RESUMEN
Air quality data on trace metals, other constituents of PM2.5, and criteria air pollutants were used to examine relationships with long-term mortality in a cohort of male U.S. military veterans, along with data on vehicular traffic density (annual vehicle-miles traveled per unit of land area). The analysis used county-level environmental data for the period 1997-2002 and cohort mortality for 1997-2001. The proportional hazards model included individual data on age, race, smoking, body mass index, height, blood pressure, and selected interactions; contextual variables also controlled for climate, education, and income. In single-pollutant models, traffic density appears to be the most important predictor of survival, but potential contributions are also seen for NO2, NO3-, elemental carbon, nickel, and vanadium. The effects of the other main constituents of PM2.5, of crustal particles, and of peak levels of CO, O3, or SO2 appear to be less important. Traffic density is also consistently the most important environmental predictor in multiple-pollutant models, with combined relative risks up to about 1.2. However, from these findings it is not possible to discern which aspects of traffic (pollution, noise, stress) may be the most relevant to public health or whether an area-based predictor such as traffic density may have an inherent advantage over localized measures of ambient air quality. It is also possible that traffic density could be a marker for unmeasured pollutants or for geographic gradients per se. Pending resolution of these issues, including replication in other cohorts, it will be difficult to formulate additional cost-effective pollution control strategies that are likely to benefit public health.
Asunto(s)
Contaminantes Atmosféricos/efectos adversos , Enfermedades Ambientales/mortalidad , Mortalidad/tendencias , Emisiones de Vehículos/efectos adversos , Veteranos/estadística & datos numéricos , Contaminantes Atmosféricos/análisis , Estudios de Cohortes , Humanos , Longevidad , Masculino , Persona de Mediana Edad , Tasa de Supervivencia , Oligoelementos/análisis , Estados Unidos/epidemiología , Emisiones de Vehículos/análisisRESUMEN
In vitro experiments were performed to determine whether 2450 MHz microwave radiation induces alkali-labile DNA damage and/or DNA-protein or DNA-DNA crosslinks in C3H 10T(1/2) cells. After a 2-h exposure to either 2450 MHz continuous-wave (CW) microwaves at an SAR of 1.9 W/kg or 1 mM cisplatinum (CDDP, a positive control for DNA crosslinks), C3H 10T(1/2) cells were irradiated with 4 Gy of gamma rays ((137)Cs). Immediately after gamma irradiation, the single-cell gel electrophoresis assay was performed to detect DNA damage. For each exposure condition, one set of samples was treated with proteinase K (1 mg/ml) to remove any possible DNA-protein crosslinks. To measure DNA-protein crosslinks independent of DNA-DNA crosslinks, we quantified the proteins that were recovered with DNA after microwave exposure, using CDDP and gamma irradiation, positive controls for DNA-protein crosslinks. Ionizing radiation (4 Gy) induced significant DNA damage. However, no DNA damage could be detected after exposure to 2450 MHz CW microwaves alone. The crosslinking agent CDDP significantly reduced both the comet length and the normalized comet moment in C3H 10T(1/2) cells irradiated with 4 Gy gamma rays. In contrast, 2450 MHz microwaves did not impede the DNA migration induced by gamma rays. When control cells were treated with proteinase K, both parameters increased in the absence of any DNA damage. However, no additional effect of proteinase K was seen in samples exposed to 2450 MHz microwaves or in samples treated with the combination of microwaves and radiation. On the other hand, proteinase K treatment was ineffective in restoring any migration of the DNA in cells pretreated with CDDP and irradiated with gamma rays. When DNA-protein crosslinks were specifically measured, we found no evidence for the induction of DNA-protein crosslinks or changes in amount of the protein associated with DNA by 2450 MHz CW microwave exposure. Thus 2-h exposures to 1.9 W/ kg of 2450 MHz CW microwaves did not induce measurable alkali-labile DNA damage or DNA-DNA or DNA-protein crosslinks.
