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Development of speech and language is rapid in early years, yet if developmental problems in speech and language are not addressed they are likely to continue and impact negatively on a child's overall development and their life trajectory. Children who have experienced abuse and or neglect are particularly vulnerable. The aim of this study was to develop a tool to assist in identifying a child's need for assessment by a speech pathologist so that there could be early identification of problems. A culturally sensitive tool was developed to be completed by the child's carer included questions on language, speech and hearing, voice, fluency, understanding sentences, vocabulary and expression. Sixty-five children aged between 4 and 8 years, who had experienced abuse and/or neglect participated in the study. Fourteen percent were Aboriginal. A speech pathologist undertook an assessment for each child and the results were compared with the information on the Small Talk tool. The Tool was found to be high in sensitivity but low in specificity, requiring further refinement. However, it has the potential to assist non speech pathologists to identify a child's need for speech and language assessment with the findings identifying the Tool as promising practice.
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Maltrato a los Niños/psicología , Trastornos del Desarrollo del Lenguaje/etiología , Adolescente , Niño , Desarrollo Infantil , Servicios de Protección Infantil/estadística & datos numéricos , Preescolar , Comunicación , Diagnóstico Precoz , Femenino , Humanos , Lenguaje , Trastornos del Desarrollo del Lenguaje/diagnóstico , Estudios Longitudinales , Masculino , Estudios Prospectivos , AutoimagenRESUMEN
AIMS: To evaluate the frequency with which hypothyroidism is associated with Type 2 diabetes, to examine gender and ethnic group differences, and to assess the possible impact of metformin therapy. To compare the prevalence of hypothyroidism in a cohort of people with Type 2 diabetes with a previously published cohort of people with Type 1 diabetes from the same centre. METHOD: We randomly surveyed the records of 922 people with Type 2 diabetes (576 men and 342 women) to identify diagnoses of hypothyroidism, based on current thyroxin replacement therapy (with previous biochemical confirmation). Four subjects had secondary hypothyroidism after radio-iodine therapy for primary hyperthyroidism and were excluded from the analysis. The prevalence of primary hypothyroidism was documented in the remaining 918 subjects. We assessed the association of metformin therapy with hypothyroidism. RESULTS: The overall prevalence of primary hypothyroidism was 11.8% (women: 22.5%; men: 5.4%, P < 0.001) in subjects with Type 2 diabetes. Inter-ethnic differences were noted, with the highest prevalence among white subjects. The prevalence of hypothyroidism was lower in subjects with Type 2 diabetes who were receiving metformin therapy (P < 0.01), and this difference was greater when assessing those who developed primary hypothyroidism after starting metformin therapy (P < 0.001) CONCLUSIONS: Our results support a relatively close association between diabetes and hypothyroidism. Hypothyroidism was more common in the cohort of white subjects than in other ethnic groups. The use of metformin therapy in people with Type 2 diabetes was associated with a significantly lower prevalence of diagnosed hypothyroidism.
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Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/epidemiología , Hipoglucemiantes/uso terapéutico , Hipotiroidismo/epidemiología , Metformina/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Etnicidad/estadística & datos numéricos , Femenino , Terapia de Reemplazo de Hormonas/estadística & datos numéricos , Humanos , Hipotiroidismo/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Prevalencia , Tiroxina/uso terapéuticoRESUMEN
Interphase nuclei have a conserved architecture: heterochromatin occupies the nuclear periphery, whereas euchromatin resides in the nuclear interior. It has recently been found that rod photoreceptor cells of nocturnal mammals have an inverted architecture, which transforms these nuclei in microlenses and supposedly facilitates a reduction in photon loss in the retina. This unique deviation from the nearly universal pattern throws a new light on the nuclear organization. In the article we discuss the implications of the studies of the inverted nuclei for understanding the role of the spatial organization of the nucleus in nuclear functions.
