Factors associated with haemoglobin concentration among Timor-Leste children aged 6-59 months.

PubMed

Agho, K E; Dibley, M J; D'Este, C; Gibberd, R

2008-06-01

The study was conducted to assess the prevalence of and factors associated with haemoglobin (Hb) concentrations among children aged 6-59 months in Timor-Leste. The 2003 Demographic and Health Survey was a multi-stage cluster survey of 4,320 households from four different geographic regions in Timor-Leste. In total, 4,514 children aged 6-59 months were included in the analysis. The prevalence of anaemia (Hb concentration <11.0g/dL) was 38.2% (638/1,668) for children aged 6-23 months and 22.6% (644/2,846) for older children (p<0.001). Girls had a higher mean Hb concentration than boys (11.9g/dL vs 11.7g/ dL, p<0.006) and children who had diarrhoea in the previous two weeks had a lower Hb concentration than children without diarrhoea (11.5g/dL vs 11.9g/dL, p<0.001). Children from the richest and middle-class households had a lower average Hb concentration than those from the poorest households (11.8g/ dL, 11.7g/dL vs 12.0g/dL, p<0.001). Children of mothers with some secondary or more education had a lower mean Hb concentration than children of mothers with completed primary, some primary and no education (11.7 g/dL vs 11.9 g/dL, 11.8 g/dL, and 11.9 g/dL, p=0.002). Children from severely-anaemic mothers had a lower mean Hb concentration than children from moderately-, mild and not anaemic mothers (10.5 g/dL vs 11.1 g/dL, 11.6 g/dL, 12.0 g/dL, p<0.001). After backward stepwise hierarchical multiple regression, wasting, male sex, recent diarrhoea, household wealth index (richest and middle-class), maternal educational status (some secondary or more and some primary), and maternal anaemic status were significantly associated with a lower Hb concentration in children and increased age of child and duration of breastfeeding (6 months) with a higher Hb concentration. Anaemia-prevention programmes among children in Timor-Leste should focus on those children aged less than two years, children with recent diarrhoea, wasted children, high socioeconomic status, and anaemic

Intravenous iron in clinical concentrations does not impair haemoglobin measurement.

PubMed

O'Loughlin, Edmond; Garnett, Peter Bj; Falkner, Nathalie M; Williams, Robin

2016-03-01

Intravenous iron is commonly administered to anaemic patients to treat iron deficiency, but due to its ferric colouration, it may interfere with the spectrophotometric assessment of haemoglobin concentrations. This paper investigates the potential interference of three clinically used intravenous iron preparations on the measurement of haemoglobin. Haemoglobin concentration was measured for neat and Hartmann's solution-diluted iron polymaltose, carboxymaltose and sucrose solutions using bedside (Radiometer HemoCue®), point-of-care (Radiometer ABL800 Flex) and laboratory (Abbott CellDyne Sapphire™) devices. Haemoglobin concentration was then assessed with the same devices utilizing anaemic whole blood with the iron solutions added. Neat iron preparations registered clinically significant haemoglobin concentrations on bedside and laboratory measurements. When intravenous iron preparations were diluted to clinical concentrations, their effect on haemoglobin measurements, either in isolation or mixed with anaemic blood, was negligible. Although neat preparations of intravenous iron do interfere with spectrophotometric analysis of haemoglobin, concentrations likely to be seen post iron infusion do not significantly interfere with haemoglobin measurement. © The Author(s) 2015.

First case of Hb Fontainebleau with sickle haemoglobin and other non-deletional α gene variants identified in neonates during newborn screening for sickle cell disorders.

PubMed

Upadhye, Dipti S; Jain, Dipty; Nair, Sona B; Nadkarni, Anita H; Ghosh, Kanjaksha; Colah, Roshan B

2012-07-01

To evaluate the significance of non-deletional α gene variants identified in neonates during newborn screening for sickle cell disorders. 1534 newborn babies were screened in the last 2 years for sickle cell disease using a targeted screening approach. Investigations included a complete blood count, high performance liquid chromatography analysis, cellulose acetate electrophoresis (pH 8.9), heat stability test, restriction digestion and Amplified Refractory Mutation System for confirmation of sickle haemoglobin (Hb S), α genotyping by multiplex PCR and DNA sequencing. Three non-deletional α gene variants, Hb Fontainebleau, Hb O Indonesia and Hb Koya Dora, were identified in heterozygous condition in newborns. This is the first report of Hb Fontainebleau in association with Hb S. The baby had anaemia at birth (Hb 11.4 g/dl) with no cyanosis, icterus or need for transfusion. She had occipital encephalocoele and was operated on day 24 to remove the mass. The baby diagnosed with Hb O Indonesia in combination with Hb S also had a low haemoglobin level of 12.7 g/dl. Newborn screening for sickle cell disorders also enabled us to identify three α globin chain variants. Two babies who inherited Hb Fontainebleau and Hb O Indonesia along with Hb S had reduced Hb levels at birth and need to be followed up.

Glycated haemoglobin (HbA1c ) and fasting plasma glucose relationships in sea-level and high-altitude settings.

PubMed

Bazo-Alvarez, J C; Quispe, R; Pillay, T D; Bernabé-Ortiz, A; Smeeth, L; Checkley, W; Gilman, R H; Málaga, G; Miranda, J J

2017-06-01

Higher haemoglobin levels and differences in glucose metabolism have been reported among high-altitude residents, which may influence the diagnostic performance of HbA 1c . This study explores the relationship between HbA 1c and fasting plasma glucose (FPG) in populations living at sea level and at an altitude of > 3000 m. Data from 3613 Peruvian adults without a known diagnosis of diabetes from sea-level and high-altitude settings were evaluated. Linear, quadratic and cubic regression models were performed adjusting for potential confounders. Receiver operating characteristic (ROC) curves were constructed and concordance between HbA 1c and FPG was assessed using a Kappa index. At sea level and high altitude, means were 13.5 and 16.7 g/dl (P > 0.05) for haemoglobin level; 41 and 40 mmol/mol (5.9% and 5.8%; P < 0.01) for HbA 1c ; and 5.8 and 5.1 mmol/l (105 and 91.3 mg/dl; P < 0.001) for FPG, respectively. The adjusted relationship between HbA 1c and FPG was quadratic at sea level and linear at high altitude. Adjusted models showed that, to predict an HbA 1c value of 48 mmol/mol (6.5%), the corresponding mean FPG values at sea level and high altitude were 6.6 and 14.8 mmol/l (120 and 266 mg/dl), respectively. An HbA 1c cut-off of 48 mmol/mol (6.5%) had a sensitivity for high FPG of 87.3% (95% confidence interval (95% CI) 76.5 to 94.4) at sea level and 40.9% (95% CI 20.7 to 63.6) at high altitude. The relationship between HbA 1c and FPG is less clear at high altitude than at sea level. Caution is warranted when using HbA 1c to diagnose diabetes mellitus in this setting. © 2017 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.

The effects of residual pump blood on patient plasma free haemoglobin levels post cardiac surgery.

PubMed

Schotola, H; Wetz, A J; Popov, A F; Bergmann, I; Danner, B C; Schöndube, F A; Bauer, M; Bräuer, A

2016-09-01

At the end of cardiopulmonary bypass, there are invariably several hundred millilitres of residual pump blood in the reservoir, which can either be re-transfused or discarded. The objective of this prospective observational study was to investigate the quality of the residual pump blood, focusing on plasma free haemoglobin (pfHb) and blood cell counts. Fifty-one consecutive patients were included in the study. Forty-nine units of residual pump blood and 58 units of transfused red blood cell (RBC) concentrates were analysed. The mean preoperative pfHb of the patients was 0.057 ± 0.062 g/l, which increased gradually to 0.55 ± 0.36 g/l on arrival in the intensive care unit postoperatively. On the first postoperative day, the mean pfHb had returned to within the normal range. Our data showed that haemoglobin, haematocrit, and erythrocyte counts of residual pump blood were approximately 40% of the values in standardised RBC concentrates. Plasma free haemoglobin was significantly higher in residual pump blood compared to RBC concentrates, and nearly twice as high as the pfHb in patient blood samples taken contemporaneously. Our findings indicate that residual pump blood pfHb levels are markedly higher compared to patients' blood and RBC concentrates, but that its administration does not significantly increase patients' pfHb levels.

Factors Associated with Haemoglobin Concentration among Timor-Leste Children Aged 6–59 Months

PubMed Central

Agho, K.E.; Dibley, M.J.; D'Este, C.; Gibberd, R.

2008-01-01

The study was conducted to assess the prevalence of and factors associated with haemoglobin (Hb) concentrations among children aged 6–59 months in Timor-Leste. The 2003 Demographic and Health Survey was a multi-stage cluster survey of 4,320 households from four different geographic regions in Timor-Leste. In total, 4,514 children aged 6–59 months were included in the analysis. The prevalence of anaemia (Hb concentration <11.0g/dL) was 38.2% (638/1,668) for children aged 6–23 months and 22.6% (644/2,846) for older children (p<0.001). Girls had a higher mean Hb concentration than boys (11.9g/dL vs 11.7g/dL, p<0.006) and children who had diarrhoea in the previous two weeks had a lower Hb concentration than children without diarrhoea (11.5g/dL vs 11.9g/dL, p<0.001). Children from the richest and middle-class households had a lower average Hb concentration than those from the poorest households (11.8g/dL, 11.7g/dL vs 12.0g/dL, p<0.001). Children of mothers with some secondary or more education had a lower mean Hb concentration than children of mothers with completed primary, some primary and no education (11.7 g/dL vs 11.9 g/dL, 11.8 g/dL, and 11.9 g/dL, p=0.002). Children from severely-anaemic mothers had a lower mean Hb concentration than children from moderately-, mild and not anaemic mothers (10.5 g/dL vs 11.1 g/dL, 11.6 g/dL, 12.0 g/dL, p<0.001). After backward stepwise hierarchical multiple regression, wasting, male sex, recent diarrhoea, household wealth index (richest and middle-class), maternal educational status (some secondary or more and some primary), and maternal anaemic status were significantly associated with a lower Hb concentration in children and increased age of child and duration of breastfeeding (6 months) with a higher Hb concentration. Anaemia-prevention programmes among children in Timor-Leste should focus on those children aged less than two years, children with recent diarrhoea, wasted children, high socioeconomic status, and anaemic

Anaemia in the sow: a cohort study to assess factors with an impact on haemoglobin concentration, and the influence of haemoglobin concentration on the reproductive performance.

PubMed

Normand, V; Perrin, H; Auvigne, V; Robert, N; Laval, A

2012-10-06

The aim of this study was to conduct a descriptive study of haemoglobin concentration found on high-prolificacy sows, to study the relationship between the concentration of haemoglobin and body reserves, and to determine whether anaemia is a risk factor for reproductive performance. A cohort of 308 sows from seven farms was followed from the last third of gestation to the confirmation of the following gestation. Haemoglobin concentration was assessed at four stages of the reproductive cycle: seven and four weeks before farrowing, a few days and three weeks after farrowing. Backfat thickness (BFT) was measured at parturition. The results were analysed using linear mixed-effect models. The mean haemoglobin concentration was 108.4 g/l. The mean modellised haemoglobin concentration of parity 1 sows with a BFT of 16 mm, sampled seven weeks before farrowing, was 118 g/l. Haemoglobin concentration of sows of parity 6 or higher was 8.0 g/l lower than those of parity 1 sows (95% confidence interval -11.0 to -5.1). Haemoglobin concentration is lower in sows with a lower BFT, whatever parity rank. There is no evidence of a relation between haemoglobin concentration and the number of total born, stillborn or number of piglets alive at three weeks and the next breeding performance.

Structural basis for ligand and innate immunity factor uptake by the trypanosome haptoglobin-haemoglobin receptor.

PubMed

Lane-Serff, Harriet; MacGregor, Paula; Lowe, Edward D; Carrington, Mark; Higgins, Matthew K

2014-12-12

The haptoglobin-haemoglobin receptor (HpHbR) of African trypanosomes allows acquisition of haem and provides an uptake route for trypanolytic factor-1, a mediator of innate immunity against trypanosome infection. In this study, we report the structure of Trypanosoma brucei HpHbR in complex with human haptoglobin-haemoglobin (HpHb), revealing an elongated ligand-binding site that extends along its membrane distal half. This contacts haptoglobin and the β-subunit of haemoglobin, showing how the receptor selectively binds HpHb over individual components. Lateral mobility of the glycosylphosphatidylinositol-anchored HpHbR, and a ∼50° kink in the receptor, allows two receptors to simultaneously bind one HpHb dimer. Indeed, trypanosomes take up dimeric HpHb at significantly lower concentrations than monomeric HpHb, due to increased ligand avidity that comes from bivalent binding. The structure therefore reveals the molecular basis for ligand and innate immunity factor uptake by trypanosomes and identifies adaptations that allow efficient ligand uptake in the context of the complex trypanosome cell surface.

Accuracy of non-invasive measurement of haemoglobin concentration by pulse co-oximetry during steady-state and dynamic conditions in liver surgery.

PubMed

Vos, J J; Kalmar, A F; Struys, M M R F; Porte, R J; Wietasch, J K G; Scheeren, T W L; Hendriks, H G D

2012-10-01

The Masimo Radical 7 (Masimo Corp., Irvine, CA, USA) pulse co-oximeter(®) calculates haemoglobin concentration (SpHb) non-invasively using transcutaneous spectrophotometry. We compared SpHb with invasive satellite-lab haemoglobin monitoring (Hb(satlab)) during major hepatic resections both under steady-state conditions and in a dynamic phase with fluid administration of crystalloid and colloid solutions. Thirty patients undergoing major hepatic resection were included and randomized to receive a fluid bolus of 15 ml kg(-1) colloid (n=15) or crystalloid (n=15) solution over 30 min. SpHb was continuously measured on the index finger, and venous blood samples were analysed in both the steady-state phase (from induction until completion of parenchymal transection) and the dynamic phase (during fluid bolus). Correlation was significant between SpHb and Hb(satlab) (R(2)=0.50, n=543). The modified Bland-Altman analysis for repeated measurements showed a bias (precision) of -0.27 (1.06) and -0.02 (1.07) g dl(-1) for the steady-state and dynamic phases, respectively. SpHb accuracy increased when Hb(satlab) was <10 g dl(-1), with a bias (precision) of 0.41 (0.47) vs -0.26 (1.12) g dl(-1) for values >10 g dl(-1), but accuracy decreased after colloid administration (R(2)=0.25). SpHb correlated moderately with Hb(satlab) with a slight underestimation in both phases in patients undergoing major hepatic resection. Accuracy increased for lower Hb(satlab) values but decreased in the presence of colloid solution. Further improvements are necessary to improve device accuracy under these conditions, so that SpHb might become a sensitive screening device for clinically significant anaemia.

Haemoglobin Rahere (beta Lys-Thr): A new high affinity haemoglobin associated with decreased 2, 3-diphosphoglycerate binding and relative polycythaemia.

PubMed Central

Lorkin, P A; Stephens, A D; Beard, M E; Wrigley, P F; Adams, L; Lehmann, H

1975-01-01

A new haemoglobin with increased oxygen affinity, beta82 (EF6) lysine leads to threonine (Hb Rahere), was found during the investigation of a patient who was found to have a raised haemoglobin concentration after a routine blood count. The substitution affects one of the 2, 3-diphosphoglycerate binding sites, resulting in an increased affinity for oxygen, but both the haem-haem interaction and the alkaline Bohr effect are normal in the haemolysate. This variant had the same mobility as haemoglobin A on electrophoresis at alkaline pH but was detected by measuring the whole blood oxygen affinity; it could be separated from haemoglobin A, however, by electrophoresis in agar at acid pH. The raised haemoglobin concentration was mainly due to a reduction in plasma volume (a relative polycythaemia) and was associated with a persistently raised white blood count. This case emphasises the need to measure the oxygen affinity of haemoglobin in all patients with absolute or relative polycythaemia when some obvious cause is not evident. PMID:124

Sea-level haemoglobin concentration is associated with greater exercise capacity in Tibetan males at 4200 m.

PubMed

Wagner, P D; Simonson, T S; Wei, G; Wagner, H E; Wuren, T; Qin, G; Yan, M; Ge, R L

2015-11-01

What is the topic of this review? Recent developments link relatively lower hemoglobin concentration in Tibetans at high altitude to exercise capacity and components of oxygen transport. What advances does it highlight? Haemoglobin concentration (ranging from 15.2 to 22.9 g dl(-1) ) in Tibetan males was negatively associated with peak oxygen (O2 ) uptake per kilogram, cardiac output and muscle O2 diffusion conductance. Most variance in the peak O2 uptake per kilogram of Tibetan males was attributed to cardiac output, muscle diffusional conductance and arterial partial pressure of CO2 . The mechanisms underlying these differences in oxygen transport in Tibetans require additional analyses. Despite residence at >4000 m above sea level, many Tibetan highlanders, unlike Andean counterparts and lowlanders at altitude, exhibit haemoglobin concentration ([Hb]) within the typical sea-level range. Genetic adaptations in Tibetans are associated with this relatively low [Hb], yet the functional relevance of the lower [Hb] remains unknown. To address this, we examined each major step of the oxygen transport cascade [ventilation (VE), cardiac output (QT) and diffusional conductance in lung (DL) and muscle (DM)] in Tibetan males at maximal exercise on a cycle ergometer. Ranging from 15.2 to 22.9 g dl(-1) , [Hb] was negatively associated with peak O2 uptake per kilogram (r = -0.45, P < 0.05) and both cardiac output (QT/kg: r = -0.54, P < 0.02) and muscle O2 diffusion conductance (DM/kg: r = -0.44, P < 0.05) but not ventilation, arterial partial pressure of O2 or pulmonary diffusing capacity. Most variance in peak O2 uptake per kilogram was attributed to QT, DM and arterial partial pressure of CO2 (r(2)  = 0.90). In summary, lack of polycythaemia in Tibetans is associated with increased exercise capacity, which is explained by elevated cardiac, muscle and, to a small extent, ventilatory responses rather than pulmonary gas exchange. Whether lower [Hb] is the

The value of routine haemoglobin concentration measurement before caesarean section.

PubMed

Vashisht, A; Yentis, S

2005-02-01

Women undergoing caesarean section routinely have a haemoglobin concentration check before delivery. We compared the haemoglobin concentration of 311 women taken at their 32-?34 week antenatal visit with their preoperative level. A significant rise from 11.04 g/dL to 11.51 g/dL was seen (mean (95% CI) 0.47 (0.37-0.57 g/dL)). This increase was most marked in the 201 women having emergency procedures, and there was a significant negative correlation between the 32 and 34 weeks level and the net change in haemoglobin concentration (r=-0.366 (P<0.001)). From our results we suggest that in women with an otherwise uncomplicated pregnancy, and a satisfactory haemoglobin concentration at 32-34 weeks, a repeat estimation of the blood count is unnecessary before operative delivery.

Glycated haemoglobin (HbA1c), diabetes and trajectories of change in episodic memory performance.

PubMed

Pappas, Colleen; Andel, Ross; Infurna, Frank J; Seetharaman, Shyam

2017-02-01

As the ageing population grows, it is important to identify strategies to moderate cognitive ageing. We examined glycated haemoglobin (HbA1c) and diabetes in relation to level and change in episodic memory in older adults with and without diabetes. Data from 4419 older adults with (n=950) and without (n=3469) diabetes participating in a nationally representative longitudinal panel study (the Health and Retirement Study) were examined. Average baseline age was 72.66 years and 58% were women. HbA1c was measured in 2006 and episodic memory was measured using immediate and delayed list recall over 4 biennial waves between 2006 and 2012. Growth curve models were used to assess trajectories of episodic memory change. In growth curve models adjusted for age, sex, education, race, depressive symptoms and waist circumference, higher HbA1c levels and having diabetes were associated with poorer baseline episodic memory (p=0.036 and <0.001, respectively) and greater episodic memory decline (p=0.006 and 0.004, respectively). The effect of HbA1c on episodic memory decline was smaller than the effect of age. The results were stronger for women than men and were not modified by age or race. When the main analyses were estimated for those with and without diabetes separately, HbA1c was significantly linked to change in episodic memory only among those with diabetes. Higher HbA1c and diabetes were both associated with declines in episodic memory, with this relationship further exacerbated by having diabetes and elevated HbA1c. HbA1c appeared more important for episodic memory performance among women than men. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Knowledge Insufficient: The Management of Haemoglobin SC Disease

PubMed Central

Pecker, Lydia H.; Schaefer, Beverly A.; Luchtman-Jones, Lori

2016-01-01

Although haemoglobin SC (HbSC) accounts for 30% of sickle cell disease (SCD) in the United States and United Kingdom, evidence-based guidelines for genotype specific management are lacking. The unique pathology of HbSC disease is complex, characterized by erythrocyte dehydration, intracellular sickling and increased blood viscosity. The evaluation and treatment of patients with HbSC is largely inferred from studies of SCD consisting mostly of haemoglobin SS (HbSS) patients. These studies are underpowered to allow definitive conclusions about HbSC. We review the pathophysiology of HbSC disease, including known and potential differences between HbSS and HbSC, and highlight knowledge gaps in HbSC disease management. Clinical and translational research is needed to develop targeted treatments and to validate management recommendations for efficacy, safety and impact on quality of life for people with HbSC. PMID:27982424

Knowledge insufficient: the management of haemoglobin SC disease.

PubMed

Pecker, Lydia H; Schaefer, Beverly A; Luchtman-Jones, Lori

2017-02-01

Although haemoglobin SC (HbSC) accounts for 30% of sickle cell disease (SCD) in the United States and United Kingdom, evidence-based guidelines for genotype specific management are lacking. The unique pathology of HbSC disease is complex, characterized by erythrocyte dehydration, intracellular sickling and increased blood viscosity. The evaluation and treatment of patients with HbSC is largely inferred from studies of SCD consisting mostly of haemoglobin SS (HbSS) patients. These studies are underpowered to allow definitive conclusions about HbSC. We review the pathophysiology of HbSC disease, including known and potential differences between HbSS and HbSC, and highlight knowledge gaps in HbSC disease management. Clinical and translational research is needed to develop targeted treatments and to validate management recommendations for efficacy, safety and impact on quality of life for people with HbSC. © 2016 John Wiley & Sons Ltd.

Antenatal Iron Supplementation Regimens for Pregnant Women in Rural Vietnam and Subsequent Haemoglobin Concentration and Anaemia among Their Infants.

PubMed

Tran, Thach Duc; Fisher, Jane; Hanieh, Sarah; Tran, Tuan; Simpson, Julie Anne; Tran, Ha; Biggs, Beverley-Ann

2015-01-01

Little evidence about the effects of antenatal iron supplementation on infant anaemia is available. The aim was to compare effects on six-month-old infants' Haemoglobin (Hb) concentration and anaemia of daily iron-folic acid (IFA), twice-weekly IFA with or without other micronutrients (MMN) and usual antenatal care in rural Vietnam. Secondary data analysis from: a prospective population-based observational study (OS) which examined effects of antenatal psychosocial factors, anaemia and iron deficiency on infant development and health; and a three-arm cluster randomised trial (CRT) of different antenatal iron supplementation regimens. In the OS 497 women (<20 weeks gestation) from 50 randomly-selected communes participated, and in the CRT 1,258 pregnant women (<16 weeks gestation) in 104 communes were allocated randomly to trial arms. The main outcome was six-month-old infant Hb concentration. Baseline data included women's socio-demographic characteristics, reproductive health, Hb and serum ferritin. Mean differences in infant Hb and odds ratios of infant anaemia between CRT arms and OS were calculated by multivariable regression models, controlling for baseline differences and clustering, using robust standard errors. Infant anaemia prevalence was 68.6% in the OS, 47.2% daily IFA, 53.5% weekly IFA, and 50.3% MMN conditions. After adjustment, mean infant haemoglobin levels in daily IFA (mean difference = 0.95 g/dL; 95%CI 0.7-11.18); weekly IFA (0.91; 95%CI 0.69-1.12) and MMN (1.04; 95%CI 0.8-1.27) were higher than in the OS. After adjustment there were lower odds ratios of anaemia among infants in the daily IFA (OR = 0.31; 95% CI 0.22-0.43), weekly IFA (0.38; 95%CI 0.26-0.54) and MMN (0.33; 95%CI 0.23-0.48) groups than in the OS. Infant anaemia is a public health problem in Vietnam and other resource-constrained countries. All supplementation regimens could have clinically significant benefits for Hb and reduce anaemia risk among six-month-old infants. Universal

Multicentre evaluation of the Premier Hb9210 HbA1c analyser

PubMed Central

John, W. Garry; Little, Randie; Sacks, David B.; Weykamp, Cas; Lenters-Westra, Erna; Hornsby, Theresa; Zhao, Zhen; Siebelder, Carla; Tennill, Alethea; English, Emma

2017-01-01

Background The accurate and precise quantification of HbA1c is essential for the diagnosis and routine monitoring of patients with diabetes. We report an evaluation of the Trinity Biotech Premier Hb9210 analyser (Bray, Ireland/Kansas City, US), a boronate affinity chromatography-based high performance liquid chromatography (HPLC) system for the measurement of glycated haemoglobin. Methods We evaluated the analytical performance of the Hb9210 as part of a multicentre evaluation. The effect of haemoglobin variants, other potential interferences and the performance in comparison to both the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) and National Glycohemoglobin Standardization Program (NGSP) reference systems, was assessed. Most of the centres participating also act as reference laboratories for both the IFCC standardisation network for HbA1c and the NGSP. Results The combined data from all centres showed total CVs of 2.71%, 2.32% and 2.14% at low medium and high values respectively for mmol/mol (SI units) and 1.62%, 1.59% and 1.68% for % (NGSP units), which are well below the recommended upper limits of 3% CV for SI (IFCC) units and 2% CV for % (NGSP). The analyser showed a good correlation to HbA1c methods currently used in clinical practice and the IFCC reference method procedure. Haemoglobin variants AC, AS, AE and AD do not affect the measurement of HbA1c. Overall the Hb9210 performs well across the whole analytical range. Conclusions The Hb9210 performs well and is suitable for clinical application in the analysis of HbA1c. PMID:25274956

The use of haemoglobin concentrations to assess physiological condition in birds: a review

PubMed Central

2015-01-01

Abstract Total blood haemoglobin concentration is increasingly being used to assess physiological condition in wild birds, although it has not been explicitly recognized how reliably this parameter reflects different components of individual quality. Thus, I reviewed over 120 published studies linking variation in haemoglobin concentrations to different measures of condition and other phenotypic or ecological traits. In most of the studied avian species, haemoglobin concentrations were positively correlated with other commonly used indices of condition, such as body mass and fat loads, as well as with quality of the diet. Also, chick haemoglobin concentrations reliably reflected the intensity of nest infestation by parasitic arthropods, and haemoglobin was suggested to reflect parasitism by haematophagous ectoparasites much more precisely than haematocrit. There was also some evidence for the negative effect of helminths on haemoglobin levels in adult birds. Finally, haemoglobin concentrations were found to correlate with such fitness-related traits as timing of arrival at breeding grounds, timing of breeding, egg size, developmental stability and habitat quality, although these relationships were not always consistent between species. In consequence, I recommend the total blood haemoglobin concentration as a relatively robust indicator of physiological condition in birds, although this parameter is also strongly affected by age, season and the process of moult. Thus, researchers are advised to control fully for these confounding effects while using haemoglobin concentrations as a proxy of physiological condition in both experimental and field studies on birds. PMID:27293692

Identification of haemoglobin New York by haemoglobin A1c measurement using the Sebia Capillarys 2 Flex Piercing system.

PubMed

Chao, Yan; Wan, Zemin; Wu, Xiaobin; Qiu, Feng; Wu, Xinzhong; Wang, Yunxiu; Ke, Peifeng; Xu, Jianhua; Zhuang, Junhua; Huang, Xianzhang

2017-01-01

Haemoglobinopathies may interfere with the haemoglobin A 1c (HbA 1c ) measurement, leading to incorrect diagnosis and inappropriate treatment. It is essential that HbA 1c assays are capable of identifying haemoglobinopathies. We report two cases of haemoglobin New York (HbNY) discovered through HbA 1c analysis using capillary electrophoresis (Capillarys 2 Flex Piercing [C2FP], Sebia). We used these samples to evaluate the ability of three other HbA 1c assays to identify this variant: ion-exchange high-performance liquid chromatography (Variant II Turbo [VII-T], Bio-Rad); boronate affinity high-performance liquid chromatography (Ultra 2 , Trinity Biotech) and immunoassay (Cobas c501 Tina-quant Generation 3, Roche Diagnostics). Each method was used for HbA 1c assay of in samples from two cases of heterozygous haemoglobinopathy: β 0 -thalassemia/HbNY (Case 1) and HbA/NY (Case 2). Only the C2FP system detected HbNY (an additional peak appeared between HbA 1c and HbA 0 ). Clinical laboratories should be aware of the limitations of their HbA 1c assay methods especially in geographic areas, where haemoglobinopathy prevalence is high.

Haemoglobin sickle D disease: A presentation with ischaemic stroke.

PubMed

Afzal, Hasnain; Umair, Syed Farrukh

2016-03-01

Haemoglobin-D, Los Angeles or Haemoglobin D-Punjab is not a rare variant of haemoglobin worldwide especially in Punjab, North western India, and South Asian continent. It can be inherited rarely as homozygous causing no symptoms or heterozygous with Haemoglobin A, commonly not related to clinical symptomatology. However, these variants can co-exist rarely with other haemoglobinopathies such as thalassemia or haemoglobin-S. We describe the case of doubly heterozygous Hb-SD Punjab in a 8 year old girl who presented with ischaemic stroke. Before this case, only one case has been reported but it was with reversible hyperbilirubinaemia in Hb-SD from Rawalpindi, Pakistan. This case images the propensity for occurrence of rare phenotype within our population and underlines the importance of genotyping to avoid erroneous management and poor counseling hence preventing life altering complications which our case developed.

The impact of sickle cell trait on glycated haemoglobin in diabetes mellitus.

PubMed

Bleyer, A J; Vidya, S; Sujata, L; Russell, G B; Akinnifesi, D; Hire, D; Shihabi, Z; Knovich, M A; Daeihagh, P; Calles, J; Freedman, B I

2010-09-01

To determine the effect of sickle cell trait on measurement of glycated haemoglobin (HbA(1c)) in African American patients with diabetes mellitus. This is a retrospective study including 885 outpatients who underwent HbA(1c) testing. Medical record review and sickle cell trait determinations based on the HbA(1c) assay were performed in African American participants. The relationship between HbA(1c) and serum glucose measurements was analysed. Data were obtained from 385 AA (109 with SCT, 22 with haemoglobin C trait and 254 without haemoglobinopathy) and 500 European American patients. In a model created through multivariate repeated-effects regression, the relationship between HbA(1c) and simultaneous serum glucose did not differ between African American subjects with and without the sickle cell trait, but differed between African American subjects without the sickle cell trait and European Americans (P = 0.0002). Sickle cell trait does not impact the relationship between HbA(1c) and serum glucose concentration. In addition, it does not appear to account for ethnic difference in this relationship between African Americans and whites.