Asunto(s)
Daño del ADN , Proteínas de Unión al ADN/efectos de la radiación , ADN/efectos de la radiación , Fibroblastos/metabolismo , Fibroblastos/efectos de la radiación , Rayos gamma , Microondas , Tolerancia a Radiación/efectos de la radiación , Álcalis/metabolismo , Animales , Células Cultivadas , Cisplatino/farmacología , Ensayo Cometa , Reactivos de Enlaces Cruzados/farmacología , ADN/efectos de los fármacos , ADN/metabolismo , Proteínas de Unión al ADN/metabolismo , Relación Dosis-Respuesta en la Radiación , Endopeptidasa K/farmacología , Fibroblastos/efectos de los fármacos , Ratones , Ratones Endogámicos C3H , Unión Proteica/efectos de la radiaciónRESUMEN
Our objective was to evaluate pretreatment predictors of longevity, particularly blood pressure, in a large cohort of hypertensive men. During 1974 to 1976, 10,367 male hypertensive veterans (47% black) were identified at screening and subsequently characterized in 32 special Veterans Administration (VA) hypertension clinics. Their mean age was 52 years and mean blood pressure (BP) 154/100 mm Hg. During an average of 21 years of follow-up, 61% died. Risk ratios for all-cause mortality as functions of BP and other risk factors are presented for each variable alone; for each variable controlling for age, race, and BP; and for a multivariate model. We observed that when the entire cohort was divided into deciles by systolic blood pressure (SBP) and by diastolic blood pressure (DBP), the risk ratios for 21-year mortality increased from lowest to highest decile by 178% for SBP and 16% for DBP. When the deciles were computed separately by age group, increases from lowest to highest decile for those less than 40 years of age were 138% for SBP and 263% for DBP. For those over 60 years, the increases were 154% and -10%, respectively. Although blacks were younger and had more severe diastolic hypertension than whites, the risk ratios were similar within each race group. Risk patterns for mean arterial pressure and pulse pressure resembled those for SBP but had smaller gradients. Survival curves for BP groups suggested constant mortality rates during follow-up. Other significant observations included decreasing mortality with increasing body mass index and increased mortality in the Stroke Belt. We concluded that pretreatment SBP strongly predicted all-cause mortality during 21-year follow-up. For the young, both SBP and DBP were strong predictors; for the elderly, only SBP was predictive.
Asunto(s)
Antihipertensivos/uso terapéutico , Presión Sanguínea/fisiología , Hipertensión/mortalidad , Adulto , Factores de Edad , Anciano , Presión Sanguínea/efectos de los fármacos , Causas de Muerte , Hospitales de Veteranos/estadística & datos numéricos , Humanos , Hipertensión/tratamiento farmacológico , Hipertensión/fisiopatología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Tasa de Supervivencia , Estados Unidos/epidemiologíaRESUMEN
This article presents the design of and some results from a new prospective mortality study of a national cohort of about 50,000 U.S. veterans who were diagnosed as hypertensive in the mid 1970s, based on approximately 21 yr of follow-up. This national cohort is male with an average age at recruitment of 51 +/- 12 yr; 35% were black and 81% had been smokers at one time. Because the subjects have been receiving care at various U.S. Veterans Administration (VA) hospitals, access to and quality of medical care are relatively homogeneous. The health endpoints available for analysis include all-cause mortality and specific diagnoses for morbidity during VA hospitalizations; only the mortality results are discussed here. Nonpollution predictor variables in the baseline model include race, smoking (ever or at recruitment), age, systolic and diastolic blood pressure (BP), and body mass index (BMI). Interactions of BP and BMI with age were also considered. Although this study essentially controls for socioeconomic status by design because of the homogeneity of the cohort, selected ecological variables were also considered at the ZIP code and county levels, some of which were found to be significant predictors. Pollutants were averaged by year and county for TSP, PM10, CO, O3, and NO2; SO2 and Pb were considered less thoroughly. Both mean and peak levels were considered for gases. SO(4)2- data from the AIRS database and PM2.5, coarse particles, PM15, and SO(4)2- from the U.S. EPA Inhalable Particulate (IP) Network were also considered. Four relevant exposure periods were defined: 1974 and earlier (back to 1953 for TSP), 1975-1981, 1982-1988, and 1989-1996. Deaths during each of the three most recent exposure periods were considered separately, yielding up to 12 combinations of exposure and mortality periods for each pollutant. Associations between concurrent air quality and mortality periods were considered to relate to acute responses; delayed associations with prior exposures were considered to be emblematic of initiation of chronic disease. Preexposure mortality associations were considered to be indirect (noncausal). The implied mortality risks of long-term exposure to air pollution were found to be sensitive to the details of the regression model, the time period of exposure, the locations included, and the inclusion of ecological as well as personal variables. Both positive and negative statistically significant mortality responses were found. Fine particles as measured in the 1979-1984 U.S. EPA Inhalable Particulate Network indicated no significant (positive) excess mortality risk for this cohort in any of the models considered. Among the positive responses, indications of concurrent mortality risks were seen for NO2 and peak O3, with a similar indication of delayed risks only for NO2. The mean levels of these excess risks were in the range of 5-9%. Peak O3 was dominant in two-pollutant models and there was some indication of a threshold in response. However, it is likely that standard errors of the regression coefficients may have been underestimated because of spatial autocorrelation among the model residuals. The significant variability of responses by period of death cohort suggests that aggregation over the entire period of follow-up obscures important aspects of the implied pollution-mortality relationships, such as early depletion of the available pool of those subjects who may be most susceptible to air pollution effects.
