Last data update: May 06, 2024. (Total: 46732 publications since 2009)
Records 1-9 (of 9 Records) |
Query Trace: Ng DL[original query] |
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Reproductive hormone concentrations and associated anatomical responses: does soy formula affect minipuberty in boys
Chin HB , Kelly A , Adgent MA , Patchel SA , James K , Vesper HW , Botelho JC , Chandler DW , Zemel BS , Schall JI , Ford EG , Darge K , Stallings VA , Baird DD , Rogan WJ , Umbach DM . J Clin Endocrinol Metab 2021 106 (9) 2635-2645 CONTEXT: Soy formula feeding is common in infancy and is a source of high exposure to phytoestrogens, documented to influence vaginal cytology in female infants. Its influence on minipuberty in males has not been established. OBJECTIVE: To assess the association between infant feeding practice and longitudinally measured reproductive hormones and hormone-responsive tissues in infant boys. DESIGN: The Infant Feeding and Early Development study was a prospective cohort of maternal-infant dyads requiring exclusive soy formula, cow-milk formula, or breastmilk feeding during study follow-up. Reproductive hormone concentrations and male anatomical measurements were longitudinally assessed from birth to 28 weeks. SETTING: Clinic-based cohort. PARTICIPANTS: 147 mother-infant boy pairs. INTERVENTIONS: not applicable. MAIN OUTCOME MEASURE: Serum testosterone and luteinizing hormone (LH) concentrations, stretched penile length, anogenital distance, and testis volume. RESULTS: Median serum testosterone was at pubertal levels at 2 weeks [176 ng/dL (quartiles:124, 232)] and remained in this range until 12 weeks, in all feeding groups. We did not observe differences in trajectories of hormone concentrations or anatomical measures between boys fed soy formula (n=55) and boys fed cow-milk formula (n=54). Compared with breastfed boys (n=38), soy-formula-fed boys had a more rapid increase in penile length (p=0.004) and slower initial lengthening of AGD (p=0.03), but no differences in hormone trajectories. CONCLUSIONS: Reproductive hormone concentrations and anatomical responses followed similar trajectories in soy and cow-milk formula-fed infant boys. Our findings suggest that these measures of early male reproductive development do not respond to phytoestrogen exposure during infancy. |
Simultaneous measurement of total estradiol and testosterone in human serum by isotope dilution liquid chromatography tandem mass spectrometry
Zhou H , Wang Y , Gatcombe M , Farris J , Botelho JC , Caudill SP , Vesper HW . Anal Bioanal Chem 2017 409 (25) 5943-5954 Reliable measurement of total testosterone and estradiol is critical for their use as biomarkers of hormone-related disorders in patient care and translational research. We developed and validated a mass spectrometry method to simultaneously quantify these analytes in human serum without chemical derivatization. Serum is equilibrated with isotopic internal standards and treated with acidic buffer to release hormones from their binding proteins. Lipids are isolated and polar impurities are removed by two serial liquid-liquid extraction steps. Total testosterone and estradiol are measured using liquid chromatography tandem mass spectrometry (LC-MS/MS) in combination of positive and negative electrospray ionization modes. The method shows broad analytical measurement range for both testosterone 0.03-48.5 nM (0.75-1400 ng/dL) and estradiol 11.0-5138 pM (2.99-1400 pg/mL) and excellent agreement with certified reference materials (mean bias less than 2.1% to SRM 971, BCR 576, 577, and 578) and a high order reference method (mean bias 1.25% for testosterone and -0.84% for estradiol). The high accuracy of the method was monitored and certified by CDC Hormone Standardization (HoSt) Program for 2 years with mean bias -0.7% (95% CI -1.6% to 0.2%) for testosterone and 0.1% (95% CI -2.2% to 2.3%) for estradiol. The method precision over a 2-year period for quality control pools at low, medium, and high concentrations was 2.7-2.9% for testosterone and 3.3-5.3% for estradiol. With the consistently excellent accuracy and precision, this method is readily applicable for high-throughput clinical and epidemiological studies. |
Harmonized reference ranges for circulating testosterone levels in men of four cohort studies in the USA and Europe
