RESUMEN
OBJECTIVE: To report the presence of microscopic neoplasms of the testis in men with anti-Ma2-associated encephalitis (Ma2-encephalitis) and to discuss the clinical implications. METHODS: Orchiectomy specimens were examined using immunohistochemistry with Ma2 and Oct4 antibodies. RESULTS: Among 25 patients with Ma2-encephalitis younger than 50 years, 19 had germ-cell tumors, and 6 had no evidence of cancer. These 6 patients underwent orchiectomy because they fulfilled five criteria: 1) demonstration of anti-Ma2 antibodies in association with MRI or clinical features compatible with Ma2-encephalitis, 2) life-threatening or progressive neurologic deficits, 3) age < 50 years, 4) absence of other tumors, and 5) new testicular enlargement or risk factors for germ-cell tumors, mainly cryptorchidism or ultrasound evidence of testicular microcalcifications. All orchiectomy specimens showed intratubular-germ cell neoplasms unclassified type (IGCNU) and other abnormalities including microcalcifications, atrophy, fibrosis, inflammatory infiltrates, or hypospermatogenesis. Ma2 was expressed by neoplastic cells in three of three patients examined. Even though most patients had severe neurologic deficits at the time of orchiectomy (median progression of symptoms, 10 months), 4 had partial improvement and prolonged stabilization (8 to 84 months, median 22.5 months) and two did not improve after the procedure. CONCLUSIONS: In young men with Ma2-encephalitis, 1) the disorder should be attributed to a germ-cell neoplasm of the testis unless another Ma2-expressing tumor is found, 2) negative tumor markers, ultrasound, body CT, or PET do not exclude an intratubular germ-cell neoplasm of the testis, and 3) if no tumor is found, the presence of the five indicated criteria should prompt consideration of orchiectomy.
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Antígenos de Neoplasias/inmunología , Autoanticuerpos/inmunología , Biomarcadores de Tumor/inmunología , Encefalitis Límbica/inmunología , Neoplasias de Células Germinales y Embrionarias/diagnóstico , Proteínas del Tejido Nervioso/inmunología , Neoplasias Testiculares/diagnóstico , Adulto , Autoanticuerpos/análisis , Autoanticuerpos/sangre , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/sangre , Encéfalo/inmunología , Encéfalo/patología , Encéfalo/fisiopatología , Diagnóstico Diferencial , Diagnóstico Precoz , Humanos , Encefalitis Límbica/sangre , Encefalitis Límbica/fisiopatología , Imagen por Resonancia Magnética , Masculino , Neoplasias de Células Germinales y Embrionarias/inmunología , Neoplasias de Células Germinales y Embrionarias/cirugía , Vías Nerviosas/inmunología , Vías Nerviosas/patología , Vías Nerviosas/fisiopatología , Orquiectomía/normas , Valor Predictivo de las Pruebas , Neoplasias Testiculares/inmunología , Neoplasias Testiculares/cirugíaRESUMEN
OBJECTIVE: Social capital describes the benefits that are derived from personal social relationships (within families and communities) and social affiliations. This investigation examined the extent to which social capital is associated with positive developmental and behavioral outcomes in high-risk preschool children. DESIGN: A cross-sectional case-control analysis of young children "doing well" and "not doing well" at baseline in four coordinated longitudinal studies. PARTICIPANTS: A total of 667 2- to 5-year-old children (mean age, 4.4 years) and their maternal caregivers who are participating in the Longitudinal Studies of Child Abuse and Neglect Consortium. At recruitment, all children were characterized by unfavorable social or economic circumstances that contributed to the identification of the children as high risk. MEASURES: Social capital was defined as benefits that accrue from social relationships within communities and families. A social capital index was created by assigning one point to each of the following indicators: 1) two parents or parent-figures in the home; 2) social support of the maternal caregiver; 3) no more than two children in the family; 4) neighborhood support; and 5) regular church attendance. Outcomes were measured with the Child Behavior Checklist, a widely used measure of behavioral/emotional problems, and with the Battelle Developmental Inventory Screening Test, a standardized test that identifies developmental deficits. Children were classified as doing well if their scores on these instruments indicated neither behavioral nor developmental problems. RESULTS: Only 13% of the children were classified as doing well. The individual indicators that best discriminated between levels of child functioning were the most direct measures of social capital-church affiliation, perception of personal social support, and support within the neighborhood. The social capital index was strongly associated with child well-being, more so than any single indicator. The presence of any social capital indicator increased the odds of doing well by 29%; adding any two increased the odds of doing well by 66%. CONCLUSIONS: Our findings suggest that social capital may have an impact on children's well-being as early as the preschool years. In these years it seems to be the parents' social capital that confers benefits on their offspring, just as children benefit from their parents' financial and human capital. Social capital may be most crucial for families who have fewer financial and educational resources. Our findings suggest that those interested in the healthy development of children, particularly children most at risk for poor developmental outcomes, must search for new and creative ways of supporting interpersonal relationships and strengthening the communities in which families carry out the daily activities of their lives.