Kinetics of NO and O2 binding to a maleimide poly(ethylene glycol)-conjugated human haemoglobin

PubMed Central

2004-01-01

The hypertensive effect observed with most cell-free haemoglobins has been proposed to result from NO scavenging. However, a newly developed PEG [poly(ethylene glycol)]-conjugated haemoglobin, MalPEG-Hb [maleimide-activated PEG-conjugated haemoglobin], is non-hypertensive with unique physicochemical properties: high O2 affinity, low co-operativity and large molecular radius. It is therefore of interest to compare the ligand-binding properties of MalPEG-Hb with unmodified cell-free HbA (stroma-free human haemoglobin). NO association rates for deoxy and oxyMalPEG-Hb and HbA were found to be identical. These results confirm the lack of correlation between hypertension and NO for a similar modified haemoglobin with high molecular radius and low p50 (pO2 at which haemoglobin is half-saturated with O2) [Rohlfs, Bruner, Chiu, Gonzales, Gonzales, Magde, Magde, Vandegriff and Winslow (1998) J. Biol. Chem. 273, 12128–12134]. The R-state O2 association kinetic constants were also the same for the two haemoglobins. However, even though the p50 of MalPEG-Hb is approx. half of that of HbA, the biphasic O2 dissociation rates measured at relatively high pO2 (150 Torr) were 2-fold higher, giving rise to a 2-fold lower R-state equilibrium association constant for MalPEG-Hb compared with HbA. Thus the O2 affinity of MalPEG-Hb is higher only at pO2 values lower than the intersection point of the O2 equilibrium curves for MalPEG-Hb and HbA. In summary, the present studies found similar rates of NO binding to HbA and MalPEG-Hb, eliminating the possibility that the lack of vasoactivity of MalPEG-Hb is simply the result of reduced molecular reactivity with NO. Alternatively, the unique O2-binding characteristics with low p50 and co-operativity suggest that the ‘R-state’ conformation of MalPEG-Hb is in a more T-state configuration and restricted from conformational change. PMID:15175010

Maternal haemoglobin concentrations before and during pregnancy and stillbirth risk: a population-based case-control study.

PubMed

Maghsoudlou, Siavash; Cnattingius, Sven; Stephansson, Olof; Aarabi, Mohsen; Semnani, Shahriar; Montgomery, Scott M; Bahmanyar, Shahram

2016-06-03

Results of previous studies on the association between maternal haemoglobin concentration during pregnancy and stillbirth risk are inconclusive. It is not clear if haemoglobin concentration before pregnancy has a role. Using prospectively collected information from pre-pregnancy and antenatal visits, we investigated associations of maternal haemoglobin concentrations before and during pregnancy and haemoglobin dilution with stillbirth risk. In a population-based case-control study from rural Golestan, a province in northern Iran, we identified 495 stillbirths (cases) and randomly selected 2,888 control live births among antenatal health-care visits between 2007 and 2009. Using logistic regression, we estimated associations of maternal haemoglobin concentrations, haemoglobin dilution at different stages of pregnancy, with stillbirth risk. Compared with normal maternal haemoglobin concentration (110-120 g/l) at the end of the second trimester, high maternal haemoglobin concentration (≥140 g/l) was associated with a more than two-fold increased stillbirth risk (OR = 2.31, 95 % CI [1.30-4.10]), while low maternal haemoglobin concentration (<110 g/l) was associated with a 37 % reduction in stillbirth risk. Haemoglobin concentration before pregnancy was not associated with stillbirth risk. Decreased haemoglobin concentration, as measured during pregnancy (OR = 0.61, 95 % CI [0.46, 0.80]), or only during the second trimester (OR = 0.75, 95 % CI [0.62, 0.90]), were associated with reduced stillbirth risk. The associations were essentially similar for preterm and term stillbirths. Haemoglobin concentration before pregnancy is not associated with stillbirth risk. High haemoglobin level and absence of haemoglobin dilution during pregnancy could be considered as indicators of a high-risk pregnancy.

Antenatal Iron Supplementation Regimens for Pregnant Women in Rural Vietnam and Subsequent Haemoglobin Concentration and Anaemia among Their Infants

PubMed Central

Tran, Thach Duc; Fisher, Jane; Hanieh, Sarah; Tran, Tuan; Simpson, Julie Anne; Tran, Ha; Biggs, Beverley-Ann

2015-01-01

Background Little evidence about the effects of antenatal iron supplementation on infant anaemia is available. The aim was to compare effects on six-month-old infants’ Haemoglobin (Hb) concentration and anaemia of daily iron–folic acid (IFA), twice-weekly IFA with or without other micronutrients (MMN) and usual antenatal care in rural Vietnam. Methods and Findings Secondary data analysis from: a prospective population-based observational study (OS) which examined effects of antenatal psychosocial factors, anaemia and iron deficiency on infant development and health; and a three-arm cluster randomised trial (CRT) of different antenatal iron supplementation regimens. In the OS 497 women (<20 weeks gestation) from 50 randomly-selected communes participated, and in the CRT 1,258 pregnant women (<16 weeks gestation) in 104 communes were allocated randomly to trial arms. The main outcome was six-month-old infant Hb concentration. Baseline data included women’s socio-demographic characteristics, reproductive health, Hb and serum ferritin. Mean differences in infant Hb and odds ratios of infant anaemia between CRT arms and OS were calculated by multivariable regression models, controlling for baseline differences and clustering, using robust standard errors. Infant anaemia prevalence was 68.6% in the OS, 47.2% daily IFA, 53.5% weekly IFA, and 50.3% MMN conditions. After adjustment, mean infant haemoglobin levels in daily IFA (mean difference = 0.95 g/dL; 95%CI 0.7-11.18); weekly IFA (0.91; 95%CI 0.69-1.12) and MMN (1.04; 95%CI 0.8-1.27) were higher than in the OS. After adjustment there were lower odds ratios of anaemia among infants in the daily IFA (OR = 0.31; 95% CI 0.22-0.43), weekly IFA (0.38; 95%CI 0.26-0.54) and MMN (0.33; 95%CI 0.23-0.48) groups than in the OS. Conclusions Infant anaemia is a public health problem in Vietnam and other resource-constrained countries. All supplementation regimens could have clinically significant benefits for Hb and reduce

Bridging Theory and Experiment to Address Structural Properties of Truncated Haemoglobins: Insights from Thermobifida fusca HbO.

PubMed

Howes, Barry D; Boechi, Leonardo; Boffi, Alberto; Estrin, Dario E; Smulevich, Giulietta

2015-01-01

In this chapter, we will discuss the paradigmatic case of Thermobifida fusca (Tf-trHb) HbO in its ferrous and ferric states and its behaviour towards a battery of possible ligands. This choice was dictated by the fact that it has been one of the most extensively studied truncated haemoglobins, both in terms of spectroscopic and molecular dynamics studies. Tf-trHb typifies the structural properties of group II trHbs, as the active site is characterized by a highly polar distal environment in which TrpG8, TyrCD1, and TyrB10 provide three potential H-bond donors in the distal cavity capable of stabilizing the incoming ligands. The role of these residues in key topological positions, and their interplay with the iron-bound ligands, has been addressed in studies carried out on the CO, F(-), OH(-), CN(-), and HS(-) adducts formed with the wild-type protein and a combinatorial set of mutants, in which the distal polar residues, TrpG8, TyrCD1, and TyrB10, have been singly, doubly, or triply replaced by a Phe residue. In this context, such a complete analysis provides an excellent benchmark for the investigation of the relationship between protein structure and function, allowing one to translate physicochemical properties of the active site into the observed functional behaviour. Tf-trHb will be compared with other members of the group II trHbs and, more generally, with members of the other trHb subgroups. © 2015 Elsevier Ltd. All rights reserved.

Foetal haemoglobin concentration at postmenstrual age is unaffected by gestational age at birth.

PubMed

Watanabe, Yuki; Osawa, Kayo; Sato, Itsuko; Iwatani, Sota; Kono, Ruri; Hayakawa, Ikuyo; Hayashi, Nobuhide; Iijima, Kazumoto; Saegusa, Jun; Morioka, Ichiro

2018-05-01

Background Our aim was to determine whether the postnatal age or postmenstrual age is a more appropriate criterion for evaluating foetal haemoglobin concentrations. Methods Blood samples ( n = 1095) were obtained from 394 infants and were divided into two groups based on gestational age at birth: <37 weeks ( n = 491) and ≥37 weeks ( n = 604). (1) Foetal haemoglobin concentrations divided by one month at age after birth were compared between the groups. (2) Foetal haemoglobin concentrations divided into ≤9 months from last menstruation and one month thereafter were compared between the groups. Results In samples from infants ≥37 weeks' gestational age at birth, the median foetal haemoglobin concentrations were 69.5%, 21.4% and 3.6% at 0-1 month, 2-3 months and ≥5 months after birth, respectively. The median foetal haemoglobin concentrations in infants <37 weeks' gestational age at birth were 75.5%, 62.7% and 5.1% at 0-1 month, 2-3 months and ≥5 months after birth, respectively. The median foetal haemoglobin concentrations in infants <37 weeks' gestational age at birth were significantly higher than that in infants ≥37 weeks' gestational age at birth at all postnatal age points. (2) There was no significant difference between the groups at all age points after nine months of postmenstrual age: 72.5 and 75.3% at 9-10 months, 25.1 and 26.6% at 11-12 months and 5.5 and 4.6% at >13 months after last menstruation in infants ≥37 and <37 weeks' gestational age at birth, respectively. Conclusions Evaluation of foetal haemoglobin concentrations at postmenstrual age is unaffected by gestational age at birth.

Malaria in Pregnancy Is a Predictor of Infant Haemoglobin Concentrations during the First Year of Life in Benin, West Africa.

PubMed

Accrombessi, Manfred; Ouédraogo, Smaïla; Agbota, Gino Cédric; Gonzalez, Raquel; Massougbodji, Achille; Menéndez, Clara; Cot, Michel

2015-01-01

Anaemia is an increasingly recognized health problem in Africa, particularly in infants and pregnant women. Although malaria is known to be the main risk factor of anaemia in both groups, the consequences of maternal factors, particularly malaria in pregnancy (MiP), on infant haemoglobin (Hb) concentrations during the first months of life are still unclear. We followed-up a cohort of 1005 Beninese pregnant women from the beginning of pregnancy until delivery. A subsample composed of the first 400 offspring of these women were selected at birth and followed until the first year of life. Placental histology and blood smear at 1st clinical antenatal visit (ANC), 2nd ANC and delivery were used to assess malaria during pregnancy. Infant Hb concentrations were measured at birth, 6, 9 and 12 months of age. A mixed multi-level model was used to assess the association between MiP and infant Hb variations during the first 12 months of life. Placental malaria (difference mean [dm] = - 2.8 g/L, 95% CI [-5.3, -0.3], P = 0.03) and maternal peripheral parasitaemia at delivery (dm = - 4.6 g/L, 95% CI [-7.9, -1.3], P = 0.007) were the main maternal factors significantly associated with infant Hb concentrations during the first year of life. Poor maternal nutritional status and malaria infection during infancy were also significantly associated with a decrease in infant Hb. Antimalarial control and nutritional interventions before and during pregnancy should be reinforced to reduce specifically the incidence of infant anaemia, particularly in Sub-Saharan countries.

Malaria in Pregnancy Is a Predictor of Infant Haemoglobin Concentrations during the First Year of Life in Benin, West Africa

PubMed Central

Accrombessi, Manfred; Ouédraogo, Smaïla; Agbota, Gino Cédric; Gonzalez, Raquel; Massougbodji, Achille; Menéndez, Clara; Cot, Michel

2015-01-01

Background Anaemia is an increasingly recognized health problem in Africa, particularly in infants and pregnant women. Although malaria is known to be the main risk factor of anaemia in both groups, the consequences of maternal factors, particularly malaria in pregnancy (MiP), on infant haemoglobin (Hb) concentrations during the first months of life are still unclear. Methods We followed-up a cohort of 1005 Beninese pregnant women from the beginning of pregnancy until delivery. A subsample composed of the first 400 offspring of these women were selected at birth and followed until the first year of life. Placental histology and blood smear at 1st clinical antenatal visit (ANC), 2nd ANC and delivery were used to assess malaria during pregnancy. Infant Hb concentrations were measured at birth, 6, 9 and 12 months of age. A mixed multi-level model was used to assess the association between MiP and infant Hb variations during the first 12 months of life. Results Placental malaria (difference mean [dm] = - 2.8 g/L, 95% CI [-5.3, -0.3], P = 0.03) and maternal peripheral parasitaemia at delivery (dm = - 4.6 g/L, 95% CI [-7.9, -1.3], P = 0.007) were the main maternal factors significantly associated with infant Hb concentrations during the first year of life. Poor maternal nutritional status and malaria infection during infancy were also significantly associated with a decrease in infant Hb. Conclusion Antimalarial control and nutritional interventions before and during pregnancy should be reinforced to reduce specifically the incidence of infant anaemia, particularly in Sub-Saharan countries. PMID:26052704

Low haemoglobin concentration in Tibetan males is associated with greater high-altitude exercise capacity.

PubMed

Simonson, T S; Wei, G; Wagner, H E; Wuren, T; Qin, G; Yan, M; Wagner, P D; Ge, R L

2015-07-15

Tibetans living at high altitude have adapted genetically such that many display a low erythropoietic response, resulting in near sea-level haemoglobin (Hb) concentration. We hypothesized that absence of the erythropoietic response would be associated with greater exercise capacity compared to those with high [Hb] as a result of beneficial changes in oxygen transport. We measured, in 21 Tibetan males with [Hb] ranging from 15.2 g dl(-1) to 22.9 g dl(-1) (9.4 mmol l(-1) to 14.2 mmol l(-1) ), [Hb], ventilation, volumes of O2 and CO2 utilized at peak exercise (V̇O2 and V̇CO2), heart rate, cardiac output and arterial blood gas variables at peak exercise on a cycle ergometer at ∼4200 m. Lung and muscle O2 diffusional conductances were computed from these measurements. [Hb] was related (negatively) to V̇O2 kg(-1) (r = -0.45, P< 0.05), cardiac output kg(-1) (QT kg(-1) , r = -0.54, P < 0.02), and O2 diffusion capacity in muscle (DM kg(-1) , r = -0.44, P<0.05), but was unrelated to ventilation, arterial partial pressure of O2 (PaO2) or pulmonary diffusing capacity. Using multiple linear regression, variance in peak V̇O2 kg(-1) was primarily attributed to QT, DM, and PCO2 (R(2) = 0.88). However, variance in pulmonary gas exchange played essentially no role in determining peak V̇O2. These results (1) show higher exercise capacity in Tibetans without the erythropoietic response, supported mostly by cardiac and muscle O2 transport capacity and ventilation rather than pulmonary adaptations, and (2) support the emerging hypothesis that the polycythaemia of altitude, normally a beneficial response to low cellular PO2, may become maladaptive if excessively elevated under chronic hypoxia. The cause and effect relationships among [Hb], QT, DM, and PCO2 remain to be elucidated. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

Preferred temperature of juvenile Atlantic cod Gadus morhua with different haemoglobin genotypes at normoxia and moderate hypoxia.

PubMed

Petersen, Maria Faldborg; Steffensen, John Fleng

2003-01-01

Atlantic cod Gadus morhua has polymorphic haemoglobin, which can be separated into two homozygous types, HbI-1 and HbI-2, and one heterozygous type HbI-1/2. The geographical distribution of Atlantic cod with the different haemoglobin types varies, with the HbI(2) allele occurring at high frequency in northern regions, and the HbI(1) allele dominant in warmer areas. To determine if temperature is a selective parameter in the distribution of the haemoglobin types, the preferred temperature of the homozygous genotypes HbI-1 and HbI-2 was measured. We found that HbI-2 cod preferred a temperature of 8.2+/-1.5 degrees C while HbI-1 cod preferred 15.4+/-1.1 degrees C, and this preference was significant. The effect of hypoxia (35% oxygen saturation) on the preferred temperature was also measured. Previous studies showed that the preferred temperature of fish decreases during hypoxia, and this was the case for HbI-1 cod, which preferred 9.8+/-1.8 degrees C during hypoxia, whereas HbI-2 cod did not show this effect. The results indicate that environmental temperature changes will lead to a distributional change in the different haemoglobin types of Atlantic cod, global warming providing an advantage for HbI-1 cod. However, since HbI-1 cod prefer a low temperature under hypoxic conditions, a combination of increased water temperature and hypoxia could be unfavourable for Atlantic cod stocks.

Defining a glycated haemoglobin (HbA1c) level that predicts increased risk of penile implant infection.

PubMed

Habous, Mohamad; Tal, Raanan; Tealab, Alaa; Soliman, Tarek; Nassar, Mohammed; Mekawi, Zenhom; Mahmoud, Saad; Abdelwahab, Osama; Elkhouly, Mohamed; Kamr, Hatem; Remeah, Abdallah; Binsaleh, Saleh; Ralph, David; Mulhall, John

2018-02-01

To re-evaluate the role of diabetes mellitus (DM) as a risk factor for penile implant infection by exploring the association between glycated haemoglobin (HbA1c) levels and penile implant infection rates and to define a threshold value that predicts implant infection. We conducted a multicentre prospective study including all patients undergoing penile implant surgery between 2009 and 2015. Preoperative, perioperative and postoperative management were identical for the entire cohort. Univariate analysis was performed to define predictors of implant infection. The HbA1c levels were analysed as continuous variables and sequential analysis was conducted using 0.5% increments to define a threshold level predicting implant infection. Multivariable analysis was performed with the following factors entered in the model: DM, HbA1C level, patient age, implant type, number of vascular risk factors (VRFs), presence of Peyronie's disease (PD), body mass index (BMI), and surgeon volume. A receiver operating characteristic (ROC) curve was generated to define the optimal HbA1C threshold for infection prediction. In all, 902 implant procedures were performed over the study period. The mean patient age was 56.6 years. The mean HbA1c level was 8.0%, with 81% of men having a HbA1c level of >6%. In all, 685 (76%) implants were malleable and 217 (24%) were inflatable devices; 302 (33.5%) patients also had a diagnosis of PD. The overall infection rate was 8.9% (80/902). Patients who had implant infection had significantly higher mean HbA1c levels, 9.5% vs 7.8% (P < 0.001). Grouping the cases by HbA1c level, we found infection rates were: 1.3% with HbA1c level of <6.5%, 1.5% for 6.5-7.5%, 6.5% for 7.6-8.5%, 14.7% for 8.6-9.5%, 22.4% for >9.5% (P < 0.001). Patient age, implant type, and number of VRFs were not predictive. Predictors defined on multivariable analysis were: PD, high BMI, and high HbA1c level, whilst a high-volume surgeon had a protective effect and was associated with a

Comparative haematological parameters of HbAA and HbAS genotype children infected with Plasmodium falciparum malaria in Yemen.

PubMed

Albiti, Anisa H; Nsiah, Kwabena

2014-04-01

Sickle haemoglobin (HbS) is known to offer considerable protection against falciparum malaria. However, the mechanism of protection is not yet completely understood. In this study, we investigate how the presence of the sickle cell trait affects the haematological profile of AS persons with malaria, in comparison with similarly infected persons with HbAA. This study is based on the hypothesis that the sickle cell trait plays a protective role against malaria. Children from an endemic malaria transmission area in Yemen were enrolled in this study. Hematological parameters were estimated using manual methods, the percentage of parasite density on stained thin smear was calculated, haemoglobin genotypes were determined on paper electrophoresis, ferritin was measured using enzyme-linked immunosorbent assay, serum iron and TIBC were assayed using spectrophotometer, transferrin saturation index was calculated by dividing serum iron by TIBC and expressing the result as a percentage. Haematological parameters were compared in HbAA- and HbAS-infected children. Falciparum malaria parasitaemia was confirmed in the blood smears of 62 children, 44 (55.7%) of AA and 18 (37.5%) AS, so there was higher prevalence in HbAA children (P = 0.047). Parasite density was lower in HbAS- than HbAA-infected children (P = 0.003). Anaemia was prominent in malaria-infected children, with high proportions of moderate and severe forms in HbAA (P = 0.001). The mean levels of haemoglobin, packed cell volume, reticulocyte count, platelets count, lymphocytes, eosinophils, and serum iron were significantly lower while total leukocytes, immature granulocytes, monocytes, erythrocyte sedimentation rate, transferrin saturation, and serum ferritin were significantly higher in HbAA-infected children than HbAS-infected children. Infection with Plasmodium falciparum malaria caused more significant haematological alterations of HbAA children than HbAS. This study supports the observation that sickle cell trait

Should glycated haemoglobin (HbA1c) be used to detect people with type 2 diabetes mellitus and impaired glucose regulation?

PubMed

Mostafa, Samiul A; Davies, Melanie J; Srinivasan, Balasubramanian Thiagarajan; Carey, Marian E; Webb, David; Khunti, Kamlesh

2010-11-01

There is a need to simplify screening tests for type 2 diabetes mellitus (T2DM) so patients can be identified earlier and more efficiently. Glycated haemoglobin (HbA1c) has been recommended by some international organisations as a diagnostic tool for detecting T2DM and impaired glucose regulation (IGR, also termed prediabetes and includes impaired fasting glucose and/or impaired glucose tolerance). The HbA1c cut-point of ≥6.5% (48 mmol/mol) has been selected as diagnostic for T2DM, while the cut-points for IGR are debated by the different international organisations: an International Expert Committee has suggested using HbA1c 6.0-6.4% (42-46 mmol/mol); however, the American Diabetes Association has recommended using HbA1c 5.7-6.4% (39-46 mmol/mol). Some countries will adopt a new method of reporting HbA1c values in millimoles per mole (mmol/mol). Use of HbA1c has some logistical advantages over using an oral glucose tolerance test (OGTT). As patients do not need to fast, appointments do not need to be limited to the morning. The HbA1c result reflects longer term glycaemia and is less affected by recent physical/emotional stress. However, there is some debate as to whether HbA1c should replace fasting plasma glucose or the OGTT. As the two tests detect different people, some individuals with diabetes detected on OGTT will no longer be classified as having T2DM using HbA1c ≥6.5% criteria. Furthermore, some medical conditions can result in HbA1c assay measurements not reflecting glycaemic control over the last 2-3 months; these include haematological disorders, renal failure, and chronic excess alcohol consumption.

A comparative evaluation of the analytical performances of Capillarys 2 Flex Piercing, Tosoh HLC-723 G8, Premier Hb9210, and Roche Cobas c501 Tina-quant Gen 2 analyzers for HbA1c determination.

PubMed

Wu, Xiaobin; Chao, Yan; Wan, Zemin; Wang, Yunxiu; Ma, Yan; Ke, Peifeng; Wu, Xinzhong; Xu, Jianhua; Zhuang, Junhua; Huang, Xianzhang

2016-10-15

Haemoglobin A 1c (HbA 1c ) is widely used in the management of diabetes. Therefore, the reliability and comparability among different analytical methods for its detection have become very important. A comparative evaluation of the analytical performances (precision, linearity, accuracy, method comparison, and interferences including bilirubin, triglyceride, cholesterol, labile HbA 1c (LA 1c ), vitamin C, aspirin, fetal haemoglobin (HbF), and haemoglobin E (Hb E)) were performed on Capillarys 2 Flex Piercing (Capillarys 2FP) (Sebia, France), Tosoh HLC-723 G8 (Tosoh G8) (Tosoh, Japan), Premier Hb9210 (Trinity Biotech, Ireland) and Roche Cobas c501 (Roche c501) (Roche Diagnostics, Germany). A good precision was shown at both low and high HbA 1c levels on all four systems, with all individual CVs below 2% (IFCC units) or 1.5% (NGSP units). Linearity analysis for each analyzer had achieved a good correlation coefficient (R 2 > 0.99) over the entire range tested. The analytical bias of the four systems against the IFCC targets was less than ± 6% (NGSP units), indicating a good accuracy. Method comparison showed a great correlation and agreement between methods. Very high levels of triglycerides and cholesterol (≥ 15.28 and ≥ 8.72 mmol/L, respectively) led to falsely low HbA 1c concentrations on Roche c501. Elevated HbF induced false HbA 1c detection on Capillarys 2FP (> 10%), Tosoh G8 (> 30%), Premier Hb9210 (> 15%), and Roche c501 (> 5%). On Tosoh G8, HbE induced an extra peak on chromatogram, and significantly lower results were reported. The four HbA 1c methods commonly used with commercial analyzers showed a good reliability and comparability, although some interference may falsely alter the result.

Correcting haemoglobin cut-offs to define anaemia in high-altitude pregnant women in Peru reduces adverse perinatal outcomes.

PubMed

Gonzales, Gustavo F; Tapia, Vilma; Gasco, Manuel

2014-07-01

To determine if correction of cut-offs of haemoglobin levels to define anaemia at high altitudes affects rates of adverse perinatal outcomes. Data were obtained from 161,909 mothers and newborns whose births occurred between 1,000 and 4,500 m above sea level (masl). Anaemia was defined with or without correction of haemoglobin (Hb) for altitude as Hb <11 g/dL. Correction of haemoglobin per altitude was performed according to guidelines from the World Health Organization. Rates of stillbirths and preterm births were also calculated. Stillbirth and preterm rates were significantly reduced in cases of anaemia calculated after correction of haemoglobin for altitude compared to values obtained without Hb correction. At high altitudes (3,000-4,500 masl), after Hb correction, the rate of stillbirths was reduced from 37.7 to 18.3 per 1,000 live births (p < 0.01); similarly, preterm birth rates were reduced from 13.1 to 8.76 % (p < 0.01). The odds ratios for stillbirths and for preterm births were also reduced after haemoglobin correction. At high altitude, correction of maternal haemoglobin should not be performed to assess the risks for preterm birth and stillbirth. In fact, using low altitude Hb cut-off is associated with predicting those at risk.

Effect of sample storage temperature and buffer formulation on faecal immunochemical test haemoglobin measurements.

PubMed

Symonds, Erin L; Cole, Stephen R; Bastin, Dawn; Fraser, Robert Jl; Young, Graeme P

2017-12-01

Objectives Faecal immunochemical test accuracy may be adversely affected when samples are exposed to high temperatures. This study evaluated the effect of two sample collection buffer formulations (OC-Sensor, Eiken) and storage temperatures on faecal haemoglobin readings. Methods Faecal immunochemical test samples returned in a screening programme and with ≥10 µg Hb/g faeces in either the original or new formulation haemoglobin stabilizing buffer were stored in the freezer, refrigerator, or at room temperature (22℃-24℃), and reanalysed after 1-14 days. Samples in the new buffer were also reanalysed after storage at 35℃ and 50℃. Results were expressed as percentage of the initial concentration, and the number of days that levels were maintained to at least 80% was calculated. Results Haemoglobin concentrations were maintained above 80% of their initial concentration with both freezer and refrigerator storage, regardless of buffer formulation or storage duration. Stability at room temperature was significantly better in the new buffer, with haemoglobin remaining above 80% for 20 days compared with six days in the original buffer. Storage at 35℃ or 50℃ in the new buffer maintained haemoglobin above 80% for eight and two days, respectively. Conclusion The new formulation buffer has enhanced haemoglobin stabilizing properties when samples are exposed to temperatures greater than 22℃.

Growth and change in blood haemoglobin concentration among underweight Malawian infants receiving fortified spreads for 12 weeks: a preliminary trial.

PubMed

Kuusipalo, Heli; Maleta, Kenneth; Briend, André; Manary, Mark; Ashorn, Per

2006-10-01

Fortified spreads (FSs) have proven effective in the rehabilitation of severely malnourished children. We examined acceptability, growth and change in blood haemoglobin (Hb) concentration among moderately underweight ambulatory infants given FS. This was a randomised, controlled, parallel-group, investigator-blind clinical trial in rural Malawi. Six- to 17-month-old underweight infants (weight for age < -2), whose weight was greater than 5.5 kg and weight-for-height z score greater than -3 received for 12 weeks at home 1 of 8 food supplementation schemes: nothing, 5, 25, 50, or 75 g/day milk-based FS or 25, 50, or 75 g/day soy-based FS. Outcome measures included change in weight, length and blood Hb concentration. A total of 126 infants started and 125 completed the intervention. All infants accepted the spread well, and no intolerance was recorded. Average weight and length gains were higher among infants receiving daily 25 to 75 g FS than among those receiving only 0 to 5 g FS. Mean Hb concentration remained unchanged among unsupplemented controls but increased by 10 to 17 g/L among infants receiving any FS. All average gains were largest among infants receiving 50 g of FS daily: mean difference (95% confidence interval) in the 12-week gain between infants in 50 g milk-based FS group and the unsupplemented group was 290 g (range, -130 to 700 g), 0.9 cm (range, -0.3 to 2.2 cm), and 17 g/L (range, 0 to 34 g/L) for weight, length and blood Hb concentration, respectively. In soy- vs milk-based FS groups, average outcomes were comparable. Supplementation with 25 to 75 g/day of highly fortified spread is feasible and may promote growth and alleviate anaemia among moderately malnourished infants. Further trials should test this hypothesis.

Accuracy of predicted haemoglobin concentration on cardiopulmonary bypass in paediatric cardiac surgery: effect of different formulae for estimating patient blood volume.

PubMed

Redlin, Matthias; Boettcher, Wolfgang; Dehmel, Frank; Cho, Mi-Young; Kukucka, Marian; Habazettl, Helmut

2017-11-01

When applying a blood-conserving approach in paediatric cardiac surgery with the aim of reducing the transfusion of homologous blood products, the decision to use blood or blood-free priming of the cardiopulmonary bypass (CPB) circuit is often based on the predicted haemoglobin concentration (Hb) as derived from the pre-CPB Hb, the prime volume and the estimated blood volume. We assessed the accuracy of this approach and whether it may be improved by using more sophisticated methods of estimating the blood volume. Data from 522 paediatric cardiac surgery patients treated with CPB with blood-free priming in a 2-year period from May 2013 to May 2015 were collected. Inclusion criteria were body weight <15 kg and available Hb data immediately prior to and after the onset of CPB. The Hb on CPB was predicted according to Fick's principle from the pre-CPB Hb, the prime volume and the patient blood volume. Linear regression analyses and Bland-Altman plots were used to assess the accuracy of the Hb prediction. Different methods to estimate the blood volume were assessed and compared. The initial Hb on CPB correlated well with the predicted Hb (R 2 =0.87, p<0.001). A Bland-Altman plot revealed little bias at 0.07 g/dL and an area of agreement from -1.35 to 1.48 g/dL. More sophisticated methods of estimating blood volume from lean body mass did not improve the Hb prediction, but rather increased bias. Hb prediction is reasonably accurate, with the best result obtained with the simplest method of estimating the blood volume at 80 mL/kg body weight. When deciding for or against blood-free priming, caution is necessary when the predicted Hb lies in a range of ± 2 g/dL around the transfusion trigger.

Purification, crystallization and preliminary crystallographic studies of haemoglobin from mongoose (Helogale parvula) in two different crystal forms induced by pH variation.

