The importance of growth hormone in the regulation of erythropoiesis, red cell mass, and plasma volume in adults with growth hormone deficiency

Total body water (TBW) is reduced in adult GH deficiency (GHD) largely due to a reduction of extracellular water. It is unknown whether total blood volume (TBV) contributes to the reduced extracellular water in GHD. GH and insulin-like growth factor I (IGF-I) have been demonstrated to stimulate erythropoiesis in vitro, in animal models, and in growing children. Whether GH has a regulatory effect on red cell mass (RCM) in adults is not known. We analyzed body composition by bioelectrical impedance and used standard radionuclide dilution methods to measure RCM and plasma volume (PV) along with measuring full blood count, ferritin, vitamin B12, red cell folate, IGF-I, IGF-binding protein-3, and erythropoietin in 13 adult patients with GHD as part of a 3-month, double blind, placebo-controlled trial of GH (0.036 U/kg.day). TBW and lean body mass significantly increased by 2.5 +/- 0.53 kg (mean +/- SEM; P < 0.004) and 3.4 +/- 0.73 kg (P < 0.004), respectively, and fat mass significantly decreased by 2.4 +/- 0.32 kg (P < 0.001) in the GH-treated group. The baseline RCM of all patients with GHD was lower than the predicted normal values (1635 +/- 108 vs. 1850 +/- 104 mL; P < 0.002). GH significantly increased RCM, PV, and TBV by 183 +/- 43 (P < 0.006), 350 +/- 117 (P < 0.03), and 515 +/- 109 (P < 0.004) mL, respectively. The red cell count increased by 0.36 +/- 0.116 x 10(12)/L (P < 0.03) with a decrease in ferritin levels by 39.1 +/- 4.84 micrograms/L (P < 0.001) after GH treatment. Serum IGF-I and IGF-binding protein-3 concentrations increased by 3.0 +/- 0.43 (P < 0.001) and 1.3 +/- 0.15 (P < 0.001) SD, respectively, but the erythropoietin concentration was unchanged after GH treatment. No significant changes in body composition or blood volume were recorded in the placebo group. Significant positive correlations could be established between changes in TBW and TBV, lean body mass and TBV (r = 0.78; P < 0.04 and r = 0.77; P < 0.04, respectively), and a significant negative correlation existed between changes in fat mass and changes in TBV in the GH-treated group (r = -0.95; P < 0.02). We conclude that 1) erythropoiesis is impaired in GHD; 2) GH stimulates erythropoiesis in adult GHD; and 3) GH increases PV and TBV, which may contribute to the increased exercise performance seen in these patients.

The consequences of growth hormone deficiency in adulthood, and the effects of growth hormone replacement

The availability of recombinant human growth hormone (GH) has resulted in investigation of the role of GH in adulthood and the effects of GH replacement in the GH-deficient adult. These studies have led to the recognition of a specific syndrome of GH-deficiency, characterized by symptoms, signs and investigative findings. Adults with long-standing growth hormone deficiency are often overweight, have altered body composition, with reduced lean body mass (LBM), increased fat mass (FM), reduced total body water and reduced bone mass. In addition, there is reduced physical and cardiac performance, altered substrate metabolism and an abnormal lipid profile predisposing to the development of cardiovascular disease. Adults with GH deficiency report reduced psychological well-being and quality of life. These changes may contribute to the morbidity and premature mortality observed in hypopituitary adults on conventional replacement therapy. GH treatment restores LBM, reduces FM, increases total body water and increases bone mass. Following GH therapy, increases are recorded in exercise capacity and protein synthesis, and "favourable" alterations occur in plasma lipids. In addition, psychological well-being and quality of life improve with replacement therapy. GH is well tolerated; adverse effects are largely related to fluid retention and respond to dose adjustment. It is likely that GH replacement will become standard therapy for the hypopituitary adult in the near future. The benefits of GH replacement in the GH-deficient adult have been unequivocally demonstrated in studies lasting up to 3 years. The results of longer term studies are awaited to determine whether these benefits are sustained over a lifetime.

