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1.
Trop Biomed ; 33(1): 88-94, 2016 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33579145

RESUMO

Seroprevalence of human toxocariasis was studied, based on 1544 samples selected from a total of 3524 submitted to the University of the West Indies in Kingston, Jamaica for diagnosis of dengue during an epidemic in 2010. The prevalence of anti-Toxocara IgG using the CELISA® (Cellabs) ELISA was 21.2% and males (24.4%) were significantly more likely to be exposed than females (17.5%) [χ2 =10.4; p=0.001]. No association was foundbetween exposure to Toxocara and area of residence (rural vs. urban) [χ2 =0.835; p = 0.409]. Prevalence of infection peaked in adolescents (10-19 years-old) and declined thereafter although a rise in prevalence was seen in older age classes. There was a high prevalence of toxocariasis in Jamaica with significant exposure among school age children with no predilection to either sex. The study will inform future work on elucidating the public health and clinical significance of toxocariasis in Jamaica.

2.
Arch Intern Med ; 136(7): 807-10, 1976 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-1065254

RESUMO

Two patients with neoplastic disease had transfusion-induced malaria. In a patient with acute myelogenous leukemia infected with Plasmodium vivax, neither his underlying disease nor intensive cytotoxic chemotherapy appeared to ameliorate or worsen the clinical course of his infection. In a splenectomized patient with metastatic carcinoma of the colon, P malariae infection was associated with a fulminant course simulating cerebral malaria. Despite delay in diagnosis, both patients responded dramatically to antimalarial chemotherapy and both developed appreciable antibody responses.


Assuntos
Neoplasias do Colo/complicações , Leucemia Mieloide Aguda/complicações , Malária/complicações , Adulto , Anticorpos/análise , Formação de Anticorpos , Cloroquina/uso terapêutico , Neoplasias do Colo/cirurgia , Feminino , Hemostasia Cirúrgica , Humanos , Leucemia Mieloide Aguda/imunologia , Leucemia Mieloide Aguda/terapia , Malária/etiologia , Malária/imunologia , Masculino , Metástase Neoplásica , Complicações Pós-Operatórias/etiologia , Reação Transfusional
3.
Arch Intern Med ; 144(10): 2083-4, 1984 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-6486992

RESUMO

Two patients had prolonged unexplained fever along with multiple negative blood cultures after cardiac valve replacement surgery. Following the administration of corticosteroids for presumed postpericardiotomy syndrome, both patients improved symptomatically and defervesced, only to have positive blood cultures for Staphylococcus epidermidis shortly thereafter. The theoretical and practical risks of the empiric use of anti-inflammatory agents for unexplained post-operative fever are reviewed. "Culture-negative" prosthetic valvular infection due to prior antibiotic prophylaxis or therapy must be strongly considered in the evaluation of such unexplained fever.


Assuntos
Corticosteroides/efeitos adversos , Endocardite Bacteriana/etiologia , Febre/tratamento farmacológico , Próteses Valvulares Cardíacas/efeitos adversos , Endocardite Bacteriana/microbiologia , Reações Falso-Negativas , Feminino , Febre/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Síndrome Pós-Pericardiotomia/tratamento farmacológico
4.
Biol Psychiatry ; 16(7): 601-26, 1981 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-7272378