PubMed

Mohamed Abubakkar, M; Saraboji, K; Ponnuswamy, M N

2013-02-01

Haemoglobin (Hb) is a respiratory pigment; it is a tetrameric protein that ferries oxygen from the lungs to tissues and transports carbon dioxide on the return journey. The oxygen affinity of haemoglobin is regulated by the concentration of oxygen surrounding it and several efforts have revealed the shapes of Hb in different states and with different functions. However, study of the molecular basis of Hbs from low-oxygen-affinity species is critically needed in order to increase the understanding of the mechanism behind oxygen adaptation. The present study reports the preliminary crystallographic study of low-oxygen-affinity haemoglobin from mongoose, a burrowing mammal. Haemoglobin from mongoose was purified by anion-exchange chromatography, crystallized using the hanging-drop vapour-diffusion method and diffraction data sets were collected from monoclinic (2.3 Å resolution) and orthorhombic (2.9 Å resolution) crystal forms obtained by pH variation. The monoclinic and orthorhombic asymmetric units contained half and a whole biological molecule, respectively.

Purification, crystallization and preliminary crystallographic studies of haemoglobin from mongoose (Helogale parvula) in two different crystal forms induced by pH variation

PubMed Central

Mohamed Abubakkar, M.; Saraboji, K.; Ponnuswamy, M. N.

2013-01-01

Haemoglobin (Hb) is a respiratory pigment; it is a tetrameric protein that ferries oxygen from the lungs to tissues and transports carbon dioxide on the return journey. The oxygen affinity of haemoglobin is regulated by the concentration of oxygen surrounding it and several efforts have revealed the shapes of Hb in different states and with different functions. However, study of the molecular basis of Hbs from low-oxygen-affinity species is critically needed in order to increase the understanding of the mechanism behind oxygen adaptation. The present study reports the preliminary crystallographic study of low-oxygen-affinity haemoglobin from mongoose, a burrowing mammal. Haemoglobin from mongoose was purified by anion-exchange chromatography, crystallized using the hanging-drop vapour-diffusion method and diffraction data sets were collected from monoclinic (2.3 Å resolution) and orthorhombic (2.9 Å resolution) crystal forms obtained by pH variation. The monoclinic and orthorhombic asymmetric units contained half and a whole biological molecule, respectively. PMID:23385751

Gender Difference in Aerobic Capacity and the Contribution by Body Composition and Haemoglobin Concentration: A Study in Young Indian National Hockey Players

PubMed Central

Kailashiya, Jyotsna

2016-01-01

Introduction Although gender difference in aerobic capacity is known, the contributing factors have been researched seldom. Aim To investigate the gender gap and the contribution by percentage Body Fat (BF), Body Mass Index (BMI) and haemoglobin concentration Hb. Materials and Methods The study was conducted on 30 (17 males, 13 females) training status matched young hockey players. Healthy players who were playing upto national level competition were included. BW (Body Weight), BF, BMI, LBM (Lean Body Mass), rHR (restring Heart Rate), HRR (Heart Rate Recovery), Hb, a/rVO2max (absolute/relative), a/rPWC (Physical Work Capacity) and RMR (Resting Metabolic Rate) were measured and analysed. Results There was significant gender difference in the measured parameters. Difference in a/rVO2max remained significant even after controlling for BF, BMI and Hb. Multiple regression and correlation analysis revealed gender difference in VO2max/LBM was due to: BMI(31.91%)>BF(27.60%)>Hb(9.91%). BMI also significantly contributed 3.66% of VO2max/LBM variance, independent of that by gender. Difference in RMR was mainly related to LBM, BF and BMI. Conclusion The study provided an understanding for gender gap in aerobic capacity. Differences in BMI & BF were one of the main reasons. PMID:28050360

Effect of once-weekly dulaglutide on glycated haemoglobin (HbA1c) and fasting blood glucose in patient subpopulations by gender, duration of diabetes and baseline HbA1c.

PubMed

Gallwitz, Baptist; Dagogo-Jack, Samuel; Thieu, Vivian; Garcia-Perez, Luis-Emilio; Pavo, Imre; Yu, Maria; Robertson, Kenneth E; Zhang, Nan; Giorgino, Francesco

2018-02-01

To evaluate the efficacy and safety of dulaglutide 1.5 and 0.75 mg in patients with type 2 diabetes by subgroups of gender, duration of diabetes and baseline glycated haemoglobin (HbA1c) in the dulaglutide clinical development programme (AWARD-1 to -6 and -8 clinical trials). Change in HbA1c was analysed by gender, duration of diabetes (<5, ≥5 years and <10, ≥10 years), and baseline HbA1c (<8.5%, ≥8.5%) in pooled and individual studies. Changes from baseline in weight, hypoglycaemia and gastrointestinal adverse events were evaluated for individual trials. In the pooled analysis of patients treated with dulaglutide 1.5 mg at 6 months, the reductions in HbA1c from baseline were similar across gender (men: least squares [LS] mean -1.26% [95% confidence interval {CI} -1.36, -1.16]; women: LS mean -1.33% [95% CI -1.43, -1.24]) and among duration of diabetes subgroups (<5 years: LS mean -1.32% [95% CI -1.43, -1.22]; ≥5 and <10 years: LS mean -1.33% [95% CI -1.43, -1.22]; ≥10 years: -1.24% [95% CI -1.35, -1.14]). Patients with baseline HbA1c ≥8.5% had greater HbA1c reductions than patients with baseline HbA1c <8.5%, (≥8.5%: LS mean -1.86% [95% CI -1.97, -1.75]; <8.5%: LS mean -1.02% [95% CI -1.12, -0.93]). Reductions in fasting blood glucose (FBG) were consistent with HbA1c changes. Similar results were observed with dulaglutide 0.75 mg. In general, body weight changes were similar among duration of diabetes and in baseline HbA1c subgroups, respectively; women had a numerically greater weight loss or less weight gain than men with both dulaglutide doses. There was no clinically meaningful difference in hypoglycaemia trends by gender or duration of diabetes. Hypoglycaemia incidence and rate were generally lower in patients with baseline HbA1c ≥8.5% than in those with <8.5%, except for the AWARD-4 study (combination with mealtime insulin). Across the AWARD studies, dulaglutide demonstrated significant improvements in glycaemic control

Paradoxical correlation between signal in functional magnetic resonance imaging and deoxygenated haemoglobin content in capillaries: a new theoretical explanation

NASA Astrophysics Data System (ADS)

Yamamoto, Toru; Kato, Toshinori

2002-04-01

Signal increases in functional magnetic resonance imaging (fMRI) are believed to be a result of decreased paramagnetic deoxygenated haemoglobin (deoxyHb) content in the neural activation area. However, discrepancies in this canonical blood oxygenation level dependent (BOLD) theory have been pointed out in studies using optical techniques, which directly measure haemoglobin changes. To explain the discrepancies, we developed a new theory bridging magnetic resonance (MR) signal and haemoglobin changes. We focused on capillary influences, which have been neglected in most previous fMRI studies and performed a combined fMRI and near-infrared spectroscopy (NIRS) study using a language task. Paradoxically, both the MR signal and deoxyHb content increased in Broca's area. On the other hand, fMRI activation in the auditory area near large veins correlated with a mirror-image decrease in deoxyHb and increase in oxygenated haemoglobin (oxyHb), in agreement with canonical BOLD theory. All fMRI signal changes correlated consistently with changes in oxyHb, the diamagnetism of which is insensitive to MR. We concluded that the discrepancy with the canonical BOLD theory is caused by the fact that the BOLD theory ignores the effect of the capillaries. Our theory explains the paradoxical phenomena of the oxyHb and deoxyHb contributions to the MR signal and gives a new insight into the precise haemodynamics of activation by analysing fMRI and NIRS data.

Effect of Capacitive and Resistive electric transfer on haemoglobin saturation and tissue temperature.

PubMed

Tashiro, Yuto; Hasegawa, Satoshi; Yokota, Yuki; Nishiguchi, Shu; Fukutani, Naoto; Shirooka, Hidehiko; Tasaka, Seishiro; Matsushita, Tomofumi; Matsubara, Keisuke; Nakayama, Yasuaki; Sonoda, Takuya; Tsuboyama, Tadao; Aoyama, Tomoki

2017-09-01

This study aims to evaluate the effects of Capacitive and Resistive electric transfer (CRet) and hotpack (HP) on haemoglobin saturation and tissue temperature. The participants were 13 healthy males (mean age 24.5 ± 3.0). They underwent three interventions on different days: (1) CRet (CRet group), (2) HP (HP group) and (3) CRet without power (sham group). The intervention and measurement were applied at the lower paraspinal muscle. Indiba ® active ProRecovery HCR902 was used in the CRet group, and the moist heat method was used in the HP group. Oxygenated, deoxygenated and total haemoglobin (oxy-Hb, deoxy-Hb, total-Hb) counts were measured before and after the 15-min interventions, together with the temperature at the skin surface, and at depths of 10 mm and 20 mm (ST, 10mmDT and 20mmDT, respectively). The haemoglobin saturation and tissue temperature were measured until 30 min after the intervention and were collected at 5-min intervals. Statistical analysis was performed for each index by using the Mann-Whitney U test for comparisons between all groups at each time point. Total-Hb and oxy-Hb were significantly higher in the CRet group than in the HP group continuously for 30 min after the intervention. The 10mmDT and 20mmDT were significantly higher in the CRet group than in the HP group from 10- to 30 min after intervention. The effect on haemoglobin saturation was higher in the CRet group than in the HP group. In addition, the CRet intervention warmed deep tissue more effectively than HP intervention.

Synthesis of Human Haemoglobin by Plants

ERIC Educational Resources Information Center

Onyesom, I.

2006-01-01

Haemoglobin, Hb is the red, protein pigment in blood that transports oxygen round the body. Decreased quantity could lead to anaemia, and when the anaemic condition turns severe, blood transfusion becomes inevitable. However, the safety of human source has become questionable in recent times, and this has aroused the interest of scientists to…

Artefactually low glycated haemoglobin in a patient with severe hypertriglyceridaemia

PubMed Central

Garrib, A; Griffiths, W; Eldridge, P; Hatton, R; Worsley, A; Crook, M

2003-01-01

This report describes a case of artefactually low glycated haemoglobin (Hb) in a patient with type II diabetes and severe hypertriglyceridaemia. The effect of hypertriglyceridaemia on glycated Hb determination using the Abbott Vision method was investigated in a series of patients with diabetes. The interference of triglycerides in glycated Hb assays was also investigated by two other methods, the Beckman Synchron CX4 delta immunoturbidimetric method, and the Primus affinity chromatography high performance liquid chromatography assay. PMID:12719463

Haemoglobin variants may cause significant differences in haemoglobin A1c as measured by high-performance liquid chromatography and enzymatic methods in diabetic patients: a cross-sectional study.

PubMed

Otabe, Shuichi; Nakayama, Hitomi; Ohki, Tsuyoshi; Soejima, Eri; Tajiri, Yuji; Yamada, Kentaro

2017-07-01

Background We aimed to determine whether the discrepancy between haemoglobin A1c values determined by high-performance liquid chromatography and enzymatic haemoglobin A1c measurements in diabetic patients was clinically relevant. Methods We randomly recruited 1421 outpatients undergoing diabetic treatment and follow-up who underwent at least three haemoglobin A1c measurements between April 2014 and March 2015 at our clinic. In 6369 samples, haemoglobin A1c was simultaneously measured by HA-8160 and MetaboLead (enzymatic assay), and the values were compared. Results haemoglobin A1c measurements by high-performance liquid chromatography and enzymatic assay were strongly correlated (correlation coefficient: 0.9828, linear approximation curve y = 0.9986x - 0.2507). Mean haemoglobin A1c (6.8 ± 1.0%) measured by high-performance liquid chromatography was significantly higher than that measured by enzymatic assay (6.5 ± 1.0%, P < 0.0001). During the sample processing, four (0.3%) subjects presented consistently lower haemoglobin A1c values (<0.7%) by high-performance liquid chromatography than those from enzymatic assay. Of these, three had Hb Toranomon [β112 (G14) Cys→Trp]. The fourth had Hb Ube-2 [α68 (E17) Asn→Asp]. One other subject presented consistently higher haemoglobin A1c values (>1%) by high-performance liquid chromatography than those from enzymatic assay and was diagnosed with a -77 (T > C) mutation in the δ-globin gene. These unrelated asymptomatic subjects had normal erythrocyte profiles, without anaemia. Conclusions We showed that haemoglobin A1c values measured by high-performance liquid chromatography were significantly higher than those measured by enzymatic assay in diabetic subjects. However, when an oversized deviation (>0.7%) between glycaemic control status and haemoglobin A1c is apparent, clinicians should check the methods used to measure haemoglobin A1c and consider the possible presence of a haemoglobin variant.

Prognostic implications of baseline anaemia and changes in haemoglobin concentrations with amphotericin B therapy for cryptococcal meningitis.

PubMed

Tugume, L; Morawski, B M; Abassi, M; Bahr, N C; Kiggundu, R; Nabeta, H W; Hullsiek, K H; Taseera, K; Musubire, A K; Schutz, C; Muzoora, C; Williams, D A; Rolfes, M A; Meintjes, G; Rhein, J; Meya, D B; Boulware, D R

2017-01-01

Anaemia represents a common toxicity with amphotericin B-based induction therapy in HIV-infected persons with cryptococcal meningitis. We sought to examine the impact of amphotericin-related anaemia on survival. We used data from Ugandan and South African trial participants to characterize the variation of haemoglobin concentrations from diagnosis to 12 weeks post-diagnosis. Anaemia severity was classified based on the haemoglobin concentration at cryptococcal meningitis diagnosis, and nadir haemoglobin values during amphotericin induction. Cox proportional hazard models were used to estimate 2- and 10-week mortality risk. We also estimated 10-week mortality risk among participants with nadir haemoglobin < 8.5 g/dL during amphotericin induction and who survived ≥ 2 weeks post-enrolment. The median haemoglobin concentration at meningitis diagnosis was 11.5 g/dL [interquartile range (IQR) 9.7-13 g/dL; n = 311] with a mean decline of 4.2 g/dL [95% confidence interval (CI) -4.6 to -3.8; P < 0.001; n = 148] from diagnosis to nadir value among participants with baseline haemoglobin ≥ 8.5 g/dL. The median haemoglobin concentration was 8.1 g/dL (IQR 6.5-9.5 g/dL) at 2 weeks, increasing to 9.4 g/dL (IQR 8.2-10.9 g/dL) by 4 weeks and continuing to increase to 12 weeks. Among participants with haemoglobin < 8.5 g/dL at diagnosis, mortality risk was elevated at 2 weeks [hazard ratio (HR) 2.7; 95% CI 1.5-4.9; P < 0.01] and 10 weeks (HR 1.8; 95% CI 1.1-2.2; P = 0.03), relative to those with haemoglobin ≥ 8.5 g/dL. New-onset anaemia occurring with amphotericin therapy did not have a statistically significant association with 10-week mortality (HR 2.0; 95% CI 0.5-9.1; P = 0.4). Amphotericin induced significant haemoglobin declines, which were mostly transient and did not impact 10-week mortality. Individuals with moderate to life-threatening anaemia at baseline had a higher mortality risk at 2 and 10 weeks post-enrolment. © 2016 British HIV Association.

Haemoglobin concentrations and infection by Giardia intestinalis in children: effect of treatment with secnidazole.

PubMed

Jiménez, J C; Rodríguez, N; Di Prisco, M C; Lynch, N R; Costa, V

1999-12-01

The blood concentrations of haemoglobin were investigated in 82 children aged 2-9 years. Fifty-seven (31 boys and 26 girls) were stool-positive for Giardia intestinalis but the other 25, used as controls, were negative. The mean (S.D.) haemoglobin concentration among the infected children was significantly lower pre-treatment than that for the control group [11.6 (1.2) v. 12.6 (1.5) g/dl; P < 0.05]. Treatment of the infected children with a single oral dose of secnidazole (30 mg/kg) led to a significant increase in their mean haemoglobin level 15 days later, from 11.6 (1.2) g/dl pre-treatment to 12.4 (1.2) g/dl post-treatment (P < 0.05). The results indicate that the therapeutic control of giardiasis could be important in programmes to combat anaemia in children living in endemic areas.

Comparison of haemoglobin assessments by HemoCue and two automated haematology analysers in young Laotian children.

PubMed

Hinnouho, Guy-Marino; Barffour, Maxwell A; Wessells, K Ryan; Brown, Kenneth H; Kounnavong, Sengchanh; Chanhthavong, Bigphone; Ratsavong, Kethmany; Kewcharoenwong, Chidchamai; Hess, Sonja Y

2017-12-02

Haemoglobin (Hb) assessment by Hemocue is used widely for anaemia screening in both adults and children. However, few studies have compared the diagnostic accuracy of Hemocue with an automated haematology analyser in young children. To compare Hb concentrations by Hemocue Hb301 and two automated haematology analysers in young children in rural communities of Lao PDR. Capillary blood was collected from 6-month-old to 23-month-old children (n=1487) for determination of Hb concentration by Hemocue Hb301. On the same day, venous blood was collected for complete blood count using one of two haematology analysers (XT-1800i, Sysmex, and BC-3000Plus, Mindray Medical International). In a subsample of children (n=129), venous Hb was also measured by HemoCue Hb301. Agreement between the two methods was estimated using Bland-Altman plots. Mean capillary Hb by Hemocue was significantly higher than mean venous Hb by haematology analysers combined (108.4±10.3 g/L vs 102.3±13.1 g/L; P<0.001), resulting in a significantly lower anaemia prevalence (Hb <110 g/L) by Hemocue (53.7% vs 73.9%; P<0.001). The Bland-Altman assessment of agreement showed a bias of 6.1 g/L and limits of agreement were -11.5 g/L to 23.7 g/L. Mean venous Hb concentration by Hemocue Hb301 (113.6±14.0 g/L) was significantly higher than mean capillary Hb concentration by Hemocue Hb301 (110.0±10.7; P=0.03 g/L), which in turn was significantly higher than mean venous Hb concentration by the Mindray BC-3000Plus (102.3±17.4 g/L). Capillary and venous Hb concentrations assessed by Hemocue Hb301 showed poor agreement compared with venous Hb by automated haematology analysers, resulting in significantly different anaemia prevalences. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Relationship between the degree of perineal trauma at vaginal birth and change in haemoglobin concentration.

PubMed

Rubio-Álvarez, Ana; Molina-Alarcón, Milagros; Hernández-Martínez, Antonio

2017-10-01

Postpartum anaemia is a problem with high prevalence that significantly affects maternal recovery. Among the causal factors is perineal trauma. However, it is still not known what degree of perineal trauma produces a greater reduction of haemoglobin. To assess the relationship between the degree of perineal trauma and change in haemoglobin concentration at vaginal birth. An observational, analytical retrospective cohort study was performed at the Mancha-Centro Hospital (Spain) during the period 2010-2014. Data were collected regarding 3479 women who gave birth vaginally. The main outcome variable was the change in haemoglobin concentration. Multivariate analysis by means of multiple linear regression was performed to control possible confounding factors and to determine the net effect of each degree of perineal trauma on haemoglobin reduction. Of the total sample, 20.1% of women (699) had an intact perineum, 41.6% (1446) experienced some form of perineal trauma, but not episiotomy, and the remaining 38.3% of women (1334) underwent an episiotomy. The average reduction of haemoglobin was 1.46g/dL (Standard Deviation (SD)=1.09g/dL) for women without episiotomy with a second degree tear and 2.07g/dL (SD=1.24g/dL) for women who had an episiotomy and no perineal tear. The greatest reduction occurred among women with episiotomy and a third or fourth degree tear with a decrease of 3.10g/dL (SD=1.32g/dL). Episiotomy is related to greater reduction of haemoglobin concentration in comparison with all degrees of spontaneous perineal trauma. The use of episiotomy should be strictly limited. Copyright © 2017 Australian College of Midwives. Published by Elsevier Ltd. All rights reserved.

False-negative rate cannot be reduced by lowering the haemoglobin concentration cut-off in colorectal cancer screening using faecal immunochemical test.

PubMed

Ibañez-Sanz, Gemma; Garcia, Montse; Milà, Núria; Rodríguez-Moranta, Francisco; Binefa, Gemma; Gómez-Matas, Javier; Benito, Llúcia; Padrol, Isabel; Barenys, Mercè; Moreno, Victor

2017-09-01

The aim of this study was to analyse false-negative (FN) results of the faecal immunochemical test (FIT) and its determinants in a colorectal cancer screening programme in Catalonia. We carried out a cross-sectional study among 218 screenees with a negative FIT result who agreed to undergo a colonoscopy. A false-negative result was defined as the detection, at colonoscopy, of intermediate/high-risk polyps or colorectal cancer in a patient with a previous negative FIT (<20 µgHb/g). Multivariate logistic regression models were constructed to identify sociodemographic (sex, age) and screening variables (quantitative faecal haemoglobin, colonoscopy findings) related to FN results. Adjusted odds ratios and their 95% confidence intervals were estimated. There were 15.6% FN FIT results. Faecal haemoglobin was undetected in 45.5% of these results and was below 4 µgHb/g in 94.0% of the individuals with a FN result. About 60% of the lesions were located in the proximal colon, whereas the expected percentage was 30%. Decreasing the positivity threshold of FIT does not increase the detection rate of advanced neoplasia, but may increase the costs and potential adverse effects.

Reticulocyte and haemoglobin profiles in elite triathletes over four consecutive seasons.

PubMed

Díaz, V; Lombardi, G; Ricci, C; Jacobs, R A; Montalvo, Z; Lundby, C; Banfi, G

2011-12-01

The World Anti-Doping Agency has implemented the Blood Passport in attempt to detect blood doping in athletes. The Blood Passport looks for uncommon changes overtime in reticulocytes percentage (Ret %), as a variable of the OFF-hr score, and haemoglobin concentration ([Hb]) reflecting potential doping violations. Few studies, however, have actually investigated the concurrent stability of Ret % and [Hb] in athletes over extended periods of time, none of which were measured in athletes who undergo strenuous and prolonged physical exercise. Measurements of Ret % and [Hb] were assessed over the course of four competitive seasons in elite triathletes (10 males and seven female). Blood was obtained at the start of the season, precompetitive period, competitive period and at the end of the competitive period. Differences (P<0.001) were observed in both [Hb] and Ret % between genders and there was a high variability between subjects. Neither males nor females exhibited differences in [Hb] across all periods within one season. Within gender, analysis revealed that Ret % varied significantly (P=0.0018) between periods only in female athletes. We conclude that Ret % and [Hb] remain stable over four consecutive seasons in elite triathletes, confirming that both parameters are valid for antidoping purposes based on the Blood Passport. In addition, Ret % fluctuations within one season require further investigation in females. © 2011 Blackwell Publishing Ltd.

Purification, crystallization and preliminary X-ray diffraction studies of parakeet (Psittacula krameri) haemoglobin.

PubMed

Jaimohan, S M; Naresh, M D; Arumugam, V; Mandal, A B

2009-10-01

Birds often show efficient oxygen management in order to meet the special demands of their metabolism. However, the structural studies of avian haemoglobins (Hbs) are inadequate for complete understanding of the mechanism involved. Towards this end, purification, crystallization and preliminary X-ray diffraction studies have been carried out for parakeet Hb. Parakeet Hb was crystallized as the met form in low-salt buffered conditions after extracting haemoglobin from crude blood by microcentrifugation and purifying the sample by column chromatography. Good-quality crystals were grown from 10% PEG 3350 and a crystal diffracted to about 2.8 A resolution. Preliminary diffraction data showed that the Hb crystal belonged to the monoclinic system (space group C2), with unit-cell parameters a = 110.68, b = 64.27, c = 56.40 A, beta = 109.35 degrees . Matthews volume analysis indicated that the crystals contained a half-tetramer in the asymmetric unit.

Haemoglobin dynamics in Papuan and non-Papuan adults in northeast Papua, Indonesia, with acute, uncomplicated vivax or falciparum malaria

PubMed Central

2013-01-01

Background Haemoglobin (Hb) recovers slowly in malaria and may be influenced by naturally acquired immunity. Hb recovery was compared in malaria immune, indigenous Papuan and non-Papuan adults with limited malaria exposure. Methods Hb concentrations were measured on Days (D) 0, 3, 7, and 28 in 57 Papuans and 105 non-Papuans treated with chloroquine, doxycycline or both drugs for acute, uncomplicated Plasmodium vivax (n?=?64) or Plasmodium falciparum (n?=?98). Results Mean (SD, range) D0 Hb was 12.7 (2.2, 7–21.3) g/dL and was similar in P. falciparum infected Papuans and non-Papuans: 12.2 vs. 12.8 g/dL (P?=?0.15) but significantly lower in: (i) P. vivax-infected Papuans vs. P. vivax-infected non-Papuans: 11.4 vs. 13.47 g/dL [∆?=?−2.07 (95% CI: –3.3 – –0.8), P?=?0.0018], (ii) all patients with splenomegaly (vs. those without splenomegaly): 12.16 vs. 13.01 g/dL [∆?=?−0.85 (−1.6– –0.085), P?=?0.029], and (iii) all females vs. all males: 10.18 vs. 13.01 g/dL [∆?=?−2.82 (−3.97 – –1.67), P?Hb. Mean D28 Hb increased to 13.6 g/dL [∆?=?1.01 (0.5-1.5) vs. D0 Hb, P?=?0.0001]. It was: (i) positively correlated with the D0 Hb (adjusted R2?=?0.24, P?=?0.000), and was significantly lower in P. vivax infected Papuans vs. non-Papuans: 12.71 vs. 14.46 g/dL [∆?=?−1.7 (−2.95– –0.5, P?=?0.006). Conclusions Haemoglobin recovery was related to baseline Hb. Vivax-infected malaria immune Papuans had persistently lower Hb concentrations compared to non-Papuans with limited malaria exposure. This haematological disadvantage remains unexplained. PMID:23777546

Diagnostic applications of newborn screening for α-thalassaemias, haemoglobins E and H disorders using isoelectric focusing on dry blood spots.

PubMed

Jindatanmanusan, Punyanuch; Riolueang, Suchada; Glomglao, Waraporn; Sukontharangsri, Yaowapa; Chamnanvanakij, Sangkae; Torcharus, Kitti; Viprakasit, Vip

2014-03-01

Neonatal screening for haemoglobin (Hb) disorders is a standard of care in several developed countries with the main objective to detect Hb S. Such practice has not been established in Thailand where α-thalassaemia and haemoglobin E (Hb E) are highly prevalent. Early identification of thalassaemias could be helpful and strengthen the programme for prevention and control for severe thalassaemias. Data from isoelectric focusing (IEF) and Isoscan® for detecting types and amount (%) of each haemoglobin in 350 newborn's dried blood spots were analysed and compared with the comprehensive genotype analysis by DNA studies as a gold standard. Based on genetic profiles, there were 10 different categories: (1) normal (n = 227), (2) α(+)-thalassaemia trait (n = 14), (3) α(0)-thalassaemia trait (n = 13), (4) β(0)-thalassaemia trait (n = 7), (5) Hb E trait (n = 72), (6) Hb E trait with α(0)-thalassaemia or homozygous α(+)-thalassaemia (n = 5), (7) Hb E trait with α(+)-thalassaemia trait (n = 5), (8) homozygous Hb E (n = 3), (9) homozygous Hb E with α(0)-thalassaemia trait (n = 1) and (10) Hb H disease (n = 3). The presence of Hb Bart's and Hb E were used to identify cases with α-thalassaemia and Hb E, respectively. We set 0.25% of Hb Bart's and 1.5% of Hb E as a cut-off level to detect α(+)-thalassaemia trait (sensitivity 92.86% and specificity 74.0%) and Hb E trait with 100% of both sensitivity and specificity for IEF diagnosis. Although molecular diagnosis seems to be better for definitive diagnosis of thalassaemia syndromes at birth, however, using our reference range described herein, IEF can be applied in a resource-limiting setting with acceptable reliability.

Usefulness of the plasma glucose concentration-to-HbA1c ratio in predicting clinical outcomes during acute illness with extreme hyperglycaemia.

PubMed

Su, Y-W; Hsu, C-Y; Guo, Y-W; Chen, H-S

2017-02-01

To evaluate the correlation between the plasma glucose-to-glycated haemoglobin ratio (GAR) and clinical outcome during acute illness. This retrospective observational cohort study enrolled 661 patients who visited the emergency department of our hospital between 1 July 2008 and 30 September 2010 with plasma glucose concentrations>500mg/dL. Systolic blood pressure, heart rate, white blood cells, neutrophils, haematocrit, blood urea nitrogen, serum creatinine, liver function and plasma glucose concentration were recorded at the initial presentation to the emergency department. Data on glycated haemoglobin over the preceding 6 months were reviewed from our hospital database. The glucose-to-HbA 1c ratio (GAR) was calculated as the plasma glucose concentration divided by glycated haemoglobin. The GAR of those who died was significantly higher than that of the survivors (81.0±25.9 vs 67.6±25.0; P<0.001). There was a trend towards a higher 90-day mortality rate in patients with higher GARs (log-rank test P<0.0001 for trend). On multivariate Cox regression analysis, the GAR was significantly related to 90-day mortality (hazard ratio [HR] for 1 standard deviation [SD] change: 1.41, 95% confidence interval [CI]: 1.22-1.63; P<0.001), but not to plasma glucose (HR: 0.89, 95% CI: 0.70-1.13; P=0.328). Rates of intensive care unit (ICU) admission and mechanical ventilator use were also higher in those with higher GARs. GAR independently predicted 90-day mortality, ICU admission and use of mechanical ventilation. It was also a better predictor of patient outcomes than plasma glucose alone in patients with extremely high glucose levels. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Establishing traceability of photometric absorbance values for accurate measurements of the haemoglobin concentration in blood

NASA Astrophysics Data System (ADS)

Witt, K.; Wolf, H. U.; Heuck, C.; Kammel, M.; Kummrow, A.; Neukammer, J.

2013-10-01

Haemoglobin concentration in blood is one of the most frequently measured analytes in laboratory medicine. Reference and routine methods for the determination of the haemoglobin concentration in blood are based on the conversion of haeme, haemoglobin and haemiglobin species into uniform end products. The total haemoglobin concentration in blood is measured using the absorbance of the reaction products. Traceable absorbance measurement values on the highest metrological level are a prerequisite for the calibration and evaluation of procedures with respect to their suitability for routine measurements and their potential as reference measurement procedures. For this purpose, we describe a procedure to establish traceability of spectral absorbance measurements for the haemiglobincyanide (HiCN) method and for the alkaline haematin detergent (AHD) method. The latter is characterized by a higher stability of the reaction product. In addition, the toxic hazard of cyanide, which binds to the iron ion of the haem group and thus inhibits the oxygen transport, is avoided. Traceability is established at different wavelengths by applying total least-squares analysis to derive the conventional quantity values for the absorbance from the measured values. Extrapolation and interpolation are applied to get access to the spectral regions required to characterize the Q-absorption bands of the HiCN and AHD methods, respectively. For absorbance values between 0.3 and 1.8, the contributions of absorbance measurements to the total expanded uncertainties (95% level of confidence) of absorbance measurements range from 1% to 0.4%.

Evaluation of Haemoglobin and Cytochrome Responses During Forearm Ischaemia Using Multi-wavelength Time Domain NIRS.

