RESUMO
To evaluate the relationship between serum adiponectin ADP (sADP) levels and the risk of metabolic syndrome (MS) and cardiovascular disease (CVD) in patients with DISH and to assess the relationship between sADP levels, and the tendency for new bone formation in these patients. sADP levels were measured in DISH and non-DISH (NDISH) patients. sADP levels were compared between the two groups and were also correlated with weight circumference, BMI, serum lipid profile, concomitant diseases, use of medications, the presence of MS, the risk of developing CVD, and the extent of bony bridges. Eighty-seven patients with DISH and 65 in NDISH were examined. A negative significant correlation between sADP and insulin resistance, and serum insulin levels in the DISH group (r = - 0.375, p = 0.0004; r = -0.386, p = 0.0002, respectively) was observed. sADP levels positively correlated with serum cholesterol and LDL levels in the DISH group. Higher sADP levels positively correlated with the extent of bony bridges (r = 0.245, p = 0.02). It appears that at least in patients with DISH, sADP has an osteogenic effect. Increasing sADP levels might reduce insulin resistance and hyperinsulinemia and reduce the CV risk and the osteogenic effect exerted by insulin. However, increasing sADP levels might directly increase new bone formation aggravating the already enhanced osteogenesis. Studies of larger populations with earlier disease might shed light on the enigmatic role played by ADP in patients with DISH and the eventual effect of manipulating its levels.
Assuntos
Adiponectina/sangue , Doenças Cardiovasculares/etiologia , Hiperostose Esquelética Difusa Idiopática/sangue , Hiperostose Esquelética Difusa Idiopática/complicações , Síndrome Metabólica/etiologia , Adulto , Idoso , Biomarcadores/sangue , Estudos de Casos e Controles , Humanos , Insulina/sangue , Resistência à Insulina , Masculino , Pessoa de Meia-IdadeRESUMO
Two Arab children from the Gaza strip presented with fever, weakness, hepatosplenomegaly, lymphadenopathy and leukocytosis. The peripheral and bone marrow blasts had an immunophenotype compatable with T-cell acute lymphoblastic leukemia, and exhibited unusual markers (CD2+, CD3+, CD4-, CD8-). Cytogenetic studies revealed t(8;14)(q24;q11), possibly involving the alpha/delta locus of the T-cell receptor gene on chromosome 14 rather than the immunoglobulin heavy-chain locus usually involved in the t(8;14)(q24;q32), which is typical for Burkitt's leukemia/lymphoma. One of the children had a brother who died of T-cell acute lymphoblastic leukemia a few years later, however, his blasts showed deletion of chromosome 12. The possible role for environmental factors associated with low socioeconomic status, as well as of genetic factors in leukemogenesis are discussed.
Assuntos
Leucemia-Linfoma de Células T do Adulto/epidemiologia , Pré-Escolar , Cromossomos Humanos Par 14 , Cromossomos Humanos Par 8 , DNA Viral/análise , Meio Ambiente , Rearranjo Gênico , Genes myc , Herpesvirus Humano 4 , Humanos , Lactente , Israel , Cariotipagem , Leucemia-Linfoma de Células T do Adulto/genética , Masculino , Translocação GenéticaRESUMO
Sixty-six SLE patients were studied for the presence of lupus type circulating anticoagulant. Forty-nine percent of them showed activity of this anticoagulant. The sensitivity of various coagulation tests was compared. Recalcification time was found to be the most sensitive screening test and the kaolin clotting time mixture test, the best for determining the presence of the anticoagulant. Tissue thromboplastin inhibition test detected only half of the patients in whom the anticoagulant was found by recalcification time and kaolin clotting time mixture test. APTT, using 2 different reagents, resulted in 73% and 52% false negatives. A numerical index for determining the presence of the anticoagulant and its quantitative evaluation is suggested. The association between thromboembolic events, recurrent abortions and the different coagulation tests is shown.