Asunto(s)
Contaminantes Atmosféricos/efectos adversos , Mortalidad/tendencias , Veteranos/estadística & datos numéricos , Anciano , Contaminación del Aire/efectos adversos , Estudios de Cohortes , Humanos , Masculino , Análisis de Regresión , Factores de RiesgoRESUMEN
BACKGROUND: Although not as prominent as cognitive decline, motor dysfunction occurs in AD, particularly in the later stages of the disease. OBJECTIVE: To determine whether early-stage AD is also characterized by motor impairment. METHODS: We examined very mildly (Clinical Dementia Rating [CDR] 0.5) and mildly (CDR 1) demented AD individuals in comparison with healthy elderly control individuals (CDR 0) on a variety of nonmotor cognitive and psychomotor measures and on four motor measures (gait velocity, finger tapping, reaction time, movement time). To minimize the possibility of extrapyramidal dysfunction contaminating the groups, only individuals who were clinically free of extrapyramidal signs were included in the study. RESULTS: Mildly demented AD individuals were slowed on all motor measures except for finger tapping. No evidence of motor dysfunction was found in the very mildly demented AD group. As expected, both AD groups were impaired on the nonmotor cognitive and psychomotor tests. CONCLUSIONS: These results indicate that AD alone, in the absence of clinically confirmed extrapyramidal dysfunction, is associated with motor slowing in a stage-dependent manner. It remains to be determined whether this motor slowing represents a general characteristic of mild AD or indicates other neuropathology such as PD or the Lewy body variant of AD.
Asunto(s)
Enfermedad de Alzheimer/fisiopatología , Enfermedad de Alzheimer/psicología , Trastornos del Movimiento/fisiopatología , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Pruebas Neuropsicológicas , Tiempo de ReacciónRESUMEN
This study was designed to determine whether two differently modulated radiofrequencies of the type generally used in cellular phone communications could elicit a general stress response in a biological system. The two modulations and frequencies studied were a frequency-modulated continuous wave (FMCW) with a carrier frequency of 835.62 MHz and a code division multiple-access (CDMA) modulation centered on 847.74 MHz. Changes in proto-oncogene expression, determined by measuring Fos, Jun, and Myc mRNA levels as well as by the DNA-binding activity of the AP1, AP2 and NF-kappaB transcription factors, were used as indicators of a general stress response. The effect of radiofrequency exposure on proto-oncogene expression was assessed (1) in exponentially growing C3H 10T 1/2 mouse embryo fibroblasts during their transition to plateau phase and (2) during transition of serum-deprived cells to the proliferation cycle after serum stimulation. Exposure of serum-deprived cells to 835.62 MHz FMCW or 847.74 MHz CDMA microwaves (at an average specific absorption rate, SAR, of 0.6 W/kg) did not significantly change the kinetics of proto-oncogene expression after serum stimulation. Similarly, these exposures did not affect either the Jun and Myc mRNA levels or the DNA-binding activity of AP1, AP2 and NF-kappaB in exponential cells during transit to plateau-phase growth. Therefore, these results suggest that the radiofrequency exposure is unlikely to elicit a general stress response in cells of this cell line under these conditions. However, statistically significant increases (approximately 2-fold, P = 0.001) in Fos mRNA levels were detected in exponential cells in transit to the plateau phase and in plateau-phase cells exposed to 835.62 MHz FMCW microwaves. For 847.74 MHz CDMA exposure, the increase was 1.4-fold (P = 0.04). This increase in Fos expression suggests that expression of specific genes could be affected by radiofrequency exposure.