PubMed

Lange, Frédéric; Dunne, Luke; Tachtsidis, Ilias

2017-01-01

We demonstrate the ability of a 16-wavelength time domain near-infrared spectroscopy system to monitor changes in oxy- and deoxy haemoglobin ([HbO 2 ] [HHb]) and the oxidation of cytochrome-c-oxidase ([oxCCO]), during forearm ischaemia. We tested two methods to retrieve the concentration changes. The first uses the measured changes in light attenuation and the modified Beer-Lambert law, and the second uses the absorption and scattering estimated by the measured time-point spread function. The system is able to retrieve the concentration changes with both methods, giving similar results. At the end of forearm ischaemia (t = 5 min), we measured an increase in [HHb] of 16.77 ± 2.52 and 16.37 ± 2.33 μMol, and a decrease in [HbO 2 ] of -6.12 ± 1.62 and -5.57 ± 2.02 μMol for method 1 and 2, respectively. At that same time, the changes in [oxCCO] were -0.36 ± 0.33 and -1.40 ± 1.20 μMol, for method 1 and 2, respectively. These small changes in [oxCCO], despite a huge change in haemoglobin, demonstrate the absence of crosstalk and are comparable to previous measurements using broadband NIRS.

Adaptation to extreme environments: structure-function relationships in Emperor penguin haemoglobin.

PubMed

Tamburrini, M; Condò, S G; di Prisco, G; Giardina, B

1994-04-15

The functional properties of the single haemoglobin (Hb) of Emperor penguin (Aptenodytes forsteri) have been investigated at different temperatures as a function of proton and organic phosphate concentration. The complete amino acid sequence has been established. Comparison with that of human HbA shows 12 substitutions in the contact regions of alpha beta dimers. In addition to overall similarities shared with most of the avian Hbs previously described, this Hb shows significant differences, which could be related to the peculiar behaviour of this penguin. In particular we may consider that: (1) the shape of the Bohr effect curve seems well adapted for gas exchange during very prolonged dives, preserving penguin Hb from a sudden and not controlled stripping of oxygen; (2) the very minor enthalpy change observed at lower pH could be an example of molecular adaptation, through which oxygen delivery becomes essentially insensitive to exposure to the extremely low temperatures of the environment. Moreover, the small alkaline Bohr effect has been found to be only chloride-linked, since the pH dependence of the oxygen affinity is totally abolished in the absence of this ion. These functional characteristics are discussed on the basis of the primary structure of alpha and beta-chains.

Routine screening for α-thalassaemia using an immunochromatographic strip assay for haemoglobin Bart's.

PubMed

Prayalaw, Patcharawadee; Fucharoen, Goonnapa; Fucharoen, Supan

2014-09-01

To evaluate an immunochromatographic (IC) strip assay for Hb Bart's as a routine screening test for α-thalassaemia in area with a high prevalence of thalassaemia and haemoglobinopathies. A total of 300 adult screen positive blood specimens were collected at an ongoing thalassaemia screening programme in northeast Thailand. Routine screening was done using red blood cell indices, osmotic fragility, and dichlorophenolindophenol tests. The IC strip assay for haemoglobin Bart's was performed on all samples. The result was evaluated against thalassaemia genotypes determined using standard haemoglobin and DNA analyses. Of 300 subjects investigated, Hb and DNA analyses identified 32 with normal genotype. The remaining subjects carried thalassaemia with as many as 16 different genotypes. Hb Bart's was detected in all cases, with several α(0)-thalassaemia (SEA type) related disorders. Of cases with α(+)-thalassaemia, 86.1% showed a positive result; 100 out of 103 Hb E carriers, all homozygous Hb E and β-thalassaemia trait were negative. Nine out of 17 cases with β-thalassaemia/Hb E disease, and one case of double heterozygote for Hb Q-Thailand and Hb E returned positive results. The overall sensitivity and specificity of the IC strip assay for detecting α(0)-thalassaemia were 100% and 73.1%, respectively. The results showed a high sensitivity for screening for α(0)-thalassaemia using IC strip assay for Hb Bart's. This simple method, used in combination with conventional screening protocols, should lead to a significant reduction in the number of referral cases for DNA analysis. Cost effectiveness in each population should be taken into consideration. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

From the Arctic to fetal life: physiological importance and structural basis of an 'additional' chloride-binding site in haemoglobin.

PubMed

De Rosa, M Cristina; Castagnola, Massimo; Bertonati, Claudia; Galtieri, Antonio; Giardina, Bruno

2004-06-15

Haemoglobins from mammals of sub-Arctic and Arctic species, as well as fetal human Hb, are all characterized by a significantly lower Delta H of oxygenation compared with the majority of mammalian haemoglobins from temperate species (exceptions are represented by some cold-resistant species, such as cow, horse and pig). This has been interpreted as an adaptive mechanism of great importance from a physiological point of view. To date, the molecular basis of this thermodynamic characteristic is still not known. In the present study, we show that binding of extra chloride (with respect to adult human Hb) ions to Hb would significantly contribute to lowering the overall heat of oxygenation, thus providing a molecular basis for the low effect of temperature on the oxygenation-deoxygenation cycle. To this aim, the oxygen binding properties of bovine Hb, bear (Ursus arctos) Hb and horse Hb, which are representative of this series of haemoglobins, have been studied with special regard to the effect of heterotropic ligands, such as organic phosphates (namely 2,3-diphosphoglycerate) and chloride. Functional results are consistent with a mechanism for ligand binding that involves an additional binding site for chloride ion. Analysis of computational chemistry results, obtained by the GRID program, further confirm the hypothesis that the reason for the lower Delta H of oxygenation is mainly due to an increase in the number of the oxygen-linked chloride-binding sites.

Derivation & validation of glycosylated haemoglobin (HbA1c) cut-off value as a diagnostic test for type 2 diabetes in south Indian population

PubMed Central

Mohan, Alladi; Reddy, S. Aparna; Sachan, Alok; Sarma, K.V.S.; Kumar, D. Prabath; Panchagnula, Mahesh V.; Rao, P.V.L.N. Srinivasa; Kumar, B. Siddhartha; Krishnaprasanthi, P.

2016-01-01

Background & Objectives: Glycosylated haemoglobin (HbA1c) has been in use for more than a decade, as a diagnostic test for type 2 diabetes. Validity of HbA1c needs to be established in the ethnic population in which it is intended to be used. The objective of this study was to derive and validate a HbA1c cut-off value for the diagnosis of type 2 diabetes in the ethnic population of Rayalaseema area of south India. Methods: In this cross-sectional study, consecutive patients suspected to have type 2 diabetes underwent fasting plasma glucose (FPG) and 2 h post-load plasma glucose (2 h-PG) measurements after a 75 g glucose load and HbA1c estimation. They were classified as having diabetes as per the American Diabetes Association criteria [(FPG ≥7 mmol/l (≥126 mg/dl) and/or 2 h-PG ≥11.1 mmol/l (≥200 mg/dl)]. In the training data set (n = 342), optimum cut-off value of HbA1c for defining type 2 diabetes was derived by receiver-operator characteristic (ROC) curve method using oral glucose tolerance test results as gold standard. This cut-off was validated in a validation data set (n = 341). Results: On applying HbA1c cut-off value of >6.3 per cent (45 mmol/mol) to the training data set, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for diagnosing type 2 diabetes were calculated to be 90.6, 85.2, 80.8 and 93.0 per cent, respectively. When the same cut-off value was applied to the validation data set, sensitivity, specificity, PPV and NPV were 88.8, 81.9, 74.0 and 92.7 per cent, respectively, although the latter were consistently smaller than the proportions for the training data set, the differences being not significant. Interpretation & conclusions: HbA1c >6.3 per cent (45 mmol/mol) appears to be the optimal cut-off value for the diagnosis of type 2 diabetes applicable to the ethnic population of Rayalaseema area of Andhra Pradesh state in south India. PMID:27934801

Optimal haematocrit in subjects with normal haemoglobin genotype (HbAA), sickle cell trait (HbAS), and homozygous sickle cell disease (HbSS).

PubMed

Bowers, A S; Pepple, D J; Reid, H L

2011-01-01

The determination of an optimal haematocrit (H0) has important clinical implications if such a level can be attained, and more importantly, maintained. This is defined as a haematocrit level, above or below which oxygen delivery is deleteriously affected. This study is designed to determine an optimal haematocrit in normal (AA), sickle cell trait (AS) and sickle cell disease (SS) subjects. Twenty-seven apparently healthy subjects having normal haemoglobin genotype, 24 with sickle cell trait and 42 with homozygous sickle cell disease were recruited into the study. Whole blood viscosity (WBV) was measured by a Wells Brookfield Cone and Plate Viscometer at a shear rate of 230 sec-1. Haematocrit was determined by an AC.Tron Coulter Counter. The optimal haematocrit was calculated as the inverse of a constant, K, which was derived from the haematocrit and viscosity data. Our findings showed that the H0 varied significantly among the 3 haemoglobin genotypes, in the order AA vs SS and AS vs SS. Additionally, the data indicated an increased H0 in subjects with sickle cell trait, suggesting a possible impairment in oxygen delivery in these individuals.

Modelling the Relative Contribution of Fasting and Post-Prandial Plasma Glucose to HbA1c in Healthy and Type 2 Diabetic Subjects

ERIC Educational Resources Information Center

Ollerton, Richard L.; Luzio, Steven D.; Owens, David R.

2004-01-01

Glycated haemoglobin (HbA1c) is regarded as the gold standard of glucose homeostasis assessment in diabetes. There has been much discussion in recent medical literature of experimental results concerning the relative contribution of fasting and post-prandial glucose levels to the value of HbA1c. A mathematical model of haemoglobin glycation is…

Cross-sectional relationship between haemoglobin concentration and measures of physical and cognitive function in an older rural South African population.

PubMed

Payne, Collin F; Davies, Justine I; Gomez-Olive, F Xavier; Hands, Katherine J; Kahn, Kathleen; Kobayashi, Lindsay C; Tipping, Brent; Tollman, Stephen M; Wade, Alisha; Witham, Miles D

2018-04-21

Age cohort differences in haemoglobin concentrations and associations with physical and cognitive performance among populations of lower income and middle-income countries have not previously been described. We examined the association between these factors among older men and women in rural South Africa. We analysed cross-sectional data from a population-based study of rural South African men and women aged 40 and over (n=4499), with data drawn from questionnaire responses, a cognitive battery, objective physical function tests and blood tests. Anaemia was defined as a haemoglobin concentration <12 g/dL for women and <13 g/dL for men. We related haemoglobin concentrations to each of age, grip strength, walk speed and a latent cognitive function z-score for men and women separately. We used unadjusted correlations and linear models to adjust for comorbidities and inflammation. In total, 1042 (43.0%) women and 833 (40.1%) men were anaemic. Haemoglobin concentrations were inversely correlated with age for men but not for women; in adjusted analyses, haemoglobin was 0.3 g/dL lower per decade older for men (95% CI 0.2 to 0.4 g/dL). In adjusted analyses, haemoglobin concentration was independently associated with grip strength in women (B=0.391, 95% CI 0.177 to 0.605), but this did not reach significance in men (B=0.266, 95% CI -0.019 to 0.552); no associations were observed between haemoglobin levels and walk speed or cognitive score. Anaemia was prevalent in this study population of middle-aged and older, rural South African adults, but in contrast to high-income countries, it was not associated with poor physical or cognitive function. Our findings need to be replicated in other populations. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Leaf Concentrate Fortification of Antenatal Protein-Calorie Snacks Improves Pregnancy Outcomes

PubMed Central

Magon, Anjna; Joshi, Pallavi; Davys (Late), Glyn; Attlee, Amita; Mathur, Beena

2014-01-01

ABSTRACT Ready-to-eat (RTE) snacks are routinely distributed to pregnant women in India. These provide protein and calories but are low in micronutrients. We investigated whether RTE snacks fortified with leaf concentrate (LC) could improve pregnancy outcomes, including maternal haemoglobin (Hb) concentrations and infants’ birthweight. This randomized controlled two-arm trial was conducted over 18 months: control (sRTE) group received standard 120 g RTE snack (102 g wheat flour, 18 g soya flour); intervention (lcRTE) group received the same snack fortified with 7 g LC. The study was conducted in Jaipur, Rajasthan, India. One hundred and five pregnant women aged 18-35 years were studied. Among the 105 women randomized to the two arms of the trial, 2 (1.9%) were severely anaemic (Hb ≤6.0 g/dL); 55 (53.4%) were moderately anaemic (Hb 6.0-8.0 g/dL); 34 (33.0%) were mildly anaemic (Hb 8.6-10.9 g/dL); and 12 (11.7%) were not anaemic (Hb ≥11.0 g/dL). In the final month of pregnancy, 83.0% (39/47) of women in the sRTE group had Hb ≤8.5 g/dL compared to 37.8% (17/45) in the lcRTE group (p<0.001). After adjustment for age and baseline Hb concentration, the difference in Hb concentrations due to LC fortification was 0.94 g/dL (95% CI 6.8-12.0; p<0.001). Mean live birthweight in the lcRTE group was 2,695 g (SD 325 g) compared to 2,545 g (297 g) in the sRTE group (p=0.02). The lcRTE snacks increased infants’ birthweight by 133.7 g (95% CI 7.3-260.2; p=0.04) compared to sRTE snacks. Leaf concentrate fortification of antenatal protein-calorie snacks in a low-income setting in India protected against declining maternal haemoglobin concentrations and increased infants’ birthweight when compared with unfortified snacks. These findings require replication in a larger trial. PMID:25395906

Leaf concentrate fortification of antenatal protein-calorie snacks improves pregnancy outcomes.

PubMed

Magon, Anjna; Collin, Simon M; Joshi, Pallavi; Davys Late, Glyn; Attlee, Amita; Mathur, Beena

2014-09-01

Ready-to-eat (RTE) snacks are routinely distributed to pregnant women in India. These provide protein and calories but are low in micronutrients. We investigated whether RTE snacks fortified with leaf concentrate (LC) could improve pregnancy outcomes, including maternal haemoglobin (Hb) concentrations and infants' birthweight. This randomized controlled two-arm trial was conducted over 18 months: control (sRTE) group received standard 120 g RTE snack (102 g wheat flour, 18 g soya flour); intervention (lcRTE) group received the same snack fortified with 7 g LC. The study was conducted in Jaipur, Rajasthan, India. One hundred and five pregnant women aged 18-35 years were studied. Among the 105 women randomized to the two arms of the trial, 2 (1.9%) were severely anaemic (Hb ≤ 6.0 g/dL); 55 (53.4%) were moderately anaemic (Hb 6.0-8.0 g/dL); 34 (33.0%) were mildly anaemic (Hb 8.6-10.9 g/dL); and 12 (11.7%) were not anaemic (Hb ≥ 11.0 g/dL). In the final month of pregnancy, 83.0% (39/47) of women in the sRTE group had Hb ≤ 8.5 g/dL compared to 37.8% (17/45) in the lcRTE group (p<0.001). After adjustment for age and baseline Hb concentration, the difference in Hb concentrations due to LC fortification was 0.94 g/dL (95% CI 6.8-12.0; p<0.001). Mean live birthweight in the lcRTE group was 2,695 g (SD 325 g) compared to 2,545 g (297 g) in the sRTE group (p=0.02). The lcRTE snacks increased infants' birthweight by 133.7 g (95% CI 7.3-260.2; p=0.04) compared to sRTE snacks. Leaf concentrate fortification of antenatal protein-calorie snacks in a low-income setting in India protected against declining maternal haemoglobin concentrations and increased infants' birthweight when compared with unfortified snacks. These findings require replication in a larger trial.

Effects of nitrite exposure on functional haemoglobin levels, bimodal respiration, and swimming performance in the facultative air-breathing fish Pangasianodon hypophthalmus.

PubMed

Lefevre, Sjannie; Jensen, Frank B; Huong, Do T T; Wang, Tobias; Phuong, Nguyen T; Bayley, Mark

2011-07-01

In this study we investigated nitrite (NO₂⁻) effects in striped catfish, a facultative air-breather. Fish were exposed to 0, 0.4, and 0.9 mM nitrite for 0, 1, 2, 4, and 7 days, and levels of functional haemoglobin, methaemoglobin (metHb) and nitrosyl haemoglobin (HbNO) were assessed using spectral deconvolution. Plasma concentrations of nitrite, nitrate, chloride, potassium, and sodium were also measured. Partitioning of oxygen consumption was determined to reveal whether elevated metHb (causing functional hypoxia) induced air-breathing. The effects of nitrite on maximum oxygen uptake (MO(2max)) and critical swimming speed (U(crit)) were also assessed. Striped catfish was highly tolerant to nitrite exposure, as reflected by a 96 h LC₅₀ of 1.65 mM and a moderate nitrite uptake into the blood. Plasma levels of nitrite reached a maximum after 1 day of exposure, and then decreased, never exceeding ambient levels. MetHb, HbNO and nitrate (a nitrite detoxification product) also peaked after 1 day and then decreased. Only high levels of nitrite and metHb caused reductions in MO(2max) and U(crit). The response of striped catfish contrasts with that seen in most other fish species and discloses efficient mechanisms of combating nitrite threats. Furthermore, even though striped catfish is an efficient air-breather, this species has the ability to sustain aerobic scope and swimming performance without air-breathing, even when faced with nitrite-induced reductions in blood oxygen carrying capacity. Our study is the first to confirm that high levels of nitrite and metHb reduce MO(2max) and thereby aerobic scope, while more moderate elevations fail to do so. Further studies are needed to elucidate the mechanisms underlying the low nitrite accumulation in striped catfish. Copyright © 2011 Elsevier B.V. All rights reserved.

Haemoglobin status and predictors of anaemia among pregnant women in Mpigi, Uganda.

PubMed

Ononge, Sam; Campbell, Oona; Mirembe, Florence

2014-10-10

Anaemia in pregnancy is a major public health problem especially in the low-income countries where it is highly prevalent. There has been no recent study in Uganda about the factors associated with anaemia in pregnancy. We aimed to assess the current haemoglobin (Hb) status and factors associated with anaemia (Hb < 11.0 g/dl) in pregnant women in Mpigi, Uganda. We assessed Hb levels of 2436 pregnant women at 28+ weeks of gestation at six health facilities, who were approached to participate in a stepped-wedge cluster-randomised trial of antenatal distribution of misoprostol (for self-administration after home birth or when oxytocin is not available). Women were administered a questionnaire and their baseline blood haemoglobin was examined using portable HemoCueR Hb 301 system. Predictors of anaemia were estimated using linear and logistic regression analysis. The mean Hb was 11.5 (± 1.38) g/dl and prevalence of anaemia (Hb < 11.0 g/dl) was 32.5% (95% CI 30.6%, 34.3%). After adjusting for measured confounders, factors associated with increased risk of anaemia in pregnancy were malaria infection (OR: 1.32, 95% CI: 1.11, 1.58), Human Immuno-deficiency Virus infection (OR: 2.13, 95% CI: 1.36, 2.90) and lack of iron supplementation (OR: 1.66, 95% CI: 1.36, 2.03). Intermittent presumptive treatment of malaria, maternal age and parity showed a weak association with anaemia in pregnancy The high prevalence of anaemia in pregnancy in our setting highlights the need to put more effort in the fight against malaria and HIV, and also ensure that pregnant women access iron supplements early in pregnancy.

Impact of a new sampling buffer on faecal haemoglobin stability in a colorectal cancer screening programme by the faecal immunochemical test.

PubMed

Grazzini, Grazia; Ventura, Leonardo; Rubeca, Tiziana; Rapi, Stefano; Cellai, Filippo; Di Dia, Pietro P; Mallardi, Beatrice; Mantellini, Paola; Zappa, Marco; Castiglione, Guido

2017-07-01

Haemoglobin (Hb) stability in faecal samples is an important issue in colorectal cancer screening by the faecal immunochemical test (FIT) for Hb. This study evaluated the performance of the FIT-Hb (OC-Sensor Eiken) used in the Florence screening programme by comparing two different formulations of the buffer, both in an analytical and in a clinical setting. In the laboratory simulation, six faecal pools (three in each buffer type) were stored at different temperatures and analysed eight times in 10 replicates over 21 days. In the clinical setting, 7695 screenees returned two samples, using both the old and the new specimen collection device (SCD). In the laboratory simulation, 5 days from sample preparation with the buffer of the old SCD, the Hb concentration decreased by 40% at room temperature (25°C, range 22-28°C) and up to 60% at outside temperature (29°C, range 16-39°C), whereas with the new one, Hb concentration decreased by 10%. In the clinical setting, a higher mean Hb concentration with the new SCD compared with the old one was found (6.3 vs. 5.0 µg Hb/g faeces, respectively, P<0.001); no statistically significant difference was found in the probability of having a positive result in the two SCDs. Better Hb stability was observed with the new buffer under laboratory conditions, but no difference was found in the clinical performance. In our study, only marginal advantages arise from the new buffer. Improvements in sample stability represent a significant target in the screening setting.

Glucose-6-Phosphate Dehydrogenase Deficiency and Haemoglobin Drop after Sulphadoxine-Pyrimethamine Use for Intermittent Preventive Treatment of Malaria during Pregnancy in Ghana - A Cohort Study.

PubMed

Owusu, Ruth; Asante, Kwaku Poku; Mahama, Emmanuel; Awini, Elizabeth; Anyorigiya, Thomas; Dosoo, David; Amu, Alberta; Jakpa, Gabriel; Ofei, Emmanuel; Segbaya, Sylvester; Oduro, Abraham Rexford; Gyapong, Margaret; Hodgson, Abraham; Bart-Plange, Constance; Owusu-Agyei, Seth

2015-01-01

Sulphadoxine-Pyrimethamine (SP) is still the only recommended antimalarial for use in intermittent preventive treatment of malaria during pregnancy (IPTp) in some malaria endemic countries including Ghana. SP has the potential to cause acute haemolysis in G6PD deficient people resulting in significant haemoglobin (Hb) drop but there is limited data on post SP-IPTp Hb drop. This study determined the difference, if any in proportions of women with significant acute haemoglobin drop between G6PD normal, partial deficient and full deficient women after SP-IPTp. Prospectively, 1518 pregnant women who received SP for IPTp as part of their normal antenatal care were enrolled. Their G6PD status were determined at enrollment followed by assessments on days 3, 7,14 and 28 to document any adverse effects and changes in post-IPTp haemoglobin (Hb) levels. The three groups were comparable at baseline except for their mean Hb (10.3 g/dL for G6PD normal, 10.8 g/dL for G6PD partial deficient and 10.8 g/dL for G6PD full defect women).The prevalence of G6PD full defect was 2.3% and 17.0% for G6PD partial defect. There was no difference in the proportions with fractional Hb drop ≥ 20% as compared to their baseline value post SP-IPTp among the 3 groups on days 3, 7, 14. The G6PD full defect group had the highest median fractional drop at day 7. There was a weak negative correlation between G6PD activity and fractional Hb drop. There was no statistical difference between the three groups in the proportions of those who started the study with Hb ≥ 8g/dl whose Hb level subsequently fell below 8g/dl post-SP IPTp. No study participant required transfusion or hospitalization for severe anaemia. There was no significant difference between G6PD normal and deficient women in proportions with significant acute haemoglobin drop post SP-IPTp and lower G6PD enzyme activity was not strongly associated with significant acute drug-induced haemoglobin drop post SP-IPTp but a larger study is

Approaching the evolutionary advantage of ancillary types of haemoglobin in Daphnia magna by simulation of oxygen supply.

PubMed

Moenickes, S; Richter, O; Pirow, R

2010-02-01

The planktonic crustacean Daphnia magna synthesizes haemoglobin (Hb) macromolecules of variant subunit composition and oxygen affinity. This is one of the strategies by which the animals cope with variations in environmental conditions such as ambient oxygen tension. The enrichment of high-affinity Hb molecules in the haemolymph of hypoxia-exposed animals is thought to reduce Hb synthesis costs due to an enhanced transport efficiency of these molecules in comparison to the low-affinity Hb molecules. How great this economic advantage is, and under which conditions this benefit disappears, is still not fully understood. Here we implemented a rigorously simplified model of the daphnid body and described the transport of oxygen from the environment via the haemolymph to the tissues in terms of the convection-diffusion-reaction equation. The model was validated by comparing various model predictions with experimental data. A sensitivity analysis was used to evaluate the influence of parameter uncertainties on the model predictions. Cost-benefit analysis revealed in which way at the system's level the increase in Hb oxygen affinity improves the oxygen loading at the respiratory surfaces and impairs the release of oxygen to the tissues. The benefit arising from the improved oxygen loading exceeds the disadvantage of impaired unloading only under conditions where the ambient oxygen tension is critically low and the Hb concentration is high. The low-affinity Hb, on the other hand, provides an advantage given that the Hb concentration is low and the ambient oxygen tension is well above the critical level. Computer-aided modelling and simulation therefore provide valuable mechanistic insights into the driving forces that could have shaped the evolution of globin genes in daphnids.

Glucose-6-Phosphate Dehydrogenase Deficiency and Haemoglobin Drop after Sulphadoxine-Pyrimethamine Use for Intermittent Preventive Treatment of Malaria during Pregnancy in Ghana – A Cohort Study

PubMed Central

Owusu, Ruth; Asante, Kwaku Poku; Mahama, Emmanuel; Awini, Elizabeth; Anyorigiya, Thomas; Dosoo, David; Amu, Alberta; Jakpa, Gabriel; Ofei, Emmanuel; Segbaya, Sylvester; Oduro, Abraham Rexford; Gyapong, Margaret; Hodgson, Abraham; Bart-Plange, Constance; Owusu-Agyei, Seth

2015-01-01

Background Sulphadoxine-Pyrimethamine (SP) is still the only recommended antimalarial for use in intermittent preventive treatment of malaria during pregnancy (IPTp) in some malaria endemic countries including Ghana. SP has the potential to cause acute haemolysis in G6PD deficient people resulting in significant haemoglobin (Hb) drop but there is limited data on post SP-IPTp Hb drop. This study determined the difference, if any in proportions of women with significant acute haemoglobin drop between G6PD normal, partial deficient and full deficient women after SP-IPTp. Methods and Findings Prospectively, 1518 pregnant women who received SP for IPTp as part of their normal antenatal care were enrolled. Their G6PD status were determined at enrollment followed by assessments on days 3, 7,14 and 28 to document any adverse effects and changes in post-IPTp haemoglobin (Hb) levels. The three groups were comparable at baseline except for their mean Hb (10.3 g/dL for G6PD normal, 10.8 g/dL for G6PD partial deficient and 10.8 g/dL for G6PD full defect women).The prevalence of G6PD full defect was 2.3% and 17.0% for G6PD partial defect. There was no difference in the proportions with fractional Hb drop ≥ 20% as compared to their baseline value post SP-IPTp among the 3 groups on days 3, 7, 14. The G6PD full defect group had the highest median fractional drop at day 7. There was a weak negative correlation between G6PD activity and fractional Hb drop. There was no statistical difference between the three groups in the proportions of those who started the study with Hb ≥ 8g/dl whose Hb level subsequently fell below 8g/dl post-SP IPTp. No study participant required transfusion or hospitalization for severe anaemia. Conclusions There was no significant difference between G6PD normal and deficient women in proportions with significant acute haemoglobin drop post SP-IPTp and lower G6PD enzyme activity was not strongly associated with significant acute drug-induced haemoglobin

Haemoglobin Pierre-Benite--a high affinity variant associated with relative polycythaemia.

PubMed

Beard, M E; Potter, H C; Spearing, R L; Brennan, S O

2001-12-01

This is the second reported example of Hb Pierre--Benite (beta90 Glu-->Asp). This mutation is associated with increased oxygen affinity and polycythaemia. No instability was found and there was no charge shift detected by cellulose acetate electrophoresis at pH 8.3. The mutation was however, clearly indicated by electrospray ionization mass spectrometry (ESI MS), which showed an abnormal beta chain with a 14 Da decrease in mass. Blood volume studies documented a relative rather than a true polycythaemia and this finding has been reported in at least two other high affinity haemoglobin variants--Hb Heathrow and Hb Rahere. This finding led to delay in diagnosis because high oxygen affinity variants are conventionally considered to cause a true polycythaemia.

The impact of the haemoglobin level on the response to radiotherapy.

PubMed

Haydaroğlu, A; Yürüt, V; Arican, A; Yalman, D; Bülent Aras, A; Esassolak, M; Ozkök, S

2002-01-01

To define the impact of preradiotherapy haemoglobin (Hb) levels on the response rate of radiotherapy in patients with head and neck, uterine cervix and lung cancer. One hundred thirteen patients- 38 with head and neck cancer, 43 with carcinona of the uterine cervix and 32 with lung cancer- were retrospectively evaluated to determine the correlation between tumor response and preradiotherapy Hb levels. Hb level of 11 g/dl was taken as cut-off value for anemia. Patients were divided in two groups according to their objective response to radiotherapy. Histologically 30 of the head and neck cancers, 36 of the cervical cancers and 17 of the lung cancers were squamous-cell carcinomas. Tumor response of the epidermoid carcinomas were significantly correlated with preradiotherapy Hb levels (p < 0.001). Tumor response in patients with head and neck and cervical cancers was significantly correlated with pretreatment Hb levels while in patients with lung cancer this correlation did not reach statistical significance (p=0.059). Preradiotherapy Hb level is an important factor in determining the efficacy of radiotherapy. Raising the Hb level before radiotherapy may have a beneficial impact on the response to radiotherapy.

Measurement of HbA1c and HbA2 by Capillarys 2 Flex Piercing HbA1c programme for simultaneous management of diabetes and screening for thalassemia

PubMed Central

Ke, Peifeng; Liu, Jiawei; Chao, Yan; Wu, Xiaobin; Xiong, Yujuan; Lin, Li; Wan, Zemin; Wu, Xinzhong; Xu, Jianhua; Zhuang, Junhua; Huang, Xianzhang

2017-01-01

Introduction Thalassemia could interfere with some assays for haemoglobin A1c (HbA1c) measurement, therefore, it is useful to be able to screen for thalassemia while measuring HbA1c. We used Capillarys 2 Flex Piercing (Capillarys 2FP) HbA1c programme to simultaneously measure HbA1c and screen for thalassemia. Materials and methods Samples from 498 normal controls and 175 thalassemia patients were analysed by Capillarys 2FP HbA1c programme (Sebia, France). For method comparison, HbA1c was quantified by Premier Hb9210 (Trinity Biotech, Ireland) in 98 thalassaemia patients samples. For verification, HbA1c from eight thalassaemia patients was confirmed by IFCC reference method. Results Among 98 thalassaemia samples, Capillarys 2FP did not provide an HbA1c result in three samples with HbH due to the overlapping of HbBart’s with HbA1c fraction; for the remaining 95 thalassaemia samples, Bland-Altman plot showed 0.00 ± 0.35% absolute bias between two systems, and a significant positive bias above 7% was observed only in two HbH samples. The HbA1c values obtained by Capillarys 2FP were consistent with the IFCC targets (relative bias below ± 6%) in all of the eight samples tested by both methods. For screening samples with alpha (α-) thalassaemia silent/trait or beta (β-) thalassemia trait, the optimal HbA2 cut-off values were ≤ 2.2% and > 2.8%, respectively. Conclusions Our results demonstrated the Capillarys 2FP HbA1c system could report an accurate HbA1c value in thalassemia silent/trait, and HbA2 value (≤ 2.2% for α-thalassaemia silent/trait and > 2.8% for β-thalassemia trait) and abnormal bands (HbH and/or HbBart’s for HbH disease, HbF for β-thalassemia) may provide valuable information for screening. PMID:28900367

Measurement of HbA1c and HbA2 by Capillarys 2 Flex Piercing HbA1c programme for simultaneous management of diabetes and screening for thalassemia.