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Núcleo Celular/ultraestructura , Células Fotorreceptoras Retinianas Bastones/citología , Animales , Evolución Biológica , Diferenciación Celular , Núcleo Celular/metabolismo , Cromosomas de los Mamíferos/ultraestructura , Eucromatina/metabolismo , Heterocromatina/metabolismo , RatonesRESUMEN
AIMS: In 1994 the Centre for Diabetes and Endocrinology (CDE) based in Johannesburg, South Africa established a novel community-based capitation and risk-sharing model for diabetes management. We here describe the model and present a recent survey of the performance/outcomes of this unique diabetes care programme. METHODS: Data on 17 043 patients managed by the CDE Diabetes Management Programme at its Centre and its 262 affiliated Centres were analysed from its national database. From this total cohort, 1520 Type 1 and 8026 Type 2 diabetes patients have been in the Programme for > 5 years. The 5-year outcome data on hospital admission rates, glycaemic control (HbA(1c)), and microvascular complication rates were assessed in this subgroup of patients. RESULTS: Major reductions in hospital admission rates for both acute metabolic emergencies and all causes (40% overall) were achieved in patients enrolled onto the Diabetes Management Programme. The mean HBA(1c) on enrolment was 9.2% for subjects with Type 1 and 8.8% for those with Type 2 diabetes. After 1 year, mean HbA(1c) fell to 7.6% and 7.3% for the Type 1 and Type 2 subjects, respectively. At 5 years the HbA(1c) remained similar at 7.7% for the Type 1 subjects and 7.4% for the Type 2 subjects, demonstrating sustained improvement. Progression of microvascular complications appears to have been delayed. CONCLUSIONS: This managed care model of diabetes care in the context of the South African Private Health Care System achieved long-term improvement in glycaemic control and all-cause hospital admission rates. This may be due to the cost-containment being in the hands of the treating doctor, supported by an annual training programme. This programme is based on an individualized and holistic approach encompassing intensive patient education to facilitate self-empowerment and including prompting for the management of risk factors.
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Servicios de Salud Comunitaria/organización & administración , Atención a la Salud/organización & administración , Atención a la Salud/normas , Diabetes Mellitus Tipo 1/terapia , Diabetes Mellitus Tipo 2/terapia , Modelos Organizacionales , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Manejo de la Enfermedad , Educación en Enfermería , Femenino , Hemoglobina Glucada/análisis , Hospitalización/economía , Hospitalización/estadística & datos numéricos , Humanos , Hipoglucemiantes/uso terapéutico , Masculino , Persona de Mediana Edad , Evaluación de Procesos y Resultados en Atención de Salud , Médicos de Familia/educación , Sudáfrica , Adulto JovenRESUMEN
BACKGROUND: Coronary heart disease (CHD) is rare in diabetic Africans in South Africa, unlike diabetic African-Americans, despite moderate levels of conventional risk factors, with absence of the usual male predominance. Because the metabolic syndrome and insulin resistance (IR) are associated with CHD, we have analyzed the prevalence and severity of the metabolic syndrome, and IR, in African and white subjects with type 2 diabetes. METHODS: A total of 500 African and 254 white diabetic patients were evaluated for features of the metabolic syndrome (International Diabetes Federation [IDF] definition); insulin resistance (homeostasis model assessment-insulin resistance [HOMA-IR]) was calculated in subgroups. RESULTS: In men, Africans had a lower body mass index (BMI) and smaller waists than white subjects (p < 0.0001); the metabolic syndrome was present in 46.5% and 74.1% of African and white patients respectively (p < 0.0001). In women, frequencies of the metabolic syndrome were similar, but severe metabolic syndrome (4 or 5 criteria) was more frequent in the white group (73.1%) than in the Africans (52.9%) (p = 0.0003). The prevalence of hypertriglyceridemia was lower in African men and women (p < 0.0001) and contributed to their lower prevalence of the metabolic syndrome/severe metabolic syndrome. Compared with the white patients, in African subjects HOMA-IR was 40% lower (p < 0.0001), and correlated with the triglyceride:high-density lipoprotein cholesterol ratio (TG:HDL-C) (r = 0.409, p < 0.0001). CONCLUSIONS: In diabetic Africans, in comparison with white patients, the lower prevalence of the metabolic syndrome in men and severe metabolic syndrome in women, and lesser insulin resistance, might contribute to their lower risk of CHD; the higher prevalence in women might contribute to the reversal of the male:female ratio. The TG:HDL-C ratio appears to be a valid estimate of insulin resistance in diabetic Africans.
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Diabetes Mellitus Tipo 2/epidemiología , Resistencia a la Insulina/etnología , Síndrome Metabólico/etnología , Síndrome Metabólico/epidemiología , Adulto , Población Negra , Índice de Masa Corporal , HDL-Colesterol/metabolismo , Diabetes Mellitus Tipo 2/diagnóstico , Femenino , Humanos , Masculino , Síndrome Metabólico/complicaciones , Persona de Mediana Edad , Prevalencia , Sudáfrica , Triglicéridos/metabolismo , Población BlancaRESUMEN
The vast majority of microscopic data in biology of the cell nucleus is currently collected using fluorescence microscopy, and most of these data are subsequently subjected to quantitative analysis. The analysis process unites a number of steps, from image acquisition to statistics, and at each of these steps decisions must be made that may crucially affect the conclusions of the whole study. This often presents a really serious problem because the researcher is typically a biologist, while the decisions to be taken require expertise in the fields of physics, computer image analysis, and statistics. The researcher has to choose between multiple options for data collection, numerous programs for preprocessing and processing of images, and a number of statistical approaches. Written for biologists, this article discusses some of the typical problems and errors that should be avoided. The article was prepared by a team uniting expertise in biology, microscopy, image analysis, and statistics. It considers the options a researcher has at the stages of data acquisition (choice of the microscope and acquisition settings), preprocessing (filtering, intensity normalization, deconvolution), image processing (radial distribution, clustering, co-localization, shape and orientation of objects), and statistical analysis.
