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1.
J Interv Card Electrophysiol ; 65(2): 491-497, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35748975

RESUMO

BACKGROUND: High-power short-duration (HPSD) radiofrequency ablation (RFA) is highly efficient and safe while reducing procedure and RF time in pulmonary vein isolation (PVI). The QDot™ catheter is a novel contact force ablation catheter that allows automated flow and power adjustments depending on the local tissue temperature to maintain a target temperature during 90 W/4 s lesions. We analysed intraprocedural data and periprocedural safety using the QDot-catheter in patients undergoing PVI for paroxysmal atrial fibrillation (PAF). METHODS: We included n = 48 patients undergoing PVI with the QDot-catheter with a temperature-controlled HPSD ablation mode with 90 W/4 s (TC-HPSD). If focal reconnection occurred besides repeat ablation, the ablation mode was changed to 50 W/15 s (QMode). N = 23 patients underwent cerebral MRI to detect silent cerebral lesions. RESULTS: Mean RF time was 8.1 ± 2.8 min, and procedure duration was 84.5 ± 30 min. The overall maximal measured catheter tip temperature was 52.0 °C ± 4.6 °C, mean overall applied current was 871 mA ± 44 mA and overall applied energy was 316 J ± 47 J. The mean local impedance drop was 12.1 ± 2.4 Ohms. During adenosine challenge, n = 14 (29%) patients showed dormant conduction. A total of n = 24 steam pops were detected in n = 18 patients (39.1%), while no pericardial tamponade occurred. No periprocedural thromboembolic complications occurred, while n = 4 patients (17.4%) showed silent cerebral lesion. CONCLUSIONS: TC-HPSD ablation with 90 W/4 s using the QDot-catheter led to a reduction of procedure and RF time, while no major complications occurred. Despite optimized temperature control and power adjustment, steam pops occurred in a rather high number of patients, while none of them leads to tamponade or to clinical or neurological deficits.


Assuntos
Fibrilação Atrial , Ablação por Cateter , Veias Pulmonares , Humanos , Veias Pulmonares/diagnóstico por imagem , Veias Pulmonares/cirurgia , Temperatura , Vapor , Desenho de Equipamento , Ablação por Cateter/métodos , Fibrilação Atrial/diagnóstico por imagem , Fibrilação Atrial/cirurgia , Fibrilação Atrial/etiologia , Imageamento por Ressonância Magnética , Resultado do Tratamento
2.
Oncoimmunology ; 7(5): e1423170, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29721376

RESUMO

Tumor cells, which undergo Epithelial-mesenchymal transition (EMT) acquire increased capacities of proliferation, invasion and have the ability to generate metastases by escaping the immune system during their systemic migration. To escape the immune system, cancer cells may induce tolerance or resist elimination by immune effectors via multiple mechanisms and we hypothesized that EMT may control the expression of immune checkpoint inhibitors, then promoting immune evasion. PD-L1 (programmed cell death ligand 1) but not PD-L2 nor Galectin 9 or Death receptor (DR4, DR5 and Fas) and ligands (FasL and TRAIL) expression was up-regulated during cytokine-driven EMT in a reversible manner. Moreover PD-L1 is overexpressed in VIMENTIN positive NSCLC tissues. We also demonstrated that the expression of PD-L1 required both TNFα and TGFß1. Indeed, TGFß1 decreased DNMT1 content and that resulted in PD-L1 promoter demethylation whereas TNFα induced the NF-κB pathway that promoted expression of demethylated PD-L1 promoter.

3.
Oncogene ; 36(34): 4859-4874, 2017 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-28414307

RESUMO

The US FDA approval of broad-spectrum histone deacetylase (HDAC) inhibitors has firmly laid the cancer community to explore HDAC inhibition as a therapeutic approach for cancer treatment. Hitting one HDAC member could yield clinical benefit but this required a complete understanding of the functions of the different HDAC members. Here we explored the consequences of specific HDAC5 inhibition in cancer cells. We demonstrated that HDAC5 inhibition induces an iron-dependent reactive oxygen species (ROS) production, ultimately leading to apoptotic cell death as well as mechanisms of mitochondria quality control (mitophagy and mitobiogenesis). Interestingly, adaptation of HDAC5-depleted cells to oxidative stress passes through reprogramming of metabolic pathways towards glucose and glutamine. Therefore, interference with both glucose and glutamine supply in HDAC5-inhibited cancer cells significantly increases apoptotic cell death and reduces tumour growth in vivo; providing insight into a valuable clinical strategy combining the selective inhibition of HDAC5 with various inhibitors of metabolism as a new therapy to kill cancer cells.