PubMed

Ke, Peifeng; Liu, Jiawei; Chao, Yan; Wu, Xiaobin; Xiong, Yujuan; Lin, Li; Wan, Zemin; Wu, Xinzhong; Xu, Jianhua; Zhuang, Junhua; Huang, Xianzhang

2017-10-01

Thalassemia could interfere with some assays for haemoglobin A 1c (HbA 1c ) measurement, therefore, it is useful to be able to screen for thalassemia while measuring HbA 1c . We used Capillarys 2 Flex Piercing (Capillarys 2FP) HbA 1c programme to simultaneously measure HbA 1c and screen for thalassemia. Samples from 498 normal controls and 175 thalassemia patients were analysed by Capillarys 2FP HbA 1c programme (Sebia, France). For method comparison, HbA 1c was quantified by Premier Hb9210 (Trinity Biotech, Ireland) in 98 thalassaemia patients samples. For verification, HbA 1c from eight thalassaemia patients was confirmed by IFCC reference method. Among 98 thalassaemia samples, Capillarys 2FP did not provide an HbA 1c result in three samples with HbH due to the overlapping of HbBart's with HbA 1c fraction; for the remaining 95 thalassaemia samples, Bland-Altman plot showed 0.00 ± 0.35% absolute bias between two systems, and a significant positive bias above 7% was observed only in two HbH samples. The HbA 1c values obtained by Capillarys 2FP were consistent with the IFCC targets (relative bias below ± 6%) in all of the eight samples tested by both methods. For screening samples with alpha (α-) thalassaemia silent/trait or beta (β-) thalassemia trait, the optimal HbA 2 cut-off values were ≤ 2.2% and > 2.8%, respectively. Our results demonstrated the Capillarys 2FP HbA 1c system could report an accurate HbA 1c value in thalassemia silent/trait, and HbA 2 value (≤ 2.2% for α-thalassaemia silent/trait and > 2.8% for β-thalassemia trait) and abnormal bands (HbH and/or HbBart's for HbH disease, HbF for β-thalassemia) may provide valuable information for screening.

The super sickling haemoglobin HbS-Oman: a study of red cell sickling, K+ permeability and associations with disease severity in patients heterozygous for HbA and HbS-Oman (HbA/S-Oman genotype).

PubMed

Al Balushi, Halima W M; Wali, Yasser; Al Awadi, Maha; Al-Subhi, Taimoora; Rees, David C; Brewin, John N; Hannemann, Anke; Gibson, John S

2017-10-01

Studying different sickle cell genotypes may throw light on the pathogenesis of sickle cell disease (SCD). Here, the clinical profile, red cell sickling and K + permeability in 29 SCD patients (15 patients with severe disease and 14 with a milder form) of HbA/S-Oman genotype were analysed. The super sickling nature of this Hb variant was confirmed. The red cell membrane permeability to K + was markedly abnormal with elevated activities of P sickle , Gardos channel and KCl cotransporter (KCC). Results were consistent with Ca 2+ entry and Mg 2+ loss via P sickle stimulating Gardos channel and KCC activities. The abnormal red cell behaviour was similar to that in the commonest genotype of SCD, HbSS, in which the level of mutated Hb is considerably higher. Although activities of all three K + transporters also correlated with the level of HbS-Oman, there was no association between transport phenotype and disease severity. The super sickling behaviour of HbS-Oman may obviate the need for solute loss and red cell dehydration to encourage Hb polymerisation, required in other SCD genotypes. Disease severity was reduced by concurrent α thalassaemia, as observed in other SCD genotypes, and represents an obvious genetic marker for prognostic tests of severity in young SCD patients of the HbA/S-Oman genotype. © 2017 John Wiley & Sons Ltd.

O2 binding and CO2 sensitivity in haemoglobins of subterranean African mole rats.

PubMed

Weber, Roy E; Jarvis, Jennifer U M; Fago, Angela; Bennett, Nigel C

2017-11-01

Inhabiting deep and sealed subterranean burrows, mole rats exhibit a remarkable suite of specializations, including eusociality (living in colonies with single breeding queens), extraordinary longevity, cancer immunity and poikilothermy, and extreme tolerance of hypoxia and hypercapnia. With little information available on adjustments in haemoglobin (Hb) function that may mitigate the impact of exogenous and endogenous constraints on the uptake and internal transport of O 2 , we measured haematological characteristics, as well as Hb-O 2 binding affinity and sensitivity to pH (Bohr effect), CO 2 , temperature and 2,3-diphosphoglycerate (DPG, the major allosteric modulator of Hb-O 2 affinity in red blood cells) in four social and two solitary species of African mole rats (family Bathyergidae) originating from different biomes and soil types across Central and Southern Africa. We found no consistent patterns in haematocrit (Hct) and blood and red cell DPG and Hb concentrations or in intrinsic Hb-O 2 affinity and its sensitivity to pH and DPG that correlate with burrowing, sociality and soil type. However, the results reveal low specific (pH independent) effects of CO 2 on Hb-O 2 affinity compared with humans that predictably safeguard pulmonary loading under hypoxic and hypercapnic burrow conditions. The O 2 binding characteristics are discussed in relation to available information on the primary structure of Hbs from adult and developmental stages of mammals subjected to hypoxia and hypercapnia and the molecular mechanisms underlying functional variation in rodent Hbs. © 2017. Published by The Company of Biologists Ltd.

Anaemia: can we define haemoglobin thresholds for impaired oxygen homeostasis and suggest new strategies for treatment?

PubMed

Hare, Gregory M T; Tsui, Albert K Y; Ozawa, Sherri; Shander, Aryeh

2013-03-01

Observational clinical studies in perioperative medicine have defined a progressive increase in mortality that is proportional to both chronic preoperative anaemia and acute interpretative reductions in haemoglobin concentration (Hb). However, this knowledge has not yet helped to define the critical Hb threshold for organ injury and mortality in specific patient populations or in individual patients. Nor has this knowledge enabled us to develop effective treatment strategies for anaemia, as evident from the lack of a demonstrable improvement in survival in patients randomised to higher Hb levels by various treatment strategies including allogeneic red blood cell transfusion, erythropoiesis-stimulating agents (ESAs) and haemoglobin-based oxygen carriers (HBOCs). These findings emphasise the need for a clearer understanding of the mechanism of anaemia-induced mortality. Towards achieving this goal, experimental studies have defined adaptive mechanism by which oxygen homeostasis is maintained during acute anaemia. The mechanisms include: (1) effective sensing of anaemia-induced tissue hypoxia; (2) adaptive cardiovascular responses to maintain adequate tissue oxygen delivery; (3) heterogeneity of organ-specific oxygen delivery to preferentially sustain vital organs which are essential for acute survival (heart and brain); (4) evidence of increased vital organ injury with interruption of cardiovascular responses to anaemia and (5) evidence of activation of adaptive cellular responses to maintain oxygen homeostasis and support survival during acute anaemia. Understanding these mechanisms may allow us to define treatment thresholds and novel treatment strategies for acute anaemia based on biological markers of tissue hypoxia. The overall goal of these approaches is to improve patient outcomes, including event-free perioperative survival. Copyright © 2012 Elsevier Ltd. All rights reserved.

Structural studies of haemoglobin from pisces species shortfin mako shark (Isurus oxyrinchus) at 1.9 Å resolution.

PubMed

Ramesh, Pandian; Sundaresan, S S; Sathya Moorthy, Pon; Balasubramanian, M; Ponnuswamy, M N

2013-11-01

Haemoglobin (Hb) is a tetrameric iron-containing protein that carries oxygen from the lungs to tissues and carbon dioxide from tissues back to the lungs. Pisces are the advanced aquatic vertebrates capable of surviving at wide depth ranges. The shortfin mako shark (SMS) is the pelagic, largest, fastest and most sophisticated species of the shark kingdom with well developed eyes. Mostly the pisces species are cold blooded in nature. Distinctly, the SMSs are warm-blooded animals with an advanced circulatory system. SMSs are capable of maintaining elevated muscle temperatures up to 33 K above the ambient water temperatures at a depth of 150-500 m. SMSs have a diverged air-breathing mechanism compared with other vertebrates. The haemoglobin molecule consists of four polypeptide chains, namely two α chains, each with 140 amino acids and two β chains each having 136 amino acids. The SMS Hb was found to crystallize in monoclinic space group P21 using the hanging-drop vapour-diffusion method at room temperature. The crystal packing parameters for the SMS Hb structure contain one whole biological molecule in the asymmetric unit with a solvent content of 47%. The SMS Hb quaternary structural features interface-interface interactions and heme binding sites are discussed with different state Hbs and the results reveal that SMS Hb adopts an unliganded deoxy T state conformation.

The double nucleation model for sickle cell haemoglobin polymerization: full integration and comparison with experimental data.

PubMed

Medkour, Terkia; Ferrone, Frank; Galactéros, Frédéric; Hannaert, Patrick

2008-06-01

Sickle cell haemoglobin (HbS) polymerization reduces erythrocyte deformability, causing deleterous vaso-occlusions. The double-nucleation model states that polymers grow from HbS aggregates, the nuclei, (i) in solution (homogeneous nucleation), (ii) onto existing polymers (heterogeneous nucleation). When linearized at initial HbS concentration, this model predicts early polymerization and its characteristic delay-time (Ferrone et al. J Mol Biol 183(4):591-610, 611-631, 1985). Addressing its relevance for describing complete polymerization, we constructed the full, non-linearized model (Simulink), The MathWorks). Here, we compare the simulated outputs to experimental progress curves (n = 6-8 different [HbS], 3-6 mM range, from Ferrone's group). Within 10% from start, average root mean square (rms) deviation between simulated and experimental curves is 0.04 +/- 0.01 (25 degrees C, n = 8; mean +/- standard error). Conversely, for complete progress curves, averaged rms is 0.48 +/- 0.04. This figure is improved to 0.13 +/- 0.01 by adjusting heterogeneous pathway parameters (p < 0.01): the nucleus stability (sigma(2) micro( cc ): + 40%), and the fraction of polymer surface available for nucleation (phi), from 5e(-7), (3 mM) to 13 (6 mM). Similar results are obtained at 37 degrees C. We conclude that the physico-chemical description of heterogeneous nucleation warrants refinements in order to capture the whole HbS polymerization process.

Prevalence of glucose-6-phosphate dehydrogenase deficiency and haemoglobin S in high and moderate malaria transmission areas of Muheza, north-eastern Tanzania.

PubMed

Segeja, M D; Mmbando, B P; Kamugisha, M L; Akida, J A; Savaeli, Z X; Minja, D T; Msangeni, H A; Lemnge, M M

2008-01-01

Glucose-6-phosphate dehydrogenase (G6PD) deficiency and haemoglobin S (HbS) are very common genetic disorders in sub Saharan Africa, where malaria is endemic. These genetic disorders have been associated with protection against malaria and are therefore under strong selection pressure by the disease. In November-December 2003, we conducted a cross-sectional survey to determine the prevalence of G6PD deficiency and HbS in the population and relate these to malaria infection and haemoglobin levels in lowland and highland areas of differing malaria transmission patterns of Muheza, Tanzania. Blood samples from 1959 individuals aged 6 months to 45 years were collected. A total of 415 (21%) and 1181 (60%) samples were analysed for G6PD deficiency and HbS, respectively. Malarial parasite prevalence was 17.2% (114/1959) in the highlands and 39.6% (49/1959) in the lowlands. Lowlands had higher prevalence of G6PD deficiency and HbS than highlands (G6PD deficiency = 11.32% (24/212) versus 4.43% (9/203), P = 0.01, and HbS = 16.04% (98/611) versus 6.32% (36/570), P = 0.0001). Logistic regression model showed an association between G6PD deficiency and altitude [lowlands] (Odds ratio [OR] 3.4, 95% CI = 1.49; 7.90, P = 0.004). In the lowlands, G6PD deficient individuals had lower mean haemoglobin (10.9g/dl) than normal ones (12.8g/dl), P = 0.01. These findings show that high malaria transmission in the lowlands might have selected for G6PD deficiency and HbS.

Alcohol consumption reduces HbA1c and glycated albumin concentrations but not 1,5-anhydroglucitol.

PubMed

Inada, Shinya; Koga, Masafumi

2017-11-01

Background The effect of alcohol consumption on glycaemic control indicators is not well known. In this study, we studied the effect of alcohol consumption on the plasma glucose and glycaemic control indicators in non-diabetic men. Methods The study enrolled 300 non-diabetic men who received a complete medical checkup (age: 52.8 ± 6.5 years, body mass index: 24.4 ± 2.8 kg/m 2 ). The subjects were divided into four groups by the amount of alcohol consumed, and the plasma glucose, HbA1c, glycated albumin (GA) and 1,5-anhydroglucitol (1,5-AG) concentrations of the groups were compared. Results As the level of alcohol consumption increased, significantly high concentrations of fasting plasma glucose (FPG) were observed, and the oral glucose tolerance test 2-h plasma glucose concentrations tended to rise. While no significant effect of alcohol consumption on HbA1c, 1,5-AG, and the 1,5-AG/FPG ratio was observed, the HbA1c/FPG ratio, GA and the GA/FPG ratio exhibited significantly low values as the level of alcohol consumption increased. In stepwise multivariate regression analysis, alcohol consumption was a significant negative independent variable for HbA1c and GA, but not for 1,5-AG. Conclusions As the level of alcohol consumption increased, the plasma glucose concentrations rose, but the HbA1c and GA concentrations were lower compared with the plasma glucose concentrations. These findings suggest that alcohol consumption may reduce HbA1c and GA concentrations, but not 1,5-AG.

Effect of the systemic inflammatory response, as provoked by elective orthopaedic surgery, on HbA1c.

PubMed

Chadburn, Andrew J; Garman, Elizabeth; Abbas, Raad; Modupe, Anu; Ford, Clare; Thomas, Osmond L; Chugh, Sanjiv; Deshpande, Shreeram; Gama, Rousseau

2017-07-01

Background In acutely ill patients with new onset hyperglycaemia, plasma glucose cannot reliably distinguish between stress hyperglycaemia and undiagnosed diabetes mellitus. We, therefore, investigated the diagnostic reliability of glycated haemoglobin (HbA1c) in acute illness by prospectively evaluating the effect of the systemic inflammatory response, as provoked by elective orthopaedic surgery, on HbA 1c . Methods HbA 1c and serum C-reactive protein concentrations were compared before and two days after elective knee or hip surgery in 30 patients without diabetes. C-reactive protein was used to assess the systemic inflammatory response. Results The mean (standard deviation) serum C-reactive protein increased following surgery (4.8 [7.5] vs. 179.7 [61.9] mg/L; P<0.0001). HbA 1c was similar before and after surgery (39.2 [5.4] vs. 38.1 [5.1] mmol/moL, respectively; P = 0.4363). Conclusions HbA 1c is unaffected within two days of a systemic inflammatory response as provoked by elective orthopaedic surgery. This suggests that HbA 1c may be able to differentiate newly presenting type 2 diabetes mellitus from stress hyperglycaemia in acutely ill patients with new onset hyperglycaemia.

The effects of age on associations between markers of HIV progression and markers of metabolic function including albumin, haemoglobin and lipid concentrations.

PubMed

Samuel, M; Jose, S; Winston, A; Nelson, M; Johnson, M; Chadwick, D; Fisher, M; Leen, C; Gompels, M; Gilson, R; Post, F A; Hay, P; Sabin, C A

2014-05-01

We investigated whether age modified associations between markers of HIV progression, CD4 T lymphocyte count and HIV RNA viral load (VL), and the following markers of metabolic function: albumin, haemoglobin, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC). A retrospective analysis of data from the United Kingdom Collaborative HIV Cohort was carried out. Analyses were limited to antiretroviral-naïve subjects to focus on the impact of HIV disease itself. A total of 16670 subjects were included in the analysis. Multilevel linear regression models assessed associations between CD4 count/VL and each of the outcomes. Statistical tests for interactions assessed whether associations differed among age groups. After adjustment for gender and ethnicity, there was evidence that lower CD4 count and higher VL were associated with lower TC, LDL-C, haemoglobin and albumin concentrations but higher triglyceride concentrations. Age modified associations between CD4 count and albumin (P < 0.001) and haemoglobin (P = 0.001), but not between CD4 count and HDL-C, LDL-C and TC, or VL and any outcome. Among participants aged < 30, 30-50 and > 50 years, a 50 cells/μL lower CD4 count correlated with a 2.4 [95% confidence interval (CI) 1.7-3.0], 3.6 (95% CI 3.2-4.0) and 5.1 (95% CI 4.0-6.1) g/L lower haemoglobin concentration and a 0.09 (95% CI 0.07-0.11), 0.12 (95% CI 0.11-0.13) and 0.16 (95% CI 0.13-0.19) g/L lower albumin concentration, respectively. We present evidence that age modifies associations between CD4 count and plasma albumin and haemoglobin levels. A given reduction in CD4 count was associated with a greater reduction in haemoglobin and albumin concentrations among older people living with HIV. These findings increase our understanding of how the metabolic impact of HIV is influenced by age. © 2013 The Authors. HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association.

Inaccuracy of haemoglobin A1c among HIV-infected men: effects of CD4 cell count, antiretroviral therapies and haematological parameters

PubMed Central

Slama, Laurence; Palella, Frank J.; Abraham, Alison G.; Li, Xiuhong; Vigouroux, Corinne; Pialoux, Gilles; Kingsley, Lawrence; Lake, Jordan E.; Brown, Todd T.; Margolick, Joseph B.; Crain, Barbara; Dobs, Adrian; Farzadegan, Homayoon; Gallant, Joel; Johnson-Hill, Lisette; Plankey, Michael; Sacktor, Ned; Selnes, Ola; Shepard, James; Thio, Chloe; Wolinsky, Steven M.; Phair, John P.; Badri, Sheila; O'Gorman, Maurice; Ostrow, David; Palella, Frank; Ragin, Ann; Detels, Roger; Martínez-Maza, Otoniel; Aronow, Aaron; Bolan, Robert; Breen, Elizabeth; Butch, Anthony; Jamieson, Beth; Miller, Eric N.; Oishi, John; Vinters, Harry; Wiley, Dorothy; Witt, Mallory; Yang, Otto; Young, Stephen; Zhang, Zuo Feng; Rinaldo, Charles R.; Kingsley, Lawrence A.; Becker, James T.; Cranston, Ross D.; Martinson, Jeremy J.; Mellors, John W.; Silvestre, Anthony J.; Stall, Ronald D.; Jacobson, Lisa P.; Munoz, Alvaro; Abraham, Alison; Althoff, Keri; Cox, Christopher; D'Souza, Gypsyamber; Golub, Elizabeth; Schollenberger, Janet; Seaberg, Eric C.; Su, Sol; Huebner, Robin E.; Dominguez, Geraldina

2014-01-01

Background There is limited evidence that among HIV-infected patients haemoglobin A1c (HbA1c) values may not accurately reflect glycaemia. We assessed HbA1c discordance (observed HbA1c − expected HbA1c) and associated factors among HIV-infected participants in the Multicenter AIDS Cohort Study (MACS). Methods Fasting glucose (FG) and HbA1c were measured at each semi-annual MACS visit since 1999. All HIV-infected and HIV-uninfected men for whom at least one FG and HbA1c pair measurement was available were evaluated. Univariate median regression determined the association between HbA1c and FG by HIV serostatus. The relationship between HbA1c and FG in HIV-uninfected men was used to determine the expected HbA1c. Generalized estimating equations determined factors associated with the Hb1Ac discordance among HIV-infected men. Clinically significant discordance was defined as observed HbA1c − expected HbA1c ≤−0.5%. Results Over 13 years, 1500 HIV-uninfected and 1357 HIV-infected men were included, with a median of 11 visits for each participant. At an FG of 125 mg/dL, the median HbA1c among HIV-infected men was 0.21% lower than among HIV-uninfected men and the magnitude of this effect increased with FG >126 mg/dL. Sixty-three percent of HIV-infected men had at least one visit with clinically significant HbA1c discordance, which was independently associated with: low CD4 cell count (<500 cells/mm3); a regimen containing a protease inhibitor, a non-nucleoside reverse transcriptase inhibitor or zidovudine; high mean corpuscular volume; and abnormal corpuscular haemoglobin. Conclusion HbA1c underestimates glycaemia in HIV-infected patients and its use in patients with risk factors for HbA1c discordance may lead to under-diagnosis and to under-treatment of established diabetes mellitus. PMID:25096078

Haemoglobin concentration and the risk of death in older adults: differences by race/ethnicity in the NHANES III follow-up.

PubMed

Patel, Kushang V; Longo, Dan L; Ershler, William B; Yu, Binbing; Semba, Richard D; Ferrucci, Luigi; Guralnik, Jack M

2009-05-01

Mildly low haemoglobin concentration is associated with increased mortality in older adults. However, this relationship has not been well characterized in racial/ethnic minorities. Therefore, this study determined the haemoglobin threshold below which risk of death is significantly increased in older non-Hispanic whites, non-Hispanic blacks, and Mexican Americans. Data on 4089 participants of the 1988-94 US National Health and Nutrition Examination Survey who were > or =65 years of age were analyzed with mortality follow-up through December 31, 2000. Mean haemoglobin in non-Hispanic whites (n = 2686) and Mexican Americans (n = 663) was 140 g/l, while in non-Hispanic blacks (n = 740) the mean was 10 g/l lower. A total of 1944 (47.5%) participants died. Among non-Hispanic whites and Mexican Americans, age- and sex-adjusted models showed that the haemoglobin thresholds below which mortality risk was significantly increased were 4 and 2 g/l respectively, above the World Health Organization (WHO) cut-off points for anaemia. In contrast, the threshold for non-Hispanic blacks was 7 g/l below the WHO criteria. Similar threshold effects were observed when analyzing haemoglobin in categories and adjusting for multiple confounders. In conclusion, the haemoglobin threshold below which mortality rises significantly is a full g/dl lower in non-Hispanic blacks than in non-Hispanic whites and Mexican Americans.

Accuracy of noninvasive haemoglobin measurement by pulse oximetry depends on the type of infusion fluid.

PubMed

Bergek, Christian; Zdolsek, Joachim H; Hahn, Robert G

2012-12-01

Measurement of blood haemoglobin concentration by pulse oximetry could be of value in determining when erythrocytes should be transfused during surgery, but the effect of infusion fluids on the results is unclear. To study the effect of crystalloid and colloid fluid on the accuracy (bias) and precision of pulse oximetry haemoglobin estimation to indicate the venous haemoglobin concentration in volunteers. Open interventional crossover study. Single university hospital. Ten male volunteers aged 18-28 (mean 22) years. Each volunteer underwent three infusion experiments on separate days and in random order. The infusions were Ringer's acetate (20 ml kg), hydroxyethyl starch 130/0.4 (10 ml kg) and a combination of both. At the end of the infusions of Ringer's acetate, pulse oximetry haemoglobin concentration had decreased more than the true haemoglobin concentration (15 vs. 8%; P < 0.005; n = 10) whereas starch solution decreased pulse oximetry haemoglobin concentration less than true haemoglobin concentration (7 vs. 11%; P < 0.02; n = 20). The same differences were seen when the fluids were infused separately and when they were combined. The overall difference between all 956 pairs of pulse oximetry haemoglobin concentration and true haemoglobin concentrations (the bias) averaged only -0.7 g l whereas the 95% prediction interval was wide, ranging from -24.9 to 23.7 g l. In addition to the choice of infusion fluid, the bias was strongly dependent on the volunteer (each factor, P < 0.001). The bias of measuring haemoglobin concentration by pulse oximetry is dependent on whether a crystalloid or a colloid fluid is infused. Trial registration ClinicalTrials identifier: NCT01195025.

Haemoglobin F Malaysia: α2γ2 1 (NA1) Glycine→Cysteine; 136 Glycine

PubMed Central

Eng, Lie-Injo Luan; Kamuzora, H.; Lehmann, H.

1974-01-01

Structural studies of an abnormal haemoglobin found in a Chinese newborn but not in her parents, showed it to be a new γ-chain variant, Hb F Malaysia. The first residue of the γ-chain was Cys and not Gly, and the γ-chain was of the type in which residue 136 is Gly and not Ala. Images PMID:4837284

Haemoglobin changes and risk of anaemia following treatment for uncomplicated falciparum malaria in sub-Saharan Africa.

PubMed

Zwang, Julien; D'Alessandro, Umberto; Ndiaye, Jean-Louis; Djimdé, Abdoulaye A; Dorsey, Grant; Mårtensson, Andreas A; Karema, Corine; Olliaro, Piero L

2017-06-23

Anaemia is common in malaria. It is important to quantitate the risk of anaemia and to distinguish factors related to the natural history of disease from potential drug toxicity. Individual-patient data analysis based on nine randomized controlled trials of treatments of uncomplicated falciparum malaria from 13 sub-Saharan African countries. Risk factors for reduced haemoglobin (Hb) concentrations and anaemia on presentation and after treatment were analysed using mixed effect models. Eight thousand eight hundred ninety-seven patients (77.0% <5 years-old) followed-up through 28 days treated with artemisinin combination therapy (ACT, 90%, n = 7968) or non-ACT. At baseline, under 5's had the highest risk of anaemia (77.6% vs. 32.8%) and higher parasitaemia (43,938 μl) than older subjects (2784 μl). Baseline anaemia increased the risk of parasitological recurrence. Hb began to fall after treatment start. In under 5's the estimated nadir was ~35 h (range 29-48), with a drop of -12.8% from baseline (from 9.8 g/dl to 8.7 g/dl, p = 0.001); in under 15's, the mean Hb decline between day 0-3 was -4.7% (from 9.4 to 9.0 g/dl, p = 0.001). The degree of Hb loss was greater in patients with high pre-treatment Hb and parasitaemia and with slower parasite reduction rates, and was unrelated to age. Subsequently, Hb increased linearly (+0.6%/day) until day 28, to reach +13.8% compared to baseline. Severe anaemia (<5 g/dl, 2 per 1000 patients) was transient and all patients recovered after day 14, except one case of very severe anaemia associated with parasite recurrence at day 28. There was no systematic difference in Hb concentrations between treatments and no case of delayed anaemia. On presentation with acute malaria young children with high parasitaemia have the highest risk of anaemia. The majority of patients experience a drop in Hb while on treatment as early as day 1-2, followed by a linear increase through follow-up. The degree of the early Hb dip is

Self-care activities and glycated haemoglobin in Iranian patients with type 2 diabetes: can coping styles and social support have a buffering role?

PubMed

Shayeghian, Zeinab; Aguilar-Vafaie, Maria E; Besharat, Mohammad Ali; Amiri, Parisa; Parvin, Mahmoud; Gillani, Kobra Roohi; Hassanabadi, Hamidreza

2015-01-01

Diabetes self-care is a key element in the overall management of diabetes. However, the importance of psychosocial factors for successful disease management is under investigated. This study aimed at exploring the role of coping styles and social support in the relationship between self-care activities and glycated haemoglobin in patients with type 2 diabetes. One hundred adults (60% female, aged 40-70 years) with type 2 diabetes completed questionnaires assessing self-care activities, coping styles and social support. In addition, a blood test was performed to obtain glycated haemoglobin levels. Result showed significant relationships of glycated haemoglobin with self-care activities, coping styles and social support. Regression analysis indicated that social support had a moderating role on the relationship between self-care activities and glycated haemoglobin, such that, at very high levels of social support the association, between Self-Care and HbA1c disappears. Findings indicate that health care providers, within the context of the Iranian social and cultural situation, should pay more attention to psychosocial factors when addressing self-care activities. Delineation of the role of coping styles and social support might be useful for identifying patients in need of particular counselling and support for improving self-care activities and HbA1c levels.

Prevalence of polymorphisms in glucose-6-phosphate dehydrogenase, sickle haemoglobin and nitric oxide synthase genes and their relationship with incidence of uncomplicated malaria in Iganga, Uganda.

PubMed

Lwanira, Catherine Nassozi; Kironde, Fred; Kaddumukasa, Mark; Swedberg, Göte

2017-08-09

Host genetics play an important role in Plasmodium falciparum malaria susceptibility. However, information on host genetic factors and their relationships with malaria in the vaccine trial site of Iganga, Uganda is limited. The main objective of this study was to determine the prevalence of selected host genetic markers and their relationship to malaria incidence in the vaccine trial site of Iganga, Uganda. In a 1-year longitudinal cohort study, 423 children aged below 9 years were recruited and their malaria episodes were investigated. Host genetic polymorphisms were assessed by PCR-RFLP, haemoglobin electrophoresis and DNA sequencing. Using a multivariate negative binomial regression model, estimates of the impact of human genetic polymorphisms on malaria incidence were performed. In all statistical tests, a P value of <0.05 was considered as significant. The prevalences of sickle cell haemoglobin trait, G6PD c.202 G>A (rs 1050828) and NOS2 -954 G>C (rs 1800482) variants were 26.6, 22.7 and 17.3%, respectively. Inducible nitric oxide synthase 2 (NOS2 -954 G>C; rs 1800482) heterozygosity was associated with lower incidence of malaria in all age groups {Adjusted incident rates ratio (aIRR) 0.59; 95% CI [0.386-0.887]; P = 0.012)}. About 4% of study subjects had co-existence of sickle cell Hb trait and G6PD deficiency. Sickle cell Hb heterozygotes (Hb AS) aged less than 1 year experienced significantly more malaria episodes annually than children with normal haemoglobin (Hb AA) {aIRR = 1.98; 95% CI [1.240-3.175]; P = 0.004}. There was no significant influence of the sickle cell trait on malaria incidence among older children of 1-9 years. Mutation (NOS2 -954 G>C; rs 1800482) of nitric oxide synthase 2 gene promoter was associated with a lower incidence of acute malaria. The normal haemoglobin (wild genotype; HbAA) was associated with reduced malaria incidence rates during the first year of life. More understanding of the interplay between host genetics and

Haemoglobin modulates NO emission and hyponasty under hypoxia-related stress in Arabidopsis thaliana.