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Núcleo Celular/ultraestructura , Microscopía Confocal/métodos , Núcleo Celular/genética , Núcleo Celular/metabolismo , Colorantes Fluorescentes , Humanos , Procesamiento de Imagen Asistido por Computador , Citometría de Barrido por Láser/métodos , Microscopía Confocal/estadística & datos numéricos , Microscopía Fluorescente/métodos , Microscopía de Fluorescencia por Excitación Multifotónica/métodos , Análisis de Componente PrincipalAsunto(s)
Glucemia/metabolismo , Peso Corporal/efectos de los fármacos , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Hipoglucemia/epidemiología , Hipoglucemiantes/uso terapéutico , Insulina/análogos & derivados , Adulto , Glucemia/efectos de los fármacos , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 1/fisiopatología , Femenino , Humanos , Insulina/uso terapéutico , Insulina Glargina , Insulina de Acción Prolongada , Masculino , Persona de Mediana EdadRESUMEN
The article reviews the existing methods of multicolor FISH on nuclear targets, first of all, interphase chromosomes. FISH proper and image acquisition are considered as two related components of a single process. We discuss (1) M-FISH (combinatorial labeling + deconvolution + wide-field microscopy); (2) multicolor labeling + SIM (structured illumination microscopy); (3) the standard approach to multicolor FISH + CLSM (confocal laser scanning microscopy; one fluorochrome - one color channel); (4) combinatorial labeling + CLSM; (5) non-combinatorial labeling + CLSM + linear unmixing. Two related issues, deconvolution of images acquired with CLSM and correction of data for chromatic Z-shift, are also discussed. All methods are illustrated with practical examples. Finally, several rules of thumb helping to choose an optimal labeling + microscopy combination for the planned experiment are suggested.
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Núcleo Celular/ultraestructura , Hibridación Fluorescente in Situ/métodos , Interfase/genética , Núcleo Celular/genética , Pintura Cromosómica , Color , Humanos , Microscopía FluorescenteRESUMEN
BACKGROUND: Circulating interleukin (IL)-6 concentrations are associated with endothelial activation in rheumatoid arthritis (RA). OBJECTIVE: To assess endothelial activation before and after suppression of cytokine production in RA. METHODS: Twenty-one patients (mean (SD) age 59 (9) years; disease duration 6 (4) years) were treated with intraarticular methylprednisolone acetate (417 (152) mg) together with disease modifying agent (DMARD) initiation (n = 10) or intensification (n = 11) employing methotrexate (n = 11), leflunomide (n = 8), minocyclin (n = 6) and sulphasalazine (n = 1). Disease activity, circulating cytokines (IL-1, tumor necrosis factor alpha (TNF-alpha) and IL-6) and biomarkers of endothelial activation (circulating vascular adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1) and endothelial leukocyte adhesion molecule-1 (ELAM-1)) were evaluated before and 2 weeks after treatment. RESULTS: The intervention resulted in reductions in 8 disease activity markers (p < or = 0.002). Serum IL-6 concentrations decreased from 17 (2.9) to 4.9 (4.6) pg/ml (p = 0.0008). Serum IL-1 and TNF-alpha levels did not change (p > or = 0.4). Serum VCAM-1 concentrations decreased from 912 (402) to 752 (252) (p = 0.003), ICAM-1 from 398 (205) to 323 (179) (p = 0.04) and ELAM-1 from 68 (28) to 53 (25) (p = 0.02) pg/ml, respectively. Baseline rheumatoid factor titers were associated with reductions in VCAM-1 (r(s) = 0.481, p = 0.03). In multivariable regression models, decreases in circulating interleukin-6 concentrations were associated with reductions in VCAM-1 (p < 0.0001), ICAM-1 (p = 0.005) and ELAM-1 (p = 0.02) independent of changes in disease activity, weight and blood pressure. CONCLUSION: Our results suggest that suppression of circulating IL-6 concentrations attenuates atherogenesis in active RA.