Assuntos
Fatores de Coagulação Sanguínea/imunologia , Fatores de Coagulação Sanguínea/análise , Testes de Coagulação Sanguínea/normas , Humanos , Inibidor de Coagulação do Lúpus , Tempo de Tromboplastina ParcialRESUMO
The effect of extracorporeal circulation on platelet count and size (mean platelet volume) was studied in 65 patients (nine bleeders and 56 nonbleeders). In addition to the above, in 20 of the patients platelet aggregation response to adenosine diphosphate, collagen, and ristocetin was measured. Platelet counts dropped postoperatively both in the bleeder and in the nonbleeder groups. The difference between them was not significant. However, the bleeders had a significantly lower mean platelet volume (7.7 +/- 0.84 versus 8.68 +/- 1.1 fl) and lower volume percentage of platelets in whole blood (0.075% +/- 0.02% versus 0.116% +/- 0.04%) (p less than 0.05) than the nonbleeders. None of the bleeders had a volume percentage of platelets in whole blood higher than 0.095%. All 20 patients studied for platelet functions had an abnormal postoperative aggregation response to adenosine diphosphate, collagen, and ristocetin. Three patterns of disturbed response to ristocetin were observed: grade I, delayed onset (14 patients); grade II, incomplete aggregation (five patients); and grade III, total lack of aggregation (one patient). All patients with delayed-onset response to ristocetin had a normal bleeding time, whereas the six patients with grade II and III responses had prolonged bleeding times and three of them had clinically significant bleeding. Factor VIII procoagulant activity, factor VIII-related antigen, factor VIII-ristocetin cofactor, and factor VIII two-dimensional electrophoresis were found normal, which suggests that the von Willebrand-like reaction to ristocetin observed in this study was caused by a defect in platelet membrane rather than by factor VIII changes.
Assuntos
Circulação Extracorpórea/efeitos adversos , Hemorragia/fisiopatologia , Agregação Plaquetária , Adolescente , Adulto , Idoso , Tempo de Sangramento , Criança , Pré-Escolar , Fator VIII/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Contagem de PlaquetasRESUMO
Donor-cell leukemia post bone marrow transplantation is a rare event. Most of the cases reported to date have developed in cells from an HLA-matched sibling, who had no evidence of malignant disease before or following the occurrence of donor-origin leukemia. We describe a 17-year-old female who developed B-cell lymphoma 9 years following the occurrence of donor-origin acute myeloid leukemia in her brother for whom she had donated marrow. Cytogenetic analysis of the tumor revealed multiple chromosomal aberrations. The donor was heterozygous for the Ashkenazi mutation of Bloom's syndrome, suggesting that donor-type leukemia could have resulted from genomic instability in the donor cells.
Assuntos
Transplante de Medula Óssea , Leucemia Mieloide Aguda/terapia , Linfoma de Células B/diagnóstico , Doadores de Tecidos , Quimeras de Transplante/genética , Adolescente , Mapeamento Cromossômico , Feminino , Teste de Histocompatibilidade , Humanos , Linfoma de Células B/genética , Masculino , Irmãos , Fatores de TempoRESUMO
Methyl tert-butyl ether (MTBE) is widely used as an additive to gasoline, to increase oxygen content and reduce tailpipe emission of pollutants. Widespread human exposure to MTBE may occur due to leakage of gasoline storage tanks and a high stability and mobility of MTBE in ground water. To compare disposition of MTBE after different routes of exposure, its biotransformation was studied in humans after oral administration in water. Human volunteers (3 males and 3 females, identical individuals, exposures were performed 4 weeks apart) were exposed to 5 and 15 mg 13C-MTBE dissolved in 100 ml of water. Urine samples from the volunteers were collected for 96 h after administration in 6-h intervals and blood samples were taken in intervals for 24 h. In urine, MTBE and the MTBE-metabolites tert-butanol (t-butanol), 2-methyl-1,2-propane diol, and 2-hydroxyisobutyrate were quantified, MTBE and t-butanol were determined in blood samples and in exhaled air in a limited study of 3 male volunteers given 15 mg MTBE in 100 ml of water. MTBE blood concentrations were 0.69 +/- 0.25 microM after 15 mg MTBE and 0.10 +/- 0.03 microM after 5 mg MTBE. MTBE was rapidly cleared from blood with terminal half-lives of 3.7 +/- 0.9 h (15 mg MTBE) and 8.1 +/- 3.0 h (5 mg MTBE). The blood concentrations of t-butanol were 1.82 +/- 0.63 microM after 15 mg MTBE and 0.45 +/- 0.13 microM after 5 mg MTBE. Approximately 30% of the MTBE dose was cleared by exhalation as unchanged MTBE and as t-butanol. MTBE exhalation was rapid and maximal MTBE concentrations (100 nmol/l) in exhaled air were achieved within 10-20 min. Clearance of MTBE by exhalation paralleled clearance of MTBE from blood. T-butanol was cleared from blood with half-lives of 8.5 +/- 2.4 h (15 mg MTBE) and 8.1 +/- 1.6 h (5 mg MTBE). In urine samples, 2-hydroxyisobutyrate was recovered as major excretory product, t-butanol and 2-methyl-1,2-propane diol were minor metabolites. Elimination half-lives for the different urinary metabolites of MTBE were between 7.7 and 17.8 h. Approximately 50% of the administered MTBE was recovered in urine of the volunteers after both exposures, another 30% was recovered in exhaled air as unchanged MTBE and t-butanol. The obtained data indicate that MTBE-biotransformation and excretion after oral exposure is similar to inhalation exposure and suggest the absence of a significant first-pass metabolism of MTBE in the liver after oral administration.
