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1.
World Neurosurg ; 163: e275-e282, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35364295

RESUMO

BACKGROUND: Surgical site infections (SSIs) after spine surgery are a significant cause of morbidity. Surgeons often prescribe oral antibiotics in the postoperative setting for infected-appearing wounds to prevent reoperation for infection; however, the efficacy of this practice has not been well studied. METHODS: Neurosurgical spine patients with clinical concerns for SSI at the University of Pennsylvania were retrospectively studied from 2014 to 2018. Clinical predictors of 90-day reoperation for infection despite antibiotic treatment and variables that influenced antibiotic prescription were analyzed. RESULTS: Three hundred and ninety-two patients were included in the study. Preoperative albumin level, days elapsed to antibiotic prescription from index surgery, preoperative hemoglobin level, surgical location, gender, discharge disposition, and level of wound concern were significant predictors of reoperation for infection on bivariate analysis. Days elapsed to antibiotic prescription, surgical location, and level of wound concern remained significant after multivariable logistic regression. Variables that significantly predicted prescription of an antibiotic include length of stay, cerebrospinal fluid leak, race, and level of wound concern. Length of stay, race, and level of wound concern remained significant after multivariable analysis. CONCLUSIONS: Wound infection remains a challenging problem in spine surgery and it is reasonable to perform early reoperation in patients with high clinical concerns for infection, because bacterial isolates are often resistant to common oral antibiotics. Patients with wounds with low clinical concerns for infection may undergo a trial of oral antibiotics; however, duration of treatment should not be prolonged.


Assuntos
Antibacterianos , Infecção da Ferida Cirúrgica , Antibioticoprofilaxia , Humanos , Reoperação/efeitos adversos , Estudos Retrospectivos , Coluna Vertebral/cirurgia , Infecção da Ferida Cirúrgica/tratamento farmacológico , Infecção da Ferida Cirúrgica/etiologia , Infecção da Ferida Cirúrgica/prevenção & controle
2.
J Am Soc Nephrol ; 32(11): 2863-2876, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34348909

RESUMO

BACKGROUND: Patients with diabetic or hypertensive kidney disease rarely undergo kidney biopsy because nephrologists commonly believe that biopsy-related risk outweighs the potential benefits of obtaining histologic information to guide clinical decisions. Although kidney function is acutely regulated, histologic changes such as interstitial fibrosis, tubular atrophy, and glomerulosclerosis may represent chronic kidney damage, and thus might provide additional information about disease severity. However, whether histologic analysis provides information complementary to clinically used kidney function measurements, such as eGFR and proteinuria, is unclear. METHODS: We performed a standardized semiquantitative histologic analysis of 859 nephrectomies obtained from individuals with or without diabetes mellitus or hypertension and varying degrees of kidney dysfunction. Changes in glomeruli, tubules, interstitium, and the vasculature were scored using 17 descriptive parameters in a standardized manner. We used multivariable linear and logistic regression analyses and unbiased, hierarchical clustering to assess associations between histologic alterations and clinical variables. RESULTS: At CKD stages 3-5, eGFR correlates reasonably well with the degree of glomerulosclerosis and interstitial fibrosis and tubular atrophy (IFTA). In patients with CKD stages 1-2, the degree of histologic damage was highly variable and eGFR poorly estimated the degree of damage. Individuals with diabetes mellitus, hypertension, or Black race had significantly more glomerulosclerosis and IFTA, at the same eGFR level. Inclusion of glomerulosclerosis improved the kidney function decline estimation, even at early disease stages. CONCLUSIONS: Histologic analysis is an important complementary method for kidney disease evaluation, especially at early disease stages. Some individuals present with relatively severe structural damage despite preserved eGFR.


Assuntos
Nefropatias Diabéticas/patologia , Taxa de Filtração Glomerular , Hipertensão/patologia , Rim/patologia , Idoso , Atrofia , Biópsia , População Negra , Nefropatias Diabéticas/fisiopatologia , Feminino , Fibrose , Humanos , Hipertensão/fisiopatologia , Rim/fisiopatologia , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Proteinúria/patologia , Proteinúria/fisiopatologia
3.
J Clin Endocrinol Metab ; 106(10): e4028-e4038, 2021 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-34089611

RESUMO

CONTEXT: Pheochromocytomas and paragangliomas (PCC/PGL) are neuroendocrine tumors with discrete catecholamine profiles that cause incompletely understood metabolic and physiologic changes. OBJECTIVE: The objective was to evaluate relationships between plasma catecholamines, body weight, and hemoglobin A1c (HbA1c). We hypothesized that individual catecholamines would correlate negatively with weight and glucose control. DESIGN: A retrospective cohort study was performed (1999-2020). Wilcoxon rank-sum tests compared nonparametric, continuous variables; mixed-effect linear modeling (MEM) evaluated relationships between catecholamines and weight or HbA1c. The median study duration was 54.2 months [interquartile range (IQR) 19.0-95.1]. SETTING: Tertiary academic hospital. PATIENTS: 360 patients were identified prospectively by referral to our center for management or surveillance of PCC/PGL. The median age was 59 years (IQR 45-67) and 56.4% (n = 203) were female. MAIN OUTCOME MEASURES: The primary and secondary outcomes were weight and HbA1c, respectively. RESULTS: On multivariable MEM, norepinephrine (P < 0.0005) negatively correlated with weight when all catecholamines and their derivatives were tried in the model, and normetanephrine (P < 0.0005) correlated when only metanephrines were included. In the surgical cohort (n = 272), normetanephrine decreased postoperatively and was inversely associated with weight (P < 0.0005). Elevated norepinephrine or normetanephrine at the study termination, indicative of metastatic and/or recurrent disease (MRD), correlated with weight loss. Norepinephrine and normetanephrine (P < 0.0005) directly correlated with HbA1c. CONCLUSION: Plasma norepinephrine and its metabolite directly correlate with HbA1c and inversely correlate with weight in PCC/PGL. After resection, declining normetanephrine levels correlate with improving HbA1c despite an increase in patient body weight. Persistently elevated catecholamines and decreasing weight are observed in MRD.