RESUMO

Ten patients with the stable syndrome of hysteria were matched for age, sex, handedness, and full-scale WAIS IQ with ten controls, ten psychotic depressives and ten schizophrenics. All were subjected to an extensive neuropsychological test battery. Compared to the controls, the hysteria group exhibited bifrontal impairment (R = L) and, globally, greater dysfunction of the nondominant hemisphere. A G analysis provided a complete separation between the hysteria and controls. However, a D-index analysis showed that the hysteria group was more impaired than normals and depressives because of greater dysfunction of the dominant hemisphere, whilst schizophrenia showed greater nondominant hemisphere dysfunction than hysteria. Further, a cluster analysis on the 40 subjects produced three clusters: normal controls, depressives, and a schizophrenia-hysteria grouping. These findings are interpreted as suggesting that dominant hemisphere dysfunction is fundamentally related to the syndrome of hysteria and that the dysfunction of the nondominant hemisphere is brought about by associated features: the female excess, the emotional instability and dysphoric mood, the presence of asymmetrical pain, and conversion symptomatology. It is further argued, in view of the familial associations, that hysteria in the female is a syndrome equivalent to psychopathy in the male (who also exhibits dominant hemisphere dysfunction) and might represent in the female a (relatively benign) variant of schizophrenia characterized by imprecise verbal communications, a subtle form of affective incongruity, together with the conversion parameter.


Assuntos
Histeria/psicologia , Transtornos Neurocognitivos/psicologia , Adulto , Transtorno Depressivo/psicologia , Dominância Cerebral , Feminino , Humanos , Masculino , Testes Psicológicos , Psicologia do Esquizofrênico
5.
Medicine (Baltimore) ; 63(3): 155-64, 1984 May.
Artigo em Inglês | MEDLINE | ID: mdl-6325849

RESUMO

Twenty-five cases of acquired immune deficiency syndrome (AIDS) complicated by opportunistic infections were diagnosed at Lenox Hill Hospital during an 18 month period and followed for at least 1 year or until the patients' deaths. Twenty-three patients were homosexual men, including 1 i.v. drug user, and 2 were heterosexual i.v. drug users, including the sole woman. Seventy infections were diagnosed. The commonest etiologic agents included Candida albicans, Pneumocystis carinii, cytomegalovirus, and Mycobacterium avium-intracellulare. Less frequent pathogens included Cryptococcus neoformans, Toxoplasma gondii, Cryptosporidium, JC virus, Mycobacterium xenopi, and Mycobacterium tuberculosis. Seven men also had Kaposi's sarcoma. Prodromal symptoms lasted up to 8 months before the diagnosis of AIDS. Immunologic and serologic evaluation demonstrated lymphopenia, polyclonal hypergammaglobulinemia, cutaneous anergy, reversal of the T-cell helper/suppressor ratio, and serologic evidence of previous exposure to CMV, EBV, and HBV. Pneumocystis pneumonia was diagnosed during life in 17 patients, by transbronchial biopsy and bronchoscopic washings, and all 17 cases were successfully treated. However, pneumocystis was more refractory to treatment than previously described and required an average of 29 days of antimicrobial therapy. Disseminated infections with atypical mycobacteria and cytomegalovirus were the leading causes of death. Bone marrow aspirates and biopsies often revealed a cellular abnormality (82%) but only occasionally yielded an infectious diagnosis (32%). However, bone marrow examinations were the major means of detecting atypical mycobacteriosis. Colonoscopic biopsies were most useful for establishing the presence of cytomegalovirus colitis. Transbronchial biopsies and bronchial washings gave a high yield of opportunistic pathogens including 34 infectious diagnoses confirmed by 31 procedures. Multiple site biopsies and close communication between the clinician and the pathologist were needed for early diagnosis of opportunistic infections. Twenty-two patients (88%) died, and the few survivors remain debilitated.


Assuntos
Síndrome da Imunodeficiência Adquirida/complicações , Infecções/etiologia , Síndrome da Imunodeficiência Adquirida/diagnóstico , Síndrome da Imunodeficiência Adquirida/mortalidade , Candidíase/diagnóstico , Candidíase/etiologia , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/etiologia , Feminino , Humanos , Infecções/diagnóstico , Masculino , Pessoa de Meia-Idade , Infecções por Mycobacterium/diagnóstico , Infecções por Mycobacterium/etiologia , Pneumonia por Pneumocystis/diagnóstico , Pneumonia por Pneumocystis/etiologia , Sarcoma de Kaposi/etiologia , Fatores de Tempo
6.
Artigo em Inglês | MEDLINE | ID: mdl-2526871

