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The influence of low natural altitudes (< 2000 m) on erythropoietic adaptation is currently unclear, with current recommendations indicating that such low altitudes may be insufficient to stimulate significant increases in haemoglobin mass (Hbmass). As such, the purpose of this study was to determine the influence of 3 weeks of live high, train high exposure (LHTH) at low natural altitude (i.e. 1800 m) on Hbmass, red blood cell count and iron profile. A total of 16 elite or well-trained runners were assigned into either a LHTH (n = 8) or CONTROL (n = 8) group. Venous blood samples were drawn prior to, at 2 weeks and at 3 weeks following exposure. Hbmass was measured in duplicate prior to exposure and at 2 weeks and at 3 weeks following exposure via carbon monoxide rebreathing. The percentage change in Hbmass from baseline was significantly greater in LHTH, when compared with the CONTROL group at 2 (3.1% vs 0.4%; p = 0.01;) and 3 weeks (3.0% vs -1.1%; p < 0.02, respectively) following exposure. Haematocrit was greater in LHTH than CONTROL at 2 (p = 0.01) and 3 weeks (p = 0.04) following exposure. No significant interaction effect was observed for haemoglobin concentration (p = 0.06), serum ferritin (p = 0.43), transferrin (p = 0.52) or reticulocyte percentage (p = 0.16). The results of this study indicate that three week of natural classic (i.e. LHTH) low altitude exposure (1800 m) results in a significant increase in Hbmass of elite distance runners, which is likely due to the continuous exposure to hypoxia. [ABSTRACT FROM AUTHOR]

SUMMARY Background Anaemia often goes unrecognised in people with early chronic kidney disease (CKD) resulting in under treatment until reaching the need for dialysis. Objectives This study aimed to determine if anaemia is adequately treated in Australians with CKD, who do not require dialysis. Design and Measurement Haemoglobin, ferritin and transferrin saturation (TSAT) data for patients with Stage 2-4 CKD were extracted from the Renal Anaemia Management database for the period 1999-2010. The data were compared with the target levels specified in the Caring for Australasians with Renal Impairment guidelines. Results Less than 50% of the patients achieved the recommended haemoglobin levels, and even fewer patients achieved the levels recommended for ferritin and TSAT. Conclusion and Application to Practice More emphasis should be placed on detection and treatment of anaemia in earlier stages of kidney disease. Poor response to erythropoiesis stimulating agent therapy should be investigated in this group and any identified causes of poor response treated. [ABSTRACT FROM AUTHOR]

Background A reliable biomarker is required in hepatology clinics for detection and follow-up of heavy alcohol consumption. Carbohydrate-deficient transferrin ( CDT) increases with sustained heavy alcohol consumption and is the most specific biomarker of ethanol ( Et OH) consumption. Recent introduction of a standardized method for measuring CDT has improved its clinical application. This study was designed to determine whether alcohol-independent factors influence CDT levels in patients with chronic liver disease ( CLD). Methods The relationship between serum % CDT and self-reported history of alcohol consumption was examined in 254 patients referred for evaluation of liver disease. CDT analysis was performed on serum collected at time of liver biopsy. Results CDT levels were not affected by severity or etiology of nonalcoholic liver disease. Thirteen of 254 subjects had a % CDT >1.7, predictive of heavy alcohol intake, 6 of whom did not acknowledge heavy drinking. Twelve of these 13 subjects were suspected heavy drinkers on review of their medical records and clinical results. Conversely, not all acknowledged heavy drinkers had % CDT >1.7. Heavy drinkers with a body mass index (BMI) in the overweight or obese range had significantly lower % CDT than lean heavy drinkers. This persisted even when lean body weight was used as an approximation of the Et OH volume of distribution. Conclusions An elevated BMI reduces the diagnostic utility of CDT at higher alcohol intake in subjects with CLD using the standardized method. In a hepatology outpatient setting, this assay is likely to be useful to confirm suspicion of heavy drinking in subjects who are not overweight, but cannot reliably identify moderate drinkers or heavy drinkers who are overweight. [ABSTRACT FROM AUTHOR]

Background: Proper ascertainment of the history of alcohol consumption by an individual is an important component of medical diagnosis of disease and influences the implementation of appropriate treatment strategies that include prescription of medication, as well as intervention for the negative physical and social consequences of hazardous/harmful levels of alcohol consumption. Biological (biometric) diagnostic tests that provide information on current and past quantity and frequency of alcohol consumption by an individual, prior to onset of organ damage, continue to be sought. Methods: Platelet monoamine oxidase B (MAO-B) protein was quantitated in 2 populations of subjects who had histories of different levels of alcohol consumption. Levels were assayed by immunoblotting or by ELISA. The development and evaluation of the new ELISA-based measure of platelet MAO-B protein levels is described. Results: One subject population constituted a nontreatment-seeking, cross-sectional subject sample, and the other population was a longitudinally followed, hospitalized group of subjects. An algorithm combining measures of platelet MAO-B protein with the plasma levels of carbohydrate-deficient transferrin (CDT) and with liver enzymes (aspartate aminotransferase or γ-glutamyltransferase [GGT]) can detect hazardous/harmful alcohol use (HHAU) with the highest sensitivity and specificity in the cross-sectional nontreatment-seeking population. In the treatment-seeking population, low MAO-B protein levels at admission are associated with heavy drinking prior to admission, and these protein levels increase over a period of abstinence from alcohol. Conclusions: The platelet MAO-B protein measurement is particularly effective for male alcohol consumers. The combined use of MAO-B protein measures together with measures of CDT and GGT does, however, improve the diagnostic utility of both markers for ascertaining HHAU in women. Furthermore, measurement of changes in platelet MAO-B protein levels during treatment for alcohol dependence may help monitor the success of the treatment program. [ABSTRACT FROM AUTHOR]