Assuntos
Neoplasias das Glândulas Suprarrenais , Peso Corporal/fisiologia , Catecolaminas/sangue , Diabetes Mellitus/epidemiologia , Paraganglioma , Feocromocitoma , Neoplasias das Glândulas Suprarrenais/sangue , Neoplasias das Glândulas Suprarrenais/complicações , Neoplasias das Glândulas Suprarrenais/epidemiologia , Idoso , Estudos de Coortes , Diabetes Mellitus/sangue , Diabetes Mellitus/etiologia , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/epidemiologia , Obesidade/etiologia , Paraganglioma/sangue , Paraganglioma/complicações , Paraganglioma/epidemiologia , Feocromocitoma/sangue , Feocromocitoma/complicações , Feocromocitoma/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Estados Unidos/epidemiologia
4.
J Endocr Soc ; 4(11): bvaa141, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-33134766

RESUMO

CONTEXT: Clinical guidelines recommend measurement of the serum prostate-specific antigen (PSA) concentration during testosterone treatment of hypogonadal men to determine whether the increase is sufficiently high to warrant urologic referral. Prior studies of the effect of testosterone treatment on PSA concentrations have been conducted in men who were mildly to moderately hypogonadal. OBJECTIVE: The objective of this work is to determine the PSA response to testosterone treatment of men who are severely hypogonadal. DESIGN AND SETTING: This retrospective cohort study was conducted at a single academic medical center. PARTICIPANTS: Eighty-five men participated who were severely hypogonadal as a result hypothalamic-pituitary or testicular disease. MAIN OUTCOME MEASURE: Changes in serum PSA concentrations were measured during testosterone treatment for up to 18 months. RESULTS: Testosterone treatment increased the median serum testosterone concentration from 36 ng/dL (interquartile range [IQR], 20-91 ng/dL) at baseline to 395 ng/dL (IQR, 266-542 ng/dL) at 6 to 18 months. This treatment resulted in a median increment in PSA above baseline of 0.70 ng/mL (IQR, 0.10-1.85 ng/mL) at 6 to 18 months. Apropos current Endocrine Society clinical guidelines, 31% of the men experienced a PSA increase above baseline greater than 1.4 ng/mL, and 13% reached an absolute PSA concentration of greater than 4.0 ng/mL. Four men were diagnosed with prostate cancer. CONCLUSIONS: The PSA response to testosterone replacement in men who are severely hypogonadal as a result of pituitary or testicular disease is greater than that previously reported in men with mild to moderate hypogonadism. These results suggest the magnitude of the PSA response to testosterone replacement is related to the degree of hypogonadism.

5.
Clin Cancer Res ; 26(2): 397-407, 2020 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-31666247

RESUMO

PURPOSE: The clinical utility of plasma cell-free DNA (cfDNA) has not been assessed prospectively in patients with glioblastoma (GBM). We aimed to determine the prognostic impact of plasma cfDNA in GBM, as well as its role as a surrogate of tumor burden and substrate for next-generation sequencing (NGS). EXPERIMENTAL DESIGN: We conducted a prospective cohort study of 42 patients with newly diagnosed GBM. Plasma cfDNA was quantified at baseline prior to initial tumor resection and longitudinally during chemoradiotherapy. Plasma cfDNA was assessed for its association with progression-free survival (PFS) and overall survival (OS), correlated with radiographic tumor burden, and subjected to a targeted NGS panel. RESULTS: Prior to initial surgery, GBM patients had higher plasma cfDNA concentration than age-matched healthy controls (mean 13.4 vs. 6.7 ng/mL, P < 0.001). Plasma cfDNA concentration was correlated with radiographic tumor burden on patients' first post-radiation magnetic resonance imaging scan (ρ = 0.77, P = 0.003) and tended to rise prior to or concurrently with radiographic tumor progression. Preoperative plasma cfDNA concentration above the mean (>13.4 ng/mL) was associated with inferior PFS (median 4.9 vs. 9.5 months, P = 0.038). Detection of ≥1 somatic mutation in plasma cfDNA occurred in 55% of patients and was associated with nonstatistically significant decreases in PFS (median 6.0 vs. 8.7 months, P = 0.093) and OS (median 5.5 vs. 9.2 months, P = 0.053). CONCLUSIONS: Plasma cfDNA may be an effective prognostic tool and surrogate of tumor burden in newly diagnosed GBM. Detection of somatic alterations in plasma is feasible when samples are obtained prior to initial surgical resection.


