RESUMO
Common polymorphisms in the vitamin D receptor (VDR) gene have been shown to correlate with bone mineral density (BMD). However, attempts to replicate the original findings in other populations have yielded variable results. These disparities may reflect ethnic or environmental differences in the expression of the VDR effect upon BMD. We examined a relatively ethnically homogeneous group of 103 healthy postmenopausal Caucasian women of Mexican descent living in Northern California. We determined the VDR genotype and measured the BMD at the lumbar spine and femoral neck by dual-energy X-ray absorptiometry, as well as several biochemical indices of mineral metabolism. The prevalence of the BB genotype, associated in previous studies with the lowest BMD, was 8% and highly linked to the tt genotype. Absolute and age-adjusted BMD at both hip and spine showed a trend toward lower BMD in the BB, AA, and tt genotypes, but this trend did not achieve statistical significance. There were no consistent intergroup differences in change in BMD over 2 years of follow-up, nor in mean serum concentrations of 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, osteocalcin, or total urinary pyridinolines. Intact parathyroid hormone concentrations were significantly higher in subjects with the AA genotype, with a trend toward higher values in those with the BB and tt genotypes as well. Our data suggest that there may be a decrease in BMD associated with the B, A, and t alleles, but the intergroup difference in BMD is 0.2-0.5 standard deviations (SD) at the lumbar spine and 0.3 SD at the femoral neck, decreases that are smaller than previously reported. Given the relatively low prevalence of the BB/tt genotype in Mexican-American Caucasians, a larger sample would be required to detect a significant association between VDR alleles and differences in BMD of the magnitude suggested by our data. We conclude that a genotype effect of this magnitude, if present, would be clinically relevant, but the impact on BMD is too small to detect with statistical significance in a study of this size.
Assuntos
Densidade Óssea/genética , Osso e Ossos/metabolismo , Americanos Mexicanos , Polimorfismo Genético , Pós-Menopausa/genética , Receptores de Calcitriol/genética , Receptores de Calcitriol/metabolismo , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Densidade Óssea/fisiologia , Feminino , Genótipo , Humanos , Pessoa de Meia-Idade , Pós-Menopausa/fisiologia , Receptores de Calcitriol/sangueRESUMO
We examined the association of bone mineral density (BMD) with a polymorphism in the gene encoding the vitamin D receptor (VDR) that causes a change in the predicted protein sequence. The polymorphism results from a C-to-T transition and creates an initiation codon (ATG) three codons proximal to a downstream start site. The polymorphism can be defined by a restriction fragment length polymorphism (RFLP) using the restriction endonuclease FokI. The presence of a FokI site, designated f, allows protein translation to initiate from the first ATG. The allele lacking the site (designated F), initiates from a second ATG site. Thus, translation products from these alleles are predicted to differ by three amino acids with the f variant elongated. In a group of 100 postmenopausal Mexican-American Caucasian women, subjects with the ff genotype (15% of the study population) had a 12.8% lower BMD at the lumbar spine than FF subjects (37% of the population) (p = 0.01). Heterozygote (Ff) subjects (48% of the population) had an intermediate BMD. This association between BMD and genotype was not apparent at the femoral neck or forearm. Over a 2-year follow-up period, a decrease in BMD at the femoral neck was greater in ff compared with FF subjects (-4.7% vs. -0.5%, p = 0.005). This trend was not apparent at the lumbar spine or forearm. There were no differences between genotype groups in measurements of 25-hydroxyvitamin D (25(OH)D), calcitriol, parathyroid hormone (PTH), osteocalcin, or urinary pyridinolines. We conclude that the FokI polymorphism of the VDR gene correlates significantly with decreased BMD at the lumbar spine and with an increased rate of bone loss at the hip in ff subjects. We emphasize that these initial data should be interpreted with caution but that the utility of this polymorphism as a genetic marker to determine BMD and osteoporosis risk warrants further study in larger populations with subjects of diverse ethnic backgrounds.
