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1.
Health Place ; 36: 134-44, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26540669

RESUMO

Published data on hospitalisation rates tend to reveal marked spatial variations within a city or region. Such variations may simply reflect corresponding variations in need at the small-area level. However, they might also be a consequence of poorer accessibility to medical facilities for certain communities within the region. To help answer this question it is important to compare these variable hospitalisation rates with small-area estimates of need. This paper first maps hospitalisation rates at the small-area level across the region of Yorkshire in the UK to show the spatial variations present. Then the Health Survey of England is used to explore the characteristics of persons with heart disease, using chi-square and logistic regression analysis. Using the most significant variables from this analysis the authors build a spatial microsimulation model of morbidity for heart disease for the Yorkshire region. We then compare these estimates of need with the patterns of hospitalisation rates seen across the region.


Assuntos
Acessibilidade aos Serviços de Saúde , Hospitalização/tendências , Morbidade/tendências , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Inglaterra , Feminino , Acessibilidade aos Serviços de Saúde/estatística & dados numéricos , Inquéritos Epidemiológicos , Cardiopatias , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise de Pequenas Áreas , Adulto Jovem
3.
Bone Marrow Transplant ; 49(7): 966-71, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24777184

RESUMO

We hypothesized that clinical risk factors could be identified within 2 weeks of onset of severe (stage 3 or 4) acute gut GVHD for identifying a patient population with a very poor outcome. Among 1462 patients who had allogeneic hematopoietic cell transplantation (HCT) between January 2000 and December 2005, 116 (7.9%) developed stage 3-4 gut GVHD. The median time for onset of stage 3-4 gut GVHD was 35 (4-135) days after allogeneic HCT. Eighty-five of the 116 patients (73%) had corticosteroid resistance before or within 2 weeks after the onset of stage 3-4 gut GVHD. Significant risk factors for mortality included corticosteroid resistance (hazards ratio (HR)=2.93; P=0.0005), age >18 years (HR=4.95; P=0.0004), increased serum bilirubin (HR 2.53; P=0.0001) and overt gastrointestinal bleeding (HR 2.88; P=0.0004). Among patients with stage 3-4 gut GVHD, the subgroup with 0, 1 or 2 risk factors had a favorable prognosis, whereas the subgroup with 3 or 4 risk factors had a dismal prognosis. This information should be considered in designing future studies of severe gut GVHD and in counseling patients about prognosis.


Assuntos
Gastroenteropatias/etiologia , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Gastroenteropatias/imunologia , Doença Enxerto-Hospedeiro/terapia , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores de Risco , Condicionamento Pré-Transplante/efeitos adversos , Condicionamento Pré-Transplante/métodos , Transplante Homólogo , Resultado do Tratamento , Adulto Jovem
4.
Bone Marrow Transplant ; 44(7): 441-7, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19308033

RESUMO

Hepatic complications of transplant are a common cause of mortality. Although mild elevations of serum aminotransferase enzymes (aspartate and alanine (AST, ALT)) do not carry an adverse prognosis, this is not the case with severe hepatocellular injury. We reviewed 6225 consecutive recipients to determine the incidence and outcomes of severe hepatocellular injury (AST >1500 U/l) before day 100, which occurred in 88 patients. Causes were sinusoidal obstruction syndrome (SOS) (n = 46), hypoxic hepatitis (n = 33), varicella zoster virus (VZV) hepatitis (n = 4), drug-liver injury (n = 2) and unknown (n = 3). The incidence declined from 1.9% in the 1990s to 1.1% recently (owing to a fivefold decline in SOS and disappearance of VZV hepatitis). In hypoxic hepatitis, peak serum AST was 3545 U/l (range, 1380-25 246) within days of shock or prolonged hypoxemia; case fatality rate was 88%. In SOS, AST increases occurred 2-6 weeks after diagnosis; peak AST was 2252 U/l (range, 1437-8281); case fatality rate was 76%, with only serum bilirubin able to distinguish survivors (2.7 vs 11.3 mg/100 ml, P=0.0009). We conclude that circulatory insults (sinusoidal injury, hypotension and hypoxemia), and not infection, are the most common cause of severe hepatocellular injury, the frequency of which has declined because of a falling incidence of SOS and VZV hepatitis.