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Artritis Reumatoide/sangre , Selectina E/sangre , Endotelio Vascular/metabolismo , Interleucina-6/sangre , Molécula 1 de Adhesión Celular Vascular/sangre , Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/fisiopatología , Quimioterapia Combinada , Femenino , Humanos , Inyecciones Intraarticulares , Interleucina-1/sangre , Isoxazoles/uso terapéutico , Leflunamida , Masculino , Metotrexato/uso terapéutico , Metilprednisolona/administración & dosificación , Metilprednisolona/uso terapéutico , Persona de Mediana Edad , Minociclina/uso terapéutico , Sulfasalazina/uso terapéutico , Factor de Necrosis Tumoral alfa/análisisRESUMEN
OBJECTIVE: To assess whether adrenocortical function was compromised in patients with active tuberculosis (TB) during the first 5 days of therapy with either a rifampicin-based or ciprofloxacin-based regimen. DESIGN: Patients were randomised into two groups of 10 each. Adrenocortical function was compared in both groups by the measurement of biochemical indices, electrolytes, osmolality and pituitary-adrenocortical hormones. Adrenal reserve was assessed by intravenous 250 mug adrenocorticotropin hormone (ACTH) stimulation tests. SETTING: Department of Medicine, Johannesburg Hospital. SUBJECTS: Twenty hospitalised patients who were diagnosed with TB. OUTCOME MEASURES: Respiratory rate, pulse rate and blood pressure were recorded, and urinary sodium and osmolality were measured. Serum ACTH, cortisol, dehydroepiandrosterone- sulphate (DHEA-S) and aldosterone were assayed. RESULTS: None of the patients demonstrated biochemical evidence of overt adrenal insufficiency. There were no significant differences between the two groups before or during therapy for any biochemical indices, electrolytes, hormones or calculated osmolality. Mean basal cortisol concentrations were substantially elevated and DHEA-S levels were consistently subnormal, resulting in a high cortisol/ DHEA-S ratio. In the ciprofloxacin group, cortisol responses to ACTH stimulation on day 1 were not significantly lower than on day 5. In the rifampicin group, cortisol concentrations decreased at each time point on day 5 compared with day 1 (p = 0.001). However, a significantly higher mean incremental rise from the basal cortisol concentration was measured on day 5 at 60 minutes (p = 0.04). In the entire cohort of 20 patients, 40% demonstrated an incremental cortisol rise of < 250 nmol/l after ACTH stimulation on day 1. CONCLUSIONS: Rifampicin did not additionally impair adrenocortical function during the initial period of therapy. The high cortisol/DHEA-S ratio might be of clinical relevance.
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Corteza Suprarrenal/metabolismo , Antibióticos Antituberculosos/uso terapéutico , Pacientes Internos , Rifampin/uso terapéutico , Tuberculosis Pulmonar/sangre , Corteza Suprarrenal/efectos de los fármacos , Hormona Adrenocorticotrópica/sangre , Adulto , Aldosterona/sangre , Biomarcadores/sangre , Ciprofloxacina/uso terapéutico , Sulfato de Deshidroepiandrosterona/sangre , Femenino , Estudios de Seguimiento , Humanos , Hidrocortisona/sangre , Inmunoensayo , Masculino , Proyectos Piloto , Estudios Prospectivos , Resultado del Tratamiento , Tuberculosis Pulmonar/tratamiento farmacológicoRESUMEN
The most common malignancy in men worldwide is cancer of the prostate. Androgens play a direct role in normal and malignant growth of prostate cells via the androgen receptor (AR). This study analyzed the polymorphic CAG repeat sequence in exon 1 of the AR gene to determine if the number of repeats might be an indicator of prostate cancer risk or aggressive disease. DNA was extracted from blood samples of 20 black and 20 white men with well-documented prostate cancer and 40 healthy controls (20 blacks and 20 whites). PCR amplification was followed by gel electrophoresis and DNA sequencing. This region normally contains between 9 and 29 repeats. Patients and controls both had minor variations in the number of repeats, which ranged from 13 to 27 with 21 being the most frequent allele. Black controls and patients both had a mean of 20 +/- 3 repeats; in whites the mean was significantly lower in patients than controls (21 +/- 2 versus 23 +/- 2; p = 0.004). Combined black and white patients also had a lower number than the combined group of controls (20 +/- 3 versus 22 +/- 3; p = 0.02). Similarly, black and white patients with aggressive disease had a lower number than patients whose disease was more slowly progressive (19 +/- 2 versus 22 +/- 3; p = 0.02). We conclude that the small differences in the number of CAG repeats in both black and white patients do not appear to be a strong indicator of risk or aggressive disease but that this size polymorphism may be one of many genetic and environmental risk factors involved in prostate cancer.