Asunto(s)
Proto-Oncogenes/efectos de la radiación , Ondas de Radio/efectos adversos , Teléfono , Factores de Transcripción/metabolismo , Animales , Ciclo Celular , Línea Celular , Medios de Cultivo , ADN/metabolismo , Proteínas de Unión al ADN/metabolismo , Expresión Génica/efectos de la radiación , Genes fos/efectos de la radiación , Genes jun/efectos de la radiación , Genes myc/efectos de la radiación , Ratones , FN-kappa B/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Estrés Fisiológico/etiología , Estrés Fisiológico/genética , Factor de Transcripción AP-1/metabolismo , Factor de Transcripción AP-2RESUMEN
BACKGROUND: The nature of cognitive performance in subjects with Parkinson disease (PD) without dementia is controversial, perhaps because of failure to exclude subjects with unrecognized very mild dementia. OBJECTIVE: To compare cognitive and motor functioning in well-characterized subjects with PD without overt dementia with healthy elderly control subjects. DESIGN: Subjects' conditions were evaluated clinically and psychometrically at entry into a longitudinal study of cognitive and motor performance in elderly subjects. Measures included a global dementia staging scale, the Washington University Clinical Dementia Rating; psychometric tests, including Logical Memory, Digit Span, Associate Learning, Information, Block Design, Digit Symbol, Trail-making A, Crossing-off, Boston Naming Test, and Word Fluency; and motor measures, including finger tapping, gait velocity, reaction time, and movement time. SETTING: A university-based research facility. SUBJECTS: There were 3 groups of subjects: healthy elderly control subjects (n=43), subjects with PD without dementia (n=58), and subjects with PD with questionable dementia (n=22), each evaluated at time of entry. RESULTS: As expected, both PD groups were impaired on motor measures (gait velocity, finger tapping, and movement time) compared with the healthy elderly control group. Neither PD group showed slowing in reaction time. The subjects with PD with questionable dementia were more impaired on Logical Memory, Block Design, Digit Symbol, and Trailmaking A compared with the subjects with PD without dementia. Although free of clinically evident cognitive dysfunction (Clinical Dementia Rating score, 0), the PD group without dementia was impaired with respect to the healthy elderly control group on all measures from the psychometric assessment except Digit Span, Associate Learning, and Word Fluency. CONCLUSIONS: The PD group without dementia showed global cognitive impairments in comparison with the healthy elderly control group, possibly because the healthy elderly control subjects represented idealized aging. Although the deficits were of small magnitude, this finding suggests that PD may predispose to subclinical cognitive impairment. Longitudinal follow-up is required to determine whether subjects with PD destined to develop overt dementia can be distinguished from those who do not.
Asunto(s)
Trastornos del Conocimiento/diagnóstico , Demencia/psicología , Enfermedad de Parkinson/psicología , Desempeño Psicomotor/fisiología , Anciano , Análisis de Varianza , Estudios de Casos y Controles , Trastornos del Conocimiento/etiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Psicometría , Tiempo de ReacciónRESUMEN
Studies of speed of cognitive processing in Parkinson's disease (PD) have yielded mixed results. This may relate in part to a differential effect on cognitive speed by the type of information to be processed. In the present study, we compared medication fasted, nondemented individuals with mild idiopathic PD (N = 26) with age-matched controls (N = 12) on a test requiring easy and hard same-different discriminations for verbal, quantitative, and spatial information, as well as on a traditional memory scanning paradigm. A voice-activated relay rather than a key press was used to eliminate the need for limb and finger movements. Simple reaction time and movement time were also measured in a task requiring subjects to move a hand held stylus to a designated target. The PD group performed as fast as the control group across all tasks except movement time. Thus, in our paradigm, the presence of PD alone does not predict cognitive slowing in the presence of motor slowing.
Asunto(s)
Cognición/fisiología , Enfermedad de Parkinson , Anciano , Femenino , Mano/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Movimiento/fisiología , Enfermedad de Parkinson/diagnóstico , Tiempo de Reacción , Índice de Severidad de la EnfermedadRESUMEN
Antithymocyte globulin (ATG) and muromonab CD3 (OKT3) are currently the only antilymphocyte preparations that are commercially available for induction immunosuppressive therapy for renal allograft transplantation in the US. ATG, in the usually prescribed doses, is more expensive than muromonab CD3, but muromonab CD3 is associated with more severe adverse effects that may affect clinical outcome and overall cost. We performed a retrospective study of all adult recipients of a first cadaveric renal allograft, who underwent transplantation between January 1991 and December 1994 who received either ATG (n = 92) or muromonab CD3 (n = 91) for induction therapy at our transplant centre. The average age of recipients was older (50 vs 44 yrs; p = 0.001) and extended donors were more commonly used in the ATG group (41 vs 13%; p = 0.0001) compared with the muromonab CD3 group. Nevertheless, at 1 year post-transplant, the incidence of rejection was lower (34 vs 47%) and graft survival was better (93 vs 85%; p = 0.03) in the ATG group. Patients who received ATG were discharged earlier (9.4 vs 13.3 days; p = 0.0001) and had similar serum creatinine levels on the day of discharge (2.4 +/- 1.5 vs 2.1 +/- 1.1 mg/dl; p = 0.25). Overall, the 1-year hospitalisation costs of transplantation and readmissions were similar [$US39,937 +/- 17,014 vs $US42,850 +/- 20,923 (currency year 1994); p = 0.22]. This is the first comparison of ATG and muromonab CD3 in renal transplant recipients to consider clinical as well as economic outcomes. For renal transplant patients in whom induction therapy is used at our centre, the initial expense of ATG can be justified by improved graft survival, fewer rejection episodes, and shorter hospital stays, which are associated with similar overall transplantation costs.