Assuntos
Hipóxia Celular/fisiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Insuficiência Hepática/epidemiologia , Insuficiência Hepática/etiologia , Fígado/patologia , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Transplante de Células-Tronco Hematopoéticas/mortalidade , Insuficiência Hepática/mortalidade , Insuficiência Hepática/terapia , Hepatopatia Veno-Oclusiva/complicações , Humanos , Hipóxia/complicações , Incidência , Fígado/irrigação sanguínea , Fígado/microbiologia , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Infecções Oportunistas/complicações , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
5.
Curr Oncol ; 14(6): 234-7, 2007 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18080015

RESUMO

Lung cancer is the leading cause of cancer death in Canada. The organization of health care services is central to the delivery of accessible, high-quality medical care and may be one factor that influences patient outcome. An exciting opportunity arose for clinicians to initiate the redesign of lung cancer services provided by three institutions in the Greater Toronto Area. This qualitative report describes the integrated lung cancer network that they developed, the innovation it has facilitated, and the systematic approach being taken to evaluate its impact. Available clinical resources were deployed to restructure services along patient-centred lines and to provide greater access to the specialist lung cancer team. A non-hierarchical clinical network was established that consolidates the lung cancer team. A multi-institutional and multidisciplinary tumour board and comprehensive thoracic oncology clinics are at its core. This innovative organizational paradigm considers all of the available services at each facility and aims to fully integrate specialists across the three institutions, thereby maximizing resource utilization. We believe that this paradigm may have wider applicability. The network is currently working to complete a current program of further service improvements and to objectively assess its impact on patient outcome.

6.
Healthc Financ Manage ; 55(7): 42-3, 2001 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-11467229

RESUMO

The decision of the California Supreme Court in Potvin v. Metropolitan Life Insurance Company, issued in 2000, held that a physician who is eliminated from a health plan's network based upon a "without-cause" termination clause in the contract nevertheless may be entitled to fair procedure rights. Although the case did not explain certain elements of the test of substantial economic power, healthcare entities can take precautions in response to the Potvin decision.


Assuntos
Direitos Civis/legislação & jurisprudência , Serviços Contratados/legislação & jurisprudência , Programas de Assistência Gerenciada/legislação & jurisprudência , Médicos/legislação & jurisprudência , California , Competição Econômica/legislação & jurisprudência , Guias como Assunto , Ginecologia , Humanos , Obstetrícia
8.
Hepatology ; 32(6): 1265-71, 2000 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11093733

RESUMO

Chronic graft-versus-host disease (GVHD) of the liver usually presents as an indolent cholestatic disease in patients with skin, mouth, and eye involvement. We observed 14 patients in whom chronic GVHD of the liver presented with marked elevations of serum aminotransferases, clinically resembling acute viral hepatitis. Onset of liver dysfunction was at 294 days (range, 74-747 days) after allogeneic hematopoietic cell transplantation and coincided with a recent cessation or taper of immunosuppressive drugs. Median peak serum alanine transaminase (ALT) was 1,640 U/L (698-2,565 U/L), and median bilirubin was 12.3 mg/dL (0.9-55.9 mg/dL). All biopsies showed characteristic features of GVHD with damaged and degenerative small bile ducts. Other features included a marked lobular hepatitis, moderate to marked amounts of hepatocyte unrest, sinusoidal inflammation with perivenular necroinflammatory foci, and many acidophilic bodies scattered throughout the lobule. When high-dose immunosuppressive therapy was instituted soon after presentation, progressive improvement and eventual normalization of liver enzymes and bilirubin levels were observed. However, in cases in which the diagnosis was not made and therapy was delayed, a progressive cholestatic picture emerged with histologic evidence of loss of small bile ducts and portal fibrosis. We conclude that a distinct syndrome of chronic liver GVHD presenting as an acute hepatitis can be recognized in a patient at risk who is receiving no, or minimal, immunosuppressive medications. Liver biopsy is necessary to exclude viral causes of liver dysfunction and to confirm characteristic abnormalities of small bile ducts. Institution of high-dose immunosuppression can prevent progressive bile duct destruction and effect resolution of jaundice if given early.