Assuntos
Hidroxibutiratos/farmacocinética , Éteres Metílicos/farmacocinética , Éteres Metílicos/toxicidade , terc-Butil Álcool/farmacocinética , terc-Butil Álcool/toxicidade , Adulto , Biotransformação , Testes Respiratórios , Carbono/química , Isótopos de Carbono , Feminino , Meia-Vida , Humanos , Hidroxibutiratos/toxicidade , Hidroxibutiratos/urina , Masculino , Éteres Metílicos/administração & dosagem , Éteres Metílicos/sangue , Éteres Metílicos/química , Éteres Metílicos/urina , Fatores de Tempo , terc-Butil Álcool/sangue , terc-Butil Álcool/urinaRESUMO
tert-Amyl methyl ether (TAME) may be widely used as an additive to gasoline in the future. The presence of this ether in gasoline reduces the tail pipe emission of pollutants. Therefore, widespread human exposure to TAME may occur. To contribute to the characterization of potential adverse effects of TAME, its biotransformation was compared in humans and rats after inhalation exposure. Human volunteers (three males and three females) and rats (five males and five females) were exposed to 4 (3.8 +/- 0.2) and 40 (38.4 +/- 1.7) ppm TAME for 4 h in a dynamic exposure system. Urine samples were collected for 72 h in 6-h intervals and blood samples were taken at regular intervals for 48 h in humans. In urine, the TAME metabolites tert-amyl alcohol (t-amyl alcohol), 2-methyl-2, 3-butane diol, 2-hydroxy-2-methylbutyric acid, and 3-hydroxy-3-methylbutyric acid were quantified. TAME and t-amyl alcohol were determined in blood samples. After the end of the exposure period, blood concentrations of TAME were 4.4 +/- 1.7 microM in humans and 9.6 +/- 1.4 microM in rats after 40 ppm TAME, and 0.6 +/- 0.1 microM in humans and 1.4 +/- 0.8 microM in rats after 4 ppm. TAME was rapidly cleared from blood in both rats and humans. The blood concentrations of t-amyl alcohol were 9.2 +/- 1.8 microM in humans and 8.1 +/- 1.5 microM in rats after 40 ppm TAME, and 1.0 +/- 0.3 microM in humans and 1.8 +/- 0.2 microM in rats after 4 ppm TAME. t-Amyl alcohol was also rapidly cleared from blood. In urine of humans, 2-methyl-2,3-butane diol, 2-hydroxy-2-methylbutyric acid, and 3-hydroxy-3-methylbutyric acid were recovered as major excretory products in urine. In rats, 2-methyl-2,3-butane diol and its glucuronide were major TAME metabolites. t-Amyl alcohol and its glucuronide were minor TAME metabolites in both species. All metabolites of TAME excreted with urine in rats were rapidly eliminated, with elimination half-lives of less than 6 h. Metabolite excretion in humans was slower and elimination half-lives of the different metabolites were between 6 and 40 h in humans. The obtained data indicate differences in TAME biotransformation and excretion between rats and humans. In rats, TAME metabolites are rapidly excreted. In humans, metabolic pathways are different and metabolite excretion is slower. Recovery of TAME metabolites in urine was higher in humans as compared to rats, suggesting more intensive biotransformation of TAME in humans.