RESUMO

Thirty-four homosexual patients with AIDS were treated for Pneumocystis carinii pneumonia between April 1984 and November 1985. All 31 survivors were treated with oral trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis immediately upon completion of intravenous therapy, despite the prior occurrence of hypersensitivity reactions to intravenous TMP-SMX in 21 of these patients. Only four patients had subsequent reactions to oral TMP-SMX requiring the drug's discontinuation. None of the patients remaining on prophylaxis developed recurrent Pneumocystis pneumonia. Oral TMP-SMX appears effective at preventing recurrent Pneumocystis pneumonia in patients with AIDS. Hypersensitivity reactions during therapy with TMP-SMX may not be a contraindication to continuation of therapy and subsequent oral prophylaxis.


Assuntos
Síndrome da Imunodeficiência Adquirida/complicações , Anti-Infecciosos/uso terapêutico , Hipersensibilidade a Drogas/etiologia , Pneumonia por Pneumocystis/prevenção & controle , Sulfametoxazol/uso terapêutico , Trimetoprima/uso terapêutico , Administração Oral , Adulto , Anti-Infecciosos/administração & dosagem , Anti-Infecciosos/efeitos adversos , Estudos de Coortes , Combinação de Medicamentos/administração & dosagem , Combinação de Medicamentos/efeitos adversos , Combinação de Medicamentos/uso terapêutico , Toxidermias/etiologia , Hipersensibilidade a Drogas/prevenção & controle , Febre/induzido quimicamente , Humanos , Injeções Intravenosas , Masculino , Recidiva , Sulfametoxazol/administração & dosagem , Sulfametoxazol/efeitos adversos , Comprimidos , Trimetoprima/administração & dosagem , Trimetoprima/efeitos adversos , Combinação Trimetoprima e Sulfametoxazol
7.
Am J Surg Pathol ; 7(6): 543-53, 1983 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-6353952

RESUMO

In the present epidemic of opportunistic infections affecting homosexual men, systemic, persistent, unexplained lymphadenopathies have frequently accompanied and often preceded other manifestations of the acquired immunodeficiency syndrome (AIDS). Studies of the lymphadenopathies associated with AIDS have not yet been published, and the lymph node lesions have been generally considered to represent reactive lymphoid hyperplasia. The present study concerns the lymph node biopsies of 36 homosexual males with systemic, persistent lymphadenopathy. The lesions were essentially uniform and consisted of focal hemorrhages, extreme hyperplasia of germinal centers, extensive cellular destruction, accumulation of neutrophils, phagocytosis of nuclear debris, proliferation of blood vessels, immunoblasts, and peculiar aggregates of clear cells. These lesions diagnosed as acute lymphadenitis accompanied diseases indicative of AIDS in six cases and preceded them by months in three cases. In two cases, the lymphadenitis was associated with Kaposi's sarcoma of lymph node and in two cases with non-Hodgkin's lymphomas. It is suggested that the systemic, persistent lymphadenitis of homosexual males is induced by a microorganism, probably a virus. The lymphotropic activity of such an agent may include the destruction of a certain class of lymphocytes leading to the induction of the acquired immunodeficiency syndrome. Under special, unknown circumstances, the uncontrolled lymph node hyperplasia may progress to the development of lymphoma.


Assuntos
Síndrome da Imunodeficiência Adquirida/patologia , Linfonodos/patologia , Síndrome da Imunodeficiência Adquirida/imunologia , Adulto , Idoso , Biópsia , Doença Crônica , Homossexualidade , Humanos , Técnicas Imunoenzimáticas , Linfonodos/imunologia , Linfadenite/patologia , Linfoma/patologia , Masculino , Pessoa de Meia-Idade , Sarcoma de Kaposi/patologia
8.
Infect Control Hosp Epidemiol ; 17(12): 819-27, 1996 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-8985772

RESUMO

This article describes the basic framework for developing a tuberculosis (TB) control program. We suggest how to assess the risk of TB in a healthcare delivery setting, how to prioritize control measures based on their effectiveness, and how to meet current regulatory requirements. In addition, we discuss some problematic issues, examples of how other hospitals have confronted these issues, and where to obtain additional information on nosocomial TB.