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Desarrollo Infantil , Composición Familiar , Relaciones Padres-Hijo , Medio Social , Apoyo Social , Estudios de Casos y Controles , Protección a la Infancia , Preescolar , Estudios Transversales , Femenino , Humanos , Renta , Modelos Logísticos , Estudios Longitudinales , Masculino , Oportunidad Relativa , Responsabilidad Parental , Religión , Factores de RiesgoRESUMEN
Enantiomers of several N-substituted 5,6,7,8,9,10-hexahydro-7,10-iminocyclohept[b]indoles were obtained by the resolution of 2-fluoro-5,6,7,8,9,10-hexahydro-7,10-iminocyclohept[b]indole and 5,6,7,8,9,10-hexahydro-7,10-iminocyclohept[b]indole followed by N-alkylation. These, as well as the racemates, were evaluated for their affinity for the 5-HT2 and D2 receptors. Those compounds possessing the 7S,10R stereochemistry were consistently recognized by the 5-HT2 and D2 receptors as the eutomer. 2-Fluoro-11-[4-(4-fluorophenyl)-4-oxobutyl]-5,6,7,8,9,10-hexahydro-7S,10 R- iminocyclohept[b]indole [(7S,10R)-8] had the highest affinity for the 5-HT2 receptor (Ki = 0.80 nM), while its distomer (7R,10S)-8 was the most selective member of this class of bridged gamma-carbolines (D2/5-HT2 = 562). Incorporation of a benzoyl or isosteric benzisoxazole moiety tethered by a four-carbon spacer to a bridged gamma-carboline nucleus, possessing the 7S,10R absolute configuration, produced high affinity ligands for the 5-HT2 and D2 receptors.
Asunto(s)
Antipsicóticos/síntesis química , Antipsicóticos/farmacología , Indoles/síntesis química , Indoles/farmacología , Receptores de Dopamina D2/efectos de los fármacos , Receptores de Serotonina/efectos de los fármacos , Antipsicóticos/química , Cromatografía Líquida de Alta Presión , Cristalografía por Rayos X , Diseño de Fármacos , Indoles/química , Receptores de Dopamina D2/metabolismo , Receptores de Serotonina/metabolismo , EstereoisomerismoRESUMEN
A series of 5,6,7,8,9,10-hexahydro-7,10-iminocyclohept[b]indoles and 6,7,8,9,10,11-hexahydro-7,11-imino-5H-cyclooct[b]indoles was prepared. Structural modifications of the lead compound, 11-[4-(4-fluorobenzoyl)propyl]-5,6,7,8,9,10-hexahydro-7,10- iminocyclohept[b]indole (5, Ki = 0.82 nM vs [3H]ketanserin) enabled the identification of the functionality necessary for high affinity at serotonin 5-HT2 and dopamine D2 receptors in ligand binding studies. The indole ring, as well as the benzoyl or isosteric benzisoxazole moiety, were essential for high affinity. Variations of the length of the side chains resulted in ligands having either selective affinity for the 5-HT2 receptor or a combination of 5-HT2 and D2 affinity. In vivo binding studies were performed on selected members in this series. The most potent member, 2-fluoro-11-[4-(4-fluorobenzoyl)butyl]-5,6,7,8,9,10-hexahydro-7,10- iminocyclohept[b]indole (36) had an ED50 of < 1 mg/kg at the 5-HT2 and D2 receptors following oral administration.