Assuntos
Poluentes Atmosféricos/farmacocinética , Éteres Metílicos/farmacocinética , Administração por Inalação , Adulto , Poluentes Atmosféricos/sangue , Poluentes Atmosféricos/urina , Animais , Biotransformação , Feminino , Humanos , Masculino , Éteres Metílicos/sangue , Éteres Metílicos/urina , Ratos , Ratos Endogâmicos F344 , Especificidade da EspécieRESUMO
Ethyl tert-butyl ether (ETBE) may be used in the future as an additive to gasoline to increase oxygen content and reduce tailpipe emissions of pollutants. Therefore, widespread human exposure may occur. To contribute to the characterization of potential adverse effects of ETBE, its biotransformation was compared in humans and rats after inhalation exposure. Human volunteers (3 males and 3 females) and rats (5 males and 5 females) were exposed to 4 (4.5+/-0.6) and 40 (40.6+/-3.0) ppm ETBE for 4 h in a dynamic exposure system. Urine samples from rats and humans were collected for 72 h at 6-h intervals, and blood samples were taken in regular intervals for 48 h. In urine, ETBE and the ETBE-metabolites tert-butanol (t-butanol), 2-methyl-1,2-propane diol, and 2-hydroxyisobutyrate were quantified; ETBE and t-butanol were determined in blood samples. After the end of the exposure period to inhalation of 40-ppm ETBE, blood concentrations of ETBE were found at 5.3+/-1.2 microM in rats and 12.1+/-4.0 microM in humans. The ETBE blood concentrations, after inhalation of 4-ppm ETBE, were 1.0+/-0.7 microM in rats and 1.3+/-0.7 microM in humans. ETBE was rapidly cleared from blood. After the end of the 40-ppm ETBE exposure period, the blood concentrations of t-butanol were 13.9+/-2.2 microM in humans and 21.7+/-4.9 microM in rats. After 4-ppm ETBE exposure, blood concentrations of t-butanol were 1.8+/-0.2 microM in humans and 5.7+/-0.8 microM in rats. t-Butanol was cleared from human blood with a half-life of 9.8+/-1.4 h in humans after 40-ppm ETBE exposure. In urine samples from controls and in samples collected from the volunteers and rats before the exposure, low concentrations of t-butanol, 2-methyl-1,2-propane diol, and 2-hydroxyisobutyrate were present. In the urine of both humans and rats exposed to ETBE, the concentrations of these compounds were significantly increased. 2-Hydroxy-isobutyrate was recovered in urine as the major excretory product formed from ETBE; t-butanol and 2-methyl-1,2-propane diol were minor metabolites. All metabolites of ETBE excreted with urine were rapidly eliminated in both species after the end of the ETBE exposure. Excretion half-lives for the different urinary metabolites of ETBE were between 10.2 and 28.3 h in humans and 2.6 and 4.7 h in rats. The obtained data indicate that ETBE biotransformation and excretion are similar for rats and humans, and that ETBE and its metabolites are rapidly excreted by both species. Between 41 and 53% of the ETBE retained after the end of the exposure was recovered as metabolites in the urine of both humans and rats.