A case of distinct difference between the measured blood Ethanol concentration and the concentration estimated by Widmark's equation

In the last century, several mathematical models have been developed to calculate blood ethanol concentrations (BAC) from the amount of ingested ethanol and vice versa. The most common one in the field of forensic sciences is Widmark's equation. A drinking experiment with 10 voluntary test persons was performed with a target BAC of 1.2 g/kg estimated using Widmark's equation as well as Watson's factor. The ethanol concentrations in the blood were measured using headspace gas chromatography/flame ionization and additionally with an alcohol Dehydrogenase (ADH)-based method. In a healthy 75-year-old man a distinct discrepancy between the intended and the determined blood ethanol concentration was observed. A blood ethanol concentration of 1.83 g/kg was measured and the man showed signs of intoxication. A possible explanation for the discrepancy is a reduction of the total body water content in older people. The incident showed that caution is advised when using the different mathematical models in aged people. When estimating ethanol concentrations, caution is recommended with calculated results due to potential discrepancies between mathematical models and biological systems

X-ray image calibration and its application to clinical orthopedics.

X-ray imaging is one of the most commonly used medical imaging modality. Albeit X-ray radiographs provide important clinical information for diagnosis, planning and post-operative follow-up, the challenging interpretation due to its 2D projection characteristics and the unknown magnification factor constrain the full benefit of X-ray imaging. In order to overcome these drawbacks, we proposed here an easy-to-use X-ray calibration object and developed an optimization method to robustly find correspondences between the 3D fiducials of the calibration object and their 2D projections. In this work we present all the details of this outlined concept. Moreover, we demonstrate the potential of using such a method to precisely extract information from calibrated X-ray radiographs for two different orthopedic applications: post-operative acetabular cup implant orientation measurement and 3D vertebral body displacement measurement during preoperative traction tests. In the first application, we have achieved a clinically acceptable accuracy of below 1° for both anteversion and inclination angles, where in the second application an average displacement of 8.06±3.71 mm was measured. The results of both applications indicate the importance of using X-ray calibration in the clinical routine.

Arterial hypertension in elderly patients

Why do we need a review specifically addressing arterial hypertension in elderly patients? First, a rterial hypertension prevalence increases with age and, therefore, a large proportion of hypertensive patients are elderly patients. Despite this fact, the specific issues of arterial hypertension in elderly patients are only marginally debated in current guidelines. Second, there are physiological changes (e.g., i ncreasing arterial stiffness, reduced body water content, decreased function of several organ systems) and pathophysiological changes (e.g. increasing prevalence of comorbidities) with increasing age, making diagnosis and therapy of arterial hypertension in elderly patients more demanding. Third, f or some recommendations (e.g., a ppropriate target blood pressure) levels of evidence are lower than in younger hypertensive patients, leading to conflicting recommendations between guidelines. This review intends to discuss some of the specific issues in elderly patients with arterial hypertension. Key words: hypertension; elderly; guidelines; geriatric assessment

Ostracoda fauna of surface sediments from the Persian Gulf

During the "Meteor"-Expedition to the Persian Gulf in March-May 1965, approximately 300 samples were collected. Most of them have been already studied by various authors in sedimentological as well as micropaleontological respects. 49 samples were selected for ostracode studies. These samples are arranged to form a long-axis section ("Laengsprofil"), and 4 shorter cross-profiles, perpendicular to the long-axis profile in the Persian Gulf and Gulf of Oman. 52 species of ostracodes in this area were specifically determined; 39 of them are described under open nomenclature. 13 species are already known from surrounding sea areas: 2 species from the Red Sea; 2 species from the east coast of Africa; 1 species from the Mediterranean Sea; and others from the Indian and Pacific Oceans. 12 species show close relationships to species from the Indopacific Ocean. The ostracode species found in the area can be grouped after the method of BRAUN-BLANQUT into 2 bioassociations. Association 1 with the following 4 characteristic species : Cytherella cf. pulchra, Loxoconcha sp. A, Neomonoceratina sp. A, Alocopocythere reticulata. Association 2 with 1 characteristic species: Ruggieria (Ruggieria) sp. B. The association 1 is widespread in the entire studied area of the Persian Gulf, where it is considered to characterize the shallow water region down to 200 m. The association 2 is restricted to the deeper water below 200 m of the inner part of the Oman Gulf. Only a few species known from the shallow water association of the Persian Gulf are present. Within the two ostracode associations mentioned above 4 zones from the total studied area could be related to the water depth. The zones A-D are characterized more or less readily by the relative abundance of certain species: Zone A : 7-30 m depth, on substrates of poorly coarse-grained clayey marl; Zone B: 30-94 m depth, on substrates of richly coarse-grained calcareous marl; Zone C: 94-1961208 m depth, on substrates of richly coarse-grained calcareous marl; Zone D: 196/208-500 m depth, on substrates of calcareous clay, poor in benthos. The regional and bathymetric distribution of the ostracode fauna in the area studied was compared in relation to 10 environmental factors: water depth, temperature, salinity, water density, O2-concentration, phosphate-silica contents, pH-values, stratification of the water body, water currents and type of sediments. The major environmental factors which appear to control the ostracode distribution are water depth (as a complex factor), O2-concentration and the type of sediment. At 3 stations (GIK01058, GIK01074 and GIK01204) species of the shallow water association were found together with a few bathyal species. These stations are situated at the outer Biaban shelf, in an area where the bottom water of the Persian Gulf flows down the slope towards the Oman Gulf. Several samples of the Zone B in the major part of the Persian Gulf show also a high species diversity containing a high percentage of subfossil ostracode carapaces. It is probable that the recent biocoenosis has been mixed with a late quarternary thanatocoenosis.