Assuntos
Antineoplásicos/farmacologia , Inibidores de Histona Desacetilases/farmacologia , Histona Desacetilases/metabolismo , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Glucose/metabolismo , Glutamina/metabolismo , Humanos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo
4.
Ann Clin Biochem ; 53(Pt 1): 58-66, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25766385

RESUMO

BACKGROUND: We evaluated the accuracy and precision of creatinine- and cystatin C-based prediction equations for estimating glomerular filtration rate compared to measured glomerular filtration rate in an antiretroviral-naive human immunodeficiency virus population. METHODS: The study population consisted of 100 treatment-naive HIV patients. Glomerular filtration rate was estimated using the Cockcroft-Gault, Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations, as well as cystatin C-based equations (CKD-EPIcystatin C, cystatin Cvan Deventer and CKD-EPIcombined)) compared to (51)Cr-EDTA plasma clearance-measured glomerular filtration rate. We calculated percentage bias, standard deviation of the differences, accuracy within 15 and 30% of measured glomerular filtration rate and sensitivity and specificity for predicting measured glomerular filtration rate <60 mL/min/1.73 m(2). RESULTS: Bias for all estimating glomerular filtration rate equations ranged from -9.4% to 38.4%. The CKD-EPIcombined without ethnicity correction factor equation had the least bias, 2.9% (-2.9 to 8.8). Bias was higher for the Modification of Diet in Renal Disease and CKD-EPI equation with the African-American ethnicity factor (38.4 and 33.7%) than without (14.2 and 15.3%). Standard deviation of the differences ranged from 29.2% (CKD-EPIcombined without ethnicity factor) to 54.0% (Modification of Diet in Renal Disease with ethnicity factor). Accuracy within 30% of measured glomerular filtration rate ranged from 78% for CKD-EPIcombined without ethnicity factor to 56.7% for the Cockcroft-Gault equation. Sensitivity for creatinine-based equations was less than 50% and for the CKD-EPIcystatin C equation was 75%. CONCLUSION: Sensitivity of creatinine-based equations for predicting glomerular filtration rate was poor in this group of patients. The CKD-EPIcombined equation performed better than creatinine-based equations.


Assuntos
Terapia Antirretroviral de Alta Atividade , Creatinina/sangue , Cistatina C/sangue , Infecções por HIV/sangue , Infecções por HIV/fisiopatologia , Testes de Função Renal/métodos , Adulto , Estudos Transversais , Feminino , Taxa de Filtração Glomerular , Infecções por HIV/tratamento farmacológico , Humanos , Testes de Função Renal/normas , Masculino , Padrões de Referência
5.
Br J Nutr ; 112(4): 590-9, 2014 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-24877635

RESUMO

Vitamin D deficiency has been implicated in the aetiology of infectious diseases and metabolic syndrome. These diseases are prevalent in the African and Asian-Indian populations of South Africa; however, there is limited data on 25-hydroxyvitamin D (25(OH)D) concentrations in these populations. The aim of the present study was to assess the vitamin D status and its predictors in healthy adults in Johannesburg. We assessed the vitamin D status of 730 adult African and Asian-Indian subjects residing in Johannesburg. The contributions of sun exposure, season, dietary intake of Ca and vitamin D, total body fat and body fat distribution to 25(OH)D concentrations were assessed. The concentrations of 25(OH)D were measured by HPLC. The contribution of 25(OH)D3 to total 25(OH)D concentrations was assessed. The mean age of the subjects was 42·6 (SD 13·1) years (range: 18-65). Concentrations of 25(OH)D < 30 nmol/l were found in 28·6 % of the Asian-Indian subjects in comparison with 5·1 % of the African subjects (P< 0·0001). Parathyroid hormone (PTH) concentrations were negatively associated with 25(OH)D concentrations, while season and sun exposure were positive predictors explaining 16 % of the variance in 25(OH)D concentrations (P< 0·0001) in the African subjects. In the Asian-Indian subjects, PTH concentrations were negatively associated with 25(OH)D concentrations, while male sex, season and Ca supplementation were positive predictors and explained 17 % of the variance in 25(OH)D concentrations (P< 0·0001). In the multivariate regression analysis, neither total body fat nor body fat distribution was predictive of 25(OH)D concentrations in either group. In conclusion, factors such as sun exposure, dietary supplement use and ethnicity are important determinants of plasma 25(OH)D concentrations.