Assuntos
Doença Enxerto-Hospedeiro/diagnóstico , Hepatite Viral Humana/diagnóstico , Transplante de Fígado , Doença Aguda , Adulto , Doença Crônica , Ciclosporina/uso terapêutico , Diagnóstico Diferencial , Quimioterapia Combinada , Feminino , Glucocorticoides/uso terapêutico , Doença Enxerto-Hospedeiro/tratamento farmacológico , Doença Enxerto-Hospedeiro/patologia , Humanos , Imunossupressores/uso terapêutico , Fígado/patologia , Masculino , Prednisona/uso terapêutico , Resultado do Tratamento
9.
Org Lett ; 2(23): 3747-50, 2000 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-11073691

RESUMO

Commercially available coals were found to be efficient heterogeneous catalysts of the Kemp elimination reaction in aqueous solutions. A pH-rate profile study suggests that catalysis originates from specific catalytic groups and not simply from the large graphitic surface area. The low-quality lignite coals, which exhibit similar catalytic efficiency per weight to that of molecularly imprinted polymers, are better catalysts for this reaction in comparison with the bituminous coals.

10.
Bioorg Med Chem Lett ; 10(20): 2353-6, 2000 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-11055354

RESUMO

A highly sensitive, inexpensive, and facile bioluminescent assay for the detection of catalytic antibodies has been developed. This assay may be used for the early detection of antibody catalysis. The efficiency of this technique was exemplified by the use of the luminescent bacterium VhM42 for monitoring an antibody-catalyzed retroaldol fragmentation reaction with aldolase antibodies 38C2 and 24H6.


Assuntos
Anticorpos Catalíticos/análise , Frutose-Bifosfato Aldolase/imunologia , Vibrio/metabolismo , Aldeídos/metabolismo , Anticorpos Catalíticos/metabolismo , Calibragem , Catálise , Cinética , Luminescência , Sensibilidade e Especificidade
11.
Am J Surg Pathol ; 24(7): 1004-8, 2000 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-10895823

RESUMO

BACKGROUND: Acute graft-versus-host disease (GVHD) of the liver is a frequent complication of allogeneic hematopoietic cell transplantation. This report describes hepatic GVHD following autologous transplantation. METHODS: We reviewed 116 consecutive autologous transplant recipients. A diagnosis of GVHD was based on histology (segmental to subtotal destruction of bile ductal epithelial cells with apoptosis and lymphocytic infiltrates), clinical criteria (elevated serum alkaline phosphatase), a response to immunosuppressive therapy, and finding no other cause for cholestatic liver disease. RESULTS: Two patients developed cholestatic liver disease (alkaline phosphatase levels over five times the normal upper limit) and had liver biopsies showing apoptotic and dysmorphic ductular epithelial cells typical of GVHD. Three additional patients developed cholestasis and intestinal symptoms but had gastric biopsies only, showing apoptotic crypt epithelial cells and crypt cell drop-out typical of GVHD. CONCLUSION: Two recipients of autologous hematopoietic cells developed histologic abnormalities of small bile ducts and cholestatic liver disease resembling GVHD of the liver after allogeneic transplant. The mechanisms of bile duct damage in this setting may involve immune dysregulation related to reconstitution of immunity with peripheral blood stem cells.


Assuntos
Apoptose , Ductos Biliares Intra-Hepáticos/patologia , Colestase/patologia , Doença Enxerto-Hospedeiro/patologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Doença Aguda , Fosfatase Alcalina/sangue , Colestase/tratamento farmacológico , Colestase/etiologia , Células Epiteliais/patologia , Feminino , Doença Enxerto-Hospedeiro/tratamento farmacológico , Doença Enxerto-Hospedeiro/etiologia , Humanos , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Prednisona/uso terapêutico
12.
Bone Marrow Transplant ; 25(11): 1157-64, 2000 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-10849528