PubMed

Hebelstrup, Kim H; van Zanten, Martijn; Mandon, Julien; Voesenek, Laurentius A C J; Harren, Frans J M; Cristescu, Simona M; Møller, Ian M; Mur, Luis A J

2012-09-01

Nitric oxide (NO) and ethylene are signalling molecules that are synthesized in response to oxygen depletion. Non-symbiotic plant haemoglobins (Hbs) have been demonstrated to act in roots under oxygen depletion to scavenge NO. Using Arabidopsis thaliana plants, the online emission of NO or ethylene was directly quantified under normoxia, hypoxia (0.1-1.0% O(2)), or full anoxia. The production of both gases was increased with reduced expression of either of the Hb genes GLB1 or GLB2, whereas NO emission decreased in plants overexpressing these genes. NO emission in plants with reduced Hb gene expression represented a major loss of nitrogen equivalent to 0.2mM nitrate per 24h under hypoxic conditions. Hb gene expression was greatly enhanced in flooded roots, suggesting induction by reduced oxygen diffusion. The function could be to limit loss of nitrogen under NO emission. NO reacts with thiols to form S-nitrosylated compounds, and it is demonstrated that hypoxia substantially increased the content of S-nitrosylated compounds. A parallel up-regulation of Hb gene expression in the normoxic shoots of the flooded plants may reflect signal transmission from root to shoot via ethylene and a role for Hb in the shoots. Hb gene expression was correlated with ethylene-induced upward leaf movement (hyponastic growth) but not with hypocotyl growth, which was Hb independent. Taken together the data suggest that Hb can influence flood-induced hyponasty via ethylene-dependent and, possibly, ethylene-independent pathways.

Endothelial cell expression of haemoglobin α regulates nitric oxide signalling.

PubMed

Straub, Adam C; Lohman, Alexander W; Billaud, Marie; Johnstone, Scott R; Dwyer, Scott T; Lee, Monica Y; Bortz, Pamela Schoppee; Best, Angela K; Columbus, Linda; Gaston, Benjamin; Isakson, Brant E

2012-11-15

Models of unregulated nitric oxide (NO) diffusion do not consistently account for the biochemistry of NO synthase (NOS)-dependent signalling in many cell systems. For example, endothelial NOS controls blood pressure, blood flow and oxygen delivery through its effect on vascular smooth muscle tone, but the regulation of these processes is not adequately explained by simple NO diffusion from endothelium to smooth muscle. Here we report a new model for the regulation of NO signalling by demonstrating that haemoglobin (Hb) α (encoded by the HBA1 and HBA2 genes in humans) is expressed in human and mouse arterial endothelial cells and enriched at the myoendothelial junction, where it regulates the effects of NO on vascular reactivity. Notably, this function is unique to Hb α and is abrogated by its genetic depletion. Mechanistically, endothelial Hb α haem iron in the Fe(3+) state permits NO signalling, and this signalling is shut off when Hb α is reduced to the Fe(2+) state by endothelial cytochrome b5 reductase 3 (CYB5R3, also known as diaphorase 1). Genetic and pharmacological inhibition of CYB5R3 increases NO bioactivity in small arteries. These data reveal a new mechanism by which the regulation of the intracellular Hb α oxidation state controls NOS signalling in non-erythroid cells. This model may be relevant to haem-containing globins in a broad range of NOS-containing somatic cells.

Effect of Age on Blood Rheology in Sickle Cell Anaemia and Sickle Cell Haemoglobin C Disease: A Cross-Sectional Study.

PubMed

Renoux, Céline; Romana, Marc; Joly, Philippe; Ferdinand, Séverine; Faes, Camille; Lemonne, Nathalie; Skinner, Sarah; Garnier, Nathalie; Etienne-Julan, Maryse; Bertrand, Yves; Petras, Marie; Cannas, Giovanna; Divialle-Doumdo, Lydia; Nader, Elie; Cuzzubbo, Daniela; Lamarre, Yann; Gauthier, Alexandra; Waltz, Xavier; Kebaili, Kamila; Martin, Cyril; Hot, Arnaud; Hardy-Dessources, Marie-Dominique; Pialoux, Vincent; Connes, Philippe

2016-01-01

Blood rheology plays a key role in the pathophysiology of sickle cell anaemia (SS) and sickle cell haemoglobin C disease (SC), but its evolution over the lifespan is unknown. Blood viscosity, red blood cell (RBC) deformability and aggregation, foetal haemoglobin (HbF) and haematocrit were measured in 114 healthy individuals (AA), 267 SS (161 children + 106 adults) and 138 SC (74 children + 64 adults) patients. Our results showed that 1) RBC deformability is at its maximal value during the early years of life in SS and SC populations, mainly because HbF level is also at its peak, 2) during childhood and adulthood, hydroxycarbamide treatment, HbF level and gender modulated RBC deformability in SS patients, independently of age, 3) blood viscosity is higher in older SS and SC patients compared to younger ones and 4) haematocrit decreases as SS patients age. The hemorheological changes detected in older patients could play a role in the progressive development of several chronic disorders in sickle cell disease, whose prevalence increases with age. Retarding these age-related haemorheological impairments, by using suitable drugs, may minimize the risks of vaso-occlusive events and chronic disorders.

Understanding the new HbA1c units for the diagnosis of Type 2 diabetes.

PubMed

Braatvedt, Geoff D; Cundy, Tim; Crooke, Michael; Florkowski, Chris; Mann, Jim I; Lunt, Helen; Jackson, Rod; Orr-Walker, Brandon; Kenealy, Timothy; Drury, Paul L

2012-09-21

In New Zealand laboratories the measurement of glycated haemoglobin (HbA1c) for diagnosis of diabetes is now only reported in SI units of mmol/mol. HbA1c is now recommended as the preferred test to diagnose diabetes in most circumstances. The requirement for a second positive test in asymptomatic individuals is retained. An HbA1c greater than and equal to 50 mmol/mol (repeated on a second occasion in asymptomatic patients) is diagnostic of diabetes and a value less than and equal to 40 mmol/mol represents normal glucose tolerance. For patients with an initial HbA1c result of 41-49 mmol/mol, cardiovascular risk assessment and lifestyle interventions are recommended with repeat HbA1c screening in 6-12 months. For patients whose HbA1c is less than and equal to 40 mmol/mol, repeat screening (including for CVD risk) at intermittent intervals is recommended as per published guidelines.

Purification, crystallization and preliminary X-ray diffraction studies of parakeet (Psittacula krameri) haemoglobin

PubMed Central

Jaimohan, S. M.; Naresh, M. D.; Arumugam, V.; Mandal, A. B.

2009-01-01

Birds often show efficient oxygen management in order to meet the special demands of their metabolism. However, the structural studies of avian haemo­globins (Hbs) are inadequate for complete understanding of the mechanism involved. Towards this end, purification, crystallization and preliminary X-ray diffraction studies have been carried out for parakeet Hb. Parakeet Hb was crystallized as the met form in low-salt buffered conditions after extracting haemoglobin from crude blood by microcentrifugation and purifying the sample by column chromatography. Good-quality crystals were grown from 10% PEG 3350 and a crystal diffracted to about 2.8 Å resolution. Preliminary diffraction data showed that the Hb crystal belonged to the monoclinic system (space group C2), with unit-cell parameters a = 110.68, b = 64.27, c = 56.40 Å, β = 109.35°. Matthews volume analysis indicated that the crystals contained a half-tetramer in the asymmetric unit. PMID:19851014

A multiplexed three-dimensional paper-based electrochemical impedance device for simultaneous label-free affinity sensing of total and glycated haemoglobin: The potential of using a specific single-frequency value for analysis.

PubMed

Boonyasit, Yuwadee; Chailapakul, Orawon; Laiwattanapaisal, Wanida

2016-09-14

A novel three-dimensional paper-based electrochemical impedance device (3D-PEID) is first introduced for measuring multiple diabetes markers. Herein, a simple 3D-PEID composed of a dual screen-printed electrode on wax-patterned paper coupled with a multilayer of magnetic paper was fabricated for label-free electrochemical detection. The results clearly demonstrated in a step-wise manner that the haptoglobin (Hp)-modified and 3-aminophenylboronic acid (APBA)-modified eggshell membranes (ESMs) were highly responsive to a clinically relevant range of total (0.5-20 g dL(-1); r(2) = 0.989) and glycated haemoglobin (HbA1c) (2.3%-14%; r(2) = 0.997) levels with detection limits (S/N = 3) of 0.08 g dL(-1) and 0.21%, respectively. The optimal binding frequencies of total haemoglobin and HbA1c to their specific recognition elements were 5.18 Hz and 9.99 Hz, respectively. The within-run coefficients of variation (CV) were 1.84%, 2.18%, 1.72%, and 2.01%, whereas the run-to-run CVs were 2.11%, 2.41%, 2.08%, and 2.21%, when assaying two levels of haemoglobin and HbA1c, respectively. The CVs for the haemoglobin and HbA1c levels measured on ten independently fabricated paper-based sheets were 1.96% and 2.10%, respectively. These results demonstrated that our proposed system achieved excellent precision for the simultaneous detection of total haemoglobin and HbA1c, with an acceptable reproducibility of fabrication. The long-term stability of the Hp-modified eggshell membrane (ESM) was 98.84% over a shelf-life of 4 weeks, enabling the possibility of storage or long-distance transport to remote regions, particularly in resource-limited settings; however, for the APBA-modified ESM, the stability was 92.35% over a one-week period. Compared with the commercial automated method, the results demonstrated excellent agreement between the techniques (p-value < 0.05), thus permitting the potential application of 3D-PEID for the monitoring of the glycaemic status in diabetic

First reported case of Haemoglobin-M Hyde Park in a Malay family living in Malaysia.

PubMed

Loong, Tang Yee; Chong, Doris Lau Sie; Jamal, A Rahman A; Murad, Nor Azian Abdul; Sabudin, Raja Zahratul Azma Raja; Fun, Leong Chooi

2016-01-01

Haemoglobin (Hb)-M Hyde Park, also known as Hb-M Akita is a rare type of hereditary Hb M due to autosomal dominant mutation of CAC>TAC on codon 92 of β globin gene resulting in the replacement of histidine by tyrosine on β globin chain. This variant Hb has a tendency to form methaemoglobin (metHb). The iron ion in metHb is oxidized to ferric (Fe3+) which is unable to carry oxygen and the patients manifest as cyanosis clinically. A 9-year-old Malay girl was incidentally found to be cyanotic when she presented to a health clinic. Laboratory investigations revealed raised methaemoglobin levels and Hb analysis findings were consistent with Hb-M Hyde Park. β gene sequencing confirmed a point mutation of CAC>TAC on codon 92 in one of the β genes. The family study done on the individuals with cyanosis showed similar findings. A diagnosis of heterozygous Hb-M Hyde Park was made. Patients with this variant Hb usually presented with cyanosis with mild haemolysis and maybe misdiagnosed as congenital heart disease. No further treatment is needed as patients are relatively asymptomatic. Although the disease is harmless in the heterozygous carriers but the offspring of the carriers may suffer severe haemolytic anaemia when the offspring also inherit other β haemoglobinopathies/thalassemia. This can happen due to high prevalence of β thalassemia carrier (3.5-4 %) found in Malaysia. At the time of writing, this is the first case of hereditary Hb-M Hyde Park diagnosed in a Malay family living in Malaysia.

Distribution of Glycated Haemoglobin According to Early-Life and Contemporary Characteristics in Adolescents and Adults without Diabetes: The 1982 and 1993 Pelotas Birth Cohorts.

PubMed

Buffarini, Romina; Restrepo-Méndez, María Clara; Silveira, Vera M; Miranda, Jaime J; Gonçalves, Helen D; Oliveira, Isabel O; Horta, Bernardo L; Gigante, Denise P; Menezes, Ana Maria; Assunção, Maria Cecília F

2016-01-01

Glycated haemoglobin (HbA1c), a marker of glucose control in individuals with diabetes mellitus, is also related with the incidence of cardiometabolic risk in populations free of disease. The aim of this study was to describe the distribution of HbA1c levels according to early-life and contemporary factors in adolescents and adults without diabetes mellitus. HbA1c was measured in adults aged 30 years and adolescents aged 18 years who are participants in the 1982 and 1993 Pelotas Birth Cohorts, respectively. Bivariate and multivariate analyses were performed to describe the HbA1c mean values according to early-life and contemporary characteristics collected prospectively since birth. The distribution of the HbA1c was approximately normal in both cohorts, with a mean (SD) 5.10% (0.43) in the 1982 cohort, and 4.89% (0.50) in the 1993 cohort. HbA1c mean levels were significantly higher in individuals self-reported as black/brown skin color compared to those self-reported as white in both cohorts. Parental history of diabetes was associated with higher HbA1c mean in adults, while stunting at one year old presented an inverse relation with the outcome in adolescents. No other early and contemporary factors were associated with HbA1c levels in adults or adolescents. We found a consistent relationship between HbA1c and skin color in both cohorts. Further research is needed to understand the role of genomic ancestry on levels of HbA1c concentrations which may inform policies and preventive actions for diabetes mellitus and cardiometabolic risk.

Sortase Independent and Dependent Systems for Acquisition of Haem and Haemoglobin in Listeria monocytogenes

PubMed Central

Xiao, Qiaobin; Jiang, Xiaoxu; Moore, Kyle J.; Shao, Yi; Pi, Hualiang; Dubail, Iharilalao; Charbit, Alain; Newton, Salete M.; Klebba, Phillip E.

2011-01-01

Summary We studied three Fur-regulated systems of Listeria monocytogenes: the srtB region, that encodes sortase-anchored proteins and a putative ABC transporter, and the fhu and hup operons, that produce putative ABC transporters for ferric hydroxamates and haemin (Hn)/haemoglobin (Hb), respectively. Deletion of lmo2185 in the srtB region reduced listerial [59Fe]-Hn transport, and purified Lmo2185 bound [59Fe]-Hn (KD = 12 nM), leading to its designation as a Hn/Hb binding protein (hbp2). Purified Hbp2 also acted as a hemophore, capturing and supplying Hn from the environment. Nevertheless, Hbp2 only functioned in [59Fe]-Hn transport at external concentrations less than 10 nM: at higher Hn levels its uptake occurred with equivalent affinity and rate without Hbp2. Similarly, deletion of sortase A had no effect on ferric siderophore or Hn/Hb transport at any concentration, and the srtA-independence of listerial Hn/Hb uptake distinguished it from comparable systems of Staphylococcus aureus. In the cytoplasmic membrane, the Hup transporter was specific for Hn: its lipoprotein (HupD) only showed high affinity for the iron porphyrin (KD = 26 nM). Conversely, the FhuD lipoprotein encoded by the fhu operon had broad specificity: it bound both ferric siderophores and Hn, with the highest affinity for ferrioxamine B (KD = 123 nM). Deletions of Hup permease components hupD, hupG, or hupDGC reduced Hn/Hb uptake, and complementation of ΔhupC and ΔhupG by chromosomal integration of hupC+ and hupG+ alleles on pPL2 restored growth promotion by Hn/Hb. However, ΔhupDGC did not completely eliminate [59Fe]-Hn transport, implying the existence of another cytoplasmic membrane Hn transporter. The overall KM of Hn uptake by wild-type strain EGD-e was 1 nM, and it occurred at similar rates (Vmax = 23 pMol/109 cells/min) to those of ferric siderophore transporters. In the ΔhupDBGC strain uptake occurred at a 3-fold lower rate (Vmax = 7 pMol/109 cells/min). The results show that at low

Erroneous HbA1c results in a patient with elevated HbC and HbF.

PubMed

Adekanmbi, Joy; Higgins, Trefor; Rodriguez-Capote, Karina; Thomas, Dylan; Winterstein, Jeffrey; Dixon, Tara; Gifford, Jessica L; Krause, Richard; Venner, Allison A; Clarke, Gwen; Estey, Mathew P

2016-11-01

HbA1c is used in the diagnosis and monitoring of diabetes mellitus (DM). Interference from hemoglobin variants is a well-described phenomenon, particularly with HPLC-based methods. While immunoassays may generate more reliable HbA1c results in the presence of some variants, these methods are susceptible to negative interference from high concentrations of HbF. We report a case where an accurate HbA1c result could not be obtained by any available method due to the presence of a compound hemoglobinopathy. HbA1c was measured by HPLC, immunoassay, and capillary electrophoresis. Hemoglobinopathy investigation consisted of a CBC, hemoglobin fractionation by HPLC and electrophoresis, and molecular analysis. HbA1c analysis by HPLC and capillary electrophoresis gave no result. Analysis by immunoassay yielded HbA1c results of 5.9% (Siemens DCA 2000+) and 5.1% (Roche Integra), which were inconsistent with other markers of glycemic control. Hemoglobinopathy investigation showed HbC with the hereditary persistence of fetal hemoglobin-2 Ghana deletion. Reliable HbA1c results may be unobtainable in the presence of some hemoglobinopathies. HPLC and capillary electrophoresis alerted the laboratory to the presence of an unusual hemoglobinopathy. Immunoassays generated falsely low results without warning, which could lead to missed diagnoses and under treatment of patients with DM. Copyright © 2016 Elsevier B.V. All rights reserved.

Hb lepore/β0-thalassaemia with α+-thalassaemia interactions, a potential diagnostic pitfall.

PubMed

Alauddin, Hafiza; Mohamad Nasir, Suziana; Ahadon, Madzlifah; Raja Sabudin, Raja Zahratul Azma; Ithnin, Azlin; Hussin, Noor Hamidah; Alias, Hamidah; Loh, C-Khai; Abdul Latiff, Zarina; Abdul Murad, Nor Azian; Othman, Ainoon

2015-12-01

Haemoglobin (Hb) Lepore is a variant Hb consisting of two α-globin and two δβ-globin chains. In a heterozygote, it is associated with clinical findings of thalassaemia minor, but interactions with other haemoglobinopathies can lead to various clinical phenotypes and pose diagnostic challenges. We reported a pair of siblings from a Malay family, who presented with pallor and hepatosplenomegaly at the ages of 21 months and 14 months old. The red cell indices and peripheral blood smears of both patients showed features of thalassaemia intermedia. Other laboratory investigations of the patients showed conflicting results. However, laboratory investigation results of the parents had led to a presumptive diagnosis of compound heterozygote Hb Lepore/β-thalassaemia and co-inheritance α+-thalassaemia (-α3.7). Hb Lepore has rarely been detected in Southeast Asian countries, particularly in Malaysia. These two cases highlight the importance of family studies for accurate diagnosis, hence appropriate clinical management and genetic counseling.

Estimation of blood haemoglobin concentration using the HemoCue during caesarean section: the effect of sampling site.

PubMed

Richards, N A; Boyce, H; Yentis, S M

2010-01-01

Haemoglobin concentration measured using the HemoCue is accurate for capillary and venous/arterial blood, provided the recommended sampling method is strictly observed. Analysis of blood, particularly of capillary samples, using the HemoCue is useful during caesarean section. The toe might be preferred to the thumb since it is numb during neuraxial anaesthesia, but whether sampling at either site is accurate in this situation, given the cardiovascular effects of anaesthesia and pregnancy, is not known. We aimed to compare haemoglobin values measured in venous and capillary samples (toe and thumb) during caesarean section under neuraxial anaesthesia. Fifty healthy women having caesarean section under spinal or combined spinal-epidural anaesthesia were included. At the end of surgery, the great toe and thumb (non-i.v. fluid side) were lanced as recommended for a HemoCue reading. A venous blood sample (non-i.v. fluid side) was also taken and sent for formal laboratory measurement and tested with the HemoCue. Bland-Altman analysis was applied to the haemoglobin values. Bias (mean difference) and precision +/- 2 SD were respectively 0.2 +/-1.6 for laboratory vs. toe, 0.1 +/-1.8 for laboratory vs. thumb, and 0.2 +/-1.6 laboratory vs. venous. Our results suggest that in terms of accuracy, the two sites are equally suitable for use during caesarean section under neuraxial anaesthesia. Copyright 2009 Elsevier Ltd. All rights reserved.

Predicting of the refractive index of haemoglobin using the Hybrid GA-SVR approach.

PubMed

Oyehan, Tajudeen A; Alade, Ibrahim O; Bagudu, Aliyu; Sulaiman, Kazeem O; Olatunji, Sunday O; Saleh, Tawfik A

2018-04-30

The optical properties of blood play crucial roles in medical diagnostics and treatment, and in the design of new medical devices. Haemoglobin is a vital constituent of the blood whose optical properties affect all of the optical properties of human blood. The refractive index of haemoglobin has been reported to strongly depend on its concentration which is a function of the physiology of biological cells. This makes the refractive index of haemoglobin an essential non-invasive bio-marker of diseases. Unfortunately, the complexity of blood tissue makes it challenging to experimentally measure the refractive index of haemoglobin. While a few studies have reported on the refractive index of haemoglobin, there is no solid consensus with the data obtained due to different measuring instruments and the conditions of the experiments. Moreover, obtaining the refractive index via an experimental approach is quite laborious. In this work, an accurate, fast and relatively convenient strategy to estimate the refractive index of haemoglobin is reported. Thus, the GA-SVR model is presented for the prediction of the refractive index of haemoglobin using wavelength, temperature, and the concentration of haemoglobin as descriptors. The model developed is characterised by an excellent accuracy and very low error estimates. The correlation coefficients obtained in these studies are 99.94% and 99.91% for the training and testing results, respectively. In addition, the result shows an almost perfect match with the experimental data and also demonstrates significant improvement over a recent mathematical model available in the literature. The GA-SVR model predictions also give insights into the influence of concentration, wavelength, and temperature on the RI measurement values. The model outcome can be used not only to accurately estimate the refractive index of haemoglobin but also could provide a reliable common ground to benchmark the experimental refractive index results

Thermal fluctuations of haemoglobin from different species: adaptation to temperature via conformational dynamics

PubMed Central

Stadler, A. M.; Garvey, C. J.; Bocahut, A.; Sacquin-Mora, S.; Digel, I.; Schneider, G. J.; Natali, F.; Artmann, G. M.; Zaccai, G.

2012-01-01

Thermodynamic stability, configurational motions and internal forces of haemoglobin (Hb) of three endotherms (platypus, Ornithorhynchus anatinus; domestic chicken, Gallus gallus domesticus and human, Homo sapiens) and an ectotherm (salt water crocodile, Crocodylus porosus) were investigated using circular dichroism, incoherent elastic neutron scattering and coarse-grained Brownian dynamics simulations. The experimental results from Hb solutions revealed a direct correlation between protein resilience, melting temperature and average body temperature of the different species on the 0.1 ns time scale. Molecular forces appeared to be adapted to permit conformational fluctuations with a root mean square displacement close to 1.2 Å at the corresponding average body temperature of the endotherms. Strong forces within crocodile Hb maintain the amplitudes of motion within a narrow limit over the entire temperature range in which the animal lives. In fully hydrated powder samples of human and chicken, Hb mean square displacements and effective force constants on the 1 ns time scale showed no differences over the whole temperature range from 10 to 300 K, in contrast to the solution case. A complementary result of the study, therefore, is that one hydration layer is not sufficient to activate all conformational fluctuations of Hb in the pico- to nanosecond time scale which might be relevant for biological function. Coarse-grained Brownian dynamics simulations permitted to explore residue-specific effects. They indicated that temperature sensing of human and chicken Hb occurs mainly at residues lining internal cavities in the β-subunits. PMID:22696485

Thermal fluctuations of haemoglobin from different species: adaptation to temperature via conformational dynamics.

PubMed

Stadler, A M; Garvey, C J; Bocahut, A; Sacquin-Mora, S; Digel, I; Schneider, G J; Natali, F; Artmann, G M; Zaccai, G

2012-11-07

Thermodynamic stability, configurational motions and internal forces of haemoglobin (Hb) of three endotherms (platypus, Ornithorhynchus anatinus; domestic chicken, Gallus gallus domesticus and human, Homo sapiens) and an ectotherm (salt water crocodile, Crocodylus porosus) were investigated using circular dichroism, incoherent elastic neutron scattering and coarse-grained Brownian dynamics simulations. The experimental results from Hb solutions revealed a direct correlation between protein resilience, melting temperature and average body temperature of the different species on the 0.1 ns time scale. Molecular forces appeared to be adapted to permit conformational fluctuations with a root mean square displacement close to 1.2 Å at the corresponding average body temperature of the endotherms. Strong forces within crocodile Hb maintain the amplitudes of motion within a narrow limit over the entire temperature range in which the animal lives. In fully hydrated powder samples of human and chicken, Hb mean square displacements and effective force constants on the 1 ns time scale showed no differences over the whole temperature range from 10 to 300 K, in contrast to the solution case. A complementary result of the study, therefore, is that one hydration layer is not sufficient to activate all conformational fluctuations of Hb in the pico- to nanosecond time scale which might be relevant for biological function. Coarse-grained Brownian dynamics simulations permitted to explore residue-specific effects. They indicated that temperature sensing of human and chicken Hb occurs mainly at residues lining internal cavities in the β-subunits.

Haemoglobin discordances in twins: due to differences in timing of cord clamping?

PubMed

Verbeek, Lianne; Zhao, Depeng P; Middeldorp, Johanna M; Oepkes, Dick; Hooper, Stuart B; Te Pas, Arjan B; Lopriore, Enrico

2017-07-01

Our objective was to study the differences in haemoglobin (Hb) at birth in dichorionic (DC) versus monochorionic (MC) twins in relation to birth order and mode of delivery. All consecutive DC twin pregnancies and uncomplicated MC twin pregnancies with two live-born twins delivered at our centre were included in this retrospective cohort study. Hb levels at birth and on day 2 were evaluated in association with birth order and mode of delivery. The occurrence of polycythaemia (venous haematocrit >65%) was also recorded. A total of 300 DC and 290 MC twin pairs were included. In DC and MC twins delivered vaginally, second-born twins had a higher Hb level at birth compared with their co-twin (mean Hb level 16.7 vs 15.9 g/dL (p<0.01) in DC twins and 17.8 vs 16.1 g/dL (p<0.01) in MC twins). In twins delivered through caesarean section, no intertwin differences in Hb levels were detected. Polycythaemia occurred significantly more often in second-born twins compared with first-born twins delivered vaginally: 10 (5%) vs 2 (1%) (p=0.02) in DC twins and 20 (12%) vs 2 (1%) (p<0.01) in MC twins. Second-born DC and MC twins delivered vaginally have higher Hb levels at birth compared with first-born twins. Intertwin Hb differences in MC twins may partly be related to blood transfusion through the vascular anastomoses. Since DC twins do not have anastomoses, other factors may lead to Hb differences, including differences in timing of umbilical cord clamping. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Studies on the interference by haemoglobin in the determination of bilirubin.

PubMed

van der Woerd-de Lange, J A; Guder, W G; Schleicher, E; Paetzke, I; Schleithoff, M; Wieland, O H

1983-07-01

Haemoglobin interference in the determination of bilirubin was compared in 7 different methods using the Jendrassik-Grof procedure, the Jendrassik-Grof-Nosslin modification, and the more recent procedures using nitrophenyldiazonium, 2,5-dichlorophenyldiazonium, 2,4-dichloraniline, and a direct reading method. To a variable degree, haemoglobin decreased the apparent absorption of the reaction product in all procedures. The extent of this decrease depended on the reagent used, the wavelength, incubation time, bilirubin concentration and the type of blank used. In an attempt to elucidate the mechanism of interference, haemoglobin was found to destroy the bilirubin diazo-compound whereas haemoglobin was ineffective. Likewise, storage of haemolytic samples for several days led to a disappearance of haemoglobin. H2O2, which had no effect in the absence of haemoglobin, potentiated the action of haemoglobin on diazobilirubin coupling. From our observations it can be concluded that haemoglobin disturbs the diazo-bilirubin reaction by a dual mechanism. H2O2, formed from oxyhaemoglobin by autoxidation, destroys the diazo bilirubin colour. In accordance with this explanation, potassium iodide stabilized the diazo compound against the peroxidative effect of oxyhaemoglobin; stabilization was not effective with superoxide dismutase, mannitol or ascorbate.

Intraerythrocytic 2,3-diphosphoglycerate concentration in hypertensive subjects before and following control by anti hypertensive treatment.

PubMed

Kasparian, H; Konstantopoulos, K; Tassiopoulos, S; Papadogiannis, D; Karadzas, N; Tassiopoulos, T

1997-09-01

We measured the 2,3-diphosphoglycerate inraerythrocytic concentration in 24 normal controls and in 24 hypertensives before and following drug therapy. In hypertensives the 2,3-diphosphoglycerate concentration was higher than that of the controls (14.96 mumol/g Hb vs 13.26 mumol/g Hb respectively); the difference is statistically significant (p < 0.001). Following control of the hypertension by drug therapy, the 2,3 DPG levels in the patients studied do not seem to differ statistically from those of the controls. This may be a consequence of lower cardiac output in hypertension which results to a lower tissue perfusion, leading to an increased concentration of deoxygenated haemoglobin in the vein blood. Measurement of 2,3-diphosphoglucerate may prove of value in estimating tissue perfusion in hypertension.

Soil-transmitted helminths and haemoglobin status among Afghan children in World Food Programme assisted schools.

PubMed

Gabrielli, A F; Ramsan, M; Naumann, C; Tsogzolmaa, D; Bojang, B; Khoshal, M H; Connolly, M; Stothard, J R; Montresor, A; Savioli, L

2005-12-01

In recent years there have been major socio-economic changes within Afghanistan such that the present public health burden of soil-transmitted helminths (STH), especially that within school-aged children, remains to be determined. A baseline parasitological survey was therefore carried out in four defined areas of Afghanistan to better assess the distribution, prevalence and intensity of STH infections prior to a nationwide de-worming campaign beginning within World Food Programme assisted schools. A cross-sectional examination of 1001 children aged between 8 and 15 years old revealed that approximately half (47.2%) were infected with at least one STH. Infections with Ascaris lumbricoides were most widespread (40.9%) and elevated prevalences were detected in urban environments; for example, schoolchildren in Kabul were more likely to be infected (OR=2.2, 95% CI 1.6-3.0) than elsewhere and these infections were often of higher intensity (OR=7.6, 95% CI 4.9-11.8). Trichuris trichiura (9.9%) and hookworms (0.7%), previously unknown from Afghanistan, were encountered. The blood haemoglobin concentration of surveyed children was also assessed: 4% resulted to be anaemic (Hb<11 g dl(-1)), and 0.4% to be severely anaemic (Hb<7 g dl(-1)).

Clinical, genetic and fertility studies of Indians with beta S-globin gene and the influence of Hb S on Plasmodium falciparum malaria infection.

PubMed

Joishy, S K; Hassan, K; Lopes, M; Lie-Injo, L E

1988-01-01

Clinical studies were carried out on mild Indian sickle cell anaemia in Malaysia, and genetic and fertility studies were carried out on 101 families with and without sickle-cell haemoglobin (Hb S). The Indian sickle cell anaemia patients reached adulthood, and pregnancies and deliveries were uneventful without blood transfusion. There was no foetal wastage and the number of children produced was not significantly different from that in families without Hb S. 28 Indian patients hospitalized with Plasmodium falciparum malaria infection were also examined for their beta S genotype. P. falciparum malaria infection occurred much more frequently in individuals without Hb S than in Hb S carriers.