Asunto(s)
Suero Antilinfocítico/uso terapéutico , Trasplante de Riñón , Muromonab-CD3/uso terapéutico , Adulto , Anciano , Femenino , Rechazo de Injerto , Supervivencia de Injerto , Costos de la Atención en Salud , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Trasplante HomólogoRESUMEN
BACKGROUND: Loss of genetic heterogeneity (allelic loss or loss of heterozygosity) on chromosome arm 8p is frequent in squamous cell carcinomas of the head and neck and has been associated with poor prognosis. We have previously demonstrated that there are three minimal regions of allelic loss on this chromosome arm. The location of each region is marked by a microsatellite locus: D8S264 (8p23), D8S552 (8p23-p22), and D8S133 (8p21). These findings imply the existence of at least three putative tumor suppressor genes on this chromosome arm that may become inactivated during the progression of squamous cell carcinoma. PURPOSE: We used allelic loss data from these three loci to determine if inactivation of these putative suppressors is associated with poor prognosis for patients with squamous cell carcinoma of the supraglottic larynx. We also used multivariate statistics to compare the prognostic power of allelic loss at these genetic markers with that of demographic, clinical, and histopathologic parameters. METHODS: We examined the D8S264, D8S552, and D8S133 microsatellites in tumors from a retrospective population of 59 patients. All patients had histologically confirmed squamous cell carcinoma of the supraglottic larynx and had been treated surgically. DNA was extracted from matched sets of normal and microdissected tumor tissue and used for polymerase chain reaction amplification of the microsatellite markers. Reaction products were separated by denaturing gel electrophoresis and visualized by autoradiography. Patient data were obtained from the original pathology report and from the tumor registry of the Department of Otolaryngology-Head and Neck Surgery, Washington University School of Medicine, St. Louis, MO. Histopathologic data were obtained by reviewing the portion of the resection specimen used for DNA extraction. Parameters whose association with reduced disease-free interval and reduced disease-specific survival was statistically significant were identified by use of the Kaplan-Meier method and the logrank statistic. Multivariate Cox proportional hazards models were used to identify independent predictors of poor prognosis. All statistical tests were two-sided. RESULTS: In this patient population, allelic loss at the D8S264 locus was associated with both shorter disease-free interval (logrank P = .028) and reduced disease-specific survival (logrank P = .004). Allelic loss at the next most centromeric locus, D8S552, had a statistically significant association with only reduced disease-specific survival (logrank P = .034), whereas allelic loss at the most centromeric region, D8S133, showed no statistically significant association with reductions in either interval. Multivariate Cox models suggested that D8S264 was the only 8p marker of the three microsatellites with a statistically significant and independent association with shortened disease-free interval (relative risk [RR] = 3.38; P = .0107) and reduced disease-specific survival (RR = 3.41; P = .0105). CONCLUSIONS: Allelic loss in the p23 region of chromosome 8 appears to be a statistically significant, independent predictor of poor prognosis in patients with supraglottic squamous cell carcinoma.
Asunto(s)
Carcinoma de Células Escamosas/genética , Deleción Cromosómica , Cromosomas Humanos Par 8 , Neoplasias Laríngeas/genética , Alelos , Carcinoma de Células Escamosas/patología , ADN de Neoplasias/genética , Supervivencia sin Enfermedad , Femenino , Glotis , Heterocigoto , Humanos , Neoplasias Laríngeas/patología , Masculino , Repeticiones de Microsatélite , Persona de Mediana Edad , Análisis Multivariante , Polimorfismo Genético , Valor Predictivo de las Pruebas , Pronóstico , Modelos de Riesgos ProporcionalesRESUMEN
PURPOSE: To compare the effect of different time delays between contrast administration and the start of spiral CT scanning on hepatic enhancement in children. MATERIALS AND METHODS: Forty-five children (2-9 years old, mean 6 years) with no evidence of hepatic disease were examined with spiral CT. Sequential spiral scans through the entire liver were performed following a uniphasic injection of nonionic contrast medium. In group 1 scanning started at 80 % of the contrast injection time, in group 2 scanning started at 100 % of injection time, and in group 3 scanning started at 150 % of injection time. Mean hepatic, aortic, and inferior vena caval enhancement were determined using regions-of-interest measurements. RESULTS: Mean hepatic enhancement was 41.4, 47.0, and 40.6 HU for the 80 %, 100 %, and 150 % injection times, respectively. Enhancement was significantly greater in the 100 % injection time group (p < 0.05). A mean aortocaval difference of greater than 10 HU was present in all examinations. CONCLUSION: Our results suggest that delaying the initiation of spiral CT scanning until the completion of the contrast injection increases hepatic enhancement in children. These data should help to improve the quality of hepatic spiral CT in pediatric patients.