RESUMO

Enumeration of CD34+ cells in the peripheral blood before apheresis predicts the quantity of those cells collected, although the cytometric techniques used are complex and expensive. We found that a subpopulation of lysis-resistant cells in the peripheral blood, identified by the Sysmex SE9500 and designated as HPC, can serve as a surrogate marker predictive of the yield of CD34+ cells. Spearman's rank statistics were used to examine the correlation between WBC, MNC, HPC and CD34+ cells in the peripheral blood and final CD34+ cell yield for 112 samples of peripheral blood and matching apheresis collections from 66 patients and donors. The results indicate that WBC and MNC in the peripheral blood were poor predictors of CD34 content, while HPC gave a correlation coefficient of 0.62. The positive predictive values of different cutoff levels of HPC in the peripheral blood ranging from 5 to 50 x 106/l increased from 0.80 to 0.93 when the target collection was 1 x 106cells/kg. However, for patients with HPC levels below various cutoff levels, the proportion of the collections not reaching that target goal ranged between 0.36 and 0.43, indicating that most collections will still exceed the target goal of CD34+ cells. When the target collection was 2.5 x 106 CD34+ cells/kg, the positive predictive value was lower and negative predictive value was higher.


Assuntos
Antígenos CD34/sangue , Remoção de Componentes Sanguíneos/instrumentação , Mobilização de Células-Tronco Hematopoéticas , Células-Tronco Hematopoéticas/citologia , Neoplasias/terapia , Adolescente , Adulto , Idoso , Antígenos CD/sangue , Biomarcadores/sangue , Remoção de Componentes Sanguíneos/métodos , Neoplasias da Mama/terapia , Criança , Pré-Escolar , Feminino , Filgrastim , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Mobilização de Células-Tronco Hematopoéticas/métodos , Células-Tronco Hematopoéticas/patologia , Humanos , Lactente , Leucemia/terapia , Linfoma não Hodgkin/terapia , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/terapia , Proteínas Recombinantes
13.
Pediatr Nephrol ; 14(4): 319-21, 2000 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-10775077

RESUMO

Two newborns with glomerulocystic kidney disease manifesting as late onset oligohydramnion and neonatal anuria, yet without severe respiratory distress, are presented. They had a similar perinatal course and associated clinical manifestations. No associated congenital or inherited malformation syndrome could be defined. Both infants' parents were first degree cousins and belonged to the same small Bedouin tribe, and neither they nor the infants' siblings had polycystic kidneys or renal insufficiency, pointing to either a possible genetic etiology or a common external toxic exposure.


Assuntos
Injúria Renal Aguda/complicações , Glomérulos Renais , Oligo-Hidrâmnio/complicações , Doenças Renais Policísticas/complicações , Adulto , Anuria/complicações , Biópsia , Feminino , Humanos , Recém-Nascido , Rim/patologia , Glomérulos Renais/patologia , Doenças Renais Policísticas/genética , Doenças Renais Policísticas/patologia , Gravidez , Crânio/diagnóstico por imagem , Crânio/embriologia , Tomografia Computadorizada por Raios X
14.
Leuk Lymphoma ; 37(3-4): 405-14, 2000 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-10752992

RESUMO

The mechanism that leads to hemopoietic failure in patients with myelodysplastic syndrome (MDS) is not well understood. There is evidence, however, that regulatory molecules such as tumor necrosis factor (TNF)-alpha, Fas (CD95), and Fas-ligand, which negatively affect hemopoiesis by way of apoptosis are upregulated. Here we analyzed marrow samples from 80 patients with MDS in regard to TNF-alpha and Fas-ligand levels and a possible correlation with various disease parameters and risk factors. TNF-alpha levels were elevated in comparison to samples from normal marrow donors, however, no significant correlation with FAB subtype, cytogenetic risk group or score by the International Prognostic Scoring System (IPSS) was observed. However, there was an inverse correlation between the cytogenetic risk category (low, intermediate, high) and levels of soluble Fas-ligand. The major source of TNF-alpha were mononuclear (non-stromal) cells which appeared to produce TNF-alpha at maximum levels. Limiting dilution analysis of CD34+ precursor cells showed that individually assayed cells, removed from companion cells that presumably provided negative signals such as TNF-alpha or Fas-ligand, were able to generate progressively increasing numbers of colonies. Stromal layers derived from MDS marrow did not have an inhibitory effect. In fact, higher colony numbers were obtained from both normal and MDS marrow derived hemopoietic precursors propagated on irradiated stromal layers from MDS marrow than on stromal layers from normal marrow. These results show that substantial numbers of normal hemopoietic precursors persist in MDS marrow. However, differentiation into mature cells is inhibited by negative signals originating from accessory or abnormal hemopoietic precursors in the non-adherent marrow fraction.