Assuntos
Poluentes Atmosféricos/farmacocinética , Etil-Éteres/farmacocinética , Administração por Inalação , Adulto , Animais , Biotransformação , Feminino , Meia-Vida , Humanos , Masculino , Ratos , Ratos Endogâmicos F344 , Especificidade da EspécieRESUMO
Methyl-tert-butyl ether (MTBE) is widely used as an additive to gasoline to increase oxygen content and reduce tail pipe emission of pollutants. Therefore, widespread human exposure may occur. To contribute to the characterization of potential adverse effects of MTBE, its biotransformation was compared in humans and rats after inhalation exposure. Human volunteers (3 males and 3 females) and rats (5 each, males and females) were exposed to 4 (4.5 +/- 0.4) and 40 (38.7 +/- 3.2) ppm MTBE for 4 h in a dynamic exposure system. Urine samples from rats and humans were collected for 72 h in 6-h intervals, and blood samples were taken in regular intervals for 48 h. In urine, MTBE and the MTBE metabolites tertiary-butanol (t-butanol), 2-methyl-1,2-propane diol, and 2-hydroxyisobutyrate were quantified; MTBE and t-butanol were determined in blood samples. After the end of the exposure period, inhalation of 40 ppm MTBE resulted in blood concentrations of MTBE 5.9 +/- 1.8 microM in rats and 6.7 +/- 1.6 microM in humans. The MTBE blood concentrations after inhalation of 4 ppm MTBE were 2.3 +/- 1.0 in rats and 1.9 +/- 0.4 microM in humans. MTBE was rapidly cleared from blood with a half-life of 2.6 +/- 0.9 h in humans and 0.5 +/- 0.2 h in rats. The blood concentrations of t-butanol were 21.8 +/- 3.7 microM in humans and 36.7 +/- 10.8 microM in rats after 40 ppm MTBE, and 2.6 +/- 0.3 in humans and 2.9 +/- 0.5 in rats after 4 ppm MTBE. In humans, t-butanol was cleared from blood with a half-life of 5.3 +/- 2.1 h. In urine samples from controls and in samples collected from the volunteers and rats before the exposure, low concentrations of t-butanol, 2-methyl-1,2-propane diol and 2-hydroxyisobutyrate were present. In urine of both humans and rats exposed to MTBE, the concentrations of these compounds were significantly increased. 2-Hydroxyisobutyrate was recovered as a major excretory product in urine; t-butanol and 2-methyl-1,2-propane diol were minor metabolites. All metabolites of MTBE excreted with urine were rapidly eliminated in both species after the end of the MTBE exposure. Elimination half-lives for the different urinary metabolites of MTBE were between 7.8 and 17.0 h in humans and 2.9 to 5.0 h in rats. The obtained data indicate that MTBE biotransformation and excretion are similar in rats and humans, and MTBE and its metabolites are rapidly excreted in both species. Between 35 and 69% of the MTBE retained after the end of the exposure was recovered as metabolites in urine of both humans and rats.
Assuntos
Poluentes Atmosféricos/farmacocinética , Éteres Metílicos/farmacocinética , Adulto , Animais , Câmaras de Exposição Atmosférica , Biotransformação , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Meia-Vida , Humanos , Hidroxibutiratos/urina , Exposição por Inalação , Masculino , Ratos , Ratos Endogâmicos F344 , Especificidade da Espécie , terc-Butil Álcool/urinaRESUMO
A 68-year-old woman with acute myelomonocytic leukemia, who was treated annually for 21 consecutive years by "therapeutic" low-dose radon gas radiation because of spondyloarthritis, is described. The karyotype of the malignant clone was 45,XX, -17, -18,del(5)(q15q33), +t(17;18)(q11.2q23). In 45% of the metaphases, the modal number was between hyperdiploid to near tetraploid. Double minute chromosomes were demonstrated in 60% of the cells. These chromosomal aberrations are suggestive of mutagen-related leukemia.
Assuntos
Aberrações Cromossômicas , Leucemia Mielomonocítica Aguda/genética , Leucemia Induzida por Radiação/genética , Mutagênicos , Radônio/efeitos adversos , Idoso , Bandeamento Cromossômico , Feminino , Humanos , Cariotipagem , Leucemia Mielomonocítica Aguda/etiologia , Doses de Radiação , Radônio/uso terapêutico , Espondilite/radioterapiaRESUMO
We report a 62-year-old man with acute myelomonocytic leukemia with bone marrow eosinophilia (M4Eo), and a deletion of the long arm of chromosome 7. The patient presented with pancytopenia, which shortly after evolved to overt leukemia. There was no response to the daunorubicin-cytosine arabinoside (Ara-C) regimen, and a remission achieved with amsacrine (AMSA)-Ara-C lasted only for a short time. On relapse, a peculiar skin rash accompanied the hematologic picture. While ANLL with chromosome 7 abnormalities usually carries adverse prognosis, patients with M4Eo (which is usually associated with chromosome 16 abnormalities) do better. The patient described here examplifies that M4Eo may be associated with del(7)(q22), and that it is the chromosomal abnormality rather than the type of leukemia that might determine the clinical outcome.
