Fosfatidilinositol 3-Quinases , Wortmanina
7.
FEBS Lett ; 441(1): 15-9, 1998 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-9877156

RESUMO

In this study we have investigated the effects of insulin, chemical and hyperthermic stresses upon the activity of the System A amino acid transporter in L6 rat muscle cells. Uptake of alpha-methyl-aminoisobutyric acid (Me-AIB), a non-metabolisable System A substrate, was increased by between 50% and 80% when muscle cells were exposed to a maximally effective concentration of insulin (100 nM), sodium arsenite (ARS, 0.5 mM) or a 42 degrees C heat shock (HS). The observed activation in System A in response to all three stimuli was maximal within 20 min and in the case of insulin and ARS primarily involved an increase in the Vmax of System A transport. In contrast, HS induced significant increases in both Vmax and Km of System A transport suggesting that hyperthermic stress may activate System A by a mechanism distinct from that mediating the effects of insulin and ARS. The hormonal stimulation of System A was blocked by the phosphoinositide 3-kinase (PI3k) inhibitor, wortmannin, but not by rapamycin or PD 98059 which respectively inhibit the mTOR and classical MAP kinase pathways. Exposure of L6 cells to ARS, but not HS, caused a 4.7-fold stimulation in MAPKAP-K2 activity that was blocked by SB 203580, a specific inhibitor of the stress activated protein kinase SAPK2/p38. However, neither SB 203580, rapamycin nor wortmannin were able to suppress the ARS- or HS-induced stimulation in System A transport. In summary, our results demonstrate that activity of the System A transporter can be rapidly upregulated in response to hormonal and stress stimuli through changes in the transport kinetics of the System A carrier. Our data show that whilst the hormonal response is PI3k dependent, the signalling mechanisms which instigate changes in System A activity in response to chemical or hyperthermic stress do not appear to involve PI3k or components of the mTOR, p42/p44 MAP kinase or SAPK2/p38 signalling pathways.


Assuntos
Aminoácidos/metabolismo , Arsenitos/farmacologia , Inibidores Enzimáticos/farmacologia , Temperatura Alta , Insulina/farmacologia , Músculo Esquelético/metabolismo , Compostos de Sódio/farmacologia , Androstadienos/farmacologia , Animais , Transporte Biológico/efeitos dos fármacos , Proteínas Quinases Dependentes de Cálcio-Calmodulina/antagonistas & inibidores , Linhagem Celular , Cicloeximida/farmacologia , Flavonoides/farmacologia , Insulina/fisiologia , Cinética , Músculo Esquelético/efeitos dos fármacos , Inibidores de Fosfoinositídeo-3 Quinase , Ratos , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Sirolimo/farmacologia , Wortmanina
8.
Eur J Cancer ; 31A(4): 444-6, 1995.
Artigo em Inglês | MEDLINE | ID: mdl-7576942

RESUMO

High levels of mRNA (as assessed by northern blot) for the high-affinity nerve growth factor receptor (p140TRK) are predictive of favourable outcome in neuroblastoma. The feasibility of determining p140trk on frozen sections using a recently developed monoclonal antibody was evaluated, and immunohistochemical findings were compared to those obtained from northern blot analysis. Primary tumour samples from 28 untreated patients were quick frozen and an indirect immunofluorescence assay was performed on 4-microns acetone-fixed cryostat sections. 9 cases were positive with immunohistochemistry, and these were among the 15 cases also positive by northern blot. None of the cases negative by northern blot were positive with immunohistochemistry. The concordance rate was 79% (P < 0.03), with a sensitivity of 60% and a specificity of 100%. Immunohistochemistry can thus be rather reliable for assessing p140trk expression, even when only very small amounts of tissue are available, such as with needle biopsy.


