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2.
QJM ; 108(10): 761-3, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-25713422

RESUMEN

We have been working on an association of physicians 'links with developing countries' scheme in Tajikistan, which is a nation of 7.5 million people, 93% of which is mountainous, of a similar size to England and Wales, landlocked, resource-poor and richly licked by the brush of history. Understanding the challenges faced by academics working with Tajikistan today requires a cursory understanding of Tajikistan's genesis. Through this lens, present-day technical, organizational and socio-political challenges can be appropriately considered, with a view to improving academic collaboration in the future.


Asunto(s)
Conducta Cooperativa , Hepatitis B/etnología , Lenguaje , Investigación/tendencias , Países en Desarrollo , Humanos , Política , Tayikistán/etnología
3.
J Am Diet Assoc ; 101(11): 1319-25, 2001 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-11716313

RESUMEN

OBJECTIVES: To study possible synergistic effects of oats and soy on reducing total and low-density lipoprotein cholesterol (LDL-C) concentrations in human beings and the efficacy and feasibility of including these adjustments to a National Cholesterol Education Program Step I diet. SUBJECT/SETTING: One hundred twenty-seven postmenopausal women with moderate hypercholesterolemia were recruited from a large Midwestern workforce and senior centers in the surrounding community. Intervention and clinical visits were conducted in these same facilities. DESIGN: After a 3-week lead-in period on the Step I diet, participants were randomly assigned to 1 of 4 dietary treatments for an additional 6 weeks: an oats/milk group, a wheat/soy group, an oats/soy group, and a wheat/milk group. Clinical measurements included blood draws, body weight and height, blood pressure, and medical history data. Three-day food records were collected at baseline and Weeks 3 and 9 of the intervention. Randomization was stratified based on the status of hormone replacement therapy and was blocked with sizes 4 or 8 for group assignment. RESULTS: After 3 weeks on the Step I diet, total cholesterol, LDL-C, and triglyceride levels; total fat and saturated fat intake, dietary cholesterol intake, Keys score, and body mass index were all reduced. Following an additional 6 weeks on the Step I diet plus intervention, total cholesterol and LDL-C were further reduced for both the oats/soy group and oats/milk group. There were no significant further changes in total cholesterol, LDL-C, or high-density lipoprotein cholesterol levels in the wheat/soy and wheat/milk groups. Body mass index remained stable in all groups from Week 3 to Week 9. APPLICATIONS: Nonpharmacologic dietary interventions like the Step I diet are feasible in a community setting and can produce rapid and significant lipid-lowering benefits. Daily consumption of 2 servings of oats can contribute to further lipid alterations in this population although soy intake at this dose may not. Palatability and convenience are important considerations in achieving dietary adherence.


Asunto(s)
Avena/metabolismo , LDL-Colesterol/sangre , Colesterol/sangre , Grasas de la Dieta/administración & dosificación , Glycine max/metabolismo , Hipercolesterolemia/dietoterapia , Anciano , Anciano de 80 o más Años , Animales , Presión Sanguínea , Índice de Masa Corporal , Registros de Dieta , Dieta con Restricción de Grasas , Femenino , Humanos , Hipercolesterolemia/sangre , Persona de Mediana Edad , Leche , Cooperación del Paciente , Educación del Paciente como Asunto , Posmenopausia , Resultado del Tratamiento , Triglicéridos/sangre , Triticum
4.
Hypertension ; 38(2): 232-7, 2001 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-11509482

RESUMEN

We compared the relations of 4 blood pressure (BP) indexes (pulse pressure [PP], systolic BP [SBP], diastolic BP [DBP], and mean arterial pressure [MAP]) with 25-year mortality rates for coronary heart disease (CHD), cardiovascular disease (CVD), and all causes in younger, middle-aged, and older men and women by using data from a long-term prospective epidemiological study of employed persons who were screened between 1967 and 1973. A single supine BP measurement was obtained at baseline. Vital status was determined through 1995. We report on 5 groups (total, 28 360 participants) consisting of men age 18 to 39, 40 to 59, and 60 to 74 years and of women age 40 to 59 and 60 to 74 years who were not receiving antihypertensive treatment, had no history of CHD, and did not have diabetes. Cox proportional hazards analyses were used to determine multivariate-adjusted hazard ratios with a 1-SD higher value for each BP index; Wald chi(2) tests were used to compare the strength of relations. Relations of PP were less strong than were those of SBP for all end points in all age/gender groups. SBP or MAP showed the strongest relations to all end points in all age/gender groups (hazard ratio, 1.17 to 1.36). The relations of SBP to death were stronger than were those of DBP, except for middle-aged men and for CVD in women. DBP showed significant positive associations with death, after control for SBP, in middle-aged participants. In conclusion, these data indicate that the long-term risk of high BP should be assessed mainly on the basis of SBP or of SBP and DBP together, not on the basis of PP, in apparently healthy adults.


