Prediction of coronary heart disease risk in HIV-infected patients with fat redistribution.
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A metabolic syndrome has been described among human immunodeficiency virus (HIV)-infected patients receiving highly active antiretroviral therapy; the syndrome is characterized by fat redistribution, insulin resistance, and dyslipidemia. We compared the 10-year coronary heart disease (CHD) risk estimates for 91 HIV-infected men and women with fat redistribution with the risk estimates for 273 age-, sex-, and body mass index (BMI)-matched subjects enrolled in the Framingham Offspring Study. Thirty HIV-infected patients without fat redistribution were also compared with 90 age- and BMI-matched control subjects. The 10-year CHD risk estimate was significantly elevated among HIV-infected patients with fat redistribution, particularly among men; however, when they were matched with control subjects by waist-to-hip ratio, the 10-year CHD risk estimate did not significantly differ between groups. HIV-infected patients without fat redistribution did not have a greater CHD risk estimate than did control subjects. In addition, the CHD risk estimate was greatest in HIV-infected patients who had primary lipoatrophy, compared with those who had either lipohypertrophy or mixed fat redistribution. Therefore, although CHD risk is increased in HIV-infected patients with fat redistribution, the pattern of fat distribution and sex are potential important components in determining the risk in this population. (+info)
Adult constipation: a review and clinical guide.
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Constipation is a common complaint that can be a symptom of serious disease. Awareness of the potential etiologies can help direct the history, physical exam and subsequent work-up for the presenting individual. This article details the differential diagnosis and pathophysiology of constipation based on a review of the literature. The article is also designed to be useful as a guide to the work-up of constipation. Key elements of the history, physical exam and testing are outlined. Included is a detailed flow diagram to guide the work-up of constipation. Testing methods and their value in the evaluation of chronic idiopathic constipation are discussed. Finally, although the focus of this article is the evaluation of constipation, a section on the treatment of constipation is included. (+info)
Disorders of cholesterol biosynthesis: prototypic metabolic malformation syndromes.
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Since 1998, five disorders involving enzyme defects in post-squalene cholesterol biosynthesis have been identified-desmosterolosis, X-linked dominant chondrodysplasia punctata, CHILD syndrome, lathosterolosis, and hydrops-ectopic calcification-moth-eaten skeletal dysplasia. They join the most common cholesterol biosynthetic disorder, Smith-Lemli-Opitz syndrome, whose underlying defect was identified in 1993. All are associated with major developmental malformations that are unusual for metabolic disorders. The existence of mouse models for five of these disorders is beginning to enable more detailed developmental and in vitro studies examining the mechanisms involved in disease pathogenesis. In this review, an overview of the cholesterol biosynthetic pathway will be presented. Clinical features of the human disorders and mouse models of post-squalene cholesterol biosynthesis will then be discussed. (+info)
Basal and dynamic proinsulin-insulin relationship to assess beta-cell function during OGTT in metabolic disorders.
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The fasting proinsulin-to-insulin ratio is a currently used marker of beta-cell dysfunction. This ratio is calculated at the basal condition, but its behavior in dynamic conditions, i.e., during glucose stimulation, could be more informative. Given the different kinetics of the peptides, a mathematical model was necessary to analyze the oral glucose tolerance test (OGTT) data of insulin, C-peptide, and proinsulin in 55 healthy (NGT), 30 impaired glucose-tolerant (IGT), and 31 type 2 diabetic (T2DM) subjects. The model provided for secretion and disappearance of the peptides and an index of beta-cell function under dynamic conditions. Total proinsulin secretion during the OGTT was not different (P > 0.053) among NGT (0.17 +/- 0.01 mmol/l in 3 h), IGT (0.22 +/- 0.02), and T2DM (0.21 +/- 0.02) subjects. The proinsulin-to-insulin molar ratio measured from basal samples was higher (P < 0.0001) in T2DM (0.39 +/- 0.05) than in NGT (0.14 +/- 0.01) and IGT (0.13 +/- 0.02) subjects, and similar results (P < 0.003) were found by the dynamic index (0.27 +/- 0.04, 0.14 +/- 0.01, 0.15 +/- 0.01 in T2DM, NGT, IGT subjects, respectively). The basal ratio significantly correlated with the dynamic index, and the regression line slope was lower than 1 (0.43 +/- 0.08, 0.61 +/- 0.10, and 0.56 +/- 0.03 in NGT, IGT, and T2DM subjects, respectively, P < 0.0001). Impaired beta-cell function in T2DM could then be indicated by proinsulin-to-insulin indexes at both basal and dynamic phases. (+info)
Disease-related metabolites in culture medium of fibroblasts from patients with D-2-hydroxyglutaric aciduria, L-2-hydroxyglutaric aciduria, and combined D/L-2-hydroxyglutaric aciduria.