Asunto(s)
Hígado/diagnóstico por imagen , Intensificación de Imagen Radiográfica , Tomografía Computarizada por Rayos X , Niño , Preescolar , Medios de Contraste/administración & dosificación , Femenino , Humanos , Yohexol/administración & dosificación , Masculino , Factores de Tiempo , Tomografía Computarizada por Rayos X/métodosRESUMEN
There has been a continuing increase in the incidence of end-stage renal disease (ESRD) in the United States, including the fraction that has been attributed to hypertension. This study was done to seek relationships between ESRD and pretreatment clinical data and between ESRD and early treated blood pressure data in a population of hypertensive veterans. We identified a total of 5730 black and 6182 nonblack male veterans as hypertensive from 1974 through 1976 in 32 Veterans Administration Hypertension Screening and Treatment Program clinics. Their mean age was 52.5 +/- 10.2 years, and their mean pretreatment blood pressure was 154.3 +/- 19.0/100.8 +/- 9.8 mm Hg. During a minimum of 13.9 years of follow-up, 5337 (44.8%) of these patients died and 245 developed ESRD. For 1055 of these subjects, pretreatment systolic blood pressure (SBP) was greater than 180 mm Hg; 901 were diabetic; 1471 had a history of urinary tract problems; and 2358 of the 9644 who were treated had an early fall in SBP of more than 20 mm Hg. We used proportional hazards modeling to fit multivariate survival models to determine the effect of the available pretreatment data and early treated blood pressure levels on ESRD. This model demonstrated the independent increased risk of ESRD associated with being black or diabetic (risk ratio, 2.2 or 1.8), having a history of urinary tract problems (risk ratio, 2.2), or having high pretreatment SBP (for SBP 165 to 180 mm Hg, risk ratio was 2.8; for SBP > 180 mm Hg, risk ratio was 7.6).(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Hipertensión/complicaciones , Fallo Renal Crónico/epidemiología , Adulto , Población Negra , Presión Sanguínea , Enfermedades Cardiovasculares/complicaciones , Estudios de Cohortes , Complicaciones de la Diabetes , Estudios de Seguimiento , Humanos , Hipertensión/tratamiento farmacológico , Incidencia , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/fisiopatología , Masculino , Persona de Mediana Edad , Pronóstico , Modelos de Riesgos Proporcionales , Factores de Riesgo , Estados Unidos , VeteranosRESUMEN
Several different investigators have reported increased stroke mortality in the southeastern United States, leading to the introduction of the term "Stroke Belt." The results presented here from the Veterans Administration Hypertension Screening and Treatment Program (HSTP) demonstrate an increased all-cause mortality among hypertensive patients seen in HSTP clinics in the southeastern United States when compared with similar patients from other HSTP clinics. Several different groupings of southeastern states were examined and compared with nine states west of the Mississippi River. A total of 11,936 male veterans, 5737 of whom were black, were identified as hypertensive during 1974-1976 in 32 HSTP clinics. Their mean age was 52.4 +/- 10.4 years, and their mean pretreatment blood pressure was 153.8 +/- 19.1/100.4 +/- 9.8 mm Hg. During a minimum of 13.9 years of follow-up, 5360 (44.9%) of these patients died. Proportional hazards modeling was used to fit a basic survival model with terms representing race, age, blood pressure, smoking, and obesity. Risk was increased with higher blood pressure, age, and smoking and with lower body mass index. For 6 HSTP clinics in an 11-state Stroke Belt (defined as states with stroke mortality > 10% above the United States average), the relative risk of death was 1.226 (95% confidence interval, 1.106-1.358) when compared with 9 states west of the Mississippi River. For two different groupings of southeastern states with 10 and 8 HSTP clinics the relative risk of death was 1.231 and 1.295.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Trastornos Cerebrovasculares/mortalidad , Hipertensión/mortalidad , Veteranos , Adulto , Negro o Afroamericano , Factores de Edad , Presión Sanguínea , Índice de Masa Corporal , Trastornos Cerebrovasculares/etnología , Trastornos Cerebrovasculares/etiología , Estudios de Cohortes , Intervalos de Confianza , Estudios de Seguimiento , Humanos , Hipertensión/complicaciones , Hipertensión/etnología , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Factores de Riesgo , Fumar , Sudeste de Estados Unidos/epidemiología , Estados Unidos/epidemiologíaRESUMEN