Assuntos
Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , DNA Tumoral Circulante/sangue , DNA Tumoral Circulante/genética , Glioblastoma/diagnóstico , Imageamento por Ressonância Magnética/métodos , Mutação , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Glioblastoma/sangue , Glioblastoma/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Prognóstico , Estudos Prospectivos , Taxa de Sobrevida , Carga Tumoral , Adulto Jovem
6.
Plast Reconstr Surg ; 134(1): 83-91, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24622572

RESUMO

BACKGROUND: The temporal region is significantly affected by both restricted and compensatory growth in unilateral coronal craniosynostosis. Recurrent deformity in this region after fronto-orbital advancement often requires a revision operation in adolescence. The authors performed a three-dimensional analysis of the temporal region in patients with unilateral coronal craniosynostosis to define the baseline deformity and the immediate and long-term changes after fronto-orbital advancement. METHODS: A retrospective analysis of patients with nonsyndromic unilateral coronal craniosynostosis who underwent reconstruction with fronto-orbital advancement or revision cranioplasty after fronto-orbital advancement between 2005 and 2010 was performed. Volumetric and craniometric computed tomographic data were obtained from the bilateral temporal regions and analyzed using the appropriate statistical tests. RESULTS: Fifteen patients immediately before and after fronto-orbital advancement and 14 precranioplasty patients were included. In all groups, the supraorbits on the synostotic sides were significantly constricted in the transverse dimension. The temporal fossa volume on the synostotic side was displaced and significantly smaller than the nonsynostotic side in all groups. The temporalis muscle of the synostotic side was smaller but disproportionately large for the temporal fossa. CONCLUSIONS: In unilateral coronal craniosynostosis, there is a baseline and persistent deficiency in the transverse dimension of the supraorbit on the synostotic side. The temporalis muscle is smaller on the synostotic side but is disproportionately large for the temporal fossa of the affected side, which is inferolaterally displaced and smaller because of compensatory growth. These subtle abnormalities in the relationships between the bony dimensions and soft tissues appear to contribute to the temporal hollow deformity often observed after fronto-orbital advancement. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.


Assuntos
Craniossinostoses/cirurgia , Osso Frontal/cirurgia , Órbita/cirurgia , Adolescente , Cefalometria , Criança , Feminino , Humanos , Masculino , Procedimentos Ortopédicos/métodos , Procedimentos de Cirurgia Plástica/métodos , Estudos Retrospectivos , Osso Temporal , Fatores de Tempo
7.
J Cardiothorac Vasc Anesth ; 28(3): 618-25, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24144627

RESUMO

OBJECTIVE: The authors sought to evaluate the efficacy of an intravenous glucagon-like peptide-1 (GLP-1) infusion, compared with placebo, to mitigate intraoperative hyperglycemia. DESIGN: Prospective, double-blinded, randomized, placebo-controlled. SETTING: University hospital. PARTICIPANTS: Diabetic (non-insulin dependent) and non-diabetic patients undergoing elective cardiac surgery with cardiopulmonary bypass. INTERVENTIONS: Patients were randomized in a 1:1 fashion to GLP-1 (7-36) amide infusion (1.5 pmol/kg/min) or placebo. Insulin was administered intraoperatively to both groups per a standardized protocol. MEASUREMENTS AND MAIN RESULTS: A total of 77 patients were included for analysis (GLP-1, n = 37; placebo, n = 40). Mean blood glucose during cardiopulmonary bypass was 127.5 mg/dL and 142.5 mg/dL (p = 0.002) in the GLP-1 and placebo groups, respectively. Mean blood glucose values during the entire intraoperative course were 12.2 mg/dL lower for subjects given GLP-1 (95% CI 2.3, 22, p = 0.015), independent of time. During the period of cardiopulmonary bypass, mean blood glucose values in subjects given GLP-1 were 14.1 mg/dL lower than those who received placebo (95% CI 3.5, 24.8, p = 0.009), independent of time. The incidence of hypoglycemia did not differ significantly between the 2 groups. CONCLUSIONS: Administration of intravenous GLP-1 (7-36) amide to patients undergoing cardiac surgery significantly reduced their plasma glucose levels intraoperatively and may represent a novel therapeutic strategy to prevent perioperative hyperglycemia.


Assuntos
Procedimentos Cirúrgicos Cardíacos/métodos , Peptídeo 1 Semelhante ao Glucagon/uso terapêutico , Hiperglicemia/prevenção & controle , Hipoglicemiantes/uso terapêutico , Fragmentos de Peptídeos/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Glicemia/metabolismo , Método Duplo-Cego , Feminino , Peptídeo 1 Semelhante ao Glucagon/administração & dosagem , Humanos , Hipoglicemiantes/administração & dosagem , Infusões Intravenosas , Cuidados Intraoperatórios , Masculino , Pessoa de Meia-Idade , Fragmentos de Peptídeos/administração & dosagem , Estudos Prospectivos , Resultado do Tratamento
8.
J Am Acad Dermatol ; 69(2): 205-13, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23648190