Factores predictores de pérdida de peso y grasa en el tratamiento dietético: sexo, edad, índice de masa corporal y consulta de asistencia

%WL: porcentaje de pérdida de peso; %FL: porcentaje de pérdida de grasa; PNLWF: pacientes que pierden peso o grasa; PLWF: pacientes que pierden peso y grasa. Objetivo: evaluar si el %WL y el %FL en el tratamiento dietético, se vieron afectados por el género, la edad, el IMC y la asistencia a la consulta. Método: 4.700 consultas, 670 pacientes (IMC ≥ 25), en el sur-este de España (2006-12). Se utilizó la dieta equilibrada e hipocalórica. Dos tipos de pacientes: PNLWF y PLWF (91,9%). Resultados: en los PLWF, los hombres y los que asisten en mayor número de ocasiones a la consulta han mostrado una mayor pérdida, frente a las mujeres (%FL: 23,0 vs 14,3%, p = 0,000; %WL: 7,7 vs 6,6%, p = 0,020), y los que asisten con menor frecuencia (%FL: 19,1 vs 7,3%, p = 0,000; %WL: 7,8 vs 2,9%, p = 0,000). El análisis de regresión multinomial (PNLWF/ PLWF) indica que solo el asistir a más de mes y medio a la consulta es un factor que influye en la pérdida, OR 8,3 (IC 95% 4,5-15,1; p = 0,000). Conclusión: la medición de la grasa corporal proporciona una información adicional al peso perdido; la mayoría de los pacientes que asisten más de mes y medio obtienen un elevado %FL; la asistencia es un factor predictor de la pérdida; el %FL indica que el tratamiento dietético juega un papel principal en la resolución de esta patología; se recomienda diseñar esquemas prácticos del proceso de actuación de los nutricionistas en función del IMCi y el variable.

Validity of BMI as a measure of obesity in Australian white Caucasian and Australian Sri lankan children

Background: Body mass index ( BMI) is used to diagnose obesity. However, its ability to predict the percentage fat mass (% FM) reliably is doubtful. Therefore validity of BMI as a diagnostic tool of obesity is questioned. Aim: This study is focused on determining the ability of BMI- based cut- off values in diagnosing obesity among Australian children of white Caucasian and Sri Lankan origin. Subjects and methods: Height and weight was measured and BMI ( W/H-2) calculated. Total body water was determined by deuterium dilution technique and fat free mass and hence fat mass derived using age- and gender- specific constants. A % FM of 30% for girls and 20% for boys was considered as the criterion cut- off level for obesity. BMI- based obesity cut- offs described by the International Obesity Task Force ( IOTF), CDC/ NCHS centile charts and BMI- Z were validated against the criterion method. Results: There were 96 white Caucasian and 42 Sri Lankan children. Of the white Caucasians, 19 ( 36%) girls and 29 ( 66%) boys, and of the Sri Lankans 7 ( 46%) girls and 16 ( 63%) boys, were obese based on % FM. The FM and BMI were closely associated in both Caucasians ( r = 0.81, P < 0.001) and Sri Lankans ( r = 0.92, P< 0.001). Percentage FM and BMI also had a lower but significant association. Obesity cut- off values recommended by IOTF failed to detect a single case of obesity in either group. However, NCHS and BMI- Z cut- offs detected cases of obesity with low sensitivity. Conclusions: BMI is a poor indicator of percentage fat and the commonly used cut- off values were not sensitive enough to detect cases of childhood obesity in this study. In order to improve the diagnosis of obesity, either BMI cut- off values should be revised to increase the sensitivity or the possibility of using other indirect methods of estimating the % FM should be explored.