Assuntos
Biomarcadores Tumorais/análise , Neuroblastoma/química , Proteínas Proto-Oncogênicas/análise , Receptores Proteína Tirosina Quinases/análise , Receptores de Fator de Crescimento Neural/análise , Northern Blotting , Criança , Técnica Indireta de Fluorescência para Anticorpo , Humanos , Proteínas de Neoplasias/análise , Proteínas Proto-Oncogênicas/genética , RNA Mensageiro/análise , Receptores Proteína Tirosina Quinases/genética , Receptor trkA , Receptores de Fator de Crescimento Neural/genética
9.
Novartis Found Symp ; 220: 243-61; discussion 261-4, 1999.
Artigo em Inglês | MEDLINE | ID: mdl-10231835

RESUMO

Agricultural pollution of the environment is jointly determined by economic decisions driving land use, production practices, and stochastic biophysical processes associated with agricultural production, land and climate characteristics. It follows that environmental and economic statistics, traditionally collected independently of each other, offer little insight into non-point pollutant loadings. We argue that effective policy development would be facilitated by integrating environmental and economic data gathering, combined with simulation modelling linking economic and biophysical components. Integrated data collection links economics, land use, production methods and environmental loadings. An integrated economic/biophysical modelling framework facilitates policy analysis because monetary incentives to reduce pollution can be evaluated in the context of market costs and returns that influence land use and production activity. This allows prediction of environmental and economic outcomes from alternative policies to solve environmental problems. We highlight steps taken to merge economic and biophysical modelling for policy analysis within the Economic Research Service of the United States Department of Agriculture. An example analysis of a policy to reduce agricultural nitrogen pollution is presented, with the economic and environmental results illustrating the value of linked economic and biophysical analysis.


Assuntos
Poluição Ambiental/economia , Poluição Ambiental/legislação & jurisprudência , Agricultura , Coleta de Dados , Fertilizantes , Humanos , Modelos Econômicos , Modelos Estatísticos , Nitrogênio , Impostos
10.
Bone Marrow Transplant ; 8(6): 465-72, 1991 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-1790426

RESUMO

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


Assuntos
Bussulfano/uso terapêutico , Linfoma de Células B/cirurgia , Linfoma não Hodgkin/tratamento farmacológico , Linfoma não Hodgkin/cirurgia , Linfoma de Células T/tratamento farmacológico , Linfoma de Células T/cirurgia , Adolescente , Bussulfano/efeitos adversos , Criança , Pré-Escolar , Terapia Combinada , Ciclofosfamida/efeitos adversos , Ciclofosfamida/uso terapêutico , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Feminino , Hepatopatia Veno-Oclusiva/induzido quimicamente , Hepatopatia Veno-Oclusiva/epidemiologia , Humanos , Incidência , Linfoma de Células B/tratamento farmacológico , Masculino , Melfalan/efeitos adversos , Melfalan/uso terapêutico
11.
Surgery ; 96(2): 184-9, 1984 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-6463858

RESUMO

One hundred twenty-nine consecutive carotid endarterectomies performed for atherosclerotic ulcerative stenosis without the use of intraoperative shunting were analyzed prospectively in an effort to determine the significance of intraoperative ischemia. Intraoperative EEG and regional cerebral blood flow measurements were used to monitor these patients. Ten of the patients were excluded because of inadequate data, but none of these 10 patients experienced a complication. Factors analyzed included preoperative risk assessment according to the Mayo Clinic system of Sundt et al., intraoperative regional cerebral blood flow measurements, and intraoperative EEG changes. The overall mortality rate was 2.5%, the major morbidity rate was 2.5%, the minor morbidity rate was 1.7%, and the rate of transient neurologic dysfunction was 1.7%. The patients' preoperative state as determined according to the Mayo Clinic system of Sundt et al. was more useful in identifying patients at risk than was intraoperative EEG and regional cerebral blood flow monitoring.


Assuntos
Artérias Carótidas/cirurgia , Circulação Cerebrovascular , Transtornos Cerebrovasculares/fisiopatologia , Eletroencefalografia , Endarterectomia/efeitos adversos , Anestesia Geral , Transtornos Cerebrovasculares/etiologia , Endarterectomia/métodos , Endarterectomia/mortalidade , Humanos , Período Intraoperatório , Monitorização Fisiológica , Estudos Prospectivos , Risco
12.
Cancer Genet Cytogenet ; 43(2): 203-9, 1989 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-2557151