RESUMO

BACKGROUND: Photosensitivity (PS) in lupus erythematosus (LE) is frequently determined by patient report. OBJECTIVE: We sought to characterize self-reported PS in cutaneous LE (CLE). METHODS: The PS survey was used to classify subject responses into 5 phenotypes: direct sun-induced CLE flare (directCLE); general exacerbation of CLE (genCLE); polymorphic light eruption-like reactions (genSkin); general pruritus/paresthesias (genRxn); and sun-induced systemic symptoms (genSys). In all, 91 subjects with CLE alone or with CLE and systemic LE were interviewed. RESULTS: In all, 81% ascribed to 1 or more PS phenotypes. CLE-specific reactions (direct sun-induced CLE flare or general exacerbation of CLE) were reported by 86% of photosensitive subjects. Higher CLE disease activity (measured by CLE Disease Area and Severity Index activity scores) was suggestive of direct sun-induced CLE flare reactions (P = .09). In all, 60% of photosensitive subjects described CLE-nonspecific reactions: polymorphic light eruption-like rash and general pruritus/paresthesias. These phenotypes often co-occurred with CLE-specific reactions and were predicted by more systemic disease activity as measured by Physicians Global Assessment (PGA) scores in regression analyses (genSkin, P = .02) and (genRxn, P = .05). In all, 36% of subjects reported systemic reactions and higher PGA scores were predictive of the sun-induced systemic symptoms phenotype (P = .02); a diagnosis of systemic LE was not (P = .14). LIMITATIONS: PS was inferred from patient report and not directly observed. CONCLUSIONS: Characterization of self-reported PS in LE reveals that patients experience combinations of CLE-specific, CLE-nonspecific, and systemic reactions to sunlight. Sun-induced CLE flares are associated with more active CLE disease. Polymorphic light eruption-like, generalized pruritus/paresthesias, and systemic reactions are associated with more active systemic disease. Recognition of PS phenotypes will permit improved definitions of clinical PS and allow for more precise investigation into its pathophysiology.


Assuntos
Lúpus Eritematoso Cutâneo/diagnóstico , Lúpus Eritematoso Cutâneo/epidemiologia , Transtornos de Fotossensibilidade/diagnóstico , Transtornos de Fotossensibilidade/epidemiologia , Adulto , Biópsia por Agulha , Estudos de Coortes , Feminino , Seguimentos , Humanos , Imuno-Histoquímica , Modelos Logísticos , Lúpus Eritematoso Cutâneo/genética , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Fenótipo , Transtornos de Fotossensibilidade/genética , Prevalência , Estudos Prospectivos , Autorrelato , Índice de Gravidade de Doença , Estatísticas não Paramétricas , Luz Solar/efeitos adversos , Inquéritos e Questionários
9.
J Rheumatol ; 38(11): 2369-75, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21885493

RESUMO

OBJECTIVE: To evaluate levels of resistin in female subjects with systemic lupus erythematosus (SLE) compared to age and race-matched controls and to determine the relationship between resistin and systemic inflammation, disease measures, and coronary artery calcification (CAC). METHODS: Resistin levels were measured on stored samples from 159 women with SLE and 70 controls as an extension of a previous cross-sectional study. Spearman correlations and multivariable regressions were used to examine whether resistin levels were associated with SLE, disease-specific and inflammatory markers, insulin resistance, and CAC. RESULTS: In a multivariable linear regression model, a diagnosis of SLE was significantly associated with higher resistin levels independent of age, race, renal function, body mass index (BMI), high-sensitivity CRP (hsCRP), hypertension, diabetes, and steroid use. In SLE, resistin levels correlated positively with Systemic Lupus International Collaborating Clinics Damage Index, glomerular filtration rate (GFR), hsCRP, erythrocyte sedimentation rate, homocysteine, and disease duration (all p < 0.03). Resistin level did not correlate with markers of insulin resistance or body adiposity, including homeostatic model assessment or BMI. Resistin levels were significantly elevated in SLE cases with CAC compared to cases without CAC (16.58 vs 13.10 ng/ml, respectively; p = 0.04). In multivariate logistic regression, the association was not present after adjustment for age, race, and GFR. CONCLUSION: SLE was independently associated with higher resistin levels. Among subjects with SLE, higher resistin level correlated positively with renal dysfunction, inflammatory markers, and disease damage but not with insulin resistance or BMI. SLE cases with CAC had higher resistin levels than cases without CAC; however, this relationship was dependent on other established risk factors.


Assuntos
Calcinose/fisiopatologia , Doença da Artéria Coronariana/fisiopatologia , Resistência à Insulina/fisiologia , Rim/fisiopatologia , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/fisiopatologia , Resistina/sangue , Adulto , Biomarcadores/sangue , Sedimentação Sanguínea , Proteína C-Reativa/metabolismo , Calcinose/epidemiologia , Estudos de Casos e Controles , Comorbidade , Doença da Artéria Coronariana/epidemiologia , Estudos Transversais , Feminino , Taxa de Filtração Glomerular/fisiologia , Homocisteína/sangue , Humanos , Modelos Logísticos , Lúpus Eritematoso Sistêmico/epidemiologia , Pessoa de Meia-Idade , Fatores de Risco
10.
J Nucl Med ; 51(3): 347-52, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20150253