Assuntos
Adiposidade , Cálcio da Dieta/uso terapêutico , Suplementos Nutricionais , Pele/efeitos da radiação , Luz Solar , Deficiência de Vitamina D/prevenção & controle , Vitamina D/uso terapêutico , 25-Hidroxivitamina D 2/sangue , Adulto , Calcifediol/sangue , Cálcio da Dieta/administração & dosagem , Estudos de Coortes , Estudos Transversais , Dieta/efeitos adversos , Dieta/etnologia , Feminino , Humanos , Índia/etnologia , Masculino , Prevalência , Estações do Ano , Caracteres Sexuais , África do Sul/epidemiologia , Saúde da População Urbana/etnologia , Vitamina D/administração & dosagem , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/epidemiologia , Deficiência de Vitamina D/etnologia
6.
Adv Clin Chem ; 61: 127-52, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24015601

RESUMO

This review discusses the state-of-the-art measurement of free and total thyroid hormones in clinical laboratories. We highlight some of the limitations of currently used immunoassays and critically discuss physical separation methods for the measurement of free thyroid hormone. Physical separation methods, such as equilibrium dialysis or ultrafiltration, followed by tandem mass spectrometry for the measurement of free thyroid hormones offer many advantages, which we feel, can deepen our understanding of thyroid hormone metabolism and improve patient diagnosis and care. Problems with direct analogue immunoassay methods for FT4/FT3 as well as immunoassay methods for total T3 at low T3 concentrations and during pregnancy are highlighted. Improved diagnosis and patient management can be achieved utilizing tandem mass spectrometry for these measurements.


Assuntos
Espectrometria de Massas em Tandem/métodos , Doenças da Glândula Tireoide/diagnóstico , Glândula Tireoide/metabolismo , Hormônios Tireóideos , Animais , Diálise/métodos , Feminino , Humanos , Imunoensaio/métodos , Imunoensaio/normas , Gravidez , Espectrometria de Massas em Tandem/normas , Doenças da Glândula Tireoide/sangue , Testes de Função Tireóidea/métodos , Testes de Função Tireóidea/normas , Glândula Tireoide/fisiopatologia , Hormônios Tireóideos/sangue , Ultrafiltração/métodos
8.
Clin Chim Acta ; 423: 135-40, 2013 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-23628525

RESUMO

BACKGROUND: Low-density lipoprotein cholesterol (LDL-C) is often calculated (cLDL-C) by the Friedewald equation, which requires high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG). Because there have been considerable changes in the measurement of HDL-C with the introduction of direct assays, several alternative equations have recently been proposed. METHODS: We compared 4 equations (Friedewald, Vujovic, Chen, and Anandaraja) for cLDL-C, using 8 different direct HDL-C (dHDL-C) methods. LDL-C values were calculated by the 4 equations and determined by the ß quantification reference method procedure in 164 subjects. RESULTS: For normotriglyceridemic samples (TG<200mg/dl), between 6.2% and 24.8% of all results exceeded the total error goal of 12% for LDL-C, depending on the dHDL-C assay and cLDL-C equation used. Friedewald equation was found to be the optimum equation for most but not all dHDL-C assays, typically leading to less than 10% misclassification of cardiovascular risk based on LDL-C. Hypertriglyceridemic samples (>200mg/dl) showed a large cardiovascular risk misclassification rate (30%-50%) for all combinations of dHDL-C assays and cLDL-C equations. CONCLUSION: The Friedewald equation showed the best performance for estimating LDL-C, but its accuracy varied considerably depending on the specific dHDL-C assay used. None of the cLDL-C equations performed adequately for hypertriglyceridemic samples.


