Adult thyroid volume determinants and reference values: a Chinese cross-sectional study.

BackgroundWe evaluated the pharmacokinetics of tenofovir alafenamide fumarate (TAF) and tenofovir in a subset of African children enrolled in the CHAPAS-4 trial.MethodsChildren aged 3–15 years with human immunodeficiency virus infection failing first-line antiretroviral therapy were randomized to emtricitabine/TAF versus standard-of-care nucleoside reverse transcriptase inhibitor combination, plus dolutegravir, atazanavir/ritonavir, darunavir/ritonavir, or lopinavir/ritonavir. Daily emtricitabine/TAF was dosed according to World Health Organization (WHO)–recommended weight bands: 120/15 mg in children weighing 14 to <25 kg and 200/25 mg in those weighing ≥25 kg. At steady state, 8–9 blood samples were taken to construct pharmacokinetic curves. Geometric mean (GM) area under the concentration–time curve (AUC) and the maximum concentration (Cmax) were calculated for TAF and tenofovir and compared to reference exposures in adults.ResultsPharmacokinetic results from 104 children taking TAF were analyzed. GM (coefficient of variation [CV%]) TAF AUClast when combined with dolutegravir (n = 18), darunavir/ritonavir (n = 34), or lopinavir/ritonavir (n = 20) were 284.5 (79), 232.0 (61), and 210.2 (98) ng*hour/mL, respectively, and were comparable to adult reference values. When combined with atazanavir/ritonavir (n = 32), TAF AUClast increased to 511.4 (68) ng*hour/mL. For each combination, tenofovir GM (CV%) AUCtau and Cmax remained below reference values in adults taking 25 mg TAF with a boosted protease inhibitors.ConclusionsIn children, TAF combined with boosted PIs or dolutegravir and dosed according to WHO-recommended weight bands provides TAF and tenofovir concentrations previously demonstrated to be well tolerated and effective in adults. These data provide the first evidence for use of these combinations in African children.Clinical Trials RegistrationISRCTN22964075.

ESTABLISHING BLOOD COUNT REFERENCE VALUES IN ADULTS FROM RIVERSIDE COMMUNITIES IN THE STATE OF AMAZONAS

Objective. The Timed Up-&amp;-Go Test (TUGT) is a clinically useful measure that has been widely used in practice toassess functional mobility in older people. Interpretation of TUGT scores relies on appropriate reference values.This study aimed to describe preliminary age- and sex-related reference values for the TUGT for Filipinos aged60–79 years.&#x0D; Methods. This is a descriptive cross-sectional study. We included Filipino adults aged 60–79 years, with no significantdisability, and resided in metropolitan areas in the National Capital Region and rural communities in southernLuzon. All participants completed the TUGT. Data were analyzed descriptively and reported as means, standarddeviations, and 95% confidence intervals.&#x0D; Results. A total of 156 community-dwelling older adults participated in the study with mean age (SD) of 68 (5)years. The majority were women (103/156, 66%). Mean (SD) TUGT score for all participants was 11.0 (2.4) seconds.Overall, men completed the test faster compared to women, and individuals in the 60–69 years age group hadshorter completion times than those in the 70–79 years age group.&#x0D; Conclusion. In the absence of definitive reference values for older Filipino adults, this study provides preliminaryguidance for interpreting TUGT performance for the purposes of screening and monitoring functional mobilityimpairments in this population.

BackgroundThere is need for locally-derived age-specific clinical laboratory reference ranges of healthy Africans in sub-Saharan Africa. Reference values from North American and European populations are being used for African subjects despite previous studies showing significant differences. Our aim was to establish clinical laboratory reference values for African adolescents and young adults that can be used in clinical trials and for patient management.Methods and FindingsA panel of 298, HIV-seronegative individuals aged 13–34 years was randomly selected from participants in two population-based cross-sectional surveys assessing HIV prevalence and other sexually transmitted infections in western Kenya. The adolescent (<18 years)-to-adults (≥18 years) ratio and the male-to-female ratio was 1∶1. Median and 95% reference ranges were calculated for immunohematological and biochemistry values. Compared with U.S-derived reference ranges, we detected lower hemoglobin (HB), hematocrit (HCT), red blood cells (RBC), mean corpuscular volume (MCV), neutrophil, glucose, and blood urea nitrogen values but elevated eosinophil and total bilirubin values. Significant gender variation was observed in hematological parameters in addition to T-bilirubin and creatinine indices in all age groups, AST in the younger and neutrophil, platelet and CD4 indices among the older age group. Age variation was also observed, mainly in hematological parameters among males. Applying U.S. NIH Division of AIDS (DAIDS) toxicity grading to our results, 40% of otherwise healthy study participants were classified as having an abnormal laboratory parameter (grade 1–4) which would exclude them from participating in clinical trials.ConclusionHematological and biochemistry reference values from African population differ from those derived from a North American population, showing the need to develop region-specific reference values. Our data also show variations in hematological indices between adolescent and adult males which should be considered when developing reference ranges. This study provides the first locally-derived clinical laboratory reference ranges for adolescents and young adults in western Kenya.