Assuntos
Infecção Hospitalar/prevenção & controle , Controle de Infecções/métodos , Tuberculose/prevenção & controle , Centers for Disease Control and Prevention, U.S. , Infecção Hospitalar/transmissão , Guias como Assunto , Humanos , Medição de Risco , Fatores de Risco , Tuberculose/transmissão , Estados Unidos , United States Occupational Safety and Health Administration
9.
Am J Clin Pathol ; 64(4): 525-30, 1975 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-1060378

RESUMO

A case of recurrent sepsis due to Aeromonas hydrophila in a patient with acute myelogenous leukemia is reported. The patient's first infection leading to bacteremia followed contamination of a mosquito bite by stagnant water. After recovery from the first bacteremia, the patient again became septic with a second strain of Aeromonas hydrophila, which again responded to antimicrobial therapy. It is hypothesized that contamination of the local water supply may have led to the establishment of a gastrointestinal carrier state that produced the second bout of Aeromonas sepsis when the patient was markedly leukopenic. The importance of the oxidase test to differentiate Aeromonas species from members of the family Enterobacteriaceae is re-emphasized.


Assuntos
Aeromonas/isolamento & purificação , Infecções por Enterobacteriaceae/complicações , Leucemia Mieloide/complicações , Adulto , Cloranfenicol/uso terapêutico , Infecções por Enterobacteriaceae/tratamento farmacológico , Infecções por Enterobacteriaceae/etiologia , Gentamicinas/uso terapêutico , Humanos , Leucemia Mieloide/microbiologia , Masculino , Recidiva
10.
Toxicol Sci ; 55(2): 327-34, 2000 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-10828264

RESUMO

A method to measure protein thiols (PrSH), reduced and oxidized, was adapted to determine PrSH depletion in isolated rainbow trout hepatocytes exposed to arylating agent 1,4-benzoquinone (BQ). Toxicant analysis revealed rapid conversion of BQ to 1, 4-hydroquinone (HQ) upon addition to hepatocytes. Hepatocytes exposed to 200 microM BQ+HQ showed 80% decline in glutathione (GSH) (1 h), 30% loss of PrSH (6 h), and no loss of viability (24 h). Recoverable oxidized PrSH was detected only after 24 h (200 microM BQ+HQ). Exposure to 600 microM BQ+HQ caused rapid (10 min) loss of > 90% GSH and > 60% PrSH, with eventual cell death. Half of the PrSH depletion at 6 h observed in hepatocytes exposed to 600 microM BQ+HQ was recoverable by reduction with dithiothreitol. Following the loss of GSH in hepatocytes exposed to 600 microM BQ+HQ, cellular PrSH were susceptible to direct arylation and oxidation. Rainbow trout hepatocytes, which contained 10-fold less GSH than rat cells, had a GSH:PrSH ratio of 1:82 compared with rat ratios of 1:2 to 1:6. The methods reported are useful for further study and discrimination of reactive modes of action needed for prediction of aquatic organism susceptibility to these types of toxicants.