Ability of Bioelectrical Impedance to Predict Percentage Fat Mass in Children of Two Different Ethnic Origins

Detailed analysis of body composition in children has helped to understand changes that occur in growth and disease. Bioelectrical impedance analysis (BIA) has gained popularity as a simple, non-invasive and inexpensive tool of body composition assessment. Being an indirect technique, prediction equations have to be used in the assessment of body composition. There are many prediction equations available in the literature for the assessment of body composition from BIA. This study aims to cross-validate some of those prediction equations to determine the suitability of their use on Australian children of white Caucasian and Sri Lankan origins. Height, weight and BIA were measured. Total body water was measured using the isotope dilution method (D2O). Fat-mass (FM) and %FM were estimated from BIA using ten prediction equations described in the literature. Five to 14.99-year-old healthy, 96 white Caucasians and 42 Sri Lankan children were studied. The equation of Schaefer et al was the most suitable prediction equation for this group with the lowest mean bias for %FM assessment in both Caucasian (–1.0±9.6%) and Sri Lankan (1.6±5.2%) children and the fat content of the individuals did not influence the predictions by this equation. Impedance index (height2/impedance) explained for 80% of TBW in white Caucasians and 93% in Sri Lankans and figures were similar for the prediction of FFM. We conclude that BIA can be used effectively in the assessment of body composition in children. However, for the assessment of body composition using BIA, either prediction equations should be derived to suit the local populations or existing equations should be cross-validated to determine their suitability before their application.

Multi-frequency segmental bio-impedance device:design, development and applications

Bio-impedance analysis (BIA) provides a rapid, non-invasive technique for body composition estimation. BIA offers a convenient alternative to standard techniques such as MRI, CT scan or DEXA scan for selected types of body composition analysis. The accuracy of BIA is limited because it is an indirect method of composition analysis. It relies on linear relationships between measured impedance and morphological parameters such as height and weight to derive estimates. To overcome these underlying limitations of BIA, a multi-frequency segmental bio-impedance device was constructed through a series of iterative enhancements and improvements of existing BIA instrumentation. Key features of the design included an easy to construct current-source and compact PCB design. The final device was trialled with 22 human volunteers and measured impedance was compared against body composition estimates obtained by DEXA scan. This enabled the development of newer techniques to make BIA predictions. To add a ‘visual aspect’ to BIA, volunteers were scanned in 3D using an inexpensive scattered light gadget (Xbox Kinect controller) and 3D volumes of their limbs were compared with BIA measurements to further improve BIA predictions. A three-stage digital filtering scheme was also implemented to enable extraction of heart-rate data from recorded bio-electrical signals. Additionally modifications have been introduced to measure change in bio-impedance with motion, this could be adapted to further improve accuracy and veracity for limb composition analysis. The findings in this thesis aim to give new direction to the prediction of body composition using BIA. The design development and refinement applied to BIA in this research programme suggest new opportunities to enhance the accuracy and clinical utility of BIA for the prediction of body composition analysis. In particular, the use of bio-impedance to predict limb volumes which would provide an additional metric for body composition measurement and help distinguish between fat and muscle content.

Fast and efficient : Postnatal growth and energy expenditure in an Arctic-breeding waterbird, the Red-throated Loon (Gavia stellata)

Peer reviewed

Lifestyle factors, adiposity and cardiometabolic risk factors in South Asian women living in Scotland