Assuntos
Algoritmos , Bioensaio/normas , Análise Química do Sangue/métodos , Análise Química do Sangue/normas , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/diagnóstico , Humanos
9.
Clin Chim Acta ; 418: 97-101, 2013 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-23328210

RESUMO

BACKGROUND: Abnormal gastrointestinal permeability has been linked to irritable bowel syndrome (IBS). The lactulose-to-mannitol ratio is traditionally used to assess small intestine permeability while sucralose and sucrose are used to assess colonic and gastric permeability respectively. We used a single 4-probe test solution to assess permeability throughout the gastrointestinal tract in IBS patients and healthy controls by measuring the recovery of the probes in urine after ingestion using a modified liquid chromatography mass spectrometry protocol. METHODS: Fasting participants (N=59) drank a permeability test solution (100ml: sucralose, sucrose, mannitol, and lactulose). Urine was collected over a 5-h period and kept frozen until analysis. Urinary sugar concentrations were measured using a liquid chromatography/triple quadruple mass spectrometer. RESULTS: Colonic permeability was significantly lower in IBS patients when compared to healthy controls (p=0.011). Gastric and small intestinal permeability did not significantly differ between the groups. CONCLUSIONS: The study demonstrates the clinical potential of this non-invasive method for assessing alterations in gastrointestinal permeability in patients with IBS.


Assuntos
Trato Gastrointestinal/metabolismo , Síndrome do Intestino Irritável/complicações , Lactulose/urina , Manitol/urina , Sacarose/análogos & derivados , Sacarose/urina , Adulto , Feminino , Trato Gastrointestinal/patologia , Humanos , Síndrome do Intestino Irritável/metabolismo , Síndrome do Intestino Irritável/patologia , Masculino , Permeabilidade , Soluções
10.
Am J Physiol Heart Circ Physiol ; 302(1): H38-50, 2012 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-22021327

RESUMO

The hallmarks of the normal heartbeat are both rapid onset of contraction and rapid relaxation as well as an inotropic response to both increased end-diastolic volume and increased heart rate. At the microscopic level, Ca(2+) plays a crucial role in normal cardiac contraction. This paper reviews the cycle of Ca(2+) fluxes during the normal heartbeat, which underlie the coupling between excitation and contraction and permit a highly synchronized action of cardiac sarcomeres. Length dependence of the response of the regulatory sarcomeric proteins mediates the Frank-Starling Law of the heart. However, Ca(2+) transport may go astray in heart disease such as in congestive heart failure, and both jeopardize systole and diastole and triggering arrhythmias. The interaction between weak and strong segments in nonuniform cardiac muscle allows partial preservation of force of contraction but may further lead to mechanoelectric feedback or reverse excitation-contraction coupling mediating an early diastolic Ca(2+) transient caused by the rapid force decrease during the relaxation phase. These rapid force changes in nonuniform muscle may cause arrhythmogenic Ca(2+) waves to propagate by the activation of neighboring sarcoplasmic reticulum by diffusing Ca(2+) ions.


Assuntos
Cálcio/metabolismo , Acoplamento Excitação-Contração , Cardiopatias/metabolismo , Proteínas Musculares/metabolismo , Contração Miocárdica , Miocárdio/metabolismo , Sarcômeros/metabolismo , Animais , Cardiopatias/fisiopatologia , Frequência Cardíaca , Humanos
11.
Circulation ; 124(20): 2202-7, 2011 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-21986285