Assuntos
Densidade Óssea/genética , Americanos Mexicanos/genética , Iniciação Traducional da Cadeia Peptídica/genética , Polimorfismo Genético , Pós-Menopausa/genética , Receptores de Calcitriol/genética , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , California , Feminino , Humanos , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de RestriçãoRESUMO
We reviewed the clinical presentation, subsequent course, and outcome of 98 patients with alpha 1-antitrypsin deficiency seen at our institution during the past 20 years to obtain answers to the following questions: (1) What prognostic factors aid in determining the course of liver disease in affected patients? (2) When is the appropriate time for referral to a liver transplant center? (3) Does breast-feeding prevent chronic liver disease? (4) What is the incidence of severe liver disease in family members? Our analysis revealed that the initial values of alanine aminotransferase, prothrombin time, and trypsin inhibitory capacity may have prognostic value. During clinical follow-up the recurrence or persistence of hyperbilirubinemia along with deteriorating results of coagulation studies indicated the need for liver transplantation because of imminent poor outcome. Girls had a worse prognosis than boys. Initial breast-feeding versus feeding of commercial formulas did not influence overall overcome. The incidence of significant liver disease among "at risk" siblings was 21% (3/14); if one assumes mendelian inheritance from heterozygous parents, the overall risk for siblings in our families was 5%.
Assuntos
Hepatopatias/sangue , Erros Inatos do Metabolismo/sangue , Deficiência de alfa 1-Antitripsina , Adolescente , Alanina Transaminase/sangue , Bilirrubina/sangue , Aleitamento Materno , Criança , Pré-Escolar , Humanos , Incidência , Lactente , Recém-Nascido , Hepatopatias/epidemiologia , Hepatopatias/genética , Erros Inatos do Metabolismo/epidemiologia , Erros Inatos do Metabolismo/genética , Valor Preditivo dos Testes , Prognóstico , Tempo de Protrombina , Fatores de Risco , Fatores SexuaisRESUMO
The representation of the visual field in areas V3 and V4 of the macaque was mapped with multiunit electrodes. Twelve Macaca fascicularis were studied in repeated recording sessions while immobilized and anesthetized. V3 is a narrow strip (4-5 mm wide) of myeloarchitectonically distinct cortex located immediately anterior to V2. It contains a systematic representation of the central 35-40 degrees of the contralateral visual field; the representation of the upper quadrant is located ventrally in the hemisphere and that of the lower quadrant, dorsally. There is a small gap between the dorsal (V3d) and ventral (V3v) portions of V3. The representation of the horizontal meridian is adjacent to that in V2 and forms the posterior border of both V3d and V3v. Most or all of the anterior border of V3d consists of the representation of the lower vertical meridian. The entire anterior border of V3v consists of the representation of the upper vertical meridian. V4 is a strip of myeloarchitectonically distinct cortex 5-8 mm wide, immediately anterior to V3. It contains a coarse, but systematic, representation of approximately the central 35-40 degrees of the contralateral visual field. The representation of the upper visual field is located ventrally in the hemisphere. Most of the representation of the lower visual field is located dorsally. The posterior border of V4 corresponds to the representation of the vertical meridian, and the representation of the horizontal meridian is located at or near its anterior border. In both V3 and V4, the representation of the central visual field is magnified relative to that of the periphery. In both areas, the size of receptive fields increases with increasing eccentricity; however, at a given eccentricity, the receptive fields of V4 are larger than those of V3.
Assuntos
Mapeamento Encefálico , Macaca fascicularis/fisiologia , Macaca/fisiologia , Córtex Visual/fisiologia , Campos Visuais , Animais , Bainha de Mielina/ultraestrutura , Neurônios/fisiologia , Neurônios/ultraestrutura , Córtex Visual/citologia , Córtex Visual/ultraestruturaRESUMO
With its great emphasis on community participation, Colombia's health policy aims to check the inordinate demand for free medical care, hospitalization, and health resources and to provide better services for the needy and the community at large. Available data are provided on the proportion of physicians to the population (6,5/10,000), and on the estimated numbers of nurses (6,070), nurse's aides (13,016), auxiliaries (25,771) and professional dentists (10,069). This is followed by data on the estimated numbers of graduates in the health professions and the target for the year 2000 (53,143 physicians, 16,469 nurses, and 21,600 dentists). Finally, recommendations are put forward on policy and education, among them that plans for the training of health manpower be consistent with the country's growth and financial capacity.