RESUMO

UNLABELLED: Theoretically, the degree of (18)F-FDG uptake in the glandular tissues of the normal breast can affect the detection of breast cancer. The aim of this prospective study was to investigate relationships among age, menopausal state, and breast density and determine whether they affect (18)F-FDG uptake in normal glandular breast tissue. METHODS: Among 250 newly diagnosed breast cancer patients, 149 patients (mean age +/- SD, 50.9 +/- 9.70 y; range, 32-77 y) were analyzed because they had normal contralateral breasts confirmed by MRI, mammography, and (18)F-FDG PET examinations. PET images were acquired 60 +/- 2 min after the administration of (18)F-FDG (5.2 MBq/kg of body weight). The maximum and average standardized uptake value (SUVmax and SUVavg, respectively) of (18)F-FDG were calculated in the normal breast. Patients were divided into groups according to qualitative breast density and menopausal state. Descriptive statistics and 2-factorial analysis of covariance were used to assess the effects of qualitative breast density, menopausal state, and age on SUVmax and SUVavg. Pearson chi(2) was used to test the relationship between menopausal state and qualitative breast density. RESULTS: The average age of patients with nondense breasts was significantly higher than that of patients with dense breasts (P < 0.01). Also, breast density related to menopausal state (P < 0.05). Dense breasts had an average SUVmax of 1.243 and mean SUVavg of 0.694, whereas nondense breasts had a mean SUVmax of 0.997 and mean SUVavg of 0.592. Analysis of covariance indicated that density and the linear effect of age were significant with regard to both SUVmax and SUVavg. After removing the linear effect of age, menopausal state had no effect on SUVmax and SUVavg. CONCLUSION: (18)F-FDG uptake significantly decreases as age increases and breast density decreases. Age and qualitative breast density are independent factors and significantly affect (18)F-FDG uptake for both SUVmax and SUVavg. Menopausal state had no effect on SUVmax and SUVavg.


Assuntos
Envelhecimento/metabolismo , Mama/citologia , Mama/metabolismo , Fluordesoxiglucose F18/farmacocinética , Menopausa/metabolismo , Adulto , Idoso , Análise de Variância , Transporte Biológico , Mama/diagnóstico por imagem , Mama/patologia , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Feminino , Humanos , Modelos Lineares , Mamografia , Pessoa de Meia-Idade , Cintilografia
11.
J Rheumatol ; 35(11): 2179-86, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18785313

RESUMO

OBJECTIVE: To determine if functional polymorphisms of folate/homocysteine pathway enzymes are associated with homocysteine concentrations and/or coronary artery calcification (CAC) scores in patients with systemic lupus erythematosus (SLE) and controls. METHODS: We investigated 163 SLE patients and 160 controls. Functional polymorphisms in 6 genes in the folate/homocysteine pathway were genotyped: 5,10-methylenetetrahydrofolate reductase (MTHFR) 677C>T, MTHFR 1298A>C, cystathionine ss-synthase (CBS) 844ins68, methionine synthase (MTR) 2756A>G, methionine synthase reductase (MTRR) 66A>G, thymidylate synthase (TYMS) 1494del6, and dihydrofolate reductase (DHFR) c.86+60_78. RESULTS: Homocysteine levels were higher in African American SLE patients than Caucasian patients and African American controls. Genotype distributions were significantly different in African American and Caucasian controls for 6 of the 7 polymorphisms. Genotype distributions for each polymorphism did not differ significantly between SLE patients and controls even after stratification by race. Glomerular filtration rate was strongly negatively correlated to homocysteine levels, and was therefore adjusted for as a covariate in the models of the effects of the polymorphisms on homocysteine levels. In SLE patients none of the 7 polymorphisms was associated with homocysteine concentrations. In Caucasian controls only MTHFR 677C>T and 1298A>C showed effects on homocysteine similar to what would be expected from the literature. There were no genotypic associations with median CAC scores in SLE patients or controls with and without stratification by race. CONCLUSION: Polymorphisms in folate/homocysteine metabolizing enzymes do not predict higher homocysteine levels or CAC scores in patients with SLE.


Assuntos
Enzimas/genética , Ácido Fólico/metabolismo , Lúpus Eritematoso Sistêmico/etnologia , Lúpus Eritematoso Sistêmico/genética , Polimorfismo Genético , 5-Metiltetra-Hidrofolato-Homocisteína S-Metiltransferase/genética , 5-Metiltetra-Hidrofolato-Homocisteína S-Metiltransferase/metabolismo , Adulto , Negro ou Afro-Americano/genética , Negro ou Afro-Americano/estatística & dados numéricos , Asiático/genética , Asiático/estatística & dados numéricos , Doença da Artéria Coronariana/etnologia , Cistationina beta-Sintase/genética , Cistationina beta-Sintase/metabolismo , Enzimas/metabolismo , Feminino , Ferredoxina-NADP Redutase/genética , Ferredoxina-NADP Redutase/metabolismo , Genótipo , Hispânico ou Latino/genética , Hispânico ou Latino/estatística & dados numéricos , Homocisteína/sangue , Humanos , Lúpus Eritematoso Sistêmico/metabolismo , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Metilenotetra-Hidrofolato Redutase (NADPH2)/metabolismo , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Tetra-Hidrofolato Desidrogenase/genética , Tetra-Hidrofolato Desidrogenase/metabolismo , Timidilato Sintase/genética , Timidilato Sintase/metabolismo , População Branca/genética , População Branca/estatística & dados numéricos
12.
J Bone Miner Res ; 23(5): 730-40, 2008 May.
Artigo em Inglês | MEDLINE | ID: mdl-18251704