RESUMO

BACKGROUND: Homozygous familial hypercholesterolemia is an inherited disorder caused by mutations in both low-density lipoprotein receptor alleles, which results in extremely elevated plasma low-density lipoprotein cholesterol concentrations and very early morbidity and mortality due to cardiovascular disease. METHODS AND RESULTS: To evaluate the impact of advances in lipid-lowering (predominantly statin) therapy on cardiovascular disease morbidity and mortality in a large cohort of patients with homozygous familial hypercholesterolemia, the records of 149 patients (81 females, 68 males) from 2 specialized lipid clinics in South Africa were evaluated retrospectively. Homozygous familial hypercholesterolemia was diagnosed by confirmation of mutations in genes affecting low-density lipoprotein cholesterol or by clinical criteria. A Cox proportional hazard model with time-varying exposure was used to estimate the risk of death and major adverse cardiovascular events among statin-treated patients compared with statin-naive patients. The hazard ratio for benefit from lipid therapy, calculated with the Cox proportional hazards model for the end point of death, was 0.34 (95% confidence interval 0.14-0.86; P=0.02), and for the end point of major adverse cardiovascular events, it was 0.49 (95% confidence interval 0.22-1.07; P=0.07). This occurred despite a mean reduction in low-density lipoprotein cholesterol of only 26.4% (from 15.9±3.9 to 11.7±3.4 mmol/L; P<0.0001) with lipid-lowering therapy. CONCLUSIONS: Lipid-lowering therapy is associated with delayed cardiovascular events and prolonged survival in patients with homozygous familial hypercholesterolemia.


Assuntos
LDL-Colesterol/genética , Homozigoto , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hiperlipoproteinemia Tipo II/tratamento farmacológico , Hiperlipoproteinemia Tipo II/mortalidade , Adolescente , Adulto , Criança , LDL-Colesterol/sangue , Estudos de Coortes , Feminino , Humanos , Hiperlipoproteinemia Tipo II/sangue , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
12.
Clin Chem ; 57(3): 490-501, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21228254

RESUMO

BACKGROUND: Our objective was to evaluate the accuracy of cardiovascular disease (CVD) risk score classification by direct LDL cholesterol (dLDL-C), calculated LDL cholesterol (cLDL-C), and non-HDL cholesterol (non-HDL-C) compared to classification by reference measurement procedures (RMPs) performed at the CDC. METHODS: We examined 175 individuals, including 138 with CVD or conditions that may affect LDL-C measurement. dLDL-C measurements were performed using Denka, Kyowa, Sekisui, Serotec, Sysmex, UMA, and Wako reagents. cLDL-C was calculated by the Friedewald equation, using each manufacturer's direct HDL-C assay measurements, and total cholesterol and triglyceride measurements by Roche and Siemens (Advia) assays, respectively. RESULTS: For participants with triglycerides<2.26 mmol/L (<200 mg/dL), the overall misclassification rate for the CVD risk score ranged from 5% to 17% for cLDL-C methods and 8% to 26% for dLDL-C methods when compared to the RMP. Only Wako dLDL-C had fewer misclassifications than its corresponding cLDL-C method (8% vs 17%; P<0.05). Non-HDL-C assays misclassified fewer patients than dLDL-C for 4 of 8 methods (P<0.05). For participants with triglycerides≥2.26 mmol/L (≥200 mg/dL) and<4.52 mmol/L (<400 mg/dL), dLDL-C methods, in general, performed better than cLDL-C methods, and non-HDL-C methods showed better correspondence to the RMP for CVD risk score than either dLDL-C or cLDL-C methods. CONCLUSIONS: Except for hypertriglyceridemic individuals, 7 of 8 dLDL-C methods failed to show improved CVD risk score classification over the corresponding cLDL-C methods. Non-HDL-C showed overall the best concordance with the RMP for CVD risk score classification of both normal and hypertriglyceridemic individuals.