A Systematic Review of Known Mechanisms of Hydroxyurea-induced Foetal Haemoglobin for Treatment of Sickle Cell Disease

PubMed Central

Pule, Gift D.; Mowla, Shaheen; Novitzky, Nicolas; Wiysonge, Charles S.; Wonkam, Ambroise

2016-01-01

Aims To report on molecular mechanisms of foetal haemoglobin (HbF) induction by hydroxyurea (HU) for the treatment of Sickle Cell Disease (SCD). Study Design Systematic review. Results Studies have provided consistent associations between genomic variations in HbF-promoting loci and variable HbF level in response to HU. Numerous signal transduction pathways have been implicated, through the identification of key genomic variants in BCL11A, HBS1L-MYB, SAR1 or XmnI polymorphism that predispose the response to the treatment, and signal transduction pathways, that modulate γ-globin expression (cAMP/cGMP; Giα/JNK/Jun; methylation and microRNA). Three main molecular pathways have been reported: 1) Epigenetic modifications, transcriptional events and signalling pathways involved in HU-mediated response, 2) Signalling pathways involving HU-mediated response and 3) Post-transcriptional pathways (regulation by microRNAs). Conclusions The complete picture of HU-mediated mechanisms of HbF production in SCD remains elusive. Research on post-transcriptional mechanisms could lead to therapeutic targets that may minimize alterations to the cellular transcriptome. PMID:26327494

Allopurinol reduces B-type natriuretic peptide concentrations and haemoglobin but does not alter exercise capacity in chronic heart failure.

PubMed

Gavin, A D; Struthers, A D

2005-06-01

To study whether the effect of allopurinol on improvement of endothelial dysfunction in chronic heart failure (CHF) translates into improved exercise capacity and to examine whether allopurinol also improves B-type natriuretic peptide (BNP), the other important prognostic marker of CHF. Randomised, double blind, placebo controlled crossover trial. Teaching hospital. 50 patients with CHF (New York Heart Association functional classes II and III) were recruited. 50 patients with CHF were randomly assigned to three months' treatment with allopurinol (300 mg/day) or placebo. At two and three months into treatment, they underwent a modified Bruce exercise protocol and a six minute walk test. Blood was taken for BNP and haemoglobin analysis. Neither exercise test was altered by allopurinol. However, plasma BNP concentrations fell significantly (p = 0.035) with allopurinol (11.9 pmol/l) versus placebo (14.4 pmol/l). Haemoglobin concentrations also fell highly significantly with allopurinol (p = 0.001). An important negative finding is that despite high hopes for it, allopurinol had no effect on exercise capacity in CHF. On the other hand, allopurinol did reduce BNP, which is the best available surrogate marker for prognosis in CHF.

Diving behaviour and haemoglobin function: the primary structure of the alpha- and beta-chains of the sea turtle (Caretta caretta) and its functional implications.

PubMed

Petruzzelli, R; Aureli, G; Lania, A; Galtieri, A; Desideri, A; Giardina, B

1996-06-15

The amino acid sequence of the alpha- and beta-chains of haemoglobin (Hb) from the loggerhead sea turtle (Caretta caretta) has been determined. Comparison with that of human Hb shows differences in several residues involved in both alpha 1 beta 1 and alpha 1 beta 2 packing contacts. On the whole, in spite of the mutations, the essential characteristics of both interfaces seem to be maintained. The functional properties of the sea turtle Hb have been investigated at different temperatures and as a function of proton, chloride and organic phosphate concentrations. In addition to overall similarities shared with most of the vertebrate Hbs previously described, this molecule shows significant differences which could be related to the life behaviour of the turtle. In fact, while the shape of the Bohr-effect curve is well adapted for gas exchange during prolonged dives, the very small enthalpy change for O2 binding ensures that O2 delivery becomes essentially insensitive to the temperature changes of the environment. Moreover, and similarly to the case of emperor penguin Hb, the small alkaline Bohr effect appears to be only choride-linked, since the pH dependence of the O2 affinity is abolished in the absence of this ion. These functional characteristics are discussed on the basis of the primary structure of alpha- and beta-chains.

Evolutionary diversification of the trypanosome haptoglobin-haemoglobin receptor from an ancestral haemoglobin receptor.

PubMed

Lane-Serff, Harriet; MacGregor, Paula; Peacock, Lori; Macleod, Olivia Js; Kay, Christopher; Gibson, Wendy; Higgins, Matthew K; Carrington, Mark

2016-04-15

The haptoglobin-haemoglobin receptor of the African trypanosome species, Trypanosoma brucei, is expressed when the parasite is in the bloodstream of the mammalian host, allowing it to acquire haem through the uptake of haptoglobin-haemoglobin complexes. Here we show that in Trypanosoma congolense this receptor is instead expressed in the epimastigote developmental stage that occurs in the tsetse fly, where it acts as a haemoglobin receptor. We also present the structure of the T. congolense receptor in complex with haemoglobin. This allows us to propose an evolutionary history for this receptor, charting the structural and cellular changes that took place as it adapted from a role in the insect to a new role in the mammalian host.

The distribution of haemoglobin S and other haemoglobin variants in a sample of Liberian paediatric subjects.

PubMed

Simbeye, A G

1978-01-01

The investigation of haemoglobin S in a sample of Liberian paediatric subjects revealed a relatively low incidence of this haemoglobin variant. There is no significant difference from its incidence in the adult population. The low frequency of haemoglobin S is rather paradoxal since malaria is still endemic in Liberia. Tribal variation has been revealed. Other haemoglobin variants were found to be rare.

Measuring glycated haemoglobin in women with gestational diabetes mellitus: How useful is it?

PubMed

Wong, Vincent W; Chong, Shanley; Mediratta, Sahil; Jalaludin, Bin

2017-06-01

Glycated haemoglobin (HbA1c) is an important tool for assessing glycaemic status in patients with diabetes, but its usefulness in gestational diabetes mellitus (GDM), is unclear. The aim of this study is to evaluate whether HbA1c in women with GDM is valuable in predicting adverse pregnancy outcomes. A retrospective review of women with GDM who had HbA1c measured at diagnosis of GDM (GHb-diag) and at 36 weeks gestation (GHb-36 weeks) was conducted. The association between HbA1c and various pregnancy outcomes was assessed RESULTS: Among 1244 women with GDM in our cohort, both GHb-diag and GHb-36 weeks were independent predictors for large-for-gestation (LGA) babies (OR 1.06, P = 0.005 and OR 1.06, P = 0.002, respectively) and neonatal hypoglycaemia (OR 1.10, P < 0.001 and OR 1.09, P < 0.001, respectively). Women with HbA1c ≥ 5.4% (35 mmol/mol) at diagnosis had significantly greater risk for LGA (15.3% vs 8.2%, P < 0.001) and neonatal hypoglycaemia (42.2% vs 23.6%, P < 0.001) than those below this cut-off. The difference between GHb-diag and GHb-36 weeks was small and improvement in HbA1c by 36 weeks was not associated with better pregnancy outcomes. We showed that measurement of HbA1c, either at the time of diagnosis of GDM or toward the end of pregnancy, were both associated with adverse pregnancy outcomes. Women with elevated HbA1c (>5.4% or 35 mmol/mol) at diagnosis of GDM should be monitored closely during pregnancy. However, there is not enough evidence to suggest that repeating HbA1c toward the end of pregnancy will provide additional information in predicting adverse pregnancy outcomes. © 2016 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.

Data analytics identify glycated haemoglobin co-markers for type 2 diabetes mellitus diagnosis.

PubMed

Jelinek, Herbert F; Stranieri, Andrew; Yatsko, Andrew; Venkatraman, Sitalakshmi

2016-08-01

Glycated haemoglobin (HbA1c) is being more commonly used as an alternative test for the identification of type 2 diabetes mellitus (T2DM) or to add to fasting blood glucose level and oral glucose tolerance test results, because it is easily obtained using point-of-care technology and represents long-term blood sugar levels. HbA1c cut-off values of 6.5% or above have been recommended for clinical use based on the presence of diabetic comorbidities from population studies. However, outcomes of large trials with a HbA1c of 6.5% as a cut-off have been inconsistent for a diagnosis of T2DM. This suggests that a HbA1c cut-off of 6.5% as a single marker may not be sensitive enough or be too simple and miss individuals at risk or with already overt, undiagnosed diabetes. In this study, data mining algorithms have been applied on a large clinical dataset to identify an optimal cut-off value for HbA1c and to identify whether additional biomarkers can be used together with HbA1c to enhance diagnostic accuracy of T2DM. T2DM classification accuracy increased if 8-hydroxy-2-deoxyguanosine (8-OhdG), an oxidative stress marker, was included in the algorithm from 78.71% for HbA1c at 6.5% to 86.64%. A similar result was obtained when interleukin-6 (IL-6) was included (accuracy=85.63%) but with a lower optimal HbA1c range between 5.73 and 6.22%. The application of data analytics to medical records from the Diabetes Screening programme demonstrates that data analytics, combined with large clinical datasets can be used to identify clinically appropriate cut-off values and identify novel biomarkers that when included improve the accuracy of T2DM diagnosis even when HbA1c levels are below or equal to the current cut-off of 6.5%. Copyright © 2016 Elsevier Ltd. All rights reserved.

Position statement of the Australian Diabetes Society: individualisation of glycated haemoglobin targets for adults with diabetes mellitus.

PubMed

Cheung, N Wah; Conn, Jennifer J; d'Emden, Michael C; Gunton, Jenny E; Jenkins, Alicia J; Ross, Glynis P; Sinha, Ashim K; Andrikopoulos, Sofianos; Colagiuri, Stephen; Twigg, Stephen M

2009-09-21

Tight glycaemic control reduces the risk of development and progression of organ complications in people with type 1 or type 2 diabetes. In this position statement, the Australian Diabetes Society recommends a general target glycated haemoglobin (HbA(1c)) level of HbA(1c) level of HbA(1c) target is based on patient-specific factors, such as the type of diabetes and its duration, pregnancy, diabetes medication being taken, presence of cardiovascular disease, risk of and problems from hypoglycaemia, and comorbidities. Management of diabetes also includes: adequate control of other cardiovascular risk factors, including weight, blood pressure and lipid serum levels; antiplatelet therapy; and smoking cessation.

Different functional modulation by heterotropic ligands (2,3-diphosphoglycerate and chlorides) of the two haemoglobins from fallow-deer (Dama dama).

PubMed

Angeletti, M; Pucciarelli, S; Priori, A M; Canofeni, S; Barra, D; Fioretti, E; Coletta, M

2001-02-01

Two haemoglobin components have been identified and purified from fallow-deer (Dama dama) erythrocytes. They are present in similar amounts and the two tetrameric molecules share the same alpha chain, while two different beta chains are detected in the two components. The beta chains differ by 14 residues, even though they both have 145 amino-acid residues, which account for a molecular mass of 16,023 and 16,064 Da, respectively, while alpha chain has 141 residues, yielding a molecular mass of 15,142 Da. Compared with human Hb, the N-terminal region of both beta chains shows deletion of Val beta 1 and the replacement of His beta 2 by a methionyl residue, a modification which is common to most ruminant haemoglobins. Although both isolated components show a low intrinsic affinity for oxygen, meaningful differences between the two haemoglobins have been found with respect to the effect of heterotropic effectors, such as 2,3-diphosphoglycerate and chloride ions. In view of the high sequence homology between the two components, the different effect of heterotropic ligands has been tentatively correlated to possible localized structural variations between beta chains of the two haemoglobin components.

Iron from haemoglobin and haemin modulates nucleotide hydrolysis in Trichomonas vaginalis.

PubMed

Vieira, Patrícia de Brum; Silva, Nícolas Luiz Feijó; Kist, Luiza Wilges; Oliveira, Giovanna Medeiros Tavares de; Bogo, Maurício Reis; Carli, Geraldo Atillio de; Macedo, Alexandre José; Tasca, Tiana

2015-04-01

Extracellular ATP may act as a danger signalling molecule, inducing inflammation and immune responses in infection sites. The ectonucleotidases NTPDase and ecto-5'-nucleotidase are enzymes that modulate extracellular nucleotide levels; these enzymes have been previously characterised in Trichomonas vaginalis. Iron plays an important role in the complex trichomonal pathogenesis. Herein, the effects of iron on growth, nucleotide hydrolysis and NTPDase gene expression in T. vaginalis isolates from female and male patients were evaluated. Iron from different sources sustained T. vaginalis growth. Importantly, iron from haemoglobin (HB) and haemin (HM) enhanced NTPDase activity in isolates from female patients and conversely reduced the enzyme activity in isolates from male patients. Iron treatments could not alter the NTPDase transcript levels in T. vaginalis. Furthermore, our results reveal a distinct ATP, ADP and AMP hydrolysis profile between isolates from female and male patients influenced by iron from HB and HM. Our data indicate the participation of NTPDase and ecto-5'-nucleotidase in the establishment of trichomonas infection through ATP degradation and adenosine production influenced by iron.

Haemoglobin scavenging after subarachnoid haemorrhage.

PubMed

Durnford, A; Dunbar, J; Galea, J; Bulters, D; Nicoll, J A R; Boche, D; Galea, I

2015-01-01

Rapid and effective clearance of cell-free haemoglobin after subarachnoid haemorrhage (SAH) is important to prevent vasospasm and neurotoxicity and improve long-term outcome. Haemoglobin is avidly bound by haptoglobin, and the complex is cleared by CD163 expressed on the membrane surface of macrophages. We studied the kinetics of haemoglobin and haptoglobin in cerebrospinal fluid after SAH. We show that haemoglobin levels rise gradually after SAH. Haptoglobin levels rise acutely with aneurysmal rupture as a result of injection of blood into the subarachnoid space. Although levels decline as haemoglobin scavenging occurs, complete depletion of haptoglobin does not occur and levels start rising again, indicating saturation of CD163 sites available for haptoglobin-haemoglobin clearance. In a preliminary neuropathological study we demonstrate that meningeal CD163 expression is upregulated after SAH, in keeping with a proinflammatory state. However, loss of CD163 occurs in meningeal areas with overlying blood compared with areas without overlying blood. Becauses ADAM17 is the enzyme responsible for shedding membrane-bound CD163, its inhibition may be a potential therapeutic strategy after SAH.

Newborn screening for sickling and other haemoglobin disorders using tandem mass spectrometry: A pilot study of methodology in laboratories in England.

PubMed

Daniel, Yvonne A; Henthorn, Joan

2016-12-01

To determine (i) if electrospray mass spectrometry-mass spectrometry with the SpOtOn Diagnostics Ltd reagent kit for sickle cell screening could be integrated into the English newborn screening programme, under routine screening conditions, and provide mass spectrometry-mass spectrometry results which match existing methods, and (ii) if common action values could be set for all manufacturers in the study, for all assessed haemoglobins, to indicate which samples require further investigation. Anonymised residual blood spots were analysed using the SpOtOn reagent kit as per manufacturer's instructions, in parallel with existing techniques at four laboratories. Mass spectrometry-mass spectrometry instrumentation at Laboratories A and B was AB Sciex (Warrington, UK) AP4000, and at Laboratories C and D, Waters Micromass (Manchester, UK), Xevo TQMS and Premier, respectively. There were 23,898 results accepted from the four laboratories. Excellent specificity at 100% sensitivity was observed for haemoglobin S, haemoglobin C, haemoglobin E and haemoglobin O Arab . A common action value was not possible for Hb C, but action values were set by manufacturer. The two haemoglobin D Punjab cases at Laboratory D were not detected using the common action value. Conversely, false-positive results with haemoglobin D Punjab were a problem at the remaining three laboratories. This multicentre study demonstrates that it is possible to implement mass spectrometry-mass spectrometry into an established screening programme while maintaining consistency with existing methods for haemoglobinopathy screening. However, one of the instruments investigated cannot be recommended for use with this application. © The Author(s) 2016.

Distribution of glycated haemoglobin and its determinants in Korean youth and young adults: a nationwide population-based study.

PubMed

Seo, Ji-Young; Hwang, Seung-Sik; Kim, Jae Hyun; Lee, Young Ah; Lee, Seong Yong; Shin, Choong Ho; Yang, Sei Won

2018-01-31

The present study aimed to describe the distribution of and to investigate the factors associated with glycated haemoglobin (HbA1c) values in Korean youth (10-19 years old) and young adults (20-29 years old). Data from the Korea Health and Nutrition Examination Survey (2011-2015) were used. A total of 6,418 participants (male 3,140 [53.2%]) aged 10-29 years were included in the analysis. Percentiles of HbA1c were calculated and HbA1c values were compared according to age, sex, and associated factors. The mean HbA1c values (% [mmol/mol]) were 5.42 ± 0.01 (35.7 ± 0.1) for youths and 5.32 ± 0.01 (34.7 ± 0.1) for young adults (P < 0.001). Male participants showed significantly higher HbA1c level than females (P < 0.001). When age was grouped into 5-year intervals, HbA1c was the highest in those aged 10-14 years and the lowest in those aged 20-24 years. After controlling for confounding variables, the HbA1c values of youths and male participants were significantly higher than those of young adults and female participants. The present study provides nationally representative data on the distribution of HbA1c values in Korean youth and young adults. There were significant differences in the level of HbA1c according to age and sex.

Evidence for a kinetic heterogeneity in ligand binding to R-state haemoglobin Kempsey [Asp-G1(99) beta----Asn].

PubMed Central

Coletta, M; Brittain, T; Brunori, M

1986-01-01

Thermodynamic and kinetic properties of O2 and CO binding to haemoglobin (Hb) Kempsey [Asp-G1(99) beta----Asn] were investigated and the activation parameters for the two ligands were determined. At every temperature the O2-binding isotherms display a weak co-operativity, n ranging between 1.1 and 1.2, and dissociation kinetics show a single-exponential behaviour. O2-binding kinetics were studied at 25 degrees C by temperature jump and are characterized at each saturation (from Y = 0.31 to Y = 1.0) by two processes, a fast bimolecular one and a slow monomolecular one (tau -1 = 20 s-1), which contributes to approx. 30% of the whole relaxation amplitude at every Y. CO-binding kinetics to Hb Kempsey were followed at several temperatures by flash photolysis and stopped flow. The process is biphasic, as reported elsewhere [Bunn, Wohl, Bradley, Cooley & Gibson (1974) J. Biol. Chem. 249, 7402-7409], and the relative contributions of the two bimolecular rates to the whole process are only slightly affected by temperature. On taking account for the fraction of dimers at every protein concentration, the slow phase corresponds to approx. 50% of the ligand binding to tetramers. Correlation of these results with previous spectroscopic data leads to the hypothesis that the biphasic time course of CO binding may be attributed to alpha/beta heterogeneity of the R-state of tetrameric Hb Kempsey. PMID:3800943

Effects of vitamin D supplementation on glycated haemoglobin and fasting glucose levels in hypertensive patients: a randomized controlled trial.

PubMed

Grübler, M R; Gaksch, M; Kienreich, K; Verheyen, N; Schmid, J; Ó Hartaigh, B; Richtig, G; Scharnagl, H; Meinitzer, A; Fahrleitner-Pammer, A; März, W; Tomaschitz, A; Pilz, S

2016-10-01

To investigate the efficacy of vitamin D supplementation on glycaemic control. The Styrian Vitamin D Hypertension Trial was a single-centre, double-blind, placebo-controlled study conducted between 2011 and 2014 at the Medical University of Graz, Austria. We enrolled 200 people with arterial hypertension and 25-hydroxyvitamin D [25(OH)D] concentrations <30 ng/mL. Study participants were randomized to receive either 2800 IU of vitamin D or placebo per day for 8 weeks. The present study was a post hoc analysis that incorporated an analysis of covariance (ancova) approach, while adjusting for baseline differences. A total of 185 participants [mean ± standard deviation age, 60.1 ± 11.3 years; 47% women; mean 25(OH)D 21.2 ± 5.6 ng/mL, mean glycated haemoglobin (HbA1c) 44.8 ± 11.8 mmol/mol and mean body mass index 30.4 ± 5.4 kg/m(2) ] completed the trial. ancova showed a mean treatment effect [95% confidence interval (CI)] on HbA1c of -3.52 (-6.7 to -0.34) mmol/mol (p = .045). There was no difference in fasting glucose -4.7 mg/dL (95% CI -16.3 to 6.9; p = .426). Vitamin D supplementation in obese hypertensive patients with low 25(OH)D reduces HbA1c levels. This finding warrants further investigation into potential vitamin D effects on glucose homeostasis. © 2016 John Wiley & Sons Ltd.

Comparative clinical evaluation of glycosylated haemoglobin level in healthy and chronic periodontitis patients: A chairside diagnostic method.

PubMed

Srinivasa, T S; Agrawal, Parul; Goyal, Pravesh; Farista, Sana; Sowmya, N K; Deonani, Sushmita

2015-01-01

Glycosylated haemoglobin (HbA1c) level can consequently be interpreted as an average of the blood glucose present over the past 3-4 months. Periodontitis is associated with glycemic control in patients with diabetes. The purpose of this study was to determine the level of HbA1c in healthy and periodontitis patients who were previously not diagnosed with diabetes mellitus. A total of 40 patients were selected for study and divided into two groups. Group 1 included patients with a healthy periodontium, and Group 2 included patients suffering from chronic periodontitis. Finger stick blood was collected by special collection unit (A1CNOW+® Bayer Health Care, Tarrytown New York, USA), for estimating level of HbA1c. Both groups showed similar HbA1c levels clinically with slight increase in levels in the test group, but was statistically significant (test--5.66 ± 0.35%, control--5.17 ± 0.3% P = 0.003). Indians are at a high-risk of developing periodontitis and diabetes. These data suggest a possible link between periodontitis and glycemic control in nondiabetic individuals, periodontal disease may be a potential contributor to the development of type 2 diabetes.

Haemoglobin Levels in Acute Coronary Syndrome Patients Admitted in Cardiology Intensive Care Units in a Tertiary Care Hospital.

PubMed

Naqvil, Syed Mujtaba Hussain; Rao, T Ramesh Kumar; Chandra, Shobha Jagdish

2015-06-01

Epidemiology of abnormal haemoglobin levels and its association with severity of coronary artery disease in Indian patients is uncertain. This prospective observational study was conducted to determine the haemoglobin levels in acute coronary syndrome (ACS) patients and the association of anaemia with the severity of coronary artery disease (CAD) on coronary angiography (CAG). The patients diagnosed with ACS (ST-elevated and non-elevated MI, unstable angina) based on ECG and cardiac enzymes and admitted in cardiology ICU were enrolled in the study after fulfilling study criteria and the baseline haemoglobin level was recorded. The severity of coronary disease of patients who underwent coronary angiography was recorded. A total of 162 patients were enrolled for the study. The overall haemoglobin of patients was 11.99 ± 2.24 g/dl with 12.46 ± 2.33 g/dl in males and 11.17 ± 1.82 g/dl in females (p < 0.05). Anaemia was found in 62.96% patients with no significant gender difference (p > 0.05), however abnormal haemoglobin level (Hb > 16g/dl) was found exclusively in 7.7% males. One hundred one patients underwent coronary angiography and anaemia was present in 60 patients (58.82%) and absent in 41 (40.59%). The difference in mean haemoglobin levels in anaemic patients with single, double, and triple vessel disease was significant (p < 0.05) and corresponding levels in non-anaemic patients were insignificant (p > 0.05). A weak correlation was observed between the haemoglobin level of patients and the percentage of obstruction in CAG (r = 0.26). The odds of having triple vessel disease in anaemic patient are 1.77 (95% CI 0.71 to 4.43). However, the association between anaemia and the severity of coronary artery disease was statistically found to be non-significant. The mean haemoglobin levels decreased as the severity of CAD increased in CAG, however the association was not established between anaemia and the severity of coronary artery disease statistically.

Local descriptive body weight and dietary norms, food availability, and 10-year change in glycosylated haemoglobin in an Australian population-based biomedical cohort.

PubMed

Carroll, Suzanne J; Paquet, Catherine; Howard, Natasha J; Coffee, Neil T; Adams, Robert J; Taylor, Anne W; Niyonsenga, Theo; Daniel, Mark

2017-02-02

Individual-level health outcomes are shaped by environmental risk conditions. Norms figure prominently in socio-behavioural theories yet spatial variations in health-related norms have rarely been investigated as environmental risk conditions. This study assessed: 1) the contributions of local descriptive norms for overweight/obesity and dietary behaviour to 10-year change in glycosylated haemoglobin (HbA 1c ), accounting for food resource availability; and 2) whether associations between local descriptive norms and HbA 1c were moderated by food resource availability. HbA 1c , representing cardiometabolic risk, was measured three times over 10 years for a population-based biomedical cohort of adults in Adelaide, South Australia. Residential environmental exposures were defined using 1600 m participant-centred road-network buffers. Local descriptive norms for overweight/obesity and insufficient fruit intake (proportion of residents with BMI ≥ 25 kg/m 2 [n = 1890] or fruit intake of <2 serves/day [n = 1945], respectively) were aggregated from responses to a separate geocoded population survey. Fast-food and healthful food resource availability (counts) were extracted from a retail database. Separate sets of multilevel models included different predictors, one local descriptive norm and either fast-food or healthful food resource availability, with area-level education and individual-level covariates (age, sex, employment status, education, marital status, and smoking status). Interactions between local descriptive norms and food resource availability were tested. HbA 1c concentration rose over time. Local descriptive norms for overweight/obesity and insufficient fruit intake predicted greater rates of increase in HbA 1c . Neither fast-food nor healthful food resource availability were associated with change in HbA 1c . Greater healthful food resource availability reduced the rate of increase in HbA 1c concentration attributed to the overweight

Red blood cells free α-haemoglobin pool: a biomarker to monitor the β-thalassemia intermedia variability. The ALPHAPOOL study.

PubMed

Vasseur, Corinne; Domingues-Hamdi, Elisa; Ledudal, Katia; Le Corvoisier, Philippe; Barau, Caroline; Ghaleh, Bijan; Rialland, Amandine; Pissard, Serge; Galactéros, Frédéric; Baudin-Creuza, Véronique

2017-10-01

The severity of β-thalassaemia (β-thal) intermedia is mainly correlated to the degree of imbalanced α/non α-globin chain synthesis. The phenotypic diversity of β-thal depends on this imbalance and reflects all possible combinations of α- and β-globin genotypes, levels of fetal haemoglobin (HbF) and co-inheritance of other modulating factors. This study aimed to demonstrate the validity of a new surrogate of α/non α-globin biosynthetic ratio by measuring the soluble α-Hb pool in lysed red blood cells. Our results confirm that the α-Hb pool measurement allows a good discrimination between β-thal intermedia patients, controls and α-thal patients (P < 0·003). Receiver operator characteristic analyses revealed an area under the curve of 0·978 for the α-Hb pool measurement at a threshold of 120 ng free α-Hb/mg of total Hb/ml of haemolysate (ppm) with a sensitivity and specificity of 86% and 100%, respectively, to discriminate between β-thal and not β-thal subjects. Significant correlations were observed between the α-Hb pool and biological parameters of β-thal, the most significant association being observed with red cell hexokinase activity. This study indicates that the α-Hb pool could be a new marker for assistance in diagnostic orientation of β-thal intermedia patients and may be clinically useful for monitoring the evolution of the disequilibrium of globin synthesis in response to treatments. © 2017 John Wiley & Sons Ltd.

Global, regional, and national trends in haemoglobin concentration and prevalence of total and severe anaemia in children and pregnant and non-pregnant women for 1995-2011: a systematic analysis of population-representative data.

PubMed

Stevens, Gretchen A; Finucane, Mariel M; De-Regil, Luz Maria; Paciorek, Christopher J; Flaxman, Seth R; Branca, Francesco; Peña-Rosas, Juan Pablo; Bhutta, Zulfiqar A; Ezzati, Majid

2013-07-01

Low haemoglobin concentrations and anaemia are important risk factors for the health and development of women and children. We estimated trends in the distributions of haemoglobin concentration and in the prevalence of anaemia and severe anaemia in young children and pregnant and non-pregnant women between 1995 and 2011. We obtained data about haemoglobin and anaemia for children aged 6-59 months and women of childbearing age (15-49 years) from 257 population-representative data sources from 107 countries worldwide. We used health, nutrition, and household surveys; summary statistics from WHO's Vitamin and Mineral Nutrition Information System; and summary statistics reported by other national and international agencies. We used a Bayesian hierarchical mixture model to estimate haemoglobin distributions and systematically addressed missing data, non-linear time trends, and representativeness of data sources. We quantified the uncertainty of our estimates. Global mean haemoglobin improved slightly between 1995 and 2011, from 125 g/L (95% credibility interval 123-126) to 126 g/L (124-128) in non-pregnant women, from 112 g/L (111-113) to 114 g/L (112-116) in pregnant women, and from 109 g/L (107-111) to 111 g/L (110-113) in children. Anaemia prevalence decreased from 33% (29-37) to 29% (24-35) in non-pregnant women, from 43% (39-47) to 38% (34-43) in pregnant women, and from 47% (43-51) to 43% (38-47) in children. These prevalences translated to 496 million (409-595 million) non-pregnant women, 32 million (28-36 million) pregnant women, and 273 million (242-304 million) children with anaemia in 2011. In 2011, concentrations of mean haemoglobin were lowest and anaemia prevalence was highest in south Asia and central and west Africa. Children's and women's haemoglobin statuses improved in some regions where concentrations had been low in the 1990s, leading to a modest global increase in mean haemoglobin and a reduction in anaemia prevalence. Further improvements are

Relationship between changes in haemoglobin mass and maximal oxygen uptake after hypoxic exposure.

PubMed

Saunders, Philo U; Garvican-Lewis, Laura A; Schmidt, Walter F; Gore, Christopher J

2013-12-01

Endurance athletes have been using altitude training for decades to improve near sea-level performance. The predominant mechanism is thought to be accelerated erythropoiesis increasing haemoglobin mass (Hb(mass)) resulting in a greater maximal oxygen uptake (VO₂(max)). Not all studies have shown a proportionate increase in VO₂(max) as a result of increased Hb(mass). The aim of this study was to determine the relationship between the two parameters in a large group of endurance athletes after altitude training. 145 elite endurance athletes (94 male and 51 female) who participated in various altitude studies as altitude or control participants were used for the analysis. Participants performed Hb(mass) and VO₂(max) testing before and after intervention. For the pooled data, the correlation between per cent change in Hb(mass) and per cent change in VO₂(max) was significant (p<0.0001, r(2)=0.15), with a slope (95% CI) of 0.48 (0.30 to 0.67) intercept free to vary and 0.62 (0.46 to 0.77) when constrained through the origin. When separated, the correlations were significant for the altitude and control groups, with the correlation being stronger for the altitude group (slope of 0.57 to 0.72). With high statistical power, we conclude that altitude training of endurance athletes will result in an increase in VO₂(max) of more than half the magnitude of the increase in Hb(mass), which supports the use of altitude training by athletes. But race performance is not perfectly related to relative VO₂(max), and other non-haematological factors altered from altitude training, such as running economy and lactate threshold, may also be beneficial to performance.

Maternal anaemia at delivery and haemoglobin evolution in children during their first 18 months of life using latent class analysis.