Uptake and incorporation of long-chain fatty acids were studied in a human colorectal cancer cell line (HT29/219) grown in culture medium supplemented with either fetal calf serum (FCS) or horse serum (HS). The cells were grown for 120 h with no change of medium; the two major cellular lipid classes, the phospholipids and the triacylglycerols, were analyzed at regular time-points. We observed significant changes in the concentration of most fatty acids throughout culture, and differences in their composition when different sera were used to supplement the medium. Minimal levels of free fatty acids were found in the cells, indicating a very small "free fatty acid pool". A major difference between the cells grown in media supplemented with different sera was the changes observed in concentrations of cellular polyunsaturated fatty acids during growth. In cells grown with FCS (in which 20:4n-6 is present), the levels of this acid in the phospholipid and triacylglycerol fractions declined rapidly during cell growth, suggesting further metabolism. In cells grown in medium supplemented with HS, 18:2n-6 was the major polyunsaturated acid present. There was clear evidence that this acid accumulated in the cellular triacylglycerol and phospholipid fractions. Furthermore, its concentration did not decline during growth in culture, suggesting minimal conversion to other polyunsaturated n-6 acids. Our results suggest that fatty acids from additional sources in the medium, for example triacylglycerols and phospholipids associated with the lipoproteins, are taken up by the cells. There is also indication of cellular fatty acid synthesis, particularly of monounsaturated and saturated acids during the culture period.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Neoplasias Colorrectales/metabolismo , Ácidos Grasos/metabolismo , Fosfolípidos/metabolismo , Triglicéridos/metabolismo , Ácido Araquidónico/metabolismo , División Celular , Medios de Cultivo , Ácidos Grasos Insaturados/metabolismo , Humanos , Cinética , Ácido Linoleico , Ácidos Linoleicos/metabolismo , Ácidos Linolénicos/metabolismo , Ácido Oléico , Ácidos Oléicos/metabolismo , Células Tumorales Cultivadas , Ácido alfa-LinolénicoRESUMEN
Human and rat whole blood were shown to metabolize the aromatic amides acetanilide and phenacetin by deacetylation followed by reacetylation in vitro. Derivatives of the parent compounds labelled with deuterium in the N-acetyl group produced non-labelled material after incubation. The reaction was monitored by capillary gas chromatographic-mass spectrometric (GC-MS) analysis. There was no significant difference in the acetyl group exchange of these substrates using blood samples donated by non-diabetic volunteers or Type 2 diabetic patients (respective mean +/- SEM values = 4.0 +/- 0.2% and 4.2 +/- 0.3% for trideuteroacetanilide, 6.2 +/- 0.6% and 6.1 +/- 0.3% for trideuterophenacetin). Increasing the glucose concentration in the incubation medium by 50 mmol/L significantly (P less than 0.01) increased deacetylation-reacetylation of trideuteroacetanilide in each group (4.6 +/- 0.2% and 4.7 +/- 0.2% for non-diabetic and diabetic subjects, respectively). In rat blood the amount of deacetylation-reacetylation was much higher: 7.2 +/- 0.6% and 8.3 +/- 0.7% for trideuteroacetanilide and trideuterophenacetin, respectively. Induction of experimental diabetes using streptozotocin did not significantly change the extent of deacetylation-reacetylation of either deuterated substrate (10.1 +/- 2.1% and 9.5 +/- 1.1%). Elevation of the incubation glucose concentration by 50 mmol/L produced an increase in acetyl group exchange (for trideuteroacetanilide) in diabetic (14.3 +/- 2.2%) and non-diabetic (10.6 +/- 1.0%) rats. The donation of acetyl groups (transacetylation) was observed after incubation of blood samples from both diabetic and non-diabetic human subjects and rats with trideuterophenacetin and a molar excess of aniline. This reaction significantly (P less than 0.001) decreased the acetyl group exchange of trideuterophenacetin (these values were 4.5 +/- 0.4% and 3.4 +/- 0.6% using samples from non-diabetic human subjects and rats, respectively) and demonstrated the ability of whole blood to catalyse transacetylation (acetyl-CoA-independent acetylation). There was correlation between the amount of (unlabelled) acetanilide produced by acetylation with acetyl-CoA and the percentage present as trideuteroacetanilide. The proportion of trideuteroacetanilide was higher using rat blood (e.g. the values for non-diabetic subjects were 25.5 +/- 1.7% vs 8.5 +/- 0.3%; P less than 0.001) although the total amount of acetanilide produced was lower (0.54 +/- 0.14 nmol vs 1.82 +/- 0.23 nmol; P less than 0.05) than that observed using human blood.