Assuntos
Doenças Cardiovasculares/classificação , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Dislipidemias/sangue , Triglicerídeos/sangue , Análise Química do Sangue/métodos , Análise Química do Sangue/normas , Análise Química do Sangue/estatística & dados numéricos , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/etiologia , Estudos de Casos e Controles , Interpretação Estatística de Dados , Dislipidemias/complicações , Jejum/sangue , Humanos , Reprodutibilidade dos Testes , Medição de Risco , Fatores de Risco , Sensibilidade e Especificidade , Ultracentrifugação
13.
Nephrol Dial Transplant ; 26(5): 1553-8, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-20961892

RESUMO

BACKGROUND: Serum creatinine (S-Cr)-based prediction equations are commonly used for estimating glomerular filtration rate (GFR). However, S-Cr concentration is also affected by other factors such as tubular secretion, muscle mass, diet, gender and age. Serum cystatin C (S-Cys C)-based prediction equations have been proposed as an improved potential alternative as S-Cys C levels are not influenced by many of the factors that affect creatinine concentration other than GFR. This may be of great benefit to patients with low muscle mass such as those infected with human immunodeficiency virus who are at increased risk for the development of renal impairment. The aim of this study was to develop and evaluate a S-Cys C-based prediction equation for different stages of renal disease in black South Africans. METHODS: One hundred patients with varying degrees of renal function were enrolled in the study. The plasma clearance of (51)Cr-EDTA, a gold standard method, was used to measure GFR (mGFR). In addition, serum was analysed for S-Cr and S-Cys C on each participant. This dataset was split into a development dataset (n = 50) and a test dataset (n = 50). The development dataset was used to formulate a S-Cys C- and S-Cr-based prediction equation using multiple linear regression analysis. These equations together with the four-variable MDRD and CKD-EPI equation were then tested on the test dataset. RESULTS: In the test dataset, accuracy within 15% of measured GFR was 68% for the S-Cys C equation and 48% for the S-Cr equation. Root mean square error for S-Cr eGFR was 10.7 mL/min/1.73 m(2) for those patients with mGFR < 60 mL/min/1.73 m(2) and 25.5 mL/min/1.73 m(2) for those patients with mGFR > 60 mL/min/1.73 m(2). Root mean square error for S-Cys C eGFR was 10.2 mL/min/1.73 m(2) for those patients with mGFR < 60 mL/min/1.73 m(2) and 11.9 mL/min/1.73 m(2) for those patients with mGFR > 60 mL/min/1.73 m(2). CONCLUSIONS: In this study, S-Cys C-based prediction equations appear to be more precise than those of S-Cr for those patients with mGFR > 60 mL/min/1.73 m(2) and may therefore be of benefit in the earlier detection of renal impairment.


Assuntos
População Negra/estatística & dados numéricos , Creatinina/sangue , Cistatina C/sangue , Taxa de Filtração Glomerular , Nefropatias/sangue , Nefropatias/diagnóstico , Adolescente , Feminino , Humanos , Testes de Função Renal , Masculino , Modelos Estatísticos , Prognóstico
14.
Clin Chem ; 57(1): 122-7, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21097676

RESUMO

BACKGROUND: Accurate measurement of free thyroxine (FT(4)) is important for diagnosing and managing thyroid disorders. Most laboratories measure FT(4) by direct analogue immunoassay methods. The validity of these methods have recently been questioned. The inverse log-linear relationship between FT(4) and thyroid-stimulating hormone (TSH) is well described and provides a physiological rationale on which to base an evaluation of FT(4) assays. METHODS: The study included 109 participants for whom FT(4) measurement was requested by their clinician. Samples were selected for inclusion to reflect a wide spectrum of TSH and albumin results. FT(4) and TSH were measured by use of the Siemens Immulite immunoassay (IA). FT(4) was also measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) (MS-FT(4)). RESULTS: The inverse log-linear correlation coefficient between TSH and FT(4) was significantly better (P < 0.0001) for MS-FT(4) (0.84, 95% CI, 0.77-0.88) than for IA-FT(4) (0.45, 95% CI, 0.29-0.59). IA-FT(4) showed a significant correlation with albumin (Spearman correlation coefficient 0.45, 95% CI, 0.29-0.5, P < 0.0001) and thyroxine-binding globulin (TBG) (Spearman correlation coefficient 0.23, 95% CI, 0.05-0.41, P = 0.02). In contrast, FT(4) measurement by LC-MS/MS did not show a significant correlation with albumin or TBG. CONCLUSIONS: The inverse log-linear relationship between FT(4) and TSH was significantly better for FT(4) measured by LC-MS/MS than by IA. The MS-FT(4) method therefore provides FT(4) results that agree clinically with those obtained for TSH. Additionally, the significant correlation between IA-FT(4) with albumin and TBG suggests that this FT(4) method depends on binding protein concentrations and consequently does not accurately reflect FT(4).