Assuntos
Aberrações Cromossômicas/genética , Deleção Cromossômica , Cromossomos Humanos Par 7 , Eosinofilia/patologia , Leucemia Mielomonocítica Aguda/genética , Medula Óssea/patologia , Bandeamento Cromossômico , Transtornos Cromossômicos , Humanos , Cariotipagem , Masculino , Pessoa de Meia-IdadeRESUMO
We describe a case of a 14.5-year-old boy with a clinically aggressive pelvic Ewing sarcoma. The tumor cells showed the presence of a typical t(11;22)(q24;q12) aberration and gains of chromosomes 8, 10, 14, and 21. To determine the size of the trisomy and tetrasomy 8 clones an interphase analysis by fluorescence in situ hybridization with a centromere-specific chromosome 8 probe was performed. Significant quantitative differences between metaphase and interphase data were obtained. It was shown that culturing of bone marrow cells leads to enrichment of tetrasomy 8 population that may be explained by the proliferative advantage of the tetrasomy 8 cells.
Assuntos
Aneuploidia , Medula Óssea/patologia , Cromossomos Humanos Par 8 , Sarcoma de Ewing/genética , Sarcoma de Ewing/patologia , Neoplasias da Coluna Vertebral/genética , Neoplasias da Coluna Vertebral/patologia , Adolescente , Divisão Celular , Células Cultivadas , Mapeamento Cromossômico , Humanos , Interfase , Cinética , Masculino , MetáfaseRESUMO
The rare t(2;14)(p13;q32) was previously described in the three pediatric patients with acute lymphatic leukemia. In these cases this abnormality was found at diagnosis, manifested the sole chromosomal abnormality, and was associated with a favorable prognosis. We here describe three cases of leukemia where such translocations were found at relapse, were associated in two of the cases with additional known characteristic chromosomal aberration, and were associated with a grave prognosis. Interestingly enough, the malignant cells of all three patients shared the same surface antigens: CD34, HLA DR, CD10, CD20, and the myeloid marker CD13. The leukemic clone exhibiting t(2;14) probably evolved from a t(1;19)6q- pre-B acute lymphatic leukemia in one of the cases, and from a chronic phase Ph1 chromosome in another. The significance of the translocation and the coexistence of CD10 and CD13 on the same cell are discussed.
Assuntos
Antígenos CD13/análise , Cromossomos Humanos Par 14 , Cromossomos Humanos Par 2 , Neprilisina/análise , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Translocação Genética , Adolescente , Adulto , Criança , Humanos , Imunofenotipagem , CariotipagemRESUMO
A case of ANLL following a myelodysplastic syndrome, probably resulting from occupational exposure to ionizing irradiation, with two cytogenetically unrelated clones, hexasomy 8 and trisomy 11, was investigated by conventional cytogenetics and FISH. Significant quantitative differences between data obtained by metaphase and interphase analysis of the hexasomy 8 clone were observed. A difference in the sensitivity to chemotherapy of the two clones was found: while the hexasomy 8 clone markedly decreased in response to treatment, the trisomy 11 clone remained unchanged.
Assuntos
Aneuploidia , Cromossomos Humanos Par 11 , Cromossomos Humanos Par 8 , Leucemia Mieloide Aguda/genética , Trissomia , Medula Óssea/ultraestrutura , Humanos , Hibridização in Situ Fluorescente , Cariotipagem , Masculino , Pessoa de Meia-IdadeRESUMO
Spectral karyotyping (SKY) is based on the simultaneous hybridization of a set of 24 chromosome-specific DNA painting probes, each labeled with a different fluor combination. Automatic classification, based on the measurement of the spectrum for each chromosome, was applied to metaphases obtained from the affected bone marrow of a neuroblastoma case. Spectral karyotyping allowed the identification of chromosomal aberrations that could not be identified by the use of the G-banding technique, and revealed a number of gains and unbalanced translocations.