Travison TG , Vesper HW , Orwoll E , Wu F , Kaufman JM , Wang Y , Lapauw B , Fiers T , Matsumoto AM , Bhasin S . J Clin Endocrinol Metab 2017 102 (4) 1161-1173 Background: Reference ranges for testosterone are essential for making a diagnosis of hypogonadism in men. Objective: To establish harmonized reference ranges for total testosterone in men that can be applied across laboratories by cross-calibrating cohort-specific assays to a reference method and standard. Population: 9054 community-dwelling men in cohort studies in the United States and Europe: Framingham Heart Study; European Male Aging Study; Osteoporotic Fractures in Men Study; Male Sibling Study of Osteoporosis. Methods: Testosterone concentrations in 100 participants in each of the four cohorts were measured using a reference method at Centers for Disease Control. Generalized additive models and Bland-Altman analyses supported the use of normalizing equations for transformation between cohort-specific and CDC values. Normalizing equations, generated using Passing-Bablok regression, were employed to generate harmonized values, which were used to derive standardized, age-specific reference ranges. Results: Harmonization procedure reduced inter-cohort variation between testosterone measurements in men of similar ages. In healthy nonobese men, 19-39 years, harmonized 2.5th, 5th, 50th, 95th and 97.5th percentile values were 264, 303, 531, 852 and 916 ng/dL, respectively. Age-specific harmonized testosterone concentrations in nonobese men were similar across cohorts and greater than in all men. Conclusion: The harmonized normal range (2.5th-to-97.5th percentile) in nonobese, population of European and American men, 19-39 years, is 264-916 ng/dL. A substantial proportion of inter-cohort variation in testosterone levels is due to assay differences. These data demonstrate the feasibility of generating harmonized reference ranges for testosterone that can be applied to assays, which have been calibrated to a reference method and calibrator. |
Cardiac tropism of Borrelia burgdorferi: an autopsy study of sudden cardiac death associated with Lyme carditis
Muehlenbachs A , Bollweg BC , Schulz TJ , Forrester JD , DeLeon Carnes M , Molins C , Ray GS , Cummings PM , Ritter JM , Blau DM , Andrew TA , Prial M , Ng DL , Prahlow JA , Sanders JH , Shieh WJ , Paddock CD , Schriefer ME , Mead P , Zaki SR . Am J Pathol 2016 186 (5) 1195-205 Fatal Lyme carditis caused by the spirochete Borrelia burgdorferi rarely is identified. Here, we describe the pathologic, immunohistochemical, and molecular findings of five case patients. These sudden cardiac deaths associated with Lyme carditis occurred from late summer to fall, ages ranged from young adult to late 40s, and four patients were men. Autopsy tissue samples were evaluated by light microscopy, Warthin-Starry stain, immunohistochemistry, and PCR for B. burgdorferi, and immunohistochemistry for complement components C4d and C9, CD3, CD79a, and decorin. Post-mortem blood was tested by serology. Interstitial lymphocytic pancarditis in a relatively characteristic road map distribution was present in all cases. Cardiomyocyte necrosis was minimal, T cells outnumbered B cells, plasma cells were prominent, and mild fibrosis was present. Spirochetes in the cardiac interstitium associated with collagen fibers and co-localized with decorin. Rare spirochetes were seen in the leptomeninges of two cases by immunohistochemistry. Spirochetes were not seen in other organs examined, and joint tissue was not available for evaluation. Although rare, sudden cardiac death caused by Lyme disease might be an under-recognized entity and is characterized by pancarditis and marked tropism of spirochetes for cardiac tissues. |
Clinicopathologic, immunohistochemical, and ultrastructural findings of a fatal case of Middle East respiratory syndrome coronavirus infection in United Arab Emirates, April 2014