Asunto(s)
Presión Sanguínea , Enfermedades Cardiovasculares/mortalidad , Enfermedad Coronaria/mortalidad , Pulso Arterial , Adolescente , Adulto , Anciano , Enfermedades Cardiovasculares/fisiopatología , Estudios de Cohortes , Enfermedad Coronaria/fisiopatología , Diástole , Femenino , Estudios de Seguimiento , Predicción , Humanos , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Sístole
5.
Arch Intern Med ; 161(12): 1501-8, 2001 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-11427097

RESUMEN

BACKGROUND: Data are limited on blood pressure (BP) in young adults and long-term mortality. Moreover, screening and hypertension treatment guidelines have been based mainly on findings for middle-aged and older populations. This study assesses relationships of BP measured in young adult men to long-term mortality due to coronary heart disease (CHD), cardiovascular diseases (CVD), and all causes. METHODS: This cohort from the Chicago Heart Association Detection Project in Industry included 10 874 men aged 18 to 39 years at baseline (1967-1973), not receiving antihypertensive drugs, and without CHD or diabetes. Relationship of baseline BP to 25-year CHD, CVD, and all-cause mortality was assessed. RESULTS: Age-adjusted association of systolic BP to CHD mortality was continuous and graded. Multivariate-adjusted CHD hazard ratios (HRs) for 1 SD higher systolic BP (15 mm Hg) and diastolic BP (10 mm Hg) were 1.26 (95% confidence interval [CI], 1.11-1.44) and 1.17 (95% CI, 1.01-1.35), respectively. Compared with the Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure stratum with normal BP (and lowest mortality rates), the large strata with high-normal BP and stage 1 hypertension had 25-year absolute risks for death of 63 and 72 per 1000, respectively, and absolute excess risks of 10 and 20 per 1000, respectively; accounted for 59.8% of all excess CHD, CVD, and all-cause mortality; and were estimated to have life expectancy shortened by 2.2 and 4.1 years, respectively. CONCLUSIONS: In young adult men, BP above normal was significantly related to increased long-term mortality due to CHD, CVD, and all causes. Population-wide primary prevention, early detection, and control of higher BP are indicated from young adulthood on.


Asunto(s)
Enfermedades Cardiovasculares/mortalidad , Causas de Muerte , Enfermedad Coronaria/mortalidad , Hipertensión/epidemiología , Adolescente , Adulto , Distribución por Edad , Determinación de la Presión Sanguínea , Enfermedades Cardiovasculares/epidemiología , Estudios de Cohortes , Comorbilidad , Intervalos de Confianza , Enfermedad Coronaria/epidemiología , Encuestas Epidemiológicas , Humanos , Masculino , Tamizaje Masivo , Análisis Multivariante , Modelos de Riesgos Proporcionales , Medición de Riesgo , Análisis de Supervivencia , Estados Unidos/epidemiología
6.
JAMA ; 284(3): 311-8, 2000 Jul 19.
Artículo en Inglés | MEDLINE | ID: mdl-10891962