Assuntos
Cariotipagem/métodos , Neuroblastoma/genética , Translocação Genética , Pré-Escolar , Feminino , Humanos , Hibridização in Situ FluorescenteRESUMO
The toxicokinetics and biotransformation of methyl-tert.butyl ether (MTBE), ethyl-tert.butyl ether (ETBE) and tert.amyl-methyl ether (TAME) in rats and humans are summarized. These ethers are used as gasoline additives in large amounts, and thus, a considerable potential for human exposure exists. After inhalation exposure MTBE, ETBE and TAME are rapidly taken up by both rats and humans; after termination of exposure, clearance by exhalation and biotransformation to urinary metabolites is rapid in rats. In humans, clearance by exhalation is slower in comparison to rats. Biotransformation of MTBE and ETBE is both qualitatively and quantitatively similar in humans and rats after inhalation exposure under identical conditions. The extent of biotransformation of TAME is also quantitatively similar in rats and humans; the metabolic pathways, however, are different. The results suggest that reactive and potentially toxic metabolites are not formed during biotransformation of these ethers and that toxic effects of these compounds initiated by covalent binding to cellular macromolecules are unlikely.
Assuntos
Poluentes Atmosféricos/farmacocinética , Etil-Éteres/farmacocinética , Éteres Metílicos/farmacocinética , Poluentes Atmosféricos/metabolismo , Poluentes Atmosféricos/toxicidade , Animais , Biotransformação , Etil-Éteres/metabolismo , Etil-Éteres/toxicidade , Humanos , Exposição por Inalação , Cinética , Éteres Metílicos/metabolismo , Éteres Metílicos/toxicidade , Ratos , Respiração , Distribuição Tecidual , Emissões de VeículosRESUMO
OBJECTIVE: To evaluate the effectiveness of the Centers for Disease Control and Prevention's CD4+ T-cell laboratory testing improvement program and the influence of other laboratory improvement programs on CD4+ T-cell testing practices. DESIGN: Surveys asking for practice changes and factors that influenced the changes, a survey of clinicians' perceptions of laboratory quality in CD4 testing, and analysis of data from the Model Performance Evaluation Program. INTERVENTIONS: Centers for Disease Control and Prevention interventions included a series of 3-day workshops on flow cytometry, CD4+ T-cell testing guidelines published in the Morbidity and Mortality Weekly Report, the Clinical Laboratory Improvement Amendments of 1988, and the Model Performance Evaluation Program. PARTICIPANTS: All known laboratories in the United States that perform clinical CD4+ T-cell testing, workshop participants, and a sample of clinicians that treat patients infected with the human immunodeficiency virus. MAIN OUTCOME MEASURES: Changes in practices, factors most influential in effecting change, and performance on samples mailed to laboratories by the Model Performance Evaluation Program; knowledge before and after presentation of material in workshops; and practicing clinicians' observations of any effects of changes in laboratory practices. RESULTS: Many existing laboratories changed practices as a result of both governmental and nongovernmental CD4+ T-cell testing improvement programs. Sources of influence varied with each testing practice. Perceptions that test results were more reproducible seemed to offset presumed increases in the time and cost of testing. Clinicians who had ordered CD4+ T-cell testing for more than 10 years noted some improvements in results reported. CONCLUSIONS: As new complex testing methodologies are introduced into clinical and public health laboratories, the users seem to seek guidance in appropriate application of preanalytic, analytic, and postanalytic phases of the testing process. Testing improvement programs from a variety of sources were credited with changing practices and should continue to provide this guidance.