RESUMO

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


Assuntos
Aberrações Cromossômicas , Cromossomos Humanos Par 1 , Neoplasias Renais/genética , Tumor de Wilms/genética , Southern Blotting , Bandeamento Cromossômico , Sondas de DNA , DNA de Neoplasias/genética , Humanos , Cariotipagem
13.
Neurosurgery ; 29(5): 727-30; discussion 730-1, 1991 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-1961403

RESUMO

The importance of cerebral ischemia produced by carotid clamping during carotid endarterectomy remains controversial. In an effort to determine the importance of cerebral ischemia during carotid endarterectomy, 369 patients undergoing 431 consecutive carotid endarterectomies were studied by Xenon-133 (133Xe) clearance and electroencephalogram (EEG) monitoring. None of the patients was shunted during the procedures. The severity of ischemia as indicated by 133Xe clearance from the ipsilateral hemisphere during 20 to 30 minutes of carotid occlusion did not predict the appearance of complications in this group of patients (chi 2 = 1.417; P = 0.841). There was a highly significant relationship between the depth of cerebral ischemia as demonstrated by 133Xe clearance and the appearance of abnormalities on the EEG (chi 2 = 42.043, P less than 0.0001). In the subgroup of patients developing abnormalities as shown by EEG, there was a negative correlation (chi 2 = 17.495; P less than 0.002) between reduction in blood flow and the appearance of complications, in that the higher the blood flow during occlusion the more likely the patient developing EEG changes would develop complications.


Assuntos
Endarterectomia das Carótidas/efeitos adversos , Complicações Intraoperatórias , Ataque Isquêmico Transitório/etiologia , Idoso , Idoso de 80 Anos ou mais , Circulação Cerebrovascular , Eletroencefalografia , Feminino , Humanos , Complicações Intraoperatórias/diagnóstico , Ataque Isquêmico Transitório/diagnóstico por imagem , Ataque Isquêmico Transitório/fisiopatologia , Masculino , Pessoa de Meia-Idade , Monitorização Intraoperatória , Estudos Prospectivos , Cintilografia , Radioisótopos de Xenônio
14.
Anticancer Res ; 13(5C): 1863-6, 1993.
Artigo em Inglês | MEDLINE | ID: mdl-7903523

RESUMO

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


Assuntos
Proteínas de Transporte/genética , Glicoproteínas de Membrana/genética , Rabdomiossarcoma/metabolismo , Sarcoma/metabolismo , Membro 1 da Subfamília B de Cassetes de Ligação de ATP , Proteínas de Transporte/metabolismo , Criança , Resistência a Medicamentos , Expressão Gênica , Humanos , Imuno-Histoquímica , Glicoproteínas de Membrana/metabolismo , RNA Mensageiro/genética , RNA Neoplásico/genética , Rabdomiossarcoma/genética , Sarcoma/genética
15.
Anticancer Res ; 12(1): 59-63, 1992.
Artigo em Inglês | MEDLINE | ID: mdl-1567182

RESUMO

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


Assuntos
DNA de Neoplasias/análise , Citometria de Fluxo , Neuroblastoma/patologia , Fase S , Divisão Celular , Criança , Pré-Escolar , Amplificação de Genes , Genes myc , Humanos , Lactente , Recém-Nascido , Neuroblastoma/genética , RNA Mensageiro/análise
16.
Am J Surg ; 155(4): 578-86, 1988 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-3128132

RESUMO

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


Assuntos
Aorta Abdominal/cirurgia , Débito Cardíaco , Consumo de Oxigênio , Aorta Abdominal/fisiopatologia , Aneurisma Aórtico/cirurgia , Constrição , Humanos , Nitroglicerina/uso terapêutico , Consumo de Oxigênio/efeitos dos fármacos , Distribuição Aleatória , Resistência Vascular
17.
Br J Radiol ; 71(850): 1093-5, 1998 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-10211073

RESUMO

We present the first reported case of endometroid adenocarcinoma of the uterine cervix in a young girl. The differential diagnosis of a vaginal mass in this age group is usually rhabdomyosarcoma, although other, rarer tumours also occur.