Assuntos
Células da Medula Óssea/patologia , Hematopoese , Síndromes Mielodisplásicas/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Adesão Celular , Separação Celular , Células Cultivadas , Criança , Pré-Escolar , Citogenética , Feminino , Hematopoese/genética , Humanos , Imunofenotipagem , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/classificação , Síndromes Mielodisplásicas/genética , Células Estromais/patologia
15.
Biol Blood Marrow Transplant ; 6(1): 25-34, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-10707996

RESUMO

Delayed platelet recovery is a significant complication after both autologous and allogeneic hematopoietic stem cell transplantation (HSCT). A multicenter, phase I dose-escalation study of recombinant human thrombopoietin (rhTPO) was conducted to assess its safety and to obtain preliminary data on its efficacy in patients with persistent severe thrombocytopenia (<20,000/microL) >35 days after HSCT. Thirty-eight patients, 37 of whom were evaluable, were enrolled in the study from April 1996 through January 1997. rhTPO was administered at doses of 0.6, 1.2, and 2.4 microg/kg as a single dose (group A) or in multiple doses every 3 days for a total of 5 doses (group B). No significant adverse effects were observed. Ten patients had recovery of platelet counts during the 28-day study period; 3 of these 10 had an increase in marrow megakaryocyte content 7 days after completing treatment with rhTPO. When all baseline marrows were compared with samples after rhTPO treatment, there was no difference in marrow megakaryocyte content (P = 0.49). This study design could not answer the question of whether the recoveries of platelet counts observed in some patients were spontaneous or influenced by rhTPO treatment; nonetheless, the authors found no correlation between the dose of rhTPO and the recovery of platelet counts. Increases in serum TPO levels were dose-dependent and remained significantly elevated for up to 72 hours after treatment. To evaluate response, further studies of treatment strategies with rhTPO in patients with delayed platelet recovery are required.


Assuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Trombocitopenia/tratamento farmacológico , Trombopoetina/administração & dosagem , Adolescente , Adulto , Idoso , Anticorpos/imunologia , Especificidade de Anticorpos , Avaliação de Medicamentos , Feminino , Sobrevivência de Enxerto/efeitos dos fármacos , Humanos , Masculino , Megacariócitos/patologia , Pessoa de Meia-Idade , Neutropenia/tratamento farmacológico , Neutropenia/etiologia , Contagem de Plaquetas/efeitos dos fármacos , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/sangue , Proteínas Recombinantes/farmacocinética , Taxa de Sobrevida , Trombocitopenia/sangue , Trombocitopenia/etiologia , Trombopoetina/imunologia , Trombopoetina/farmacocinética , Fatores de Tempo
16.
Blood ; 95(4): 1188-94, 2000 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-10666189