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Hidrocarburos Aromáticos con Puentes/síntesis química , Carbolinas/síntesis química , Receptores de Dopamina D2/metabolismo , Receptores de Serotonina/metabolismo , Animales , Sitios de Unión , Hidrocarburos Aromáticos con Puentes/química , Hidrocarburos Aromáticos con Puentes/metabolismo , Carbolinas/química , Carbolinas/metabolismo , Masculino , Ratones , Relación Estructura-ActividadRESUMEN
A series of 5,6,7,8,9,10-hexahydro-7,10-iminocyclo[b]indoles substituted at the 5 and/or 11 positions was synthesized from tropinone. Affinity for sigma binding sites was determined using [3H]-N,N'-di-o-tolylguanidine ([3H]DTG) and [3H]-(+)-3-(3-hydroxyphenyl)-N-1-propylpiperidine ([3H]-(+)-3-PPP) and for the dopamine D2 receptor labeled with [3H]sulpiride. Nearly all compounds studied in this series possessed a higher affinity for [3H]DTG than [3H]-(+)-PPP-labeled sigma sites, suggesting that [3H]DTG and [3H]-(+)-3-PPP radioligands label pharmacologically distinct sigma binding sites, as reported previously. Substitution at the 11 position with side chains containing a four-carbon tether resulted in compounds having the highest affinity for the [3H]DTG-labeled sigma site. The most potent and selective member of this series was 11-[4-(2-furanyl)butyl]-5,6,7,8,9,10-hexahydro-7,10-iminocyclohept [b] indole (40). Enantioselectivity was investigated by preparing the (+)- and (-)-isomers of 40. These studies revealed that (+)-40 was more potent at the [3H]-DTG-labeled sigma site whereas (-)-40 had a higher affinity at sigma sites labeled with [3H]-(+)-PPP. Racemic 40 was observed to possess a higher affinity than either of its respective enantiomers at both the [3H]DTG- and [3H]-(+)-3-PPP-labeled sites, suggesting an allosteric interaction.
Asunto(s)
Carbolinas/síntesis química , Carbolinas/metabolismo , Receptores de Dopamina D2/metabolismo , Receptores sigma/metabolismo , Animales , Unión Competitiva , Encéfalo/metabolismo , Guanidinas/metabolismo , Cobayas , Técnicas In Vitro , Piperidinas/metabolismo , Ensayo de Unión Radioligante , Ratas , Estereoisomerismo , Relación Estructura-Actividad , Sulpirida/metabolismo , Difracción de Rayos XRESUMEN
Plantwide analyses of the mortality experience of 8147 foundrymen revealed excesses for several diseases including lung cancer. Using indirect measures of smoking, it appeared that most, if not all, of the excess of lung cancer deaths could be explained by smoking habits. To explore further the possible association between these mortality excesses and foundry exposures, jobs were grouped into six work areas on the basis of similarities in production processes. The findings of analyses by work areas support the inferences from plantwide observations. No evidence was found of a relationship between lung cancer and foundry exposures. The pattern of mortality from emphysema and cerebrovascular disease in the different work areas paralleled that of lung cancer, suggesting that mortality from these diseases may have been influenced by a common etiologic agent, probably tobacco smoke. The data also reveal possible associations between metal pattern-making and colon cancer, silica or metal dust and stomach cancer, and carbon monoxide and ischemic heart disease.
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Metalurgia/estadística & datos numéricos , Mortalidad , Análisis de Área Pequeña , Adulto , Trastornos Cerebrovasculares/mortalidad , Estudios de Cohortes , Neoplasias Colorrectales/mortalidad , Enfermedad Coronaria/mortalidad , Humanos , Neoplasias Pulmonares/mortalidad , Masculino , Neoplasias Gástricas/mortalidadRESUMEN
BACKGROUND AND METHODS: In warm climates throughout the world, there is a deficit of births during the spring season. To determine whether this deficit might reflect a deleterious effect of heat on the male reproductive capacity during the previous summer, we obtained semen specimens in summer and winter from normal men who worked outdoors in the vicinity of San Antonio, Texas, and we performed automated semen analyses with an image-analysis system. RESULTS: Pairwise comparisons among 131 men without azoospermia who contributed specimens in both summer and winter revealed significant reductions during the summer in sperm concentration, total sperm count per ejaculate, and concentration of motile sperm. The mean decreases in these values after adjustment for potential confounding characteristics were 32 percent (95 percent confidence limits, 28 and 44 percent), 24 percent (95 percent confidence limits, 18 and 43 percent), and 28 percent (95 percent confidence limits, 24 and 44 percent), respectively (P less than 0.0001). The lower a subject's average sperm concentration and motile-sperm concentration, the greater the reduction. We found no correlation, however, between the number of hours per day spent working during summer in settings without air conditioning and either the summer sperm concentration or the difference in concentration between summer and winter. Among the children of the men in the study whose wives were living near San Antonio during the year before they gave birth, a disproportionately low number were born during the spring. CONCLUSIONS: Semen quality deteriorates during the summer. This phenomenon may account at least in part for the reduction in the birth rate during the spring in regions with warm climates.