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Población Negra , Predisposición Genética a la Enfermedad , Neoplasias de la Próstata/genética , Receptores Androgénicos/genética , Secuencias Repetidas en Tándem , Población Blanca , ADN/sangre , Exones , Humanos , Masculino , Reacción en Cadena de la Polimerasa , Análisis de Secuencia de ADNRESUMEN
Congenital generalized lipodystrophy, or Berardinelli-Seip syndrome (BSCL), is a rare autosomal recessive disease characterized by a near-absence of adipose tissue from birth or early infancy and severe insulin resistance. Other clinical and biological features include acanthosis nigricans, hyperandrogenism, muscular hypertrophy, hepatomegaly, altered glucose tolerance or diabetes mellitus, and hypertriglyceridemia. A locus (BSCL1) has been mapped to 9q34 with evidence of heterogeneity. Here, we report a genome screen of nine BSCL families from two geographical clusters (in Lebanon and Norway). We identified a new disease locus, designated BSCL2, within the 2.5-Mb interval flanked by markers D11S4076 and D11S480 on chromosome 11q13. Analysis of 20 additional families of various ethnic origins led to the identification of 11 families in which the disease cosegregates with the 11q13 locus; the remaining families provide confirmation of linkage to 9q34. Sequence analysis of genes located in the 11q13 interval disclosed mutations in a gene homologous to the murine guanine nucleotide-binding protein (G protein), gamma3-linked gene (Gng3lg) in all BSCL2-linked families. BSCL2 is most highly expressed in brain and testis and encodes a protein (which we have called seipin) of unknown function. Most of the variants are null mutations and probably result in a severe disruption of the protein. These findings are of general importance for understanding the molecular mechanisms underlying regulation of body fat distribution and insulin resistance.
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Cromosomas Humanos Par 11/genética , Subunidades gamma de la Proteína de Unión al GTP , Lipodistrofia/congénito , Lipodistrofia/genética , Proteínas/genética , Acantosis Nigricans/complicaciones , Cromosomas Humanos Par 9/genética , Análisis por Conglomerados , Análisis Mutacional de ADN , Complicaciones de la Diabetes , Femenino , Genes Recesivos , Ligamiento Genético , Marcadores Genéticos , Pruebas Genéticas , Haplotipos , Hepatomegalia/complicaciones , Proteínas de Unión al GTP Heterotriméricas/genética , Humanos , Hiperandrogenismo/complicaciones , Hipertrigliceridemia/complicaciones , Resistencia a la Insulina/genética , Líbano/epidemiología , Lipodistrofia/complicaciones , Lipodistrofia/epidemiología , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Mutación , Noruega/epidemiología , Especificidad de Órganos , Linaje , Estructura Terciaria de Proteína , Proteínas/metabolismo , Homología de Secuencia de AminoácidoRESUMEN
Abnormalities observed in intermediary metabolism may be related to the pathogenesis of obesity-related diseases such as type 2 diabetes. Glycerol and lactate production was estimated in the sc adipose tissue of two anatomical regions of 10 lean (LW), 10 obese (OW), and 10 matched diabetic (DW) black urban women. This was done with the sc microdialysis technique and combined with adipose tissue blood flow (ATBF) rates calculated from (133)Xe clearance. Biochemical measurements were made in the postabsorptive and postprandial state. Bioimpedance and computed tomography scans were used to define body composition. DW present with more visceral fat (DW, 138 +/- 5.0; OW, 66.6 +/- 5.0 cm; P < 0.01). This was associated with elevated free testosterone levels (DW, 1.21 +/- 0.1; OW, 0.75 +/- 0.1 nmol/L; P < 0.05). The fasting FFA, glycerol, and lactate levels increased across the three groups (LW < OW < DW). During the oral glucose tolerance test, glucose levels were elevated in DW, with higher insulin levels [0 h: DW, 207 +/- 8.6; OW, 100 +/- 7.2 pmol/L (P < 0.01); 1 h: DW, 410 +/- 15.2; OW, 320 +/- 10.9 pmol/L (P < 0.05)], but with a flat Cpeptide response (1 h: DW, 932 +/- 40; OW, 1764 +/- 40 pmol/L; P < 0.05). Plasma lactate levels increased significantly in LW and OW at 1 h (P < 