RESUMO

INTRODUCTION: Estrogen depletion after menopause is accompanied by bone loss and architectural deterioration of trabecular bone. The hypothesis underlying this work is that the microMRI-based virtual bone biopsy can capture the temporal changes of scale and topology of the trabecular network and that estrogen supplementation preserves the integrity of the trabecular network. MATERIALS AND METHODS: Subjects studied were early postmenopausal women, 45-55 yr of age (N = 65), of whom 32 were on estrogen (estradiol group), and the remainder were not (control group). Early menopause was defined by amenorrhea for 6-24 mo and elevated serum follicle-stimulating hormone (FSH) concentration. The subjects were evaluated with three imaging modalities at baseline and 12 and 24 mo to determine the temporal changes in trabecular and cortical architecture and density. microMRI of the distal radius and tibia was performed at 137 x 137 x 410-microm(3) voxel size. The resulting bone volume fraction maps were Fourier interpolated to a final voxel size of 45.7 x 45.7 x 136.7 microm(3), binarized, skeletonized, and subjected to 3D digital topological analysis (DTA). Skeletonization converts trabecular rods to curves and plates to surfaces. Parameters quantifying scale included BV/TV, whereas DTA parameters included the volume densities of curves (C) and surface (S)-type voxels, as well as composite parameters: the surface/curve ratio (S/C), and erosion index (EI, ratio of the sum of parameters expected to increase with osteoclastic resorption divided by the sum of those expected to decrease). For comparison, pQCT of the same peripheral locations was conducted, and trabecular density and cortical structural parameters were measured. Areal BMD of the lumbar vertebrae and hip was also measured. RESULTS: Substantial changes in trabecular architecture of the distal tibia, in particular as they relate to topology of the network, were detected after 12 mo in the control group. S/C decreased 5.6% (p < 0.0005), and EI increased 7.1% (p < 0.0005). Most curve- and profile-type voxels (representative of trabecular struts), increased significantly (p < 0.001). Curve and profile edges resulting from disconnection of rod-like trabeculae increased by 9.8% and 5.1% (p = 0.0001 and <0.001, respectively). Similarly, DXA BMD in the spine and hip decreased 2.6% and 1.3% (p < 0.0001 and <0.005, respectively), and pQCT cortical area decreased 3.6% (p = 0.0001). However, neither trabecular density nor BV/TV changed. Furthermore, none of the parameters measured in the estradiol group were significantly different after 12 mo. Substantial differences in the mean changes from baseline between the estradiol treatment and control groups, in particular after 24 mo, were observed, with relative group differences as large as 13% (S/C, p = 0.005), and the relative changes in the two groups had the opposite sign for most parameters. The observed temporal alterations in architecture are consistent with remodeling changes that involve gradual conversion of plate-like to rod-like trabecular bone along with disconnection of trabecular elements, even in the absence of a net loss of trabecular bone. The high-resolution 3D rendered images provide direct evidence of the above remodeling changes in individual subjects. The radius structural data indicated similar trends but offered no definitive conclusions. CONCLUSIONS: The short-term temporal changes in trabecular architecture after menopause, and the protective effects of estradiol ensuring maintenance of a more plate-like TB architecture, reported here, have not previously been observed in vivo. This work suggests that MRI-based in vivo micromorphometry of trabecular bone has promise as a tool for monitoring osteoporosis treatment.


Assuntos
Remodelação Óssea , Osso e Ossos/anatomia & histologia , Estradiol/administração & dosagem , Osteoporose/prevenção & controle , Pós-Menopausa , Feminino , Humanos , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade
13.
Arthritis Rheum ; 54(7): 2220-7, 2006 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-16802358

RESUMO

OBJECTIVE: To compare the incidence and extent of coronary artery calcification (CAC) as measured by electron beam computed tomography (EBCT) in patients with systemic lupus erythematosus (SLE) and controls, and to identify variables associated with CAC in patients with SLE. METHODS: Female patients with SLE and matched controls were recruited; EBCT of the coronary arteries was performed, and laboratory values (including the homocysteine concentration, the lipid level, the high-sensitivity C-reactive protein [hsCRP] concentration, the glomerular filtration rate [GFR], and the level of soluble CD154 [sCD154]) were determined. For patients, the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index and the SLE Disease Activity Index scores were recorded. Tests of association between the CAC score and the above-mentioned variables were performed. RESULTS: The incidence of CAC was higher in patients with SLE than in controls (P = 0.009), and patients had a higher mean raw CAC (rCAC) score (87.9 versus 9.6 in controls; P = 0.02). In particular, more CAC-positive patients than CAC-positive controls had rCAC scores above the 75th percentile (P = 0.003). Among both patients and controls, those with CAC were approximately 10 years older than those without CAC. In addition to age, a significant determinant of positive CAC status in both groups was the number of cardiovascular risk factors. In patients with SLE, CAC was associated with a higher homocysteine concentration, a lower GFR, and longer disease duration. In controls, the total cholesterol level correlated positively with CAC. When multivariate logistic regression methods were applied to candidate explanatory variables, homocysteine concentration, age, and disease duration (but not the levels of sCD154 or hsCRP) contributed significantly to CAC status. The methylenetetrahydrofolate reductase C677T genotype was not a predictor of hyperhomocysteinemia or CAC status. CONCLUSION: Among patients with SLE, the homocysteine concentration, the GFR, age, and disease duration were associated with CAC. CAC occurred more frequently and was more extensive in patients with SLE than in controls, suggesting that EBCT could be used to detect premature atherosclerosis in the former group. An elevated homocysteine concentration might identify patients with SLE who are likely to have premature atherosclerosis and who would benefit from evaluation of CAC by EBCT.