RESUMO

We carried out bone marrow transplantation (BMT) in 50 patients with myelodysplastic syndrome (MDS) who were 55.3 to 66.2 years of age (median, 58.8 years). According to the criteria of the French-American-British (FAB) classification, 13 patients had refractory anemia (RA), 19 had RA with excess blasts (RAEB), 16 had RAEB in transformation or acute myelogenous leukemia (RAEB-T/AML), and 2 had chronic myelomonocytic leukemia (CMML). According to the recently established International Prognostic Scoring System (IPSS), available for 45 patients, 2 patients were considered low risk; 14, intermediate 1 risk; 19, intermediate 2 risk; and 10, high risk. Conditioning regimens were cyclophosphamide (CY) (120 mg/kg of body weight) plus 12-Gy fractionated total-body irradiation (FTBI) (n = 15), CY plus FTBI with lung and liver shielding (n = 4), busulfan (7 mg/kg) plus FTBI (n = 4), or busulfan (16 mg/kg) plus CY (n = 27). The busulfan-plus-CY group included 16 patients in whom busulfan was targeted to plasma levels of 600 to 900 ng/mL. In these 16 patients, steady-state levels of busulfan actually achieved were 714 to 961 ng/mL (mean +/- SD, 845 +/- 64 ng/mL; median, 838 ng/mL). The donors were HLA-identical siblings for 34 patients, HLA-nonidentical family members for 4, identical twins for 4, and unrelated volunteers for 6. All 46 patients surviving > 21 days had engraftment, and 22 patients (44%) are surviving 9 to 80 months after BMT. Specifically, among 13 patients with RA, 1 had relapse (cumulative incidence [CI] at 3 years, 8%) and 8 are surviving, for a Kaplan-Meier (KM) estimate of survival at 3 years of 59% (disease-free survival [DSF], 53%). Among 19 patients with RAEB, 3 had relapse (CI at 3 years, 16%), and 8 are surviving disease free (KM estimate at 3 years, 46%). Among 18 patients with RAEB-T/AML or CMML, 6 had relapse (CI at 3 years, 28%), and the KM estimate of DSF at 3 years is 33%. Relapse-free survival had an inverse correlation with cytogenetic risk classification and with the risk score according to the IPSS. Survival in all FAB categories was highest among patients enrolled in a protocol in which busulfan plasma levels were targeted to 600 to 900 ng/mL. These data indicate that BMT can be carried out successfully in patients with MDS who are older than 55 years of age. (Blood. 2000;95:1188-1194)


Assuntos
Transplante de Medula Óssea , Transplante de Células-Tronco Hematopoéticas , Síndromes Mielodisplásicas/terapia , Transplante Homólogo , Transplante Isogênico , Idoso , Anemia Refratária com Excesso de Blastos/mortalidade , Anemia Refratária com Excesso de Blastos/terapia , Ciclofosfamida/uso terapêutico , Fracionamento da Dose de Radiação , Doença Enxerto-Hospedeiro/prevenção & controle , Humanos , Terapia de Imunossupressão/métodos , Doadores Vivos , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/mortalidade , Recidiva , Estudos Retrospectivos , Análise de Sobrevida , Fatores de Tempo , Transplante Homólogo/imunologia , Transplante Isogênico/imunologia , Irradiação Corporal Total
17.
Biol Blood Marrow Transplant ; 5(5): 316-21, 1999.
Artigo em Inglês | MEDLINE | ID: mdl-10534062

RESUMO

We have previously described pharmacokinetic studies with a dimethylsulfoxide-based intravenous busulfan preparation in a canine model and in preliminary clinical trials. Using the same intravenous busulfan preparation, we carried out a dose escalation study to determine a marrow-ablative dose and to test the ability of autologous marrow to reconstitute hematopoiesis in dogs so treated. Busulfan was given intravenously at doses of 3.75 to 40 mg/kg. Marrow ablation was achieved at 20 mg/kg given either as a single dose or in four daily increments of 5 mg/kg each. There was a relative sparing of lymphocytes. A busulfan dose of 40 mg/kg resulted in severe central nervous system toxicity. Otherwise, nonhematopoietic toxicity was minimal and restricted to mild hepatic abnormalities. Four dogs were given busulfan at 20 mg/kg followed 30 hours later by infusion of autologous marrow, and all showed prompt and complete hematopoietic reconstitution. The area under the curve (AUC) determined by busulfan concentration in plasma over time was dose dependent, ranging from 12 to 100 microg x h/mL for busulfan doses of 3.75-20 mg/kg. There was a suggestion that the plasma half-life increased at the highest busulfan doses used. Intravenous administration of busulfan circumvented differences in bioavailability; nevertheless, considerable variations in the pharmacokinetic parameters were observed between individual animals. Thus, intravenous busulfan can be given safely and is effective in ablating hematopoiesis. However, factors other than absorption influence the AUC, and individualization of dosing may be required even with intravenous administration of the drug.