The evolution of the main serum opsonins in neonates and infants of varying gestational age was investigated to provide reference values for these opsonins in early infancy. Serum concentrations of immunoglobulins, IgG subclasses, C3, C4 and fibronectin were serially measured from birth until the age of 6 months in term and preterm infants. Measurements were performed by rate nephelometry. Five hundred and sixty six neonates (gestational age 26-41 weeks) were examined at birth, 233 at 1 month, 218 at 3 months, and 147 at 6 months, respectively. The same measurements were performed in 54 pairs of neonatal/maternal samples and in 230 apparently healthy adults. Gestational age had a significant impact on serum IgG, IgG subclasses, C3 and C4 up till the third month, and on fibronectin until the first month. No such impact was observed for IgA and IgM. Sixteen per cent of the neonates had IgM concentrations higher than 0.2 g/l at birth, suggesting that the critical concentration of serum IgM at birth for suspected intrauterine infection should be reconsidered. Concentrations of all opsonins at birth were significantly lower than adult reference values. They only approached or even reached adult values by the third or the sixth month. Data from analysis of the neonatal and the corresponding maternal sera indicate that there is a preferential active transplacental transport of IgG subclasses in the order of IgG1, IgG3, IgG2 and IgG4. These results show that concentrations of immunoglobulins, C3, C4 and fibronectin undergo changes during the first months of life, depending not only on the infants' postnatal age but also on gestational age.

Although urinary biochemical markers can be assessed by their ratio to urinary creatinine (U-Cr) concentration, reference values in adults may not be applicable to children because the amount of Cr excreted varies by body size. We therefore measured the relationship between age and the ratios of urinary β-2-microglobulin (U-β2MG), N-acetyl-β-d-glucosaminidase (U-NAG), calcium (U-Ca) and protein (U-Pr) concentration to those of U-Cr in children. Fifty-seven patients aged >1 year with benign familial hematuria (median age, 6.3 years) were divided into three age groups: 1-4, 5-9, and ≥10 years. Urinary biomarkers were assayed using actual values; ratios to actual U-Cr values; and our standardized metric, namely 100-fold the ratio of serum Cr to U-Cr concentration; and the relationship of each of these to age was determined. The ratios of U-β2MG, U-NAG and U-Ca to Cr varied significantly by age, being higher in younger than in older children, but the actual and standardized values of each did not vary by age, nor did any measurement of U-Pr. The ratios of urinary markers of tubular function, including U-β2MG, U-NAG and U-Ca, to Cr vary by age, being higher in younger children. In contrast, the ratios of urinary markers of glomerular filtration (such as U-Pr)to Cr do not vary by age, making them suitable for corrections relative to Cr.

<b>Introduction:</b> While peak in- and expiratory flow rates offer valuable information for diagnosis and monitoring in respiratory disease, these indices are usually considered too variable to be used for quantification in clinical practice. <b>Aims and Objectives:</b> To develop a method for reproducible measurement of maximal inspiratory flow rates and construct reference equations for peak in- and expiratory flows (PIF, PEF), allowing for age and height dependence of the limits of normal. <b>Methods:</b> With coaching for maximal effort, 187 healthy Caucasian subjects (20-80 years) performed at least 3 combined forced inspiratory and expiratory maneuvers, until at least 2 peak inspiratory flow measurements were within 10% of each other. The effect on PIF preceded by a slow expiration instead of a forced expiration, and PIF repeatability over 3 different days were also investigated in subgroups. <b>Results:</b> A valid PIF could be obtained within 3.3+0.6(SD) attempts, resulting in an overall within-test PIF variability of 4.6±3.2(SD)%. Reference values and limits of normal for PIF, FIF₅₀ and PEF were obtained according to the LMS statistical method. A slow instead of a forced expiration prior to forced inspiration resulted in a significant (p&lt;0.001) but small PIF increase (2.5% on average). There were no significant between-day PIF differences (P&gt;0.1). Over the entire age range, inter-subject PIF variability was smaller than in previous reports. <b>Conclusions:</b> When adhering to similar criteria for the measurement of effort-dependent portions of inspiratory and expiratory flow-volume curves, performed according to current ATS/ERS standards, it is possible to obtain reproducible PIF and PEF values for use in routine practice.