Assuntos
Benzoquinonas/toxicidade , Glutationa/metabolismo , Fígado/efeitos dos fármacos , Oncorhynchus mykiss/metabolismo , Compostos de Sulfidrila/metabolismo , Alquilação , Animais , Benzoquinonas/metabolismo , Separação Celular , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Ditiotreitol , Feminino , Dissulfeto de Glutationa/metabolismo , Hidroquinonas/metabolismo , Fígado/citologia , Fígado/metabolismo , Masculino , Oxirredução
11.
Toxicol Sci ; 72(1): 66-76, 2003 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-12604835

RESUMO

The toxicity of four quinones, 2,3-dimethoxy-1,4-naphthoquinone (DMONQ), 2-methyl-1,4-naphthoquinone (MNQ), 1,4-naphthoquinone (NQ), and 1,4-benzoquinone (BQ), which redox cycle or arlyate in mammalian cells, was determined in isolated trout (Oncorhynchus mykiss) hepatocytes. More than 70% of cells died in 3 h when exposed to BQ or NQ; 50% died in 7 h when exposed to MNQ, with no mortality compared to controls after 7 h DMONQ exposure. A suite of biochemical parameters was assessed for ability to discriminate these reactivity pathways in fish. Rapid depletion of glutathione (GSH) with appearance of glutathione disulfide (GSSG) and increased dichlorofluoroscein fluorescence were used as indicators of redox cycling, noted with DMONQ, MNQ, and NQ. Depletion of GSH with no GSSG accumulation, and loss of free protein thiol (PrSH) groups (nonreducible) indicated direct arylation by BQ. All toxicants rapidly oxidized NADH, with changes in NADPH noted later (BQ, NQ, MNQ) or not at all (DMONQ). Biochemical measures including cellular energy status, cytotoxicity, and measures of reactive oxygen species, along with the key parameters of GSH and PrSH redox status, allowed differentiation of responses associated with lethality. Chemicals that arylate were more potent than redox cyclers. Toxic pathway discrimination is needed to group chemicals for potency predictions and identification of structural parameters associated with distinct types of reactive toxicity, a necessary step for development of mechanistically based quantitative structure-activity relationships (QSARs) to predict chemical toxic potential. The commonality of reactivity mechanisms between rodents and fish was also demonstrated, a step essential for species extrapolations.


Assuntos
Benzoquinonas/toxicidade , Hepatócitos/efeitos dos fármacos , Naftoquinonas/toxicidade , Oncorhynchus mykiss/metabolismo , Vitamina K 3/toxicidade , Adenina/metabolismo , Animais , Benzoquinonas/química , Morte Celular/efeitos dos fármacos , Feminino , Glutationa/metabolismo , Dissulfeto de Glutationa/metabolismo , Masculino , Estrutura Molecular , Naftoquinonas/química , Oxirredução , Oxigênio/metabolismo , Piridinas/metabolismo , Relação Quantitativa Estrutura-Atividade , Espécies Reativas de Oxigênio/metabolismo , Compostos de Sulfidrila/metabolismo , Vitamina K 3/química
12.
Am J Ophthalmol ; 97(2): 133-42, 1984 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-6320647

RESUMO

A prospective evaluation of ophthalmologic findings in 26 patients (25 men and one woman) with the acquired immune deficiency syndrome disclosed that 19 patients had significant ocular abnormalities. These included isolated retinal hemorrhages, cotton-wool spots, cytomegalovirus retinitis, acute retinal necrosis, cranial nerve palsies, and orbital Kaposi's sarcoma. Hemorrhages and cotton-wool spots appeared and disappeared spontaneously. Cytomegalovirus retinitis and acute retinal necrosis were progressive and destructive. The fundus findings did not correlate with the patient's general clinical status.


Assuntos
Síndrome da Imunodeficiência Adquirida/complicações , Oftalmopatias/etiologia , Adulto , Doenças dos Nervos Cranianos/etiologia , Infecções por Citomegalovirus/etiologia , Feminino , Humanos , Linfedema/etiologia , Masculino , Pessoa de Meia-Idade , Necrose , Pneumonia por Pneumocystis/etiologia , Estudos Prospectivos , Retina/patologia , Descolamento Retiniano/etiologia , Hemorragia Retiniana/etiologia , Retinite/etiologia
13.
J Pain Symptom Manage ; 10(3): 249-53, 1995 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-7629419

RESUMO

Delirium is reported to be a common problem in terminally ill patients. The poor prognosis given to these patients may result in the failure to recognize the causes that are easily treated and may be reversible. We present four patients in whom a comprehensive assessment revealed a number of reversible causes of delirium, resulting in a treatment approach that significantly improved the patients' cognition and quality of life.