RESUMEN

CONTEXT: Based on observational and interventional data for middle-aged cohorts (aged 40-64 years), serum cholesterol level is known to be an established major risk factor for coronary heart disease (CHD). However, findings for younger people are limited, and the value of detecting and treating hypercholesterolemia in younger adults is debated. OBJECTIVE: To evaluate the long-term impact of unfavorable serum cholesterol levels on risk of death from CHD, cardiovascular disease (CVD), and all causes. DESIGN, SETTING, AND PARTICIPANTS: Three prospective studies, from which were selected 3 cohorts of younger men with baseline serum cholesterol level measurements and no history of diabetes mellitus or myocardial infarction. A total of 11,017 men aged 18 through 39 years screened in 1967-1973 for the Chicago Heart Association Detection Project in Industry (CHA); 1266 men aged 25 through 39 years examined in 1959-1963 in the Peoples Gas Company Study (PG); and 69,205 men aged 35 through 39 years screened in 1973-1975 for the Multiple Risk Factor Intervention Trial (MRFIT). MAIN OUTCOME MEASURES: Cause-specific mortality during 25 (CHA), 34 (PG), and 16 (MRFIT) years of follow-up; mortality risks; and estimated life expectancy in relation to baseline serum cholesterol levels. RESULTS: Death due to CHD accounted for 26%, 34%, and 28% of all deaths in the CHA, PG, and MRFIT cohorts, respectively; and CVD death for 34%, 42%, and 39% of deaths in the same cohorts, respectively. Men in all 3 cohorts with unfavorable serum cholesterol levels (200-239 mg/dL [5.17-6.18 mmol/L] and >/=240 mg/dL [>/=6.21 mmol/L]) had strong gradients of relative mortality risk. For men with serum cholesterol levels of 240 mg/dL or greater (>/=6.21 mmol/L) vs favorable levels (<200 mg/dL [<5.17 mmol/L]), CHD mortality risk was 2.15 to 3.63 times greater; CVD disease mortality risk was 2.10 to 2.87 times greater; and all-cause mortality was 1.31 to 1.49 times greater. Hypercholesterolemic men had age-adjusted absolute risk of CHD death of 59 per 1000 men in 25 years (CHA cohort), 90 per 1000 men in 34 years (PG cohort), and 15 per 1000 men in 16 years (MRFIT cohort). Absolute excess risk was 43.6 per 1000 men (CHA), 81.4 per 1000 men (PG), and 12.1 per 1000 men (MRFIT). Men with favorable baseline serum cholesterol levels had an estimated greater life expectancy of 3.8 to 8.7 years. CONCLUSIONS: These results demonstrate a continuous, graded relationship of serum cholesterol level to long-term risk of CHD, CVD, and all-cause mortality, substantial absolute risk and absolute excess risk of CHD and CVD death for younger men with elevated serum cholesterol levels, and longer estimated life expectancy for younger men with favorable serum cholesterol levels. JAMA. 2000;284:311-318


Asunto(s)
Enfermedades Cardiovasculares/mortalidad , Colesterol/sangre , Enfermedad Coronaria/mortalidad , Adulto , Enfermedades Cardiovasculares/etiología , Causas de Muerte , Estudios de Cohortes , Enfermedad Coronaria/etiología , Humanos , Hipercolesterolemia/complicaciones , Esperanza de Vida , Masculino , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Factores de Riesgo
7.
JAMA ; 282(21): 2012-8, 1999 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-10591383

RESUMEN

CONTEXT: Three major coronary risk factors-serum cholesterol level, blood pressure, and smoking-increase incidence of coronary heart disease (CHD) and related end points. In previous investigations, risks for low-risk reference groups were estimated statistically because samples contained too few such people to measure risk. OBJECTIVE: To measure long-term mortality rates for individuals with favorable levels for all 3 major risk factors, compared with others. DESIGN: Two prospective studies, involving 5 cohorts based on age and sex, that enrolled persons with a range of risk factors. Low risk was defined as serum cholesterol level less than 5.17 mmol/L (<200 mg/dL), blood pressure less than orequal to 120/80 mm Hg, and no current cigarette smoking. All persons with a history of diabetes, myocardial infarction (MI), or, in 3 of 5 cohorts, electrocardiogram (ECG) abnormalities, were excluded. SETTING AND PARTICIPANTS: In 18 US cities, a total of 72144 men aged 35 through 39 years and 270671 men aged 40 through 57 years screened (1973-1975) for the Multiple Risk Factor Intervention Trial (MRFIT); in Chicago, a total of 10025 men aged 18 through 39 years, 7490 men aged 40 through 59 years, and 6229 women aged 40 through 59 years screened (1967-1973) for the Chicago Heart Association Detection Project in Industry (CHA) (N = 366559). MAIN OUTCOME MEASURES: Cause-specific mortality during 16 (MRFIT) and 22 (CHA) years, relative risks (RRs) of death, and estimated greater life expectancy, comparing low-risk subcohorts vs others by age strata. RESULTS: Low-risk persons comprised only 4.8% to 9.9% of the cohorts. All 5 low-risk groups experienced significantly and markedly lower CHD and cardiovascular disease death rates than those who had elevated cholesterol level, or blood pressure, or smoked. For example, age-adjusted RRs of CHD mortality ranged from 0.08 for CHA men aged 18 to 39 years to 0.23 for CHA men aged 40 through 59 years. The age-adjusted relative risks (RRs) for all cardiovascular disease mortality ranged from 0.15 for MRFIT men aged 35 through 39 years to 0.28 for CHA men aged 40 through 59 years. The age-adjusted RR for all-cause mortality rate ranged from 0.42 for CHA men aged 40 through 59 years to 0.60 for CHA women aged 40 through 59 years. Estimated greater life expectancy for low-risk groups ranged from 5.8 years for CHA women aged 40 through 59 years to 9.5 years for CHA men aged 18 through 39 years. CONCLUSIONS: Based on these very large cohort studies, for individuals with favorable levels of cholesterol and blood pressure who do not smoke and do not have diabetes, MI, or ECG abnormalities, long-term mortality is much lower and longevity is much greater. A substantial increase in the proportion of the population at lifetime low risk could contribute decisively to ending the CHD epidemic.