Assuntos
Adenocarcinoma/patologia , Neoplasias do Colo do Útero/patologia , Adenocarcinoma/terapia , Criança , Feminino , Humanos , Histerectomia , Imageamento por Ressonância Magnética , Recidiva Local de Neoplasia/terapia , Neoplasias do Colo do Útero/terapia
18.
Cochrane Database Syst Rev ; (1): CD003380, 2004.
Artigo em Inglês | MEDLINE | ID: mdl-14974014

RESUMO

BACKGROUND: Depression is the fourth most important disease in the estimation of the burden of disease Murray 1996 and is a common problem with prevalence rates estimated to be as high as 8% in young people. Depression in young people is associated with poor academic performance, social dysfunction, substance abuse, suicide attempts, and completed suicide (NHMRC 1997). This has precipitated the development of programmes aimed at preventing the onset of depression. This review evaluates evidence for the effectiveness of these prevention programmes. OBJECTIVES: To determine whether psychological and/or educational interventions (both universal and targeted) are effective in reducing risk of depressive disorder by reducing depressive symptoms immediately after intervention or by preventing the onset of depressive disorder in children and adolescents over the next one to three years. SEARCH STRATEGY: The Cochrane Depression, Anxiety and Neurosis Group trials register (August 2002), MEDLINE (1966 to December Week 3 2002), EMBASE (1980 to January Week 2 2003), PsychInfo (1886 to January Week 2 2003) and ERIC (1985 to December 2002) were searched. In addition, conference abstracts, the reference lists of included studies, and other reviews were searched and experts in the field were contacted. SELECTION CRITERIA: Each identified study was assessed for possible inclusion by two independent reviewers based on the methods sections. The determinants for inclusion were that the trial include a psychological and/or educational prevention programme for young people aged 5 to 19 years-old, who did not meet DSM or ICD criteria for depression and/or did not fall into the clinical range on standardised, validated, and reliable rating scales of depression. DATA COLLECTION AND ANALYSIS: The methodological quality of the included trials was assessed by two independent reviewers according to a list of pre-determined criteria, which were based on quality ratings devised by Moncrieff and colleagues (Moncrieff 2001). Outcome data was extracted and entered into Revman 4.2. Means and standard deviations for continuous outcomes and number of events for dichotomous outcomes were extracted where available. For trials where the required data were not reported or could not be calculated, further details were requested from first authors. If no further details were provided, the trial was included in the review and described, but not included in the meta-analysis. Results were presented for each type of intervention: targeted or universal interventions; and educational or psychological interventions and if data were provided, by gender. Where possible data were combined in meta-analyses to give a treatment effect across all trials. Sensitivity analysis were conducted on studies rated as "adequate" or "high" quality, that is with a score over 22, based on the scale by Moncrieff et al (Moncrieff 2001). The presence of publication bias was assessed using funnel plots. MAIN RESULTS: Studies were divided into those that compared intervention with an active comparison or placebo (i.e. a control condition that resembles the intervention being investigated but which lacks the elements thought to be active in preventing depression) and those that used a "wait-list" or no intervention comparison group. Only two studies fell into the former category and neither showed effectiveness although one study was inadequately powered to show a difference and in the other the "placebo" contained active therapeutic elements, reducing the ability to demonstrate a difference from intervention. Psychological interventions were effective compared with non-intervention immediately after the programmes were delivered with a significant reduction in scores on depression rating scales for targeted (standardised mean difference (SMD) of -0.26 and a 95% confidence interval (CI) of -0.40 to -0.13 ) but not universal interventions (SMD -0.21, 95% CI -0.48, 0.06), with a significant effect maintained on pooling data (SMD -0.26, 95% CI -0.36, -0.15). While small effect sizes were reported, these were associated with a significant reduction in depressive episodes. The overall risk difference after intervention translates to "numbers needed to treat" (NNT) of 10. The most effective study is the targeted programme by Clarke (Clarke 2001) where the initial effect size of -0.46 is associated with an initial risk difference of -0.22 and NNT 5. There was no evidence of effectiveness for educational interventions. Reports of effectiveness for boys and girls were contradictory. The quality of many studies was poor, and only two studies made allocation concealment explicit. Sensitivity analysis of only high quality studies did not alter the results significantly. The only analysis in which there was significant statistical heterogeneity was the sub-group analysis by gender where there was variability in the response to different programmes for both girls and boys. For the most part funnel plots indicate findings are robust for short term effects with no publication bias evident. There are too few studies to comment on whether there is publication bias for studies reporting long-term (12-36 month) follow-up. REVIEWER'S CONCLUSIONS: Although there is insufficient evidence to warrant the introduction of depression prevention programmes currently, results to date indicate that further study would be worthwhile. There is a need to compare interventions with a placebo or some sort of active comparison so that study participants do not know whether they are in the intervention group or not, to investigate the impact of booster sessions to see if effectiveness immediately after intervention can be prolonged, ideally for a year or longer, and to consider practical implementation of prevention programmes when choosing target populations. Until now most studies have focussed on psychological interventions. The potential effectiveness of educational interventions has not been fully investigated. Given the gender differences in prevalence, and the change in these that occurs in adolescence with a disproportionate increase in prevalence rates for girls, it is likely that girls and boys will respond differently to interventions. Although differences have been reported in studies in this review the findings are contradictory and a more definitive delineation of gender specific responses to interventions would be helpful.