To ensure a successful pregnancy, a delicate immunological balance is essential at the feto-maternal interface. Dysregulation of the complement system is linked to adverse pregnancy outcomes such as fetal growth restriction, preeclampsia and preterm birth. However, it is unknown how this translates into umbilical cord concentrations of complement factors. Umbilical cord blood samples were collected from 12 term vaginal births, 12 term elective caesarean sections, 11 preterm births, and 14 cases of preeclampsia. C1q, C4, C3, MBL, Factor H and properdin concentrations were measured. In term pregnancies, MBL, factor H and properdin concentrations were significantly lower in elective caesarean sections compared to vaginal deliveries. In preeclampsia, umbilical cord blood showed lower concentrations of C1q and MBL and a higher concentration of properdin compared to term deliveries (n=24). Within the preeclampsia group, C1q, factor H and properdin correlated to gestational age. Early onset preeclampsia showed significantly lower concentrations of C1q, factor H and properdin compared to late onset preeclampsia. Preterm births compared to term births had significantly lower concentrations of C1q, C4, C3 and MBL. Concentrations of C1q, C4, C3, and MBL in umbilical cord blood are lower in cases of preeclampsia and preterm births compared to term pregnancies. The complement system in fetuses seems to develop throughout gestation, approaching concentrations at term that are similar with established reference values in adults. Higher concentrations of lectin and alternative pathway components in term births versus term elective caesarean sections likely highlight the inflammatory process associated with labour.

Introduction: The purpose of this study was to establish reference ranges of total thyroid volume among clinically euthyroid Nepalese population using Ultrasonography and correlate this volume with age, sex, individual&rsquo;s built and geographic location. Methods: This was a prospective cross sectional study involving 485 clinically euthyroid individuals. B - mode Ultrasonography was used to measure the total thyroid volume by combining the volume of both the lobes obtained by using formula for prolate ellipsoid. Age specific reference values for thyroid volume were obtained and Pearson correlation test was used to see the relationship with various factors. Results: Among 485 individuals between 1 to 83 years of age, 221(45.57%) were males and 264(54.43%) were females. Maximum [354 individuals (72.99%)] were from hilly region and minimum [16 individual (3.30%)] were from Himalayan region. Mean thyroid volume was 6.629 &plusmn; 2.5025 ml. In general, thyroid volume was found to be more in older individuals than in young age group. There was no significant difference of thyroid volume between males and females. Thyroid volume best correlated with body surface area (r=0.444, p&lt;0.0001). The volume had a positive correlation with weight (r=0.443, p&lt;0.0001), body mass index (r=0.371, p&lt;0.0001) and height (r=0.320, p&lt;0.0001) of the individual. Conclusions: This study estimated the reference range of total thyroid volume for Nepalese population. These ranges are significantly lower than the WHO/ICCIDD thyroid volume references and reference values obtained in various other countries. Total thyroid volume best correlated with Body surface area. Keywords: Body surface area; clinically euthyroid; total thyroid volume; ultrasonography DOI: http://dx.doi.org/10.3126/joim.v32i2.4944 Journal of Institute of Medicine, August, 2010; 32: 36-43

Transpulmonary thermodilution is well established as a tool for in-depth hemodynamic monitoring of critically ill patients during surgical procedures and intensive care. It permits easy assessment of graft function following cardiac transplantation and guides post-operative volume and catecholamine therapy. Since no pulmonary catheter is needed, transpulmonary thermodilution could be useful in experimental cardiac pig-to-baboon xenotransplantation. However, normal values for healthy animals have not yet been reported. Here, we present data from piglets and baboons before xenotransplantation experiments and highlight differences between the two species and human reference values. Transpulmonary thermodilution from baboons (body weight 10-34kg) and piglets (body weight 10-38kg) were analyzed. Measurements were taken in steady state after induction of general anesthesia before surgical procedures commenced. Cardiac index (CI), mean arterial pressure (MAP), systemic vascular resistance index (SVRI), parameters quantifying cardiac filling (global end-diastolic volume index, GEDI), and pulmonary edema (extravascular lung water, ELWI) were assessed. Preload, afterload, and contractility parameters clearly correlated with total body weight or body surface area. Baboons had lower CI values than weight-matched piglets (4.2±0.9l/min/m2 vs 5.3±1.0/min/m2 , P<.01). MAP and SVRI were higher in baboons than piglets (MAP: 99±22mmHg vs 62±11mmHg, P<.01; SVRI: 1823±581dyn*s/cm5 *m2 vs 827±204dyn*s/cm5 *m2 , P<.01). GEDI and ELWI did differ significantly between both species, but measurements were within similar ranges (GEDI: 523±103mL/m2 vs 433±78mL/m2 , P<.01; ELWI: 10±3mL/kg vs 11±2mL/kg, P<.01). Regarding adult human reference values, CI was similar to both baboons and piglets, but all other parameters were different. Parameters of preload, afterload, and contractility differ between baboons and piglets. In particular, baboons have a much higher afterload than piglets, which might be instrumental in causing perioperative xenograft dysfunction and post-operative myocardial hypertrophy after orthotopic pig-to-baboon cardiac xenotransplantation. Most transpulmonary thermodilution-derived parameters obtained from healthy piglets and baboons lie outside the reference ranges for humans, so human normal values should not be used to guide treatment in those animals. Our data provide reference values as a basis for developing algorithms for perioperative hemodynamic management in pig-to-baboon cardiac xenotransplantation.