Assuntos
Calcinose/patologia , Doença da Artéria Coronariana/patologia , Homocisteína/sangue , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/patologia , Antagonistas Adrenérgicos beta/uso terapêutico , Adulto , Calcinose/diagnóstico , Calcinose/etiologia , Estudos de Casos e Controles , Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/etiologia , Feminino , Taxa de Filtração Glomerular , Humanos , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Pessoa de Meia-Idade , Polimorfismo Genético , Valor Preditivo dos Testes , Análise de Regressão , Índice de Gravidade de Doença , Tomografia Computadorizada por Raios X/métodos
14.
Anesth Analg ; 102(3): 868-75, 2006 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-16492843

RESUMO

Continuous pulse oximetry (CPOX) has the potential to increase vigilance and decrease pulmonary complications and thus decrease intensive care unit (ICU) admissions. In a randomized nonblinded study of 1219 subjects we compared the effects of CPOX and standard monitoring on the rate of transfer to an ICU from a 33-bed postcardiothoracic surgery care floor. There was no difference in the rate of ICU readmission between the CPOX and standard monitor groups. Despite older age and comorbidity, estimated cost to time of censoring (enrollment to completion of the study) was less in the monitored patients who required ICU transfer than in the unmonitored patients who required ICU transfer (mean estimated cost difference of 28,195 dollars; P = 0.04). Use of CPOX altered the reasons that patients were transferred to an ICU but did not affect the rate of transfer. The duration, and thus estimated cost, of ICU stay was significantly less in the CPOX-monitored group. The potential for CPOX to allow for early intervention, or perhaps prevention of pulmonary complications, needs to be explored. Routine CPOX monitoring did not reduce transfer to ICU, mortality, or overall estimated cost of hospitalization, and it is unclear if there is any real benefit from the application of this technology in patients on a general care floor who are recovering from cardiothoracic surgery.


Assuntos
Unidades de Terapia Intensiva , Monitorização Fisiológica , Oximetria , Admissão do Paciente , Cuidados Pós-Operatórios , Idoso , Idoso de 80 Anos ou mais , Intervalos de Confiança , Feminino , Humanos , Unidades de Terapia Intensiva/economia , Unidades de Terapia Intensiva/estatística & dados numéricos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Monitorização Fisiológica/economia , Monitorização Fisiológica/métodos , Monitorização Fisiológica/estatística & dados numéricos , Oximetria/economia , Oximetria/métodos , Oximetria/estatística & dados numéricos , Admissão do Paciente/economia , Admissão do Paciente/estatística & dados numéricos , Cuidados Pós-Operatórios/economia , Cuidados Pós-Operatórios/métodos , Cuidados Pós-Operatórios/estatística & dados numéricos , Estudos Prospectivos
15.
J Clin Endocrinol Metab ; 88(4): 1497-502, 2003 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-12679429

RESUMO

Bone strength depends on trabecular architecture, characterized by interconnected plates and rods. In osteoporosis, the plates become fenestrated, resulting in more rods that deteriorate and become disconnected. In men, hypogonadism is a common cause of osteoporosis. To determine whether male hypogonadism affects trabecular architecture, we selected 10 men with severe, untreated hypogonadism, and for each hypogonadal man, we selected a eugonadal man matched for race and age. Trabecular architecture in the distal tibia was assessed by magnetic resonance microimaging. Two composite topological indices were determined: the ratio of surface voxels (representing plates) to curve voxels (representing rods), which is higher when architecture is more intact; and the erosion index, a ratio of parameters expected to increase upon architectural deterioration to those expected to decrease, which is higher when deterioration is greater. The surface/curve ratio was 36% lower (P = 0.004), and the erosion index was 36% higher (P = 0.003) in the hypogonadal men than in the eugonadal men. In contrast, bone mineral density of the spine and hip were not significantly different between the two groups. We conclude that male hypogonadism is associated with marked deterioration of trabecular architecture and to a greater degree than bone densitometry of the spine and hip suggests.