Asunto(s)
Estaciones del Año , Recuento de Espermatozoides , Motilidad Espermática , Adulto , Tasa de Natalidad , Clima , Humanos , Masculino , Persona de Mediana Edad , TexasRESUMEN
A retrospective cohort mortality study was conducted among 8147 men and 627 women employed in a gray iron foundry for at least 6 months between 1950 and 1979. More than 1700 deaths occurred during a 35-year period of observation. Standardized mortality ratios (SMRs) for all causes were close to expected values based on the US general population as the standard. The mortality of nonwhite men was significantly increased for lung cancer (SMR 132) and ischemic heart disease (SMR 126). Other moderate, but nonsignificant excesses were noted among nonwhite men for cancers of the stomach, pancreas, and prostate, for diabetes mellitus and pulmonary emphysema, and among white men for cancers of the lung and stomach, gastric and duodenal ulcers, pulmonary emphysema, and suicide. Small mortality increases were observed in both racial groups for cerebrovascular disease. The lack of a trend with time since hire and duration of foundry employment suggests that lung cancer mortality may not be associated with exposure to the foundry environment. Utilizing indirect measures of smoking, it appears that virtually all excess lung cancer deaths among whites and at least some of the excess among nonwhites could be explained by smoking habits. Similarly, smoking may have been responsible for the mortality excesses from emphysema, cerebrovascular diseases, and ischemic heart disease.
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Hierro/efectos adversos , Metalurgia , Enfermedades Profesionales/mortalidad , Dióxido de Silicio/efectos adversos , Adulto , Factores Epidemiológicos , Métodos Epidemiológicos , Femenino , Humanos , Masculino , Enfermedades Profesionales/epidemiología , Enfermedades Profesionales/etiologíaRESUMEN
Automated semen analyses revealed differences of 21% to 30% in concentration-related parameters and 5% to 11% in motion-related parameters between means of groups of replicate specimens. Disparities among videotapes produced by two laboratory technicians accounted for the divergence in concentration-related parameters. This resulted partially from differences between the two technicians in propensity to dilute concentrated specimens. The causes of the greater portion of disparities between videotaping technicians, however, have not been identified. Differences in motion-related parameters could not be ascribed to technicians, but the basis for these differences is also unknown. The results suggest that values obtained from the CellSoft image analysis system may not be comparable between technicians or laboratories, despite use of identical computer parameter settings. Until effective quality control measures have been implemented, such comparisons must be made with caution.
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Diagnóstico por Computador , Variaciones Dependientes del Observador , Semen/citología , Grabación de Cinta de Video , Humanos , Masculino , Estaciones del Año , Recuento de Espermatozoides , Motilidad EspermáticaRESUMEN
A retrospective investigation of semen quality was undertaken at a fertility clinic in New Orleans. Semen specimens obtained during the summer had significantly lower sperm concentration, total sperm per ejaculate, percent motile sperm, and motile sperm concentration than samples provided at other times of year. Substantial summer deterioration in semen quality was likely to occur only among men whose work places were probably not air-conditioned. These findings suggest that the deleterious effects of summer heat on spermatogenic cells or on epididymal spermatozoa may reduce male fertility and account, at least partially, for the deficit of spring births in warm climates throughout the world.
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Calor/efectos adversos , Infertilidad Masculina/etiología , Semen/análisis , Análisis de Varianza , Humanos , Masculino , Estudios Retrospectivos , Estaciones del Año , Recuento de Espermatozoides , Motilidad EspermáticaRESUMEN
This report presents the findings of a case-control study of lung cancer among workers at a rubber manufacturing plant. Detailed work histories of 40 lung cancer deaths, which occurred during 1977 and 1978, were compared with those of 146 controls who were individually matched to cases on age, sex, and race; 66 of the controls were also matched on year of first hire. Elevated odds ratios were noted for different durations of employment in four work areas: Reclaim Operation, Chemicals, Special Products Manufacture, and Curing Preparation. A clear trend of increasing odds ratios with increasing durations of exposure was observed for the first three of these work areas. Several chemicals used in these processes are known respiratory system hazards. The results of this study suggest an association between lung cancer mortality risk and employment in Reclaim Operation, Chemicals, and Special Products Manufacture. A moderate excess risk was observed in these areas among both smokers and nonsmokers, although the risk was greater among the smokers.