Asunto(s)
Arilamina N-Acetiltransferasa/metabolismo , Acetanilidas/metabolismo , Acetilación , Compuestos de Anilina/farmacología , Animales , Arilamina N-Acetiltransferasa/sangre , Glucemia/análisis , Cromatografía Líquida de Alta Presión , Deuterio , Diabetes Mellitus/sangre , Diabetes Mellitus Experimental/sangre , Cromatografía de Gases y Espectrometría de Masas , Glucosa/farmacología , Humanos , Masculino , Fenacetina/metabolismo , Ratas , Ratas EndogámicasRESUMEN
The determination of long-chain fatty acids in the phospholipid, triglyceride and free fatty acid fractions of HT29/219 colon cancer cells grown in a medium containing either foetal calf serum or horse serum, was carried out using gas chromatography - mass spectrometry. Several bonded-phase capillary columns were tested for the separation of the fatty acid methyl esters, and a 30-m poly(ethylene glycol) column was found to give optimum separation. The mass spectrometer was set to the multiple ion detection mode to increase the sensitivity of the recording of the characteristic ions, consisting of the molecular ion and the base peak. The phospholipid and triglyceride compositions of the cells were different when the cells were grown in media containing different sera. Differences were also found in the turnover of the acids in the different lipid fractions, the phospholipids being the most important, when the cells were grown in different media. The cellular metabolism and turnover of certain fatty acids differed from others in the same cell. These differences emphasise the importance of a precise knowledge of the lipid composition of the culture medium in in vitro studies of cancer cells.
Asunto(s)
Ácidos Grasos/análisis , Células Tumorales Cultivadas/análisis , Cromatografía de Gases y Espectrometría de Masas , Humanos , Fosfolípidos/análisisRESUMEN
Triacylglycerols from rat adipose tissue were chromatographed by high-performance liquid chromatography (HPLC), with a gradient of propan-2-ol in acetonitrile as the mobile phase. Fractions of the material eluting from the column were collected and analysed by automated gas - liquid chromatography of the fatty acid methyl esters obtained after transmethylation. Triacylglycerols were identified by using a combination of their fatty acid content and elution time from the HPLC column. Fractions corresponding to whole peaks or groups of peaks were also collected and re-chromatographed on a liquid chromatography - mass spectrometry system equipped with a belt interface. For most triacylglycerols, good agreement was obtained between the two methods, although mass spectrometric identification of the early eluting peaks was complicated by poor resolution of the triacylglycerols on the HPLC system.
Asunto(s)
Triglicéridos/análisis , Tejido Adiposo/análisis , Animales , Cromatografía de Gases , Cromatografía Líquida de Alta Presión , Cromatografía Liquida , Espectrometría de Masas , RatasRESUMEN
Induction of experimental diabetes using streptozotocin significantly reduced the extent of sulphamethazine acetylation by Sprague-Dawley rats. This treatment did not significantly change the total amount of sulphonomide excreted in the urine. The in vitro blood N-acetyltransferase activity of rats treated with streptozotocin was significantly higher than that of untreated animals. Increasing the in vitro glucose concentration of blood samples from both groups significantly increased the amount of acetylsulphamethazine produced.
Asunto(s)
Acetiltransferasas/metabolismo , Arilamina N-Acetiltransferasa/metabolismo , Diabetes Mellitus Experimental/metabolismo , Sulfametazina/metabolismo , Acetilación , Animales , Arilamina N-Acetiltransferasa/sangre , Glucemia/análisis , Cromatografía Líquida de Alta Presión , Glucosa/farmacología , Masculino , Ratas , Ratas Endogámicas , Sulfametazina/orinaRESUMEN
As polyunsaturated fatty acids have better antibacterial properties than saturated fatty acids, the cerumen of seven patients with recurrent otitis externa and seven unaffected subjects was analysed to determine their ratio. There was no significant difference in either the overall ratio of unsaturated/saturated fatty acids or in the amounts of the individual fatty acids from the cerumen of either group.