Ng DL , Al Hosani F , Keating MK , Gerber SI , Jones TL , Metcalfe MG , Tong S , Tao Y , Alami NN , Haynes LM , Mutei MA , Abdel-Wareth L , Uyeki TM , Swerdlow DL , Barakat M , Zaki SR . Am J Pathol 2016 186 (3) 652-8 Middle East respiratory syndrome coronavirus (MERS-CoV) infection causes an acute respiratory illness and is associated with a high case fatality rate; however, the pathogenesis of severe and fatal MERS-CoV infection is unknown. We describe the histopathologic, immunohistochemical, and ultrastructural findings from the first autopsy performed on a fatal case of MERS-CoV in the world, which was related to a hospital outbreak in the United Arab Emirates in April 2014. The main histopathologic finding in the lungs was diffuse alveolar damage. Evidence of chronic disease, including severe peripheral vascular disease, patchy cardiac fibrosis, and hepatic steatosis, was noted in the other organs. Double staining immunoassays that used anti-MERS-CoV antibodies paired with immunohistochemistry for cytokeratin and surfactant identified pneumocytes and epithelial syncytial cells as important targets of MERS-CoV antigen; double immunostaining with dipeptidyl peptidase 4 showed colocalization in scattered pneumocytes and syncytial cells. No evidence of extrapulmonary MERS-CoV antigens were detected, including the kidney. These results provide critical insights into the pathogenesis of MERS-CoV in humans. |
Thyroid hormones and timing of pubertal onset in a longitudinal cohort of females, Northern California, 2006-11
Wilken JA , Greenspan LC , Kushi LH , Voss RW , Windham GC . Paediatr Perinat Epidemiol 2016 30 (3) 285-93 BACKGROUND: Pubertal timing is regulated by a complex interplay of hormones. Few studies have evaluated the role of thyroid hormones in pubertal onset. We investigated the associations between blood concentrations of free and total thyroxine (FT4, TT4), free triiodothyronine, and thyroid stimulating hormone and pubertal onset among females. METHODS: Participants included 323 Kaiser Permanente Northern California members followed at annual intervals during 2004-11, who provided a blood sample during the first 3 years of the study. Thyroid hormone concentrations were measured in serum in the first blood specimen available for each participant. Pubertal onset was defined as Tanner stage ≥2 for breast (thelarche) and pubic hair (pubarche) development. Associations between thyroid hormones and pubertal onset were assessed by multivariable logistic regression and Cox proportional hazards modelling. RESULTS: At blood draw, participants were age 6.5-10.1 (median 7.7) years, 10% had reached thelarche, and 12% had reached pubarche. Participants were followed 0-5 years after blood draw (median 4). At most recent clinical visit, participants were age 6.7-14.7 (median 12.3) years, 92% had reached thelarche, and 89% had reached pubarche. No associations were identified between having reached thelarche or pubarche at time of blood draw and thyroid hormones. Examined longitudinally, higher concentrations of pre-pubertal FT4 and TT4 were associated with earlier pubarche (adjusted hazard ratio (HR) 1.41, 95% confidence interval (CI) 1.06, 1.86; per ng/dL and aHR 1.07, 95% CI 1.02, 1.12; per mug/dL respectively). CONCLUSIONS: Higher pre-pubertal concentrations of FT4 and TT4 are associated with earlier pubarche. |
Serum Total Testosterone Concentrations in the US Household Population from the NHANES 2011-2012 Study Population
Vesper HW , Wang Y , Vidal M , Cook Botelho J , Caudill SP . Clin Chem 2015 BACKGROUND: Limited information is available about testosterone concentrations representative of the general US population, especially children, women, and non-Hispanic Asians. METHODS: We obtained nationally representative data for total testosterone (totalT), measured with standardized LC-MS/MS, for the US population age 6 years and older from the 2011-2012 National Health and Nutrition Examination Survey (NHANES). We analyzed 6746 serum samples and calculated the geometric means, distribution percentiles, and covariate-adjusted geometric means by age, sex, and race/ethnicity. RESULTS: The 10th-90th percentiles of totalT values in adults (≤20 years) was 150-698 ng/dL (5.20-24.2 nmol/L) in men, 7.1-49.8 ng/dL (0.25-1.73 nmol/L) in women, and 1.0-9.5 ng/dL (0.04-0.33 nmol/L) in children (6-10 years old). Differences among race/ethnic groups existed in children and men: covariate-adjusted totalT values in non-Hispanic Asians were highest among children (58% compared to non-Hispanic black children) and lowest among men (12% compared to Mexican-American men). Covariate-adjusted totalT values in men were higher at age 55-60 years compared to ages 35 and 80 years, a pattern different from that observed in previous NHANES cycles. CONCLUSIONS: TotalT patterns were different among age groups in men compared with previous NHANES cycles. Covariate-adjusted totalT values peaked at age 55-60 years in men, which appeared to be consistent with the increased use of exogenous testosterone. Differences among race/ethnic groups existed and appeared more pronounced in children than adults. |