South Asians migrating to the Western world have a 3 to 5-fold higher risk of developing type 2 diabetes and double the risk of cardiovascular disease (CVD) than the background population of White European descent, without exhibiting a proportional higher prevalence of conventional cardiometabolic risk factors. Notably, women of South Asian descent are more likely to be diagnosed with type 2 diabetes as they grow older compared with South Asian men and, in addition, they have lost the cardio-protective effects of being females. Despite South Asian women in Western countries being a high risk group for developing future type 2 diabetes and CVD, they have been largely overlooked. The aims of this thesis were to compare lifestyle factors, body composition and cardiometabolic risk factors in healthy South Asian and European women who reside in Scotland, to examine whether ethnicity modifies the associations between modifiable environmental factors and cardiometabolic risks and to assess whether vascular reactivity is altered by ethnicity or other conventional and novel CVD risks. I conducted a cross-sectional study and recruited 92 women of South Asian and 87 women of White European descent without diagnosed diabetes or CVD. Women on hormone replacement therapy or hormonal contraceptives were excluded too. Age and body mass index (BMI) did not differ between the two ethnic groups. Physical activity was assessed and with self-reported questionnaires and objectively with the use of accelerometers. Cardiorespiratory fitness was quantified with the predicted maximal oxygen uptake (VO2 max) during a submaximal test (Chester step test). Body composition was assessed with skinfolds measured at seven body sites, five body circumferences, measurement of abdominal subcutaneous (SAT) and visceral adipose tissue (VAT) with the use of magnetic resonance imaging (MRI) and liver fat with the use MR spectroscopy. Dietary density was assessed with food frequency questionnaires. Vascular response was assessed by measuring the response to acetylcholine and sodium nitroprusside with the use of Laser Doppler Imaging with Iontophoresis (LDI-ION) and the response to shear stress with the use of Peripheral Arterial Tonometry (EndoPAT). The South Asian women exhibited a metabolic profile consistent with the insulin resistant phenotype, characterised by greater levels of fasting insulin, lower levels of high density lipoprotein (HDL) and higher levels of triglycerides (TG) compared with their European counterparts. In addition, the South Asians had greater levels of glycated haemoglobin (HbA1c) for any given level of fasting glucose. The South Asian women engaged less time weekly with moderate to vigorous physical activity (MVPA) and had lower levels of cardiorespiratory fitness for any given level of physical activity than the women of White descent. In addition, they accumulated more fat centrally for any given BMI. Notably, the South Asians had equivalent SAT with the European women but greater VAT and hepatic fat for any given BMI. Dietary density did not differ among the groups. Increasing central adiposity had the largest effect on insulin resistance in both ethic groups compared with physical inactivity or decreased cardiorespiratory fitness. Interestingly, ethnicity modified the association between central adiposity and insulin resistance index with a similar increase in central adiposity having a substantially larger effect on insulin resistance index in the South Asian women than in the Europeans. I subsequently examined whether ethnic specific thresholds are required for lifestyle modifications and demonstrated that South Asian women need to engage with MVPA for around 195 min.week-1 in order to equate their cardiometabolic risk with that of the Europeans exercising 150 min.week-1. In addition, lower thresholds of abdominal adiposity and BMI should apply for the South Asians compared with the conventional thresholds. Although the South Asians displayed an adverse metabolic profile, vascular reactivity measured with both methods did not differ among the two groups. An additional finding was that menopausal women with hot flushing of both ethnic groups showed a paradoxical vascular profile with enhanced skin perfusion (measured with LDI-ION) but decreased reactive hyperaemia index (measured with EndoPAT) compared with asymptomatic menopausal women. The latter association was independent of conventional CVD risk factors. To conclude, South Asian women without overt disease who live in Scotland display an adverse metabolic profile with steeper associations between lifestyle risk factors and adverse cardiometabolic outcomes compared with their White counterparts. Further work in exploring ethnic specific thresholds in lifestyle interventions or in disease diagnosis is warranted.

Bioelectric Impedance Analysis in the Diagnosis of Vesicoureteral Reflux

Background: Vesicoureteral reflux (VUR) is a common abnormality of the urinary tract in childhood. Objectives: As urine enters the ureters and renal pelvis during voiding in vesicoureteral reflux (VUR), we hypothesized that change in body water composition before and after voiding may be less different in children with VUR. Patients and Methods: Patients were grouped as those with VUR (Group 1) and without VUR (Group 2). Bioelectric impedance analysis was performed before and after voiding, and third space fluid (TSF) (L), percent of total body fluid (TBF%), extracellular fluid (ECF%), and intracellular fluid (ICF%) were recorded. After change of TSF, TBF, ECF, ICF (ΔTSF, ΔTBF%, ΔECF%, ΔICF%), urine volume (mL), and urine volume/body weight (mL/kg) were calculated. Groups 1 and 2 were compared for these parameters. In addition, pre- and post-voiding body fluid values were compared in each group. Results: TBF%, ECF%, ICF%, and TSF in both pre- and post-voiding states and ΔTBF%, ΔECF%, ΔICF%, and ΔTSF after voiding were not different between groups. However, while post-voiding TBF%, ECF% was significantly decreased in Group 1 (64.5 ± 8.1 vs 63.7 ± 7.2, P = 0.013 for TBF%), there was not post-voiding change in TSF in the same group. On the other hand, there was also a significant TSF decrease in Group 2. Conclusions: Bladder and ureter can be considered as the third space. Thus, we think that BIA has been useful in discriminating children with VUR as there was no decreased in patients with VUR, although there was decreased TSF in patients without VUR. However, further studies are needed to increase the accuracy of this hypothesis.