Assuntos
Tireotropina/sangue , Tiroxina/sangue , Albuminas/análise , Humanos , Imunoensaio , Conceitos Matemáticos , Estudos Prospectivos , Curva ROC , Espectrometria de Massas em Tandem , Globulina de Ligação a Tiroxina/análise
15.
AIDS Res Hum Retroviruses ; 25(8): 771-81, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19619010

RESUMO

The aim of this study was to determine the patterns of change in body fat and metabolic parameters in a South African cohort on a first line ART regimen containing stavudine. Fasting lipogram, blood glucose and insulin levels, CD4 cell count, viral load, BMI, waist-to-hip ratio (WHR), and skinfold thickness at the triceps, scapula, and iliac crest were measured before starting ART in 42 (27 female) subjects. Repeat measurements were performed at four monthly intervals for 2 years. Lipodystrophy was diagnosed using patient perception and assessment by a physician. At baseline, subjects who went on to develop lipodystrophy (LD group) were fatter and had higher skinfold thickness at all three sites and higher insulin levels than subjects who never developed lipodystrophy (NLD group). The WHR increased to a greater extent while hip circumference and tricep skinfolds fell more significantly in the LD than NLD group. Triglyceride and cholesterol levels increased significantly in both groups while lactate and glucose levels increased more and insulin levels increased less in the LD than the NLD group. Neither viral load nor CD4 count differed between the groups during the study. Viral load correlated positively with insulin levels at baseline. Thus, lipodystrophy in the South African population is characterized by a higher BMI before initiation of ART and lipoatrophy of the arms and hips, lipohypertrophy of the waist, and increased lactate production. When compared to the NLD group, the LD subjects display attenuated insulin secretory output in response to a higher weight gain.


Assuntos
Tecido Adiposo/efeitos dos fármacos , Antirretrovirais/efeitos adversos , Infecções por HIV , HIV/efeitos dos fármacos , Lipodistrofia/induzido quimicamente , Estavudina/efeitos adversos , Adulto , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/metabolismo , Humanos , Insulina/sangue , Lipídeos/sangue , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Fatores de Risco , África do Sul
16.
Clin Chem ; 54(7): 1197-202, 2008 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-18487286

RESUMO

BACKGROUND: The 4-variable Modification of Diet in Renal Disease (4-v MDRD) and Cockcroft-Gault (CG) equations are commonly used for estimating glomerular filtration rate (GFR); however, neither of these equations has been validated in an indigenous African population. The aim of this study was to evaluate the performance of the 4-v MDRD and CG equations for estimating GFR in black South Africans against measured GFR and to assess the appropriateness for the local population of the ethnicity factor established for African Americans in the 4-v MDRD equation. METHODS: We enrolled 100 patients in the study. The plasma clearance of chromium-51-EDTA ((51)Cr-EDTA) was used to measure GFR, and serum creatinine was measured using an isotope dilution mass spectrometry (IDMS) traceable assay. We estimated GFR using both the reexpressed 4-v MDRD and CG equations and compared it to measured GFR using 4 modalities: correlation coefficient, weighted Deming regression analysis, percentage bias, and proportion of estimated GFR within 30% of measured GFR (P(30)). RESULTS: The Spearman correlation coefficient between measured and estimated GFR for both equations was similar (4-v MDRD R(2) = 0.80 and CG R(2) = 0.79). Using the 4-v MDRD equation with the ethnicity factor of 1.212 as established for African Americans resulted in a median positive bias of 13.1 (95% CI 5.5 to 18.3) mL/min/1.73 m(2). Without the ethnicity factor, median bias was 1.9 (95% CI -0.8 to 4.5) mL/min/1.73 m(2). CONCLUSIONS: The 4-v MDRD equation, without the ethnicity factor of 1.212, can be used for estimating GFR in black South Africans.