0.001), but remained lower in LW vs. OW for all time points. ATBF was highest in LW [abdominal, 0 h: DW, 4.5 +/- 0.2; OW, 1.7 mL/100 g.min (P < 0.01); femoral, 0 h: DW, 3.4 +/- 0.2; OW, 1.8 +/- 0.3 mL/100 g.min (P < 0.01)]. ATBF did not increase in DW during the oral glucose tolerance test. Glycerol release (GR) was used to assess the lipolytic rate and was highest in LW in the abdominal area [0 h: LW, 1.7 +/- 0.2; OW, 1.1 +/- 0.2 micromol/kg.min (P < 0.05); DW, 0.78 +/- 0.05 micromol/kg.min (P < 0.05 vs. OW)]. By contrast, GR was higher in the femoral area of OW (0 h: OW, 1.6 +/- 0.2; LW, 1.15 +/- 0.1 micromol/kg.min; P < 0.05). Regional differences were observed for GR in both OW and DW (femoral > abdominal). Lactate release (LR) was low in DW [abdominal, 0 h: DW, 3.5 +/- 0.4; OW, 7.8 +/- 1.0 micromol/kg.min (P < 0.001); femoral, 0 h: DW, 3.1 +/- 0.3; OW, 9.0 +/- 0.9 micromol/kg.min (P < 0.001)]. LR was appropriately low for body fat mass in LW, with a brisk increase between 0 and 1.5 h. A negative correlation exists between GR (abdominal area) and insulin levels in the postabsorptive state (P < 0.0001). In conclusion, 1) the fasting lipolytic rate is associated with insulin levels; 2) OW and DW have more adipose tissue insulin resistance than LW; 3) OW and DW have a brisker lipolysis in the femoral area; and 4) in DW, higher visceral mass is associated with elevated free testosterone and FFA concentrations. Obesity in the black population is therefore characterized by a marked degree of adipose tissue lipolysis. This degree of resistance together with increasing body fat mass may predispose the obese women to developing type 2 diabetes. Once this disease is established, the onset of adipose tissue vascular insulin resistance will sustain ongoing insulin resistance, even in the presence of relative insulinopenia.
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Tejido Adiposo/metabolismo , Diabetes Mellitus Tipo 2/fisiopatología , Diabetes Mellitus/fisiopatología , Glicerol/sangre , Ácido Láctico/sangre , Obesidad/fisiopatología , Tejido Adiposo/irrigación sanguínea , Adulto , Población Negra , Composición Corporal , Péptido C/sangre , Ácidos Grasos no Esterificados/sangre , Femenino , Alimentos , Prueba de Tolerancia a la Glucosa , Humanos , Sudáfrica , Testosterona/sangre , Población UrbanaRESUMEN
Hypothalamic-pituitary-adrenal underactivity has been reported in rheumatoid arthritis (RA). This phenomenon has implications with regard to the pathogenesis and treatment of the disease. The present study was designed to evaluate the secretion of the adrenal androgen dehydroepiandrosterone sulfate (DHEAS) and its relation to clinical variables in RA, spondyloarthropathy (Spa), and undifferentiated inflammatory arthritis (UIA). Eighty-seven patients (38 with RA, 29 with Spa, and 20 with UIA) were studied, of whom 54 were women. Only 12 patients (14%) had taken glucocorticoids previously. Age-matched, healthy women (134) and men (149) served as controls. Fasting blood samples were taken for determination of the erythrocyte sedimentation rate (ESR), serum DHEAS and insulin, and plasma glucose. Insulin resistance was estimated by the homeostasis-model assessment (HOMAIR). DHEAS concentrations were significantly decreased in both women and men with inflammatory arthritis (IA) (P < 0.001). In 24 patients (28%), DHEAS levels were below the lower extreme ranges found for controls. Multiple intergroup comparisons revealed similarly decreased concentrations in each disease subset in both women and men. After the ESR, previous glucocorticoid usage, current treatment with nonsteroidal anti-inflammatory drugs, duration of disease and HOMAIR were controlled for, the differences in DHEAS levels between patients and controls were markedly attenuated in women (P = 0.050) and were no longer present in men (P = 0.133). We concluded that low DHEAS concentrations are commonly encountered in IA and, in women, this may not be fully explainable by disease-related parameters. The role of hypoadrenalism in the pathophysiology of IA deserves further elucidation. DHEA replacement may be indicated in many patients with IA, even in those not taking glucocorticoids.