Asunto(s)
Enfermedades Cardiovasculares/mortalidad , Causas de Muerte , Esperanza de Vida , Adulto , Presión Sanguínea , Colesterol/sangre , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mortalidad , Modelos de Riesgos Proporcionales , Factores de Riesgo , Fumar , Estados Unidos/epidemiología
8.
N Engl J Med ; 339(16): 1122-9, 1998 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-9770560

RESUMEN

BACKGROUND: People without major risk factors for cardiovascular disease in middle age live longer than those with unfavorable risk-factor profiles. It is not known whether such low-risk status also results in lower expenditures for medical care at older ages. We used data from the Chicago Heart Association Detection Project in Industry to assess the relation of a low risk of cardiovascular disease in middle age to Medicare expenditures later in life. METHODS: We studied 7039 men and 6757 women who were 40 to 64 years of age when surveyed between 1967 and 1973 and who survived to have at least two years of Medicare coverage in 1984 through 1994. Men and women classified as being at low risk for cardiovascular disease were those who had the following characteristics at the time they were initially surveyed: serum cholesterol level, <200 mg per deciliter (5.2 mmol per liter); blood pressure, < or =120/80 mm Hg; no current smoking; an absence of electrocardiographic abnormalities; no history of diabetes; and no history of myocardial infarction. We compared Medicare costs for the 279 men (4.0 percent) and 298 women (4.4 percent) who had this low-risk profile with those for the rest of the study group, who were not at low risk. Health Care Financing Administration charges for services to Medicare beneficiaries were used to estimate average annual health care costs (total costs, those for cardiovascular diseases, and those for cancer). RESULTS: Average annual health care charges were much lower for persons at low risk - the total charges for the men at low risk were less than two thirds of the charges for the men not at low risk ($1,615 less); for the women at low risk, the charges were less than one half of those for the women not at low risk ($1,885 less). Charges related to cardiovascular disease were lower for the low-risk groups of men and women than for those not at low risk (by $979 and $556, respectively), and charges related to cancer were also lower (by $134 and $189). CONCLUSIONS: People with favorable cardiovascular risk profiles in middle age had lower average annual Medicare charges in older age. Having optimal status with respect to major cardiovascular risk factors may result not only in greater longevity but also in lower health care costs.


Asunto(s)
Enfermedades Cardiovasculares/economía , Costos de la Atención en Salud/estadística & datos numéricos , Medicare/economía , Adulto , Enfermedades Cardiovasculares/epidemiología , Chicago/epidemiología , Femenino , Estudios de Seguimiento , Gastos en Salud/estadística & datos numéricos , Servicios de Salud/estadística & datos numéricos , Precios de Hospital/estadística & datos numéricos , Humanos , Masculino , Medicare/estadística & datos numéricos , Persona de Mediana Edad , Neoplasias/economía , Factores de Riesgo , Estados Unidos
9.
J Forensic Sci ; 43(5): 974-9, 1998 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-9729814