Assuntos
População Negra , Dieta , Taxa de Filtração Glomerular , Insuficiência Renal Crônica/etnologia , Adulto , Negro ou Afro-Americano , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Matemática , Pessoa de Meia-Idade , Estudos Prospectivos , Insuficiência Renal Crônica/dietoterapia , Insuficiência Renal Crônica/fisiopatologia , África do Sul/epidemiologia
17.
Pediatr Surg Int ; 19(1-2): 35-9, 2003 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-12721720

RESUMO

Renal and perinephric abscess in children are uncommon. Three basic pathophysiologic mechanisms are involved, namely, hematogenous spread, ascending infection and contamination by proximity to an infected area. Six pediatric patients diagnosed with renal abscess were treated at our institution from 1990-2000. Five patients were females; ages ranged from 3-17 years (mean 11.8 years). Diagnosis, as expected, was not readily apparent at presentation. Computerized tomography and renal sonograms were the most useful imaging modalities. Gram-negative bacteria were commonly isolated; only one patient grew Staphylococcus aureus. All patients received broad-spectrum intravenous antibiotics. Additional treatments consisted of percutaneous drainage (4 patients), exploratory laparotomy (1 patient, for presumed Wilm's tumor) and nephrectomy (2 patients). A new classification of the etiologic mechanisms of this condition is proposed along with a simple and practical treatment algorithm.


Assuntos
Abscesso/fisiopatologia , Abscesso/terapia , Perinefrite/fisiopatologia , Perinefrite/terapia , Abscesso/microbiologia , Adolescente , Algoritmos , Antibacterianos/uso terapêutico , Criança , Pré-Escolar , Terapia Combinada , Drenagem , Feminino , Humanos , Laparotomia , Masculino , Nefrectomia , Perinefrite/microbiologia , Estudos Retrospectivos , Resultado do Tratamento
18.
Pediatr Surg Int ; 18(2-3): 213-7, 2002 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-11956804

RESUMO

The treatment of vascular malformations (VM) of the extremities is controversial. Six patients with large, localized, symptomatic VMs of the extremities underwent surgical excision. In five cases abnormal vessels were apparent under the skin; in two of these there was also red discoloration of the skin secondary to skin involvement. Magnetic resonance imaging was the most helpful imaging modality in evaluating these patients. Subfascial resection was performed in five cases. Muscle was involved in four patients and was removed in all four cases. At follow-up, there was improvement in symptoms and function with no clinically apparent recurrence an average of 30 months following the operation. There was improvement in pain intensity from an average of 4.3 on a scale of 1 to 10 before surgery to 1.3 after surgery. Surgical excision of localized VMs that are extensive and include fascia and muscle, as appropriate, can successfully improve pain and function without evidence of recurrence at 1 to 5 years of follow-up.


Assuntos
Perna (Membro)/irrigação sanguínea , Doenças Vasculares/cirurgia , Adolescente , Malformações Arteriovenosas/diagnóstico , Malformações Arteriovenosas/cirurgia , Criança , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Tomografia Computadorizada por Raios X , Doenças Vasculares/diagnóstico
20.
Pediatr Radiol ; 30(3): 186-9, 2000 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-10755760

RESUMO

OBJECTIVES: Questionnaires (984) were submitted to pediatric radiologists to determine how often odontoid fractures were missed on lateral views and detected on open-mouth odontoid views in children under 5 years. Other questions relating to imaging protocols of the odontoid also were included, and there were 432 respondents. RESULTS: Of these, 161 respondents indicated that an open-mouth odontoid view was not routinely included in their imaging protocol. CONCLUSIONS: There was considerable variability on how the problem of imaging of the odontoid was addressed, but overall there were enough data to begin to consider the concept that the open-mouth odontoid might not be needed in patients under 5 years of age if a lateral view is normal.


Assuntos
Processo Odontoide/diagnóstico por imagem , Fraturas da Coluna Vertebral/diagnóstico por imagem , Pré-Escolar , Humanos , Lactente , Boca , Processo Odontoide/lesões , Padrões de Prática Médica/estatística & dados numéricos , Radiografia , Inquéritos e Questionários
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