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Glándulas Suprarrenales/metabolismo , Insuficiencia Suprarrenal/sangre , Artritis Reumatoide/sangre , Sulfato de Deshidroepiandrosterona/sangre , Espondilitis Anquilosante/sangre , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Glucemia/análisis , Sedimentación Sanguínea , Femenino , Humanos , Insulina/sangre , Resistencia a la Insulina/fisiología , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVE: The rate of glucose disposal was determined in 10 black and 10 white obese nondiabetic urban women from South Africa to assess insulin resistance. DESIGN AND METHODS: Euglycemic hyperinsulinemic clamp and body composition analysis. RESULTS: Age, body mass index (BMI), anthropometric measurements and body composition were similar in both groups of women. A five-level computed tomography (CT) scan showed a similar mean subcutaneous fat mass in both groups of women (black obese women 555 +/- 9.0 vs white obese women 532 +/- 6.0 cm2), but less visceral fat in black obese women (90 +/- 3.0 vs 121 +/- 3.1 cm2; P< 0.05). Black obese women had higher fasting free fatty acid (997 +/- 69 vs 678 +/- 93 micromol/l; P < 0.05) and lactate concentrations (1,462 +/- 94 vs 1,038 +/- 39 micromol/l; P < 0.05), but lower fasting insulin levels (87 +/- 12 vs 155 +/- 9 pmol/l; P < 0.001). Black obese women also had a more favorable HDL: total cholesterol ratio (30.5% vs 23.0%; P< 0.04). The mean glucose disposal rate (M) and disposal expressed as glucose sensitivity index (M/I) were reduced in the black obese women vs white obese women (M: 7.1 +/- 0.8 vs 13.7 +/- 1.0 mmol/kg min(-1) x 100; P< 0.01, and M/I: 0.12 +/- 0.01 vs 0.24 +/- 0.02 mmol/kg x min(-1)/pmol/1 x 1,000; P < 0.01). Only black obese women showed a significant decrease in C-peptide levels during the clamp (2.9 +/- 0.22 vs 1.2 +/- 0.12 nmol/l; P<0.001). During the euglycemic period, the black obese women had higher lactate levels at all time points, but only the white obese women had increased lactate levels (918 +/- 66 to 1,300 +/- 53 micromol/l; P< 0.05). CONCLUSION: Black obese women demonstrate a higher degree of insulin resistance, despite less visceral fat and a higher HDL: total-cholesterol ratio. In addition, endogenous beta-cell secretory function in black obese women appears to be more sensitive to the suppressive effect of exogenous insulin administration. The significant increase in lactate levels in white obese women confirms that they are more insulin sensitive.
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Negro o Afroamericano/estadística & datos numéricos , Glucemia/metabolismo , Composición Corporal , Resistencia a la Insulina , Lípidos/sangre , Obesidad/metabolismo , Adulto , Población Negra , Índice de Masa Corporal , Péptido C/sangre , Femenino , Técnica de Clampeo de la Glucosa , Humanos , Insulina/sangre , Lactatos/sangre , Obesidad/etnología , Prevalencia , Sudáfrica/epidemiología , Población Blanca/estadística & datos numéricosRESUMEN
AIMS: This study investigated the association between glutamic acid decarboxylase antibodies (GAD-AB) and Type 1, Type 2, pancreatic and lipoatrophic diabetes mellitus (DM) in South African patients. METHODS: Four groups were selected: group A, 100 Black Type 1 DM patients (age at onset < 35 years, body mass index (BMI) < 27 kg/m2 and insulin dependent within 1 year of presentation); group B, 80 Black Type 2 DM patients (age at onset > 35 years, BMI > 27 kg/m2 and controlled on oral hypoglycaemic agents for at least 1 year after presentation); group C, 10 patients of varying ethnicity with DM or impaired glucose tolerance secondary to chronic pancreatitis; group D, five patients of varying ethnicity with DM associated with total lipodystrophy. Fifty healthy Black control subjects were also studied (group E). Serum GAD-AB and random C-peptide levels were measured by radioimmunoassay. RESULTS: Mean C-peptide concentration was significantly lower in Type 1 DM patients than Type 2 DM patients (P < 0.00001). Forty-four patients with Type 1 DM were GAD-AB-positive compared to two patients with Type 2 DM. Two control subjects were also GAD-AB-positive. No patient in the other groups had a titre > 1 U/ml. Type 1 DM patients who were GAD-AB-positive did not differ from those who were GAD-AB-negative for age at onset, duration of DM or C-peptide concentrations. CONCLUSIONS: Auto-immune beta-cell destruction has an important role in the pathogenesis of Type 1 DM amongst African patients. However, Type 2 African DM patients and other diabetes subtypes are largely GAD-AB-negative.
Asunto(s)
Autoanticuerpos/inmunología , Diabetes Mellitus/inmunología , Glutamato Descarboxilasa/inmunología , Adulto , Población Negra , Péptido C/sangre , Diabetes Mellitus/sangre , Diabetes Mellitus/clasificación , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 1/inmunología , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/inmunología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedades Pancreáticas/sangre , Enfermedades Pancreáticas/inmunología , Radioinmunoensayo , SudáfricaRESUMEN
BACKGROUND: Intestinal intussusception is a rare event during pregnancy. The diagnosis of intestinal obstruction from any cause in pregnancy is made more difficult by the common overlapping complaints of nausea, vomiting and abdominal pain, which may persist during the second trimester. CASE: Intestinal obstruction occurred at 17 weeks' gestation. A preoperative diagnosis of intussusception was made by ultrasound by demonstrating multiple ecodense and ecolucent rings in the right lower quadrant of the abdomen. CONCLUSION: Ultrasonography may support the diagnosis of intussusception in pregnant women with intestinal obstruction.