RESUMEN

Fingernail and toenail specimens were obtained from 18 suspected cocaine users. The nails were cut, heated under methanolic reflux, and the methanolic extracts were purified by solid-phase extraction. Gas chromatography/mass spectrometry was utilized for the qualitative and quantitative analysis of nine cocaine analytes. Comparison of conventional postmortem analysis of blood and urine with nail analysis revealed a marked increase in the detection of cocaine use by nail analysis. Cocaine analytes were present in 14 (82.3%) subjects utilizing nail analysis. Out of those 14 subjects, only 5 (27.7%) were positive by conventional postmortem drug analysis. Cocaine and benzoylecgonine were the predominant analytes in all positive nail specimens. Anhydroecgonine methyl ester, ecgonine methyl ester, ecgonine ethyl ester, cocaethylene, norcocaine, and norbenzoylecgonine were detected in a limited number of specimens. The ratio of cocaine to benzoylecgonine ranged from 2-10:1. These findings suggest that nails may be a useful alternative matrix for the detection of cocaine exposure.


Asunto(s)
Cocaína/análisis , Medicina Legal/métodos , Uñas/química , Detección de Abuso de Sustancias/métodos , Adolescente , Adulto , Cocaína/análogos & derivados , Femenino , Cromatografía de Gases y Espectrometría de Masas , Humanos , Drogas Ilícitas/análisis , Masculino , Persona de Mediana Edad , Uñas/anatomía & histología
11.
J Chromatogr B Biomed Sci Appl ; 692(1): 61-5, 1997 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-9187384

RESUMEN

A novel, simple and economic liquid-liquid extraction method for isolating cocaine from urine was developed utilizing gas chromatography-mass spectrometry (GC-MS) for analysis and quantification. The use of a single nonpolar organic solvent allowed only nonpolar analytes to be extracted from the biological fluid, and consequently, no derivatization step was necessary before GC-MS analysis. Large numbers of specimens (>60) can be extracted in approximately 3 h with this procedure. The method is highly precise (C.V. <7%), accurate (>98%), sensitive (limit of detection of 5 ng/ml) and has a mean recovery of 48.8%.


Asunto(s)
Cocaína/orina , Detección de Abuso de Sustancias/métodos , Alcanos , Cocaína/análogos & derivados , Cocaína/aislamiento & purificación , Cromatografía de Gases y Espectrometría de Masas , Humanos , Sensibilidad y Especificidad
12.
J Clin Epidemiol ; 49(8): 849-57, 1996 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-8699203

RESUMEN

Associations of body mass index (BMI), two measures of percent body fat derived from skinfolds, body weight adjusted for height, triceps and subscapular skinfolds, and their sum, with 22-year coronary heart disease (CHD) mortality were compared in 1707 white men ages 40-55 years at baseline (1958) and free of CHD and cancer in 1961 in the Western Electric Study. Because associations of adiposity measures with CHD mortality differed by length of follow-up, analyses were conducted separately for the first 14 years of follow-up and years 15 through 22. In Cox regression analyses, none of the adiposity measures was significantly related to CHD mortality for the first 14 years of follow-up. For years 15-22, all adiposity measures, except triceps skinfold, were significantly related with adjustment for age, as well as eight other covariates. These results indicate that a positive relation of adiposity to CHD risk may not become apparent until several years after the assessment of adiposity.


Asunto(s)
Tejido Adiposo , Enfermedad Coronaria/mortalidad , Adulto , Índice de Masa Corporal , Chicago/epidemiología , Enfermedad Coronaria/complicaciones , Humanos , Masculino , Persona de Mediana Edad , Modelos Teóricos , Obesidad/complicaciones , Modelos de Riesgos Proporcionales , Factores de Riesgo , Grosor de los Pliegues Cutáneos , Factores de Tiempo
13.
Reprod Toxicol ; 10(3): 199-207, 1996.
Artículo en Inglés | MEDLINE | ID: mdl-8738556