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Neoplasias Pulmonares/etiología , Enfermedades Profesionales/etiología , Goma/efectos adversos , Adulto , Anciano , Anciano de 80 o más Años , Métodos Epidemiológicos , Femenino , Humanos , Neoplasias Pulmonares/mortalidad , Masculino , Persona de Mediana Edad , Factores de Riesgo , Fumar/efectos adversosRESUMEN
A retrospective cohort mortality study was conducted on 17,601 white and 4,722 nonwhite male workers in the Florida phosphate mining and chemical processing industry. Concerns about potential risks from naturally-occurring sources of ionizing radiation and anecdotal reports of lung cancer among workers prompted this investigation. Historical follow-up was conducted for the years 1949 to 1978. In comparison with U.S. rates, small excess of mortality rates of lung cancer were observed for white (standardized mortality ratio [SMR] equals 1.22) and nonwhite workers (SMR = 1.24); however, these excesses disappeared when contrasts were made with prevailing rates in Florida. Emphysema mortality was also slightly elevated in comparison with U.S. rates; the SMRs were 1.48 and 1.73 for white and nonwhite workers, respectively. Neither disease was related to overall length of employment. Detailed analyses of mortality in relation to work assignments are presented in the companion article.
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Industria Química , Minería , Enfermedades Profesionales/mortalidad , Fosfatos , Adulto , Enfisema/mortalidad , Florida , Humanos , Neoplasias Pulmonares/mortalidad , Masculino , Persona de Mediana Edad , Neoplasias/mortalidad , Fosfatos/efectos adversos , Estudios Retrospectivos , Estados UnidosRESUMEN
Small excesses of lung cancer and emphysema mortality had been detected among an historical cohort of 17,601 white and 4,722 nonwhite Florida phosphate industry workers. Internal mortality rate comparisons were made between worker subcohorts classified according to length of employment in 16 work areas and according to employment duration in jobs grouped by potential exposures to 10 agents, including alpha radiation. The only consistent associations seen were increased lung cancer mortality rates among long-term workers in plant-wide services and skilled crafts jobs. There was no evidence to support causal associations with exposures characteristic of the phosphate industry.
Asunto(s)
Industria Química , Neoplasias Pulmonares/mortalidad , Minería , Enfermedades Profesionales/mortalidad , Fosfatos , Adulto , Florida , Humanos , Masculino , Persona de Mediana Edad , Fosfatos/efectos adversosRESUMEN
A retrospective cohort mortality study was conducted among 8375 white male employees who had worked at the Oak Ridge National Laboratory for at least one month between 1943 and 1972. This plant has been the site of energy related research, including uranium and plutonium reactor technology and radioisotope production. Radiation doses, primarily from gamma rays, were generally low; the median cumulative exposure for workers was 0.16 rems. Historical follow up was conducted for the years 1943-77 and ascertainment of vital status was achieved for 92.3% of the cohort. Standardised mortality ratios (SMRs) were computed to contrast the subjects' cause specific mortality experience with that of the United States white male population. The observed number of 966 deaths from all causes was 73% of the number expected. Mortality deficits were also seen for arteriosclerotic heart disease (SMR = 0.75; 344 observed) and all cancers (SMR = 0.78; 194 observed). These results are indicative of the healthy worker effect and the favourable influence on health of the cohort's relatively high socioeconomic status. Non-statistically significant raised SMRs were seen for all leukaemias (SMR = 1.49, 16 observed), cancer of the prostate (SMR = 1.16, 14 observed), and Hodgkin's disease (SMR = 1.10, 5 observed). Internal comparisons of mortality (standardised rate ratios, SRRs) were made between subgroups of the cohort according to radiation dose level and duration of employment in various job categories. No consistent gradients of cause specific mortality were detected for radiation exposure. Leukaemia mortality was highest among workers with greater than or equal to 10 years employment in engineering (SRR = 2.40) and maintenance (SRR = 3.12) jobs. The association of leukaemia with employment in engineering was unexpected; maintenance jobs entail potential exposures to radiation and to a wide range of organic chemicals; metals, and other substances.