Assuntos
Delírio/terapia , Assistência Terminal , Idoso , Feminino , Humanos , Masculino
14.
Br J Ophthalmol ; 67(6): 372-80, 1983 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-6303386

RESUMO

Two homosexual males with the "gay bowel syndrome' experienced an acute unilateral loss of vision. Both patients had white intraretinal lesions, which became confluent. One of the cases had a depressed cell-mediated immunity; both patients ultimately died after a prolonged illness. In one patient cytomegalovirus was cultured from a vitreous biopsy. Autopsy revealed disseminated cytomegalovirus in both patients. Widespread retinal necrosis was evident, with typical nuclear and cytoplasmic inclusions of cytomegalovirus. Electron microscopy showed herpes virus, while immunoperoxidase techniques showed cytomegalovirus. The altered cell-mediated response present in homosexual patients may be responsible for the clinical syndromes of Kaposi's sarcoma and opportunistic infection by Pneumocystis carinii, herpes simplex, or cytomegalovirus.


Assuntos
Síndrome da Imunodeficiência Adquirida/complicações , Infecções por Citomegalovirus/etiologia , Retinite/etiologia , Adulto , Citomegalovirus/isolamento & purificação , Infecções por Citomegalovirus/patologia , Angiofluoresceinografia , Homossexualidade , Humanos , Masculino , Retina/patologia , Retinite/microbiologia , Retinite/patologia , Corpo Vítreo/microbiologia
15.
Clin Nephrol ; 21(4): 197-204, 1984 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-6733986

RESUMO

To determine the nature and frequency of renal disorders in AIDS we reviewed the records of thirty-two patients hospitalized over a twenty-two month period. Group I, including all patients with AIDS who demonstrated proteinuria and/or renal insufficiency, numbered thirteen patients, in ten of whom renal tissue was available. Renal abnormalities included proteinuria in twelve patients, which exceeded two grams per day in seven. The glomerular histologic lesions included focal glomerulosclerosis, diffuse mesangial hypercellularity, diffuse proliferative glomerulonephritis, and membranoproliferative glomerulonephritis. The nonglomerular histologic lesions included acute tubular necrosis, nephrocalcinosis, focal interstitial nephritis, and one case each of intrarenal cryptococcal infection and renal cell carcinoma. Nine of these thirteen patients developed renal insufficiency, and four of them required dialysis. Their mortality by the end of the study period was eleven of thirteen patients (85 percent), significantly worse in the short term than AIDS patients without renal problems. The patients in Group I were compared to the nineteen AIDS patients without renal abnormalities in Group II. The Group I patients had a higher incidence of oral and esophageal candidiasis, other fungal infections, and infections with Mycobacterium avium-intracellulare. They also had a higher incidence of exposure to aminoglycoside antibiotics and amphotericin B, and experienced more clinical shock than their Group II counterparts. It is concluded that patients with AIDS may demonstrate renal abnormalities on the basis of immune, hemodynamic, infectious, and neoplastic derangements.


Assuntos
Síndrome da Imunodeficiência Adquirida/complicações , Nefropatias/complicações , Injúria Renal Aguda/complicações , Adulto , Feminino , Glomerulonefrite/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Proteinúria/complicações , Estudos Retrospectivos
16.
J Palliat Care ; 9(3): 4-8, 1993.
Artigo em Inglês | MEDLINE | ID: mdl-7903694

RESUMO

This article outlines the approach to the management of delirium developed by the staff of the palliative care unit at the Edmonton General Hospital. Delirium occurs commonly in the terminally ill and is associated with a poor prognosis. Management requires a clear understanding of what delirium is, how to assess it, investigations for reversible causes, and the medical treatments that are most useful. If not well managed, delirium can be a very distressing symptom for the patient and family as well as having a very destructive impact on the functioning of a palliative care unit.