Assuntos
Osso e Ossos/patologia , Hipogonadismo/patologia , Absorciometria de Fóton , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Densidade Óssea , Cálcio da Dieta/administração & dosagem , Estradiol/sangue , Humanos , Hipogonadismo/fisiopatologia , Fator de Crescimento Insulin-Like I/análise , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Coluna Vertebral , Testosterona/sangue , Tíbia/patologia
16.
Arch Dermatol ; 138(8): 1054-60, 2002 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-12164743

RESUMO

OBJECTIVE: To determine the efficacy of multimodality biologic response therapy for patients with cutaneous T-cell lymphoma (CTCL). DESIGN: Retrospective cohort study over a 14-year period. SETTING: Tertiary care university hospital. PATIENTS: A consecutive sample of patients was studied, all 47 of whom carried the clinical and laboratory diagnosis of CTCL: 68% of patients had stage III or IV disease, and 89% had circulating malignant T cells. INTERVENTIONS: All 47 patients received photopheresis for 6 or more cycles. Thirty-one patients received treatment with a combination of photopheresis and 1 or more systemic immunostimulatory agents, including interferon alfa, interferon gamma, sargramostim, or systemic retinoids for 3 or more months. MAIN OUTCOME MEASURES: Differences in pretreatment prognostic factors, response rates, and survival between patients receiving multimodality therapy and single-modality therapy or historical controls. RESULTS: A total of 79% of patients responded to therapy: 26% had complete remission, and 53% had a partial remission. Median survival from initiation of therapy was 74 months. Median survival for patients with stages III and IV and peripheral blood involvement was 55 months compared with 31 months for historical controls. Compared with the photopheresis monotherapy group, the patients receiving combination immunomodulatory therapy had a worse prognosis at the time of treatment initiation based on multiple prognostic factors. The positive response rates and median survival times were 84% and 74 months, respectively, compared with 75% and 66 months, respectively, for the combination immunomodulatory and photopheresis monotherapy groups (P =.47 for positive response rates and P =.51 for survival). CONCLUSIONS: Patients with advanced CTCL and multiple poor prognostic factors who receive treatment with combination immunomodulatory therapy experience higher clinical response rates and longer survival than historical controls. Although the group who received combination therapy had worse prognostic factors at baseline, they had better response rates and overall survival compared with those receiving photopheresis monotherapy.


Assuntos
Adjuvantes Imunológicos/uso terapêutico , Linfoma Cutâneo de Células T/patologia , Linfoma Cutâneo de Células T/terapia , Fotoferese , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/terapia , Estudos de Coortes , Terapia Combinada , Feminino , Humanos , Linfoma Cutâneo de Células T/mortalidade , Masculino , Estadiamento de Neoplasias , Avaliação de Resultados em Cuidados de Saúde , Estudos Retrospectivos , Neoplasias Cutâneas/mortalidade , Taxa de Sobrevida
17.
Semin Nucl Med ; 32(1): 70-6, 2002 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-11839072

RESUMO

It has been reported that there is a high correlation between fluorodeoxyglucose (FDG) uptake in the aorta and macrophage content of atherosclerotic lesions in an experimental rabbit model. We evaluated the frequency of FDG uptake in the large arteries in relation to the atherogenic risk factors. We also investigated whether FDG uptake of the large arteries is related to clinically known coronary artery disease. The presence of FDG uptake was assessed in the abdominal aorta (AA), iliac (IA), and proximal femoral arteries (FAs) in 156 patients. Medical history of the atherogenic risk factors (age, cigarette smoking, hypertension, diabetes, high cholesterol, and obesity) and coronary artery disease (CAD) was identified for each patient. The frequency of vascular FDG uptake was compared between the patients without risk factors (Group I, 23 patients) and those with at least 1 risk factor (Group II, 133 patients). The correlation of each risk factor and known CAD with arterial FDG uptake was also assessed in the 3 different arteries. There was a significant difference in the frequency of FDG uptake between the 2 groups for the FA (22% vs 70%) and IA (30% vs 54%), but not for the AA (35% vs 53%). Among all risk factors, age was the most significant and consistent factor correlating with FDG uptake in all 3 arteries. Hypercholesterolemia also correlated consistently with FDG uptake in all 3 arteries. The correlation between the remaining risk factors and arterial FDG uptake was rather artery specific than consistent throughout all 3 arteries. A higher frequency of FDG uptake in the FA was seen in patients with CAD compared with those without CAD. Not all risk factors correlated with FDG uptake in different arteries. Among the risk factors, age and hypercholesterolemia most consistently correlated with FDG uptake in the AA, and the IA and proximal FAs. The positive correlation of arterial FDG uptake with the atherogenic risk factors suggested a promising role for FDG-PET imaging in the diagnosis of atherosclerosis and follow-up after treatment intervention.


Assuntos
Artérias/diagnóstico por imagem , Artérias/metabolismo , Arteriosclerose/diagnóstico por imagem , Doença da Artéria Coronariana/diagnóstico por imagem , Fluordesoxiglucose F18/farmacocinética , Adolescente , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Aorta Abdominal/diagnóstico por imagem , Aorta Abdominal/metabolismo , Arteriosclerose/epidemiologia , Criança , Comorbidade , Doença da Artéria Coronariana/epidemiologia , Doença da Artéria Coronariana/metabolismo , Diabetes Mellitus/epidemiologia , Feminino , Artéria Femoral/diagnóstico por imagem , Artéria Femoral/metabolismo , Humanos , Hipercolesterolemia/epidemiologia , Artéria Ilíaca/diagnóstico por imagem , Artéria Ilíaca/metabolismo , Masculino , Pessoa de Meia-Idade , Obesidade/epidemiologia , Cintilografia , Compostos Radiofarmacêuticos/farmacocinética , Fatores de Risco
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