BackgroundDespite the widespread use of fractional exhaled nitric oxide (FENO) as a biomarker of airways inflammation, there are no published papers describing normal FENO values in a large group of healthy adults.ObjectiveThe aim of this study was to establish adult FENO reference values according to the international guidelines.MethodsFENO was measured in 204 healthy, non-smoking adults with normal spirometry values using the on-line single-breath technique, and the results were analysed chemiluminescently.ResultsThe main result of the study was the significant difference in FENO values between men and women, thus indicating that gender-based reference FENO values are necessary. The FENO levels obtained at expiratory flows of 50 ml/s ranged from 2.6 to 28.8 ppb in men, and from 1.6 to 21.5 ppb in women.ConclusionWe propose reference FENO values for healthy adult men and women that could be used for clinical and research purposes.

Osteosclerosis (OMIM: 144750) is a type of autosomal dominant bone disease caused by a mutation in the low-density lipoprotein receptor-related protein 5 (LRP5) gene. The case of a Chinese family with two affected individuals is reported in the present study in order to investigate the clinical characteristics and virulence genes of this sclerosing bone disorder. Biochemical and radiographic examinations and bone mineral density (BMD) and genetic analyses were performed in two patients and eight other family members. The 40-year-old proband (II-1) and her 64-year-old mother (I-2) both had chronic lumbodorsal pain, an elongated mandible and torus palatinus in the center of the hard palate. No fractures were observed in any of the family members. Skull, mandibular and pelvic X-rays in each of the two patients revealed thickened cranial plates, an enlarged sella turcica, an elongated mandible and cortical thickening of the long bones. The BMD values of the two patients was significantly higher than the standard age- and sex-matched adult mean reference values. Both patients had higher serum sclerostin levels, while their renal function markers and serum calcium, phosphonium, parathyroid hormone (PTH) and 25(OH)D levels were within the normal ranges. The heterozygous missense mutation p.Ala242Thr in exon 4 of the LRP5 gene was detected in the two patients, while the other family members and 200 healthy donors had normal wild-type genotypes. The A242T mutation in the LRP5 gene resulted in a high bone mass phenotype with an elongated mandible and torus palatinus in this osteosclerotic family.

Hepatocyte growth factor (HGF) has been reported recently to be a prognostic factor of acute pulmonary disorders. Regarding the clinical relationships of HGF with neonates, Khan et al reported the...

A retrospective analysis of quantitative and qualitative immunoglobulin G (IgG) results from 253 children who were either medically and neurologically normal or highly unlikely to have abnormalities of CSF IgG is reported. Normal values in this reference population vary with age for CSF/albumin IgG ratio and CSF/serum IgG index and are significantly different from the adult reference values. The rate of false positivity is lower for quantitative values than for qualitative IgG determinations (oligoclonal bands).

SUMMARY Fetal and neonatal lamb hemostasis were studied from the 60th day of pregnancy to birth. Platelet counts and blood coagulation, as assessed by tests such as recalcification time and thromboelastography, were similar in fetuses, neonates, and adult sheep. The values of coagulation factors were low, ie, vitamin K-dependent Factors II, VII, IX, and X remained unchanged (30 and 40% of adult reference values) until the last 10 days of gestation, and then increased until birth (40 to 60%). Values of fibrinogen and Factor V followed a similar pattern, although their activities became identical to adult values at birth. Also, we measured values of protein C and antithrombin III, which are synthesized by the liver. The importance of hepatic failure and fetal vitamin K deficiency were discussed. Factors VIII and XII activities increased gradually during pregnancy to reach adult values at birth. Fetal fibrinolytic activity increased. This could not be explained by the values of tissue-type plasminogen activator (it was not detectable) or by the presence of its fast acting inhibitor, whose concentration did not decrease.