Tissue and cellular tropism, pathology and pathogenesis of Ebola and Marburg viruses
Martines RB , Ng DL , Greer PW , Rollin PE , Zaki SR . J Pathol 2015 235 (2) 153-74 Ebola viruses and Marburg viruses include some of the most virulent and fatal pathogens known to humans. These viruses cause severe haemorrhagic fevers, with case fatality rates in the range 25-90%. The diagnosis of filovirus using formalin-fixed tissues from fatal cases poses a significant challenge. The most characteristic histopathological findings are seen in the liver; however, the findings overlap with many other viral and non-viral haemorrhagic diseases. The need to distinguish filovirus infections from other haemorrhagic fevers, particularly in areas with multiple endemic viral haemorrhagic agents, is of paramount importance. In this review we discuss the current state of knowledge of filovirus infections and their pathogenesis, including histopathological findings, epidemiology, modes of transmission and filovirus entry and spread within host organisms. The pathogenesis of filovirus infections is complex and involves activation of the mononuclear phagocytic system, with release of pro-inflammatory cytokines, chemokines and growth factors, endothelial dysfunction, alterations of the innate and adaptive immune systems, direct organ and endothelial damage from unrestricted viral replication late in infection, and coagulopathy. Although our understanding of the pathogenesis of filovirus infections has rapidly increased in the past few years, many questions remain unanswered. |
Reference ranges for testosterone in men generated using liquid chromatography tandem mass spectrometry in a community-based sample of healthy nonobese young men in the Framingham Heart Study and applied to three geographically distinct cohorts
Bhasin S , Pencina M , Jasuja GK , Travison TG , Coviello A , Orwoll E , Wang PY , Nielson C , Wu F , Tajar A , Labrie F , Vesper H , Zhang A , Ulloor J , Singh R , D'Agostino R , Vasan RS . J Clin Endocrinol Metab 2011 96 (8) 2430-9 CONTEXT: Reference ranges are essential for partitioning testosterone levels into low or normal and making the diagnosis of androgen deficiency. We established reference ranges for total testosterone (TT) and free testosterone (FT) in a community-based sample of men. METHODS: TT was measured using liquid chromatography tandem mass spectrometry in nonobese healthy men, 19-40 yr old, in the Framingham Heart Study Generation 3; FT was calculated. Values below the 2.5th percentile of reference sample were deemed low. We determined the association of low TT and FT with physical dysfunction, sexual symptoms [European Male Aging Study (EMAS) only], and diabetes mellitus in three cohorts: Framingham Heart Study generations 2 and 3, EMAS, and the Osteoporotic Fractures in Men Study. RESULTS: In a reference sample of 456 men, mean (sd), median (quartile), and 2.5th percentile values were 723.8 (221.1), 698.7 (296.5), and 348.3 ng/dl for TT and 141. 8 (45.0), 134.0 (60.0), and 70.0 pg/ml for FT, respectively. In all three samples, men with low TT and FT were more likely to have slow walking speed, difficulty climbing stairs, or frailty and diabetes than those with normal levels. In EMAS, men with low TT and FT were more likely to report sexual symptoms than men with normal levels. Men with low TT and FT were more likely to have at least one of the following: sexual symptoms (EMAS only), physical dysfunction, or diabetes. CONCLUSION: Reference ranges generated in a community-based sample of men provide a rational basis for categorizing testosterone levels as low or normal. Men with low TT or FT by these criteria had higher prevalence of physical dysfunction, sexual dysfunction, and diabetes. These reference limits should be validated prospectively in relation to incident outcomes and in randomized trials. |
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