RESUMEN

Following a recommendation from the International Conference on Harmonisation, pharmaceutical companies are now monitoring possible drug effects on sperm motility in the rat during preclinical safety studies by assessing sperm motility (velocity). However, it is not known precisely how changes in sperm motility relate to fertility. Therefore, the effects of alpha-chlorohydrin on sperm motility were investigated and related to fertility both in vivo and in vitro. alpha-Chlorohydrin was given orally to male rats using a range of doses: 0, 5, 10, and 20 mg/kg for at least 5 consecutive days. Sperm were than assessed for motility using a standard scoring system (operators' observation of sperm) that graded degree of motility (i.e., 0 = i mmotile to 4 = very motile). The results showed a dose-related decrease in sperm motility. The sperm also appeared to move with a "jerky" action. Surprisingly, when this was correlated to fertility, none of the females mated with treated males became pregnant. A dose-related decrease in pregnancy would perhaps have been expected. There was no effect on sperm morphology, and testicular and epididymal pathology were only seen after doses of 20 mg/kg. When sperm from untreated rats were incubated with alpha-chlorohydrin in vitro at concentrations of 0, 0.5, 1.0, and 1.5 mM, sperm motility and motion were similarly affected as observed in vivo. However, the fertilization capacity (in vitro fertilization) of the treated sperm showed a concentration-related reduction in percentage fertilization, and there was also evidence of abnormal embryo development. These findings suggest that the present standard scoring system used in preclinical safety studies is not a comprehensive indicator of sperm function and/or fertility. A better understanding of sperm movement, therefore, is desirable so effects on sperm motility can be related to fertility.


Asunto(s)
Fertilidad/efectos de los fármacos , Motilidad Espermática/efectos de los fármacos , alfa-Clorhidrina/toxicidad , Administración Oral , Animales , Embrión de Mamíferos/anomalías , Epidídimo/efectos de los fármacos , Epidídimo/patología , Femenino , Fertilización In Vitro , Técnicas In Vitro , Masculino , Tamaño de los Órganos/efectos de los fármacos , Embarazo , Ratas , Ratas Wistar , Testículo/efectos de los fármacos , Testículo/patología , Pruebas de Toxicidad/normas , alfa-Clorhidrina/administración & dosificación
14.
Regul Toxicol Pharmacol ; 23(1 Pt 1): 69-73, 1996 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-8628922

RESUMEN

The purpose of this study was to establish the timing of the onset of implantation in both the Harlan Porcellus Dutch and New Zealand White rabbit and the Han Wistar rat. Implantation was initiated on Day 5 (rat) and 7 (rabbit) and established by Day 7 and 8 of gestation in the rat and rabbit, respectively. Recent guidelines on toxicity testing during embryo-fetal development studies require that maternal exposure to pharmaceutical compounds does not occur until after implantation has taken place. In order to ensure that this is the case, female Harlan Porcellus Dutch and New Zealand White rabbits and Han Wistar rats were sacrificed on different days of gestation, over the expected periods of implantation. The presence of preimplantation blastocysts in the uterus was investigated, and evidence of established implantation sites was assessed.


Asunto(s)
Implantación Tardía del Embrión/fisiología , Implantación del Embrión , Animales , Compuestos Azo , Blastocisto/ultraestructura , Colorantes , Transferencia de Embrión , Femenino , Edad Gestacional , Conejos , Distribución Aleatoria , Ratas , Ratas Wistar , Especificidad de la Especie , Factores de Tiempo , Azul de Tripano , Útero/ultraestructura
15.
Steroids ; 59(12): 702-11, 1994 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-7900169

RESUMEN

The synthesis of several hydroxylated steroids via conjugate addition of Fleming's silyl-cuprate reagent, (PhMe2Si)2CuLi, a masked hydroxyl group, to the appropriate enone was studied. By this means 7 alpha-hydroxytestosterone (7) was obtained in good yield from 17 beta-hydroxyandrosta-4,6-dien-3-one (1a), though similar reactions on 17 beta-hydroxyandrosta-1,4-dien-3-one (8) gave a low yield of 1 alpha-hydroxytestosterone (13) chiefly through the poor conversion of the phenylsilyl intermediate into the halogenosilane. 3 beta,16 alpha-Dihydroxy-5 alpha-pregnan-20-one (18b) was obtained in a similar manner from 3 beta-hydroxy-5 alpha-pregn-16-en-20-one and 5 alpha-cholestane-1 alpha,3 alpha-diol(17) was produced from the 1-en-3-one (14) via conjugate addition of the silyl group, reduction of the carbonyl function, and oxidative removal of the silyl group.