Assuntos
Delírio/terapia , Hospitais para Doentes Terminais , Assistência Terminal/métodos , Antipsicóticos/uso terapêutico , Protocolos Clínicos , Delírio/diagnóstico , Delírio/etiologia , Humanos , Entrevista Psiquiátrica Padronizada , Planejamento de Assistência ao Paciente
17.
SAR QSAR Environ Res ; 25(4): 253-87, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24779615

RESUMO

A rule-based expert system (ES) was developed to predict chemical binding to the estrogen receptor (ER) patterned on the research approaches championed by Gilman Veith to whom this article and journal issue are dedicated. The ERES was built to be mechanistically transparent and meet the needs of a specific application, i.e. predict for all chemicals within two well-defined inventories (industrial chemicals used as pesticide inerts and antimicrobial pesticides). These chemicals all lack structural features associated with high affinity binders and thus any binding should be low affinity. Similar to the high-quality fathead minnow database upon which Veith QSARs were built, the ERES was derived from what has been termed gold standard data, systematically collected in assays optimized to detect even low affinity binding and maximizing confidence in the negatives determinations. The resultant logic-based decision tree ERES, determined to be a robust model, contains seven major nodes with multiple effects-based chemicals categories within each. Predicted results are presented in the context of empirical data within local chemical structural groups facilitating informed decision-making. Even using optimized detection assays, the ERES applied to two inventories of >600 chemicals resulted in only ~5% of the chemicals predicted to bind ER.


Assuntos
Sistemas Inteligentes , Substâncias Perigosas/toxicidade , Relação Quantitativa Estrutura-Atividade , Anti-Infecciosos/classificação , Anti-Infecciosos/toxicidade , Substâncias Perigosas/classificação , Praguicidas/classificação , Praguicidas/toxicidade , Receptores de Estrogênio/metabolismo , Testes de Toxicidade/métodos
18.
SAR QSAR Environ Res ; 25(4): 289-323, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24779616

RESUMO

Regulatory agencies are charged with addressing the endocrine disrupting potential of large numbers of chemicals for which there is often little or no data on which to make decisions. Prioritizing the chemicals of greatest concern for further screening for potential hazard to humans and wildlife is an initial step in the process. This paper presents the collection of in vitro data using assays optimized to detect low affinity estrogen receptor (ER) binding chemicals and the use of that data to build effects-based chemical categories following QSAR approaches and principles pioneered by Gilman Veith and colleagues for application to environmental regulatory challenges. Effects-based chemical categories were built using these QSAR principles focused on the types of chemicals in the specific regulatory domain of concern, i.e. non-steroidal industrial chemicals, and based upon a mechanistic hypothesis of how these non-steroidal chemicals of seemingly dissimilar structure to 17ß-estradiol (E2) could interact with the ER via two distinct binding types. Chemicals were also tested to solubility thereby minimizing false negatives and providing confidence in determination of chemicals as inactive. The high-quality data collected in this manner were used to build an ER expert system for chemical prioritization described in a companion article in this journal.


Assuntos
Estrogênios/classificação , Animais , Disruptores Endócrinos/química , Disruptores Endócrinos/classificação , Disruptores Endócrinos/toxicidade , Estrogênios/toxicidade , Parabenos/química , Parabenos/classificação , Parabenos/toxicidade , Fenóis/química , Fenóis/classificação , Fenóis/toxicidade , Relação Quantitativa Estrutura-Atividade , Receptores de Estrogênio/metabolismo , Salicilatos/química , Salicilatos/classificação , Salicilatos/toxicidade , Truta
19.
AIDS ; 7 Suppl 1: S171-2, 1993.
Artigo em Inglês | MEDLINE | ID: mdl-8363781
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