Objectives: Aboriginal children in tropical Australia have a high prevalence of both iron deficiency and acute infections, making it difficult to differentiate their relative contributions to anaemia. The aims of this study were to compare soluble transferrin receptor with ferritin in iron deficiency anaemia (IDA), and to examine how best to distinguish the effect of iron deficiency from infection on anaemia.Methods: We conducted a prospective study of 228 admissions to Royal Darwin Hospital in children from 6 to 60 months of age. Transferrin receptor concentrations were measured by a particle-enhanced immunoturbidimetric assay and ferritin by a microparticle enzyme immunoassay.Results: On multiple regression, the best explanatory variables for haemoglobin differences (r2=33.7%, P<0.001) were mean corpuscular volume (MCV), red cell distribution width (RDW) and C-reactive protein (CRP); whereas transferrin receptor and ferritin were not significant (P>0.4). Using > or =2 abnormal indices (MCV, RDW, blood film)+haemoglobin <110 g/l as the reference standard for IDA, transferrin receptor produced a higher area under the curve on receiver operating characteristic curve analysis than ferritin (0.79 vs. 0.64, P<0.001) or the transferrin receptor-ferritin index (0.77). On logistic regression, the effect of acute infection (CRP) on haemoglobin was significant (P<0.001) at cut-offs of 105 and 110 g/l, but not at 100 g/l when only iron deficiency indicators (MCV, RDW, blood film) were significant.Conclusions: Transferrin receptor does not significantly improve the diagnosis of anaemia (iron deficiency vs. infection) over full blood count and CRP, but in settings with a high burden of infectious diseases and iron deficiency, it is a more reliable adjunctive measure of iron status than ferritin. [ABSTRACT FROM AUTHOR]

Background: Heme and iron homeostasis is perturbed in Alzheimer's disease (AD); therefore, the aim of the study was to examine the levels and association of heme with iron-binding plasma proteins in cognitively normal (CN), mild cognitive impairment (MCI), and AD individuals from the Australian Imaging, Biomarker and Lifestyle Flagship Study of Ageing (AIBL) and Kerr Anglican Retirement Village Initiative in Ageing Health (KARVIAH) cohorts., Methods: Non-targeted proteomic analysis by high-resolution mass spectrometry was performed to quantify relative protein abundances in plasma samples from 144 CN individuals from the AIBL and 94 CN from KARVIAH cohorts and 21 MCI and 25 AD from AIBL cohort. ANCOVA models were utilized to assess the differences in plasma proteins implicated in heme/iron metabolism, while multiple regression modeling (and partial correlation) was performed to examine the association between heme and iron proteins, structural neuroimaging, and cognitive measures., Results: Of the plasma proteins implicated in iron and heme metabolism, hemoglobin subunit β (p = 0.001) was significantly increased in AD compared to CN individuals. Multiple regression modeling adjusted for age, sex, APOEε4 genotype, and disease status in the AIBL cohort revealed lower levels of transferrin but higher levels of hemopexin associated with augmented brain amyloid deposition. Meanwhile, transferrin was positively associated with hippocampal volume and MMSE performance, and hemopexin was negatively associated with CDR scores. Partial correlation analysis revealed lack of significant associations between heme/iron proteins in the CN individuals progressing to cognitive impairment., Conclusions: In conclusion, heme and iron dyshomeostasis appears to be a feature of AD. The causal relationship between heme/iron metabolism and AD warrants further investigation.

Plasma iron levels are decreased in Alzheimer's disease (AD) and associated with an idiopathic anemia. We examined iron-binding plasma proteins from AD patients and healthy controls from the Australian Imaging, Biomarkers and Lifestyle (AIBL) Flagship Study of Ageing using size exclusion chromatography-inductively coupled plasma-mass spectrometry. Peak area corresponding to transferrin (Tf) saturation was directly compared to routine pathological testing. We found a significant decrease in transferrin-associated iron in AD that was missed by routine pathological tests of transferrin saturation, and that was able to discriminate between AD and controls. The AD cases showed no significant difference in transferrin concentration, only a decrease in total transferrin-bound iron. These findings support that a previously identified decrease in plasma iron levels in AD patients within the AIBL study is attributable to decreased loading of iron into transferrin, and that this subtle but discriminatory change is not observed through routine pathological testing.