Assuntos
Contagem de Linfócito CD4/métodos , Linfócitos T CD4-Positivos/imunologia , Infecções por HIV/imunologia , Laboratórios/normas , Patologia Clínica/normas , Garantia da Qualidade dos Cuidados de Saúde/normas , Educação , Estudos de Avaliação como Assunto , Citometria de Fluxo/métodos , Citometria de Fluxo/normas , Guias como Assunto , Humanos , Controle de Qualidade , Reprodutibilidade dos Testes , Estados UnidosRESUMO
The biotransformation of methyl tert-butyl ether (MTBE), ethyl tert-butyl ether (ETBE), and tert-amyl methyl ether (TAME) was studied in humans and in rats after inhalation of 4 and 40 ppm of MTBE, ETBE, and TAME, respectively, for 4 hours, and the biotransformation of MTBE and TAME was studied after ingestion exposure in humans to 5 and 15 mg in water. tert-Butyl alcohol (TBA), a TBA conjugate, 2-methyl-1,2-propanediol, and 2-hydroxyisobutyrate were found to be metabolites of MTBE and ETBE. tert-Amyl alcohol (TAA), free and glucuronidated 2-methyl-2,3-butanediol (a glucuronide of TAA), 2-hydroxy-2-methyl butyrate, and 3-hydroxy-3-methyl butyrate were found to be metabolites of TAME. After inhalation, MTBE, ETBE, and TAME were rapidly taken up by both rats and humans; after termination of exposure, clearance from blood of the ethers by exhalation and biotransformation to urinary metabolites occurred with half-times of less than 7 hours in rats and humans. Biotransformation of MTBE and ETBE was similar in humans and rats after inhalation exposure. 2-Hydroxyisobutyrate was recovered as a major product in urine. All metabolites of MTBE and ETBE excreted with urine were eliminated with half-times of less than 20 hours. Biotransformation of TAME was qualitatively similar in rats and humans, but the metabolic pathways were different. In humans, 2-methyl-2,3-butanediol, 2-hydroxy-2-methyl butyrate, and 3-hydroxy-3methyl butyrate were recovered as major urinary products. In rats, however, 2-methyl-2,3-butanediol and its glucuronide were major TAME metabolites recovered in urine. After ingestion of MTBE and TAME, both compounds were rapidly absorbed from the gastrointestinal tract. Hepatic first-pass metabolism of these ethers was not observed, and a significant part of the administered dose was transferred into blood and cleared by exhalation. Metabolic pathways for MTBE and TAME and kinetics of excretion were identical after ingestion and inhalation exposures. Results of studies presented here suggest (1) that excretion of MTBE, ETBE, and TAME in rats and humans is rapid, (2) that biotransformation and excretion of MTBE and ETBE are identical in rats, and (3) that biotransformation and excretion of TAME is quantitatively different in rats and humans.
Assuntos
Poluentes Atmosféricos/farmacocinética , Etil-Éteres/farmacocinética , Éteres Metílicos/farmacocinética , Tosilarginina Metil Éster/farmacocinética , Administração Oral , Adulto , Poluentes Atmosféricos/metabolismo , Animais , Biomarcadores , Biotransformação , Etil-Éteres/administração & dosagem , Etil-Éteres/metabolismo , Feminino , Humanos , Exposição por Inalação , Cinética , Masculino , Éteres Metílicos/administração & dosagem , Éteres Metílicos/metabolismo , Ratos , Ratos Endogâmicos F344 , Tosilarginina Metil Éster/administração & dosagem , Tosilarginina Metil Éster/metabolismoRESUMO
OBJECTIVES: To evaluate the effectiveness of an educational program using a combination of live satellite programming and individualized instruction. A secondary goal was to develop an evaluation strategy that would be useful to other educators who provide distance-based educational programs. SETTING: A program designed for public health officers who would serve as laboratory directors in local public health laboratories was presented live by satellite in June 1993. PRACTICE DESCRIPTION: The course emphasized good laboratory practice as needed to direct a laboratory performing moderate complexity tests. Physicians who completed the course received 20 continuing medical education credits and qualified as laboratory directors under the Clinical Laboratory Improvement Amendments of 1988 (CLIA 88). MAIN OUTCOME MEASURES: Increase in participants' knowledge of good laboratory practices and application of the practices in their laboratories. RESULTS: Participant satisfaction levels in areas ranging from quality of the video transmission to meeting the course objectives were favorable. Participants demonstrated a significant gain in scores on a test given before and after the course. Problem solving exercises posed during the telecast demonstrated that the participants were actively involved and had completed the self-study material. A sample of participants surveyed several months after the course indicated that many had applied the course material in their workplaces. CONCLUSIONS: Distance-based education using a combination of interactive videoconferencing and self-study material can be a useful tool to enhance cognitive skills for a geographically diverse group of individuals. If carefully planned in advance, evaluation of distance-based educational programs can provide information that verifies the effectiveness of the program.