Assuntos
Depressão/prevenção & controle , Transtorno Depressivo/prevenção & controle , Adolescente , Adulto , Criança , Pré-Escolar , Depressão/diagnóstico , Transtorno Depressivo/diagnóstico , Feminino , Humanos , Masculino , Psicoterapia/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto
19.
Am Surg ; 49(8): 405-10, 1983 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-6614660

RESUMO

Thirty-six patients sustaining blunt and penetrating injuries to the popliteal artery underwent vascular reconstruction with an average ischemic interval of eight and one-half hours (range: four to 14 hours). There were 16 associated venous injuries, 15 nerve injuries, and 20 fractures with or without knee dislocations. Arterial repair was performed by saphenous vein interposition graft in 23 patients and by end-to-end anastomosis in 16 patients (three patients had more than one operation). Eight of the venous injuries were reconstructed and the remaining eight veins were ligated. Fasciotomy was performed in 22 patients. Skeletal stabilization by external support was necessary in 12 instances and by internal fixation in eight patients. Five patients required amputation after vascular reconstruction failed. The presence of an ischemic interval greater than ten hours, associated fractures, and/or knee dislocation carried a serious prognosis for limb survival.


Assuntos
Artéria Poplítea/lesões , Adolescente , Adulto , Amputação Cirúrgica , Feminino , Fixação Interna de Fraturas , Fraturas Ósseas/etiologia , Fraturas Ósseas/cirurgia , Humanos , Isquemia/etiologia , Masculino , Pessoa de Meia-Idade , Nervo Fibular/lesões , Artéria Poplítea/cirurgia , Veia Safena/transplante , Nervo Tibial/lesões , Procedimentos Cirúrgicos Vasculares , Ferimentos não Penetrantes/complicações , Ferimentos não Penetrantes/cirurgia , Ferimentos Penetrantes/complicações , Ferimentos Penetrantes/cirurgia
20.
Am Surg ; 46(5): 289-94, 1980 May.
Artigo em Inglês | MEDLINE | ID: mdl-7386995

RESUMO

During a 12 year period ending in 1977, 65 patients had surgical treatment of ruptured abdominal aortic aneurysms. Hospital mortality was 48 per cent (31/65 patients). Preoperative shock (P = 0.05), intraoperative blood loss (P less than 0.01), postoperative respiratory complications (P less than 0.05) and renal failure (P less than 0.05) all significantly influenced early mortality as did multiple subsystem complications (P less than 0.01). Late mortality was 26 per cent, comparable to series of unruptured aortic aneurysm resection survivors. Increased awareness of the problem by physicians, and hence, more aggressive elective treatment of abdominal aortic aneurysms should lower the frequency of this problem, and improved intraoperative and postoperative care should improve survival of those patients whose aneurysms rupture.


Assuntos
Ruptura Aórtica/cirurgia , Idoso , Alabama , Aorta Abdominal/cirurgia , Ruptura Aórtica/mortalidade , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias
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