Asunto(s)
Colestanol/análogos & derivados , Pregnanolona/análogos & derivados , Testosterona/análogos & derivados , Androstenos/síntesis química , Colestanol/síntesis química , Cobre/química , Espectroscopía de Resonancia Magnética , Pregnanolona/síntesis química , Testosterona/síntesis química
16.
Exp Mol Pathol ; 58(3): 179-93, 1993 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-8519345

RESUMEN

Phthalate esters are widely used in the manufacture of plastics and have been shown to cause testicular toxicity, purportedly, by targeting the Sertoli cell alone. Recent evidence, however, indicates that a paracrine control exists between Sertoli and Leydig cells and the breakdown of one component of this relationship is therefore detrimental to normal function. However, no data that explore the influence of testicular toxins on Leydig cell structure and function have been published hitherto. The preliminary studies reported here were initiated to test the hypothesis that phthalate intoxication may adversely alter Leydig cell structural and functional integrity. Four phthalate esters, namely, di(2-ethylhexyl) phthalate (DEHP, di-n-pentyl phthalate (DPP)., di-n-octyl phthalate (DOP), and diethyl phthalate (DEP) were investigated in vivo and their monoesters (MEHP, MPP, MOP, and MEP, respectively) in vitro for indications of Leydig cell toxicity in the rat. Rats were dosed by oral gavage with 2 g phthalate diester/kg/day in corn oil vehicle for 2 days, while Leydig cell primary cultures were incubated with 1,000 microM monoester for 2 hr. Light and electron microscopy were undertaken to determine the type and degree of any changes. Phthalate esters exerted a direct effect on Leydig cell structure and function (as determined by testosterone output) with correlation of the in vitro and in vivo effects of MEHP (DEHP) and MOP (DOP). No effects on Leydig cell structure or function were seen with MPP (DPP), although Sertoli cell cytoplasmic rarefaction and vacuolation were observed in vivo. DEP produced Leydig cell ultrastructural alterations in vivo. We conclude that individual phthalate esters may exert effects on both Sertoli and Leydig cells or one cell type alone.


Asunto(s)
Células Intersticiales del Testículo/efectos de los fármacos , Ácidos Ftálicos/toxicidad , Animales , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Dietilhexil Ftalato/toxicidad , Ésteres , Cinética , Células Intersticiales del Testículo/patología , Células Intersticiales del Testículo/ultraestructura , Hormona Luteinizante/farmacología , Masculino , Microscopía Electrónica , Ratas , Ratas Wistar , Relación Estructura-Actividad , Testosterona/metabolismo , Factores de Tiempo
17.
Cell Tissue Res ; 268(1): 17-30, 1992 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-1499049

RESUMEN

Mononucleated cells derived from canine bone marrow were maintained in vitro for up to 6 weeks. The culture characteristics and development of these cells were evaluated by histological, ultrastructural and histochemical methods. Within 1 week the cells had fused together to form flattened, multinucleated cells. Further fusing with one another and other mononucleated cells produced large (diameters more than 300 microns), multinucleated cells which frequently contained more than 50 nuclei per cell and exhibited ultrastructural and histochemical features that were strikingly similar to those displayed by osteoclasts. The confluent monolayer of mono- and multinucleated cells present at 4 weeks had, by the sixth week, become altered such that fibroblast overgrowth obliterated all other cells. During the development of the culture adipocytes became differentiated from mononuclear cells and frequently were located within spherical multicellular aggregates (spheroids). Functional assessments were employed to investigate whether the multinucleated cells generated in this way, represented osteoclast-like cells, or alternatively, were related to macrophage polykarya as found in foreign body granulomata in vivo. Neither resorption pits on sperm whale dentine slivers (diagnostic of osteoclasts), nor formation of granulomata in vitro, were observed. We believe that the present results indicate that the multinucleated cells generated from canine bone marrow mononuclear precursors in vitro, merit designation as osteoclast-like cells. Definitive characterisation however, must await further functional assessments of hormone responsiveness.