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BACKGROUND: D-2-Hydroxyglutaric aciduria (D-2-HGA), L-2-hydroxyglutaric aciduria (L-2-HGA), and the combined D/L-2-hydroxyglutaric aciduria (D/L-2-HGA) are poorly understood organic acidurias. To investigate the usefulness of cultured human skin fibroblasts for both diagnostic and research purposes, we measured disease-related metabolites in the cell culture medium. METHODS: We measured D-2-hydroxyglutarate (D-2-HG), L-2-hydroxyglutarate (L-2-HG), succinate, 2-ketoglutarate, and citrate in fibroblast cell medium by stable-isotope-dilution gas chromatography-mass spectrometry and glutamine, glutamic acid, and lysine with an amino acid analyzer. We used six cell lines from patients with D-2-HGA, two from patients with L-2-HGA, three from patients with D/L-2-HGA, and seven control cell lines. Culture medium was analyzed after a 96-h incubation period. RESULTS: Culture media from cell lines from D-2-HGA patients contained D-2-HG at concentrations 5- to 30-fold higher than media from controls, whereas the concentration of L-2-HG in media was not increased. Media from L-2-HGA cell lines showed a fivefold increase in L-2-HG compared with controls. Media containing fibroblasts from D/L-2-HGA patients contained moderately increased amounts of both D-2-HG and L-2-HG. For all cell lines, succinate concentrations in the blank medium were higher than after 96 h of incubation with the exception of two of three D/L-2-HGA cell lines. Media of D-2-HGA cell lines had 2-ketoglutarate concentrations that were 40% of that for controls. Glutamic acid concentrations in media of these cell lines were 60% lower than in controls. CONCLUSIONS: Cell culture media from fibroblasts from patients with D-2-HGA, L-2-HGA, or D/L-2-HGA contain increased amounts the corresponding 2-HGs, demonstrating the suitability of fibroblasts for both diagnosis of and research concerning 2-HGAs. (+info)
Age-related contribution of Lp(a) with coronary artery calcification in patients with acute coronary syndrome: a potential role of metabolic disorder in calcified plaque.
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Lp(a) and coronary artery calcification (CAC) have recently been reported as predictors of plaque instability, but this is surrounded by much controversy. We investigated the influence of Lp(a) and CAC compared other acute coronary syndrome (ACS) risk factors. 698 patients diagnosed with at least minimal coronary artery obstructive disease from a coronary angiography were randomly selected using SPSS. Lp(a), other lipid profiles and past histories were checked, and CAC semi quantitatively graded on stored fluoroscopic images. The prevalence of CAC was significantly higher in the ACS than the non-ACS group (38.0% vs. 29.9%, p=0.026). The serum level of Lp(a) (26.89 +/- 30.64 vs. 20.85 +/- 21.63, p < 0.01) and prevalence of positive Lp(a) (> 35 mg/dl) was higher in the ACS group (24% vs. 15.7%, p < 0.01). The risk of ACS was higher in the patients with both CAC and elevated an Lp(a) than in those with only one (OR: 2.16, p=0.009, 95% CI; 1.213 - 3.843 vs. OR: 1.79, p < 0.001, 95% CI; 1.300 - 2.456). The risk of ACS was increased 1.451 times (p=0.040, 95% CI; 1.071- 2.071) in patients with CAC and 1.648 times (p=0.014, 95% CI; 1.107- 2.455) in patients with a Lp(a) > 35 mg/dl. In the younger patients (< 60 years), the Lp(a), but not the CAC, was an independent risk factor for ACS (OR=2.248, p=0.005, 95% CI; 1.281-3.943). In the older patients (> 60 years), CAC, but not the Lp(a), was an independent risk factor (OR=1.775, p=0.021, 95% CI; 1.090 - 2.890). Both the Lp(a) and CAC were risk factors for ACS, and they had a synergistic effect on its development. In the younger Lp(a), and the older CAC, was the more potent risk factor for ACS, respectively. (+info)
Contribution of selected metabolic diseases to early childhood deaths--Virginia, 1996-2001.
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Sudden infant death syndrome (SIDS), or the death of an infant aged <1 year that remains unexplained after a thorough investigation, is the third most common cause of death among infants in the United States. Sudden, unexplained deaths also occur among children aged >/=1 year; however, the number of these deaths is not well documented. Certain cases of SIDS and sudden unexplained death beyond infancy might be attributable to complications of unrecognized metabolic diseases. Tandem mass spectrometry (tandem MS) can be used to screen for several of these disorders. Despite the low prevalence of these diseases, newborn screening for these disorders has been found to compare favorably with the cost of other screening programs. However, the contribution of these diseases to early childhood deaths is not well understood. To determine the proportion of sudden, unexpected early childhood deaths associated with selected metabolic diseases, CDC, the Office of the Chief Medical Examiner (ME) in Virginia, and a private laboratory conducted a population- based study. This report summarizes the results of the study, which indicate that 1% of children had a positive postmortem metabolic screen using tandem MS. Of the eight children with positive screening tests, seven might have had improved outcomes had they been identified and treated during the newborn period. The use of tandem MS in newborn screening programs could offer an opportunity to prevent early childhood mortality. (+info)
Tumoral calcium pyrophosphate dihydrate deposition disease. Report of a case with a review of the literature.
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In a 56-year-old female patient with a mass at the proximal end of the left third finger for 22 years, the lesion enlarged obviously during the last 4 years. Initial diagnosis was chondroma with malignant change, and disarticulation of the finger was performed. Pathological diagnosis was "secondary chondrosarcoma". Microscopically, the mass contained a large amount of amorphous basophilic phosphate deposits surrounded by fibrous capsule. The pyrophosphate deposits consisted of birefringent needle shaped or rhomboid crystals which can be identified by polarizing microscope. It can be distinguished as tumoral calcium pyrophosphate dihydrate deposition disease, differing from tophaceous pseudogout, tumoral calcinosis and chondrocalcinosis. Nine cases were collected from the literature and the clinical, radiological and pathological features were discussed. (+info)