Assuntos
Bussulfano/administração & dosagem , Hematopoese/efeitos dos fármacos , Agonistas Mieloablativos/administração & dosagem , Animais , Contagem de Células Sanguíneas , Transplante de Medula Óssea , Bussulfano/sangue , Bussulfano/farmacocinética , Bussulfano/toxicidade , Cães , Relação Dose-Resposta a Droga , Injeções Intravenosas , Contagem de Leucócitos , Modelos Biológicos , Neutrófilos/efeitos dos fármacos , Contagem de Plaquetas , Transplante Autólogo
18.
Am J Clin Pathol ; 112(4): 513-23, 1999 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-10510674

RESUMO

A vexing problem after hematopoietic cell transplantation (HCT) for leukemia is assessing the biologic significance of low numbers of cells "suspicious" for relapse seen in morphologic review of peripheral blood smears (PBSs). In 27 patients, in apparent hematologic remission after HCT for leukemia, we studied the nature of such cells in PBSs to the endpoint of leukemic relapse by using multidimensional flow cytometry (MDF) on blood or bone marrow aspirates. Based on abnormal cytometric maturational patterns, +/- cell sorting of blasts with fluorescence in situ hybridization with informative markers, we differentiated benign recovering myeloid and lymphoid precursors from leukemic cells. In 17 patients, blasts were characterized by MDF as normal early hematopoietic precursors, lymphoblasts, or NK cells. Of these patients, 16 remained in remission for at least 42 days. In 10 patients, blasts were characterized by MDF as a malignant immunophenotype; 9 relapsed within 10 days and 1 relapsed 280 days after a graft-vs-leukemia effect. MDF status was strongly associated with a 90 x probability of relapse even after adjusting for other potential variables. Morphologic triggered MDF characterization of peripheral blasts is a powerful and rapid tool for distinguishing immature regenerative forms from early leukemic relapse.


Assuntos
Crise Blástica/etiologia , Citometria de Fluxo , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Adolescente , Adulto , Separação Celular , Criança , Pré-Escolar , Feminino , Humanos , Imunofenotipagem , Hibridização in Situ Fluorescente , Leucemia/terapia , Masculino , Pessoa de Meia-Idade , Prognóstico
19.
Bioorg Med Chem Lett ; 9(13): 1745-50, 1999 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-10406635

RESUMO

A structure-activity relationship study with a series of aldol substrates shows that the mechanism of the antibody 38C2-catalyzed retrograde aldol reaction depends on the nature of the substrate With electron-deficient substrates an early deprotonation precedes the C-C bond cleavage while with electron-rich substrates the catalytic mechanism involves an initial C-C bond cleavage leading to a positively charged intermediate.


Assuntos
Anticorpos Catalíticos/química , Frutose-Bifosfato Aldolase/química , Frutose-Bifosfato Aldolase/imunologia , Cinética , Modelos Químicos , Bases de Schiff , Relação Estrutura-Atividade
20.
Am J Epidemiol ; 149(11): 1025-9, 1999 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-10355378

RESUMO

The authors estimated the number of clinically recognized pregnancies that occurred annually from 1981 to 1991 in the United States by type of outcome and by race. Estimates of the numbers of livebirths, induced abortions, ectopic pregnancies, and fetal deaths were obtained by using data from the Centers for Disease Control and Prevention in Atlanta, Georgia. The number of spontaneous abortions was estimated by using previously published, age-specific rates. More than 67 million pregnancies occurred during the study period. Overall, 62.5% of these pregnancies resulted in livebirths, 21.9% in legal induced abortions, 13.8% in spontaneous abortions, 1.3% in ectopic pregnancies, and 0.5% in fetal deaths. These data can be used to provide denominators for the calculation of a variety of pregnancy outcome-specific rates.


Assuntos
Gravidez/estatística & dados numéricos , Aborto Espontâneo/epidemiologia , Etnicidade/estatística & dados numéricos , Feminino , Morte Fetal/epidemiologia , Humanos , Resultado da Gravidez/epidemiologia , Gravidez Ectópica/epidemiologia , Estados Unidos/epidemiologia
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