Asunto(s)
Células de la Médula Ósea , Células Gigantes/citología , Osteoclastos/citología , Animales , Resorción Ósea , Diferenciación Celular , Fusión Celular , Células Cultivadas , Perros , Microscopía Electrónica , Microscopía Electrónica de Rastreo
18.
Biochem J ; 249(3): 925-8, 1988 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-2833234

RESUMEN

The mechanisms of the requirement of glucose for steroidogenesis were investigated by monitoring the uptake of the glucose analogue 2-deoxy-D-glucose by rat testis and tumour Leydig cells. The characteristics of glucose transport in both of these cell types were found to resemble those of the facilitated-diffusion systems for glucose found in most other mammalian cells. The Leydig cells took up 2-deoxy-D-glucose but not L-glucose, and the uptake was inhibited by both cytochalasin B and forskolin. In the presence of luteinizing hormone, the rate of 2-deoxy-D-glucose uptake by both cell types was increased by approx. 50%. In addition to D-glucose, it was shown that the Leydig cells could also utilize 3-hydroxybutyrate or glutamine to maintain steroidogenesis.


Asunto(s)
Desoxiazúcares/farmacocinética , Desoxiglucosa/farmacocinética , Células Intersticiales del Testículo/metabolismo , Neoplasias Testiculares/metabolismo , Testosterona/biosíntesis , Animales , Transporte Biológico/efectos de los fármacos , Bucladesina/farmacología , Colforsina/farmacología , Citocalasina B/farmacología , Técnicas In Vitro , Células Intersticiales del Testículo/efectos de los fármacos , Hormona Luteinizante/farmacología , Masculino , Ratas
19.
Am J Emerg Med ; 3(3): 177-81, 1985 May.
Artículo en Inglés | MEDLINE | ID: mdl-3994792

RESUMEN

An analysis was undertaken of 8,470 visits to a pediatric emergency department (ED) over a three-month period during 1975-76. The ED was busiest in the evening and on weekends. Visits were overwhelmingly for acute conditions, which varied seasonally. Very young children accounted for a large proportion of visits (22.3% less than 1 year old, 47.0% less than 3 years old). The proportion of very young children increased as the hour of day got later. Overall, 7.3% of visits resulted in admission to the hospital, and 10% of children less than 1 year old were admitted. Admission rates were significantly higher on the day and night shifts than in the evenings, and rates were higher on weekdays than on weekends. Visits were mainly by children living in areas near the hospital, and children from the most distant areas were significantly more likely to be admitted than those from the nearest areas. The authors conclude that the documented ED usage patterns reflect the conditions of the children seen (age, medical problems, and severity of illness) and diminished availability of other services on weekends and evening. This indicates reasonable utilization of medical services and suggests the need for non-ED sources of care at times of peak ED use. These ED usage patterns in the 1970s are similar to those described in the 1960s, and together with the earlier data they provide a basis for comparison of utilization patterns during the current period of rapidly changing health-service reimbursement schemes.


Asunto(s)
Servicios de Salud del Niño/estadística & datos numéricos , Servicio de Urgencia en Hospital/estadística & datos numéricos , Adolescente , Factores de Edad , Niño , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Admisión del Paciente , Factores Sexuales , Factores de Tiempo , Estados Unidos , Población Urbana
20.
Pediatr Emerg Care ; 1(1): 22-7, 1985 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-3916458

RESUMEN

The possibility that Medicaid has encouraged pediatric emergency department (ED) use was explored as part of a study of 8470 ED visits to a pediatric teaching hospital in the period from 1975 to 1976. The proportion of the population on Aid to Dependent Children (proportion on ADC) was taken as a reasonable proxy for prevalence of Medicaid coverage of children in an area. Visit subgroups were compared using mean proportions on ADC in the census tracts of origin to measure relative rates of ED use by poor children. If Medicaid has promoted use of the ED instead of other facilities, the data would be expected to indicate relatively heavy ED use by residents of tracts with a high prevalence of Medicaid: (1) during the week when other facilities are most available; and (2) for minor problems which do not result in admission. The data show no differences in the mean proportion on ADC in the census tracts of origin of ED visits on weekdays as compared to weekends or for visits which resulted in admission as compared with those which did not. The data challenge the idea that Medicaid has encouraged pediatric ED use.


Asunto(s)
Servicio de Urgencia en Hospital/estadística & datos numéricos , Medicaid , Pediatría , Ayuda a Familias con Hijos Dependientes , Humanos , Estados Unidos
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