Asunto(s)
Dolor Abdominal/etiología , Válvula Ileocecal , Intususcepción/diagnóstico , Complicaciones del Embarazo/diagnóstico , Atención Prenatal , Adulto , Diagnóstico Diferencial , Femenino , Humanos , Enfermedades del Íleon/diagnóstico , Intususcepción/complicaciones , Intususcepción/diagnóstico por imagen , Intususcepción/cirugía , Embarazo , Complicaciones del Embarazo/diagnóstico por imagen , Complicaciones del Embarazo/cirugía , Segundo Trimestre del Embarazo , Cuidados Preoperatorios , Ultrasonografía PrenatalRESUMEN
OBJECTIVES: Insulin resistance (IR) has been increasingly implicated in the pathogenesis of gout. The lipoprotein abnormalities described in hyperuricaemic subjects are similar to those associated with IR, and insulin influences renal urate excretion. In this study it was investigated whether dietary measures, reported to be beneficial in IR, have serum uric acid (SU) and lipid lowering effects in gout. METHODS: Thirteen non-diabetic men (median age 50, range 38-62) were enrolled. Each patient had had at least two gouty attacks during the four months before enrollment. Dietary recommendations consisted of calorie restriction to 6690 kJ (1600 kcal) a day with 40% derived from carbohydrate, 30% from protein, and 30% from fat; replacement of refined carbohydrates with complex ones and saturated fats with mono- and polyunsaturated ones. At onset and after 16 weeks, fasting blood samples were taken for determination of SU, serum cholesterol (C), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), and triglycerides (TGs). Results were expressed as median (SD). RESULTS: At onset, the body mass index (BMI) was 30.5 (8.1) kg/m(2). Dietary measures resulted in weight loss of 7.7 (5.4) kg (p=0.002) and a decrease in the frequency of monthly attacks from 2.1 (0.8) to 0.6 (0.7) (p=0.002). The SU decreased from 0.57 (0.10) to 0.47 (0.09) mmol/l (p=0.001) and normalised in 7 (58%) of the 12 patients with an initially raised level. Serum cholesterol decreased from 6.0 (1.7) to 4.7 (0. 9) mmol/l (p=0.002), LDL-C from 3.5 (1.2) to 2.7 (0.8) mmol/l (p=0. 004), TGs from 4.7 (4.2) to 1.9 (1.0) mmol/l (p=0.001), and C:HDL-C ratios from 6.7 (1.7) to 5.2 (1.0) (p=0.002). HDL-C levels increased insignificantly. High baseline SU, frequency of attacks, total cholesterol, LDL-C and TG levels, and total C:HDL-C ratios correlated with higher decreases in the respective variables upon dietary intervention (p<0.05). CONCLUSION: The results suggest that weight reduction associated with a change in proportional macronutrient intake, as recently recommended in IR, is beneficial, reducing the SU levels and dyslipidaemia in gout. Current dietary recommendations for gout may need re-evaluation.
Asunto(s)
Grasas Insaturadas en la Dieta/administración & dosificación , Proteínas en la Dieta/administración & dosificación , Gota/sangre , Gota/dietoterapia , Lipoproteínas/sangre , Ácido Úrico/sangre , Pérdida de Peso , Adulto , Índice de Masa Corporal , Dieta Reductora , Estudios de Seguimiento , Humanos , Resistencia a la Insulina , Lipoproteínas/efectos de los fármacos , Masculino , Persona de Mediana Edad , Obesidad/dietoterapia , Proyectos Piloto , SíndromeRESUMEN
Elevated serum concentrations of endothelium-associated adhesion molecules occur in Graves' disease. However, no data exist in African subjects, among whom the incidence is rising. Therefore, 20 black South Africans with Graves' hyperthyroidism were evaluated and 10 healthy controls were also studied. Quantitative determinations of soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), and soluble E-Selectin (sE-Selectin) were performed in serum samples by an enzyme-linked immunosorbent assay. Mean levels of sVCAM-1 were significantly increased in the thyrotoxic patients compared to controls, but this did not apply to the other adhesion molecules. The presence of ophthalmopathy in 12 patients did not further increase the mean sVCAM-1 concentration, and the administration of antithyroid medication in 5 patients had no measurable effect. In conclusion, sVCAM-1 appears to be a useful marker of active Graves' disease in black South Africans although it does not seem to reflect the occurrence of eye involvement in such patients.