PubMed

Koura, Kobto G; Ouédraogo, Smaïla; Cottrell, Gilles; Le Port, Agnès; Massougbodji, Achille; Garcia, André

2012-01-01

Anaemia during pregnancy and at delivery is an important public health problem in low- and middle-income countries. Its association with the children's haemoglobin level over time remains unclear. Our goals were to identify distinct haemoglobin level trajectories using latent class analysis and to assess the association between these trajectories and maternal anaemia and other risk factors. A prospective study of children from birth to 18 months of life was conducted in a rural setting in Tori-Bossito, Benin. The main outcome measure was the haemoglobin levels repeatedly measured at 3, 6, 9, 12, 15 and 18 months. Variables were collected from the mothers at delivery and from their children at birth and during the follow-up. The analyses were performed by means of Latent Class Analysis which has never been used for this kind of data. All the analyses were performed with Stata software, version 11.0, using the generalized linear latent and mixed model (GLLAMM) framework. We showed that 33.7% of children followed a low haemoglobin trajectory and 66.3% a high trajectory during the first 18 months of life. Newborn anaemia, placental malaria, malaria attack, sickle cell trait and male gender were significantly associated with a lower children's haemoglobin level over time, whereas maternal age, children living in a polygamous family and with good feeding practices had a higher Hb level in the first18 months. We also showed that maternal anaemia was a predictor for 'low haemoglobin level trajectory' group membership but have no significant effect on children haemoglobin level over time. Latent Class Analyses framework seems well suited to analyse longitudinal data under the hypothesis that different subpopulations of subjects are present in the data, each with its own set of parameters, with distinctive evolutions that themselves may reflect distinctive aetiologies.

Maternal Anaemia at Delivery and Haemoglobin Evolution in Children during Their First 18 Months of Life Using Latent Class Analysis

PubMed Central

Koura, Kobto G.; Ouédraogo, Smaïla; Cottrell, Gilles; Le Port, Agnès; Massougbodji, Achille; Garcia, André

2012-01-01

Background Anaemia during pregnancy and at delivery is an important public health problem in low- and middle-income countries. Its association with the children’s haemoglobin level over time remains unclear. Our goals were to identify distinct haemoglobin level trajectories using latent class analysis and to assess the association between these trajectories and maternal anaemia and other risk factors. Method A prospective study of children from birth to 18 months of life was conducted in a rural setting in Tori-Bossito, Benin. The main outcome measure was the haemoglobin levels repeatedly measured at 3, 6, 9, 12, 15 and 18 months. Variables were collected from the mothers at delivery and from their children at birth and during the follow-up. The analyses were performed by means of Latent Class Analysis which has never been used for this kind of data. All the analyses were performed with Stata software, version 11.0, using the generalized linear latent and mixed model (GLLAMM) framework. Results We showed that 33.7% of children followed a low haemoglobin trajectory and 66.3% a high trajectory during the first 18 months of life. Newborn anaemia, placental malaria, malaria attack, sickle cell trait and male gender were significantly associated with a lower children’s haemoglobin level over time, whereas maternal age, children living in a polygamous family and with good feeding practices had a higher Hb level in the first18 months. We also showed that maternal anaemia was a predictor for ‘low haemoglobin level trajectory’ group membership but have no significant effect on children haemoglobin level over time. Conclusion Latent Class Analyses framework seems well suited to analyse longitudinal data under the hypothesis that different subpopulations of subjects are present in the data, each with its own set of parameters, with distinctive evolutions that themselves may reflect distinctive aetiologies. PMID:23185556

Chapter 8 Haemoglobin, ferritin and erythropoietin amongst UK adult dialysis patients in 2010: national and centre-specific analyses.

PubMed

Webb, Lynsey; Gilg, Julie; Wilkie, Martin

2012-01-01

The UK Renal Association (RA) and National Institute for Health and Clinical Excellence (NICE) have published clinical practice guidelines which include recommendations for management of anaemia in established renal failure. To determine the extent to which the guidelines for anaemia management are met in the UK. Quarterly data were obtained regarding haemoglobin (Hb) and factors that influence Hb from renal centres in England, Wales, Northern Ireland (EWNI) and the Scottish Renal Registry for the incident and prevalent renal replacement therapy (RRT) cohorts for 2010. In the UK, in 2010 53.6% of patients commenced dialysis therapy with Hb ≥ 10.0 g/dl (median Hb 10.1 g/dl). The median Hb of haemodialysis (HD) patients was 11.5 g/dl with an interquartile range (IQR) of 10.5-12.3 g/dl. Of HD patients 84.6% had Hb ≥ 10.0 g/dl. The median Hb of peritoneal dialysis (PD) patients in the UK was 11.6 g/dl (IQR 10.6-12.5 g/dl). Of UK PD patients, 87.2% had Hb ≥ 10.0 g/dl. The median ferritin in HD patients in EWNI was 444 µg/L (IQR 299-635) and 96% of HD patients had a ferritin ≥ 100 µg/L. The median ferritin in PD patients was 264 µg/L (IQR 148-426) with 86% of PD patients having a ferritin ≥ 100 µg/L. In EWNI the mean Erythropoietin Stimulating Agent (ESA) dose was higher for HD than PD patients (9,020 vs. 6,202 IU/week). Of prevalent HD patients, 52.7% had Hb ≥ 10 and ≤ 12 g/dl. Of prevalent PD patients, 54.3% had Hb 10.5-12.5 g/dl. Copyright © 2012 S. Karger AG, Basel.

Global, regional, and national trends in haemoglobin concentration and prevalence of total and severe anaemia in children and pregnant and non-pregnant women for 1995–2011: a systematic analysis of population-representative data

PubMed Central

Stevens, Gretchen A; Finucane, Mariel M; De-Regil, Luz Maria; Paciorek, Christopher J; Flaxman, Seth R; Branca, Francesco; Peña-Rosas, Juan Pablo; Bhutta, Zulfiqar A; Ezzati, Majid

2013-01-01

Summary Background Low haemoglobin concentrations and anaemia are important risk factors for the health and development of women and children. We estimated trends in the distributions of haemoglobin concentration and in the prevalence of anaemia and severe anaemia in young children and pregnant and non-pregnant women between 1995 and 2011. Methods We obtained data about haemoglobin and anaemia for children aged 6–59 months and women of childbearing age (15–49 years) from 257 population-representative data sources from 107 countries worldwide. We used health, nutrition, and household surveys; summary statistics from WHO's Vitamin and Mineral Nutrition Information System; and summary statistics reported by other national and international agencies. We used a Bayesian hierarchical mixture model to estimate haemoglobin distributions and systematically addressed missing data, non-linear time trends, and representativeness of data sources. We quantified the uncertainty of our estimates. Findings Global mean haemoglobin improved slightly between 1995 and 2011, from 125 g/L (95% credibility interval 123–126) to 126 g/L (124–128) in non-pregnant women, from 112 g/L (111–113) to 114 g/L (112–116) in pregnant women, and from 109 g/L (107–111) to 111 g/L (110–113) in children. Anaemia prevalence decreased from 33% (29–37) to 29% (24–35) in non-pregnant women, from 43% (39–47) to 38% (34–43) in pregnant women, and from 47% (43–51) to 43% (38–47) in children. These prevalences translated to 496 million (409–595 million) non-pregnant women, 32 million (28–36 million) pregnant women, and 273 million (242–304 million) children with anaemia in 2011. In 2011, concentrations of mean haemoglobin were lowest and anaemia prevalence was highest in south Asia and central and west Africa. Interpretation Children's and women's haemoglobin statuses improved in some regions where concentrations had been low in the 1990s, leading to a modest global increase in

Population-based colorectal cancer screening programmes using a faecal immunochemical test: should faecal haemoglobin cut-offs differ by age and sex?

PubMed

Arana-Arri, Eunate; Idigoras, Isabel; Uranga, Begoña; Pérez, Raquel; Irurzun, Ana; Gutiérrez-Ibarluzea, Iñaki; Fraser, Callum G; Portillo, Isabel

2017-08-29

The Basque Colorectal Cancer Screening Programme has both high participation rate and high compliance rate of colonoscopy after a positive faecal occult blood test (FIT). Although, colorectal cancer (CRC) screening with biannual (FIT) has shown to reduce CRC mortality, the ultimate effectiveness of the screening programmes depends on the accuracy of FIT and post-FIT colonoscopy, and thus, harms related to false results might not be underestimated. Current CRC screening programmes use a single faecal haemoglobin concentration (f-Hb) cut-off for colonoscopy referral for both sexes and all ages. We aimed to determine optimum f-Hb cut-offs by sex and age without compromising neoplasia detection and interval cancer proportion. Prospective cohort study using a single-sample faecal immunochemical test (FIT) on 444,582 invited average-risk subjects aged 50-69 years. A result was considered positive at ≥20 μg Hb/g faeces. Outcome measures were analysed by sex and age for a wide range of f-Hb cut-offs. We analysed 17,387 positive participants in the programme who underwent colonoscopy. Participation rate was 66.5%. Men had a positivity rate for f-Hb of 8.3% and women 4.8% (p < 0.0001). The detection rate for advanced neoplasia (cancer plus advanced adenoma) was 44.0‰ for men and 15.9‰ for women (p < 0.0001). The number of colonoscopies required decreased in both sexes and all age groups through increasing the f-Hb cut-off. However, the loss in CRC detection increased by up to 28.1% in men and 22.9% in women. CRC missed were generally at early stages (Stage I-II: from 70.2% in men to 66.3% in women). This study provides detailed outcomes in men and women of different ages at a range of f-Hb cut-offs. We found differences in positivity rates, neoplasia detection rate, number needed to screen, and interval cancers in men and women and in younger and older groups. However, there are factors other than sex and age to consider when consideration is given to setting

Erythropoiesis-stimulating agent dosing, haemoglobin and ferritin levels in UK haemodialysis patients 2005-13.

PubMed

Birnie, Kate; Caskey, Fergus; Ben-Shlomo, Yoav; Sterne, Jonathan A C; Gilg, Julie; Nitsch, Dorothea; Tomson, Charles

2017-04-01

Erythropoiesis-stimulating agents (ESAs) with intravenous iron supplementation are the main treatment for anaemia in patients with chronic kidney disease. Although observational studies suggest better outcomes for patients who achieve higher haemoglobin (Hb) levels, randomized controlled trials comparing higher and lower Hb targets have led to safety concerns over higher targets and to changes in treatment guidelines. Quarterly data from 2005 to 2013 were obtained on 28 936 haemodialysis patients from the UK Renal Registry. We examined trends in ESA use and average dose, Hb and ferritin values over time and Hb according to the UK Renal Association guideline range. The average ESA dose declined over time, with sharper decreases of epoetin seen towards the end of 2006 and from 2009. Average Hb for patients on ESAs was 114.1 g/L [95% confidence interval (CI) 113.7, 114.6] in the first quarter of 2005, which decreased to 109.6 g/L (95% CI 109.3, 109.9) by the end of 2013. Average serum ferritin was 353 µg/L (95% CI 345, 360) at the start of 2005, increasing to 386 µg/L (95% CI 380, 392) in the final quarter of 2013. The percentage of patients with Hb in the range of 100-120 g/L increased from 46.1 at the start of 2005 to 57.6 at the end of 2013. Anaemia management patterns for haemodialysis patients changed in the UK between 2005 and 2013. These patterns most likely reflect clinician response to emerging trial evidence and practice guidelines. Registries play an important role in continued observation of anaemia management and will monitor further changes as new evidence on optimal care emerges. © The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA.

Estimation of glycaemic control in the past month using ratio of glycated albumin to HbA1c.

PubMed

Musha, I; Mochizuki, M; Kikuchi, T; Akatsuka, J; Ohtake, A; Kobayashi, K; Kikuchi, N; Kawamura, T; Yokota, I; Urakami, T; Sugihara, S; Amemiya, S

2018-04-13

To evaluate comprehensively the use of the glycated albumin to HbA 1c ratio for estimation of glycaemic control in the previous month. A total of 306 children with Type 1 diabetes mellitus underwent ≥10 simultaneous measurements of glycated albumin and HbA 1c . Correlation and concordance rates were examined between HbA 1c measurements taken 1 month apart (ΔHbA 1c ) and glycated albumin/HbA 1c ratio fluctuations were calculated as Z-scores from the cohort value at enrolment of this study cohort (method A) or the percent difference from the individual mean over time (method B). Fluctuations in glycated albumin/HbA 1c ratio (using both methods) were weakly but significantly correlated with ΔHbA 1c , whereas concordance rates were significant for glycaemic deterioration but not for glycaemic improvement. Concordance rates were higher using method B than method A. The glycated albumin/HbA 1c ratio was able to estimate glycaemic deterioration in the previous month, while estimation of glycaemic improvement in the preceding month was limited. Because method B provided a better estimate of recent glycaemic control than method A, the individual mean of several measurements of the glycated albumin/HbA 1c ratio over time may also identify individuals with high or low haemoglobin glycation phenotypes in a given population, such as Japanese children with Type 1 diabetes, thereby allowing more effective diabetes management. © 2018 Diabetes UK.

Analysis of Mitochondrial haemoglobin in Parkinson's disease brain.

PubMed

Shephard, Freya; Greville-Heygate, Oliver; Liddell, Susan; Emes, Richard; Chakrabarti, Lisa

2016-07-01

Mitochondrial dysfunction is an early feature of neurodegeneration. We have shown there are mitochondrial haemoglobin changes with age and neurodegeneration. We hypothesised that altered physiological processes are associated with recruitment and localisation of haemoglobin to these organelles. To confirm a dynamic localisation of haemoglobin we exposed Drosophila melanogaster to cyclical hypoxia with recovery. With a single cycle of hypoxia and recovery we found a relative accumulation of haemoglobin in the mitochondria compared with the cytosol. An additional cycle of hypoxia and recovery led to a significant increase of mitochondrial haemoglobin (p<0.05). We quantified ratios of human mitochondrial haemoglobin in 30 Parkinson's and matched control human post-mortem brains. Relative mitochondrial/cytosolic quantities of haemoglobin were obtained for the cortical region, substantia nigra and cerebellum. In age matched post-mortem brain mitochondrial haemoglobin ratios change, decreasing with disease duration in female cerebellum samples (n=7). The change is less discernible in male cerebellum (n=18). In cerebellar mitochondria, haemoglobin localisation in males with long disease duration shifts from the intermembrane space to the outer membrane of the organelle. These new data illustrate dynamic localisation of mitochondrial haemoglobin within the cell. Mitochondrial haemoglobin should be considered in the context of gender differences characterised in Parkinson's disease. It has been postulated that cerebellar circuitry may be activated to play a protective role in individuals with Parkinson's. The changing localisation of intracellular haemoglobin in response to hypoxia presents a novel pathway to delineate the role of the cerebellum in Parkinson's disease. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Dietary determinants for Hb-acrylamide and Hb-glycidamide adducts in Danish non-smoking women.

PubMed

Outzen, Malene; Egeberg, Rikke; Dragsted, Lars; Christensen, Jane; Olesen, Pelle T; Frandsen, Henrik; Overvad, Kim; Tjønneland, Anne; Olsen, Anja

2011-05-01

Acrylamide (AA) is a probable human carcinogen that is formed in heat-treated carbohydrate-rich foods. The validity of FFQ to assess AA exposure has been questioned. The aim of the present cross-sectional study was to investigate dietary determinants of Hb-AA and Hb-glycidamide (GA) adducts. The study included 537 non-smoking women aged 50-65 years who participated in the Diet, Cancer and Health cohort (1993-97). At study baseline, blood samples and information on dietary and lifestyle variables obtained from self-administered questionnaires were collected. From blood samples, Hb-AA and Hb-GA in erythrocytes were analysed by liquid chromatography/MS/MS. Dietary determinants were evaluated by multiple linear regression analyses adjusted for age and smoking behaviour among ex-smokers. The median for Hb-AA was 35 pmol/g globin (5th percentile 17, 95th percentile 89) and for Hb-GA 21 pmol/g globin (5th percentile 8, 95th percentile 49). Of the dietary factors studied, intakes of coffee and chips were statistically significantly associated with a 4 % per 200 g/d (95 % CI 2, 7; P < 0·0001) and an 18 % per 5 g/d (95 % CI 6, 31; P = 0·002) higher Hb-AA, respectively. This model explained 17 % of the variation in Hb-AA. Intakes of coffee and biscuits/crackers were statistically significantly associated with a 3 % per 200 g/d (95 % CI 1, 6; P = 0·005) and 12 % per 10 g/d (95 % CI 3, 23; P = 0·01) higher Hb-GA, respectively. This model explained 12 % of the variation in Hb-GA. In conclusion, only a few dietary determinants of Hb-AA and Hb-GA were identified. Thus, the present study implies that dietary intake measured by an FFQ explains only to a limited extent the variation in Hb-AA and Hb-GA concentrations.

Erythropoiesis-stimulating agent dosing, haemoglobin and ferritin levels in UK haemodialysis patients 2005–13

PubMed Central

Caskey, Fergus; Ben-Shlomo, Yoav; Sterne, Jonathan A.C.; Gilg, Julie; Nitsch, Dorothea; Tomson, Charles

2017-01-01

ABSTRACT Background: Erythropoiesis-stimulating agents (ESAs) with intravenous iron supplementation are the main treatment for anaemia in patients with chronic kidney disease. Although observational studies suggest better outcomes for patients who achieve higher haemoglobin (Hb) levels, randomized controlled trials comparing higher and lower Hb targets have led to safety concerns over higher targets and to changes in treatment guidelines. Methods: Quarterly data from 2005 to 2013 were obtained on 28 936 haemodialysis patients from the UK Renal Registry. We examined trends in ESA use and average dose, Hb and ferritin values over time and Hb according to the UK Renal Association guideline range. Results: The average ESA dose declined over time, with sharper decreases of epoetin seen towards the end of 2006 and from 2009. Average Hb for patients on ESAs was 114.1 g/L [95% confidence interval (CI) 113.7, 114.6] in the first quarter of 2005, which decreased to 109.6 g/L (95% CI 109.3, 109.9) by the end of 2013. Average serum ferritin was 353 µg/L (95% CI 345, 360) at the start of 2005, increasing to 386 µg/L (95% CI 380, 392) in the final quarter of 2013. The percentage of patients with Hb in the range of 100–120 g/L increased from 46.1 at the start of 2005 to 57.6 at the end of 2013. Conclusions: Anaemia management patterns for haemodialysis patients changed in the UK between 2005 and 2013. These patterns most likely reflect clinician response to emerging trial evidence and practice guidelines. Registries play an important role in continued observation of anaemia management and will monitor further changes as new evidence on optimal care emerges. PMID:27190350

Threshold Haemoglobin Levels and the Prognosis of Stable Coronary Disease: Two New Cohorts and a Systematic Review and Meta-Analysis

PubMed Central

Shah, Anoop D.; Nicholas, Owen; Timmis, Adam D.; Feder, Gene; Abrams, Keith R.; Chen, Ruoling; Hingorani, Aroon D.; Hemingway, Harry

2011-01-01

Background Low haemoglobin concentration has been associated with adverse prognosis in patients with angina and myocardial infarction (MI), but the strength and shape of the association and the presence of any threshold has not been precisely evaluated. Methods and findings A retrospective cohort study was carried out using the UK General Practice Research Database. 20,131 people with a new diagnosis of stable angina and no previous acute coronary syndrome, and 14,171 people with first MI who survived for at least 7 days were followed up for a mean of 3.2 years. Using semi-parametric Cox regression and multiple adjustment, there was evidence of threshold haemoglobin values below which mortality increased in a graded continuous fashion. For men with MI, the threshold value was 13.5 g/dl (95% confidence interval [CI] 13.2–13.9); the 29.5% of patients with haemoglobin below this threshold had an associated hazard ratio for mortality of 2.00 (95% CI 1.76–2.29) compared to those with haemoglobin values in the lowest risk range. Women tended to have lower threshold haemoglobin values (e.g, for MI 12.8 g/dl; 95% CI 12.1–13.5) but the shape and strength of association did not differ between the genders, nor between patients with angina and MI. We did a systematic review and meta-analysis that identified ten previously published studies, reporting a total of only 1,127 endpoints, but none evaluated thresholds of risk. Conclusions There is an association between low haemoglobin concentration and increased mortality. A large proportion of patients with coronary disease have haemoglobin concentrations below the thresholds of risk defined here. Intervention trials would clarify whether increasing the haemoglobin concentration reduces mortality. Please see later in the article for the Editors' Summary PMID:21655315

Electrochemical studies on polysorbate-20 (Tween 20)-entrapped haemoglobin and its application in a hydrogen peroxide biosensor.

PubMed

Ma, Xiang; Chen, Ting; Liu, Lifang; Li, Genxi

2005-06-01

Haemoglobin (Hb) was entrapped in polysorbate 20 and then modified on a pyrolytic graphite electrode. Electrochemical studies revealed that a pair of stable and well-defined redox peaks attributed to the direct redox reaction of Hb could be observed in a phosphate buffer solution (pH 6.0). The anodic and cathodic peaks were located at -236 and -316 mV (versus a saturated calomel reference electrode) separately. The formal potential, E0', was linearly varied with pH in the range from 3.0 to 10.0 with a slope of -48.0 mV.pH-1. Moreover, the protein was capable of catalysing the reduction of H2O2. Accordingly, an unmediated biosensor for H2O2 was prepared with a linear range from 8.0x10(-7) to 1.0x10(-3) M. This biosensor exhibited good stability, sensitivity and reproducibility.

Measurements of red cell deformability and hydration reflect HbF and HbA2 in blood from patients with sickle cell anemia.

PubMed

Parrow, Nermi L; Tu, Hongbin; Nichols, James; Violet, Pierre-Christian; Pittman, Corinne A; Fitzhugh, Courtney; Fleming, Robert E; Mohandas, Narla; Tisdale, John F; Levine, Mark

2017-06-01

Decreased erythrocyte deformability, as measured by ektacytometry, may be associated with disease severity in sickle cell anemia (SCA). Heterogeneous populations of rigid and deformable cells in SCA blood result in distortions of diffraction pattern measurements that correlate with the concentration of hemoglobin S (HbS) and the percentage of irreversibly sickled cells. We hypothesize that red cell heterogeneity, as well as deformability, will also be influenced by the concentration of alternative hemoglobins such as fetal hemoglobin (HbF) and the adult variant, HbA 2 . To test this hypothesis, we investigate the relationship between diffraction pattern distortion, osmotic gradient ektacytometry parameters, and the hemoglobin composition of SCA blood. We observe a correlation between the extent of diffraction pattern distortions and percentage of HbF and HbA 2 . Osmotic gradient ektacytometry data indicate that minimum elongation in the hypotonic region is positively correlated with HbF, as is the osmolality at which it occurs. The osmolality at both minimum and maximum elongation is inversely correlated with HbS and HbA 2 . These data suggest that HbF may effectively improve surface-to-volume ratio and osmotic fragility in SCA erythrocytes. HbA 2 may be relatively ineffective in improving these characteristics or cellular hydration at the levels found in this patient cohort. Copyright © 2017. Published by Elsevier Inc.

Effects of a cinnamon extract on plasma glucose, HbA, and serum lipids in diabetes mellitus type 2.

PubMed

Mang, B; Wolters, M; Schmitt, B; Kelb, K; Lichtinghagen, R; Stichtenoth, D O; Hahn, A

2006-05-01

According to previous studies, cinnamon may have a positive effect on the glycaemic control and the lipid profile in patients with diabetes mellitus type 2. The aim of this trial was to determine whether an aqueous cinnamon purified extract improves glycated haemoglobin A1c (HbA1c), fasting plasma glucose, total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL) and triacylglycerol concentrations in patients with type 2 diabetes. A total of 79 patients with diagnosed diabetes mellitus type 2 not on insulin therapy but treated with oral antidiabetics or diet were randomly assigned to take either a cinnamon extract or a placebo capsule three times a day for 4 months in a double-blind study. The amount of aqueous cinnamon extract corresponded to 3 g of cinnamon powder per day. The mean absolute and percentage differences between the pre- and post-intervention fasting plasma glucose level of the cinnamon and placebo groups were significantly different. There was a significantly higher reduction in the cinnamon group (10.3%) than in the placebo group (3.4%). No significant intragroup or intergroup differences were observed regarding HbA1c, lipid profiles or differences between the pre- and postintervention levels of these variables. The decrease in plasma glucose correlated significantly with the baseline concentrations, indicating that subjects with a higher initial plasma glucose level may benefit more from cinnamon intake. No adverse effects were observed. The cinnamon extract seems to have a moderate effect in reducing fasting plasma glucose concentrations in diabetic patients with poor glycaemic control.

Influence of Erythropoiesis-Stimulating Agents on HbA1c and Fructosamine in Patients with Haemodialysis.

PubMed

Rasche, Franz Maximilian; Ebert, Thomas; Beckmann, Julia; Busch, Volker; Barinka, Filip; Rasche, Wilma Gertrud; Lindner, Tom H; Schneider, Jochen G; Schiekofer, Stephan

2017-06-01

HbA1c is the most accepted laboratory parameter for the long term observation of glucose control. There is still much of a debate about the use of HbA1c as a metabolic indicator in diabetic patients (DM) on haemodialysis (HD) and erythropoiesis-stimulating agent (ESA) therapy because of the altered erythrocyte turn over in patients with chronic kidney disease and haemodialysis (CKD5D). In 102 CKD5 patients with and without diabetes mellitus, we examined the dose dependent variability in HbA1c and fructosamine levels under haemodialysis and treated with epoetin α (n=48) and a new generation agent with continuous stimulation of methoxy polyethylene glycol epoetin beta (C.E.R.A.; n=54). HbA1c levels were affected by therapy with ESA treatments. ESA dose was inversely correlated with HbA1c and an escalation of 10.000 IU per week induced an estimated decrease of HbA1c of 0.6 percent. In addition, the increase of reticulocyte number as a marker for erythropoiesis was significantly inversely correlated with the increase of ΔHbA1c. ESA treatments had no such effect on the alternative metabolic parameter fructosamine. When compared, both therapeutic agents had comparable success in attaining haemoglobin (Hb) target values. C.E.R.A. showed better correlation and was more effective over a longer dose interval. Our results show that HbA1c levels in patients should be carefully interpreted based on interfering factors. Nevertheless, HbA1c is currently the most consistent parameter for use ascertaining metabolic status of patients suffering from diabetes mellitus. © Georg Thieme Verlag KG Stuttgart · New York.

From tissue iron retention to low systemic haemoglobin levels, new pathophysiological biomarkers of human abdominal aortic aneurysm.

PubMed

Martinez-Pinna, R; Lindholt, J S; Madrigal-Matute, J; Blanco-Colio, L M; Esteban-Salan, M; Torres-Fonseca, M M; Lefebvre, T; Delbosc, S; Laustsen, J; Driss, F; Vega de Ceniga, M; Gouya, L; Weiss, G; Egido, J; Meilhac, O; Michel, J-B; Martin-Ventura, J

2014-07-03

Iron deposits are observed in tissue of abdominal aortic aneurysm (AAA) patients, although the underlying mechanisms are not completely elucidated. Therefore we explored circulating markers of iron metabolism in AAA patients, and tested if they could serve as biomarkers of AAA. Increased red blood cell (RBC)-borne iron retention and transferrin, transferrin receptor and ferritin expression was observed in AAA tissue compared to control aorta (immunohistochemistry and western blot). In contrast, decreased circulating iron, transferrin, mean corpuscular haemoglobin concentration (MCHC) and haemoglobin concentration, along with circulating RBC count, were observed in AAA patients (aortic diameter >3 cm, n=114) compared to controls (aortic diameter <3 cm, n=88) (ELISA), whereas hepcidin concentrations were increased in AAA subjects (MS/MS assay). Moreover, iron, transferrin and haemoglobin levels were negatively, and hepcidin positively, correlated with aortic diameter in AAA patients. The association of low haemoglobin with AAA presence or aortic diameter was independent of specific risk factors. Moreover, MCHC negatively correlated with thrombus area in another cohort of AAA patients (aortic diameter 3-5 cm, n=357). We found that anaemia was significantly more prevalent in AAA patients (aortic diameter >5 cm, n=8,912) compared to those in patients with atherosclerotic aorto-iliac occlusive disease (n=17,737) [adjusted odds ratio=1.77 (95% confidence interval: 1.61;1.93)]. Finally, the mortality risk among AAA patients with anaemia was increased by almost 30% [adjusted hazard ratio: 1.29 (95% confidence interval: 1.16;1.44)] as compared to AAA subjects without anaemia. In conclusion, local iron retention and altered iron recycling associated to high hepcidin and low transferrin systemic concentrations could lead to reduced circulating haemoglobin levels in AAA patients. Low haemoglobin levels are independently associated to AAA presence and clinical outcome.

Improving access to HbA1c in sub-Saharan Africa (IA3) cohort: cohort profile.

PubMed

Balde, Naby; Camara, Alioune; Sobngwi-Tambekou, Joelle; Balti, Eric Vounsia; Tchatchoua, Alain; Fezeu, Leopold; Limen, Serge; Ngamani, Sylvie; Ngapout, Suzanne; Kengne, Andre Pascal; Sobngwi, Eugene

2017-01-01

Glycated haemoglobin (HbA1c) is the best surrogate of average blood glucose control in diabetic patients, and lowering HbA1c significantly reduces diabetes complications. Moreover, immediate feedback of HbA1c measurement to patients may improve control. However, HbA1c is unavailable in most parts of Africa, a continent with one of the highest burden of diabetes. To translate these evidences, we are conducting a multicentric project in 10 health care facilities in Guinea and Cameroon to evaluate the feasibility and one-year benefit of affordable HbA1c measurement with immediate feedback to patients on diabetes control and related outcomes. We consecutively enrolled patients with diabetes mellitus independently of the type of disease. We hypothesised an average 1%-decrease in HbA1c in a 1000-patient study population, with a 20% increase in the number of patients reaching treatment goals within 12 months of intervention and follow-up. A total of 1, 349 diabetic patients aged 56.2±12.6 years are enrolled (813 in Cameroon and 536 in Guinea) of whom 59.8% are women. The mean duration of diabetes is 7.4±6.3 years and baseline HbA1c is 9.7±2.6% in Guinea and 8.6±2.5% in Cameroon. To investigate whether the introduction of routine HbA1c measurement with immediate feedback to patients and provision of relevant education would improve diabetes control after one year. The impact of the intervention on diabetes associated-complications and mortality warrant further assessment in the long term.

Factors associated with high levels of glycated haemoglobin in patients with type 1 diabetes: a multicentre study in Brazil

PubMed Central

Andrade, Carine Sousa; Ribeiro, Guilherme Sousa; Santos, Carlos Antonio Souza Teles; Neves, Raimundo Celestino Silva; Moreira, Edson Duarte

2017-01-01

Objective Long-term complications of type 1 diabetes mellitus (DM1) can be prevented with adequate glycaemic control. However, high levels of glycated haemoglobin (HbA1c) occur in 60%–90% of the patients with DM1. Thus, we aimed to investigate the role of sociodemographic, behavioural and clinical factors on the HbA1c levels of patients with DM1 in Brazil. Design, setting and participants A cross-sectional study was conducted in ambulatory patients with DM1 aged ≥18 years from 10 Brazilian cities. Sociodemographic, behavioural and clinical data were obtained through interviews. Main outcome measures HbA1c level was measured by liquid chromatography. Hierarchical multiple variable linear regression models were used to identify factors correlated with high levels of HbA1c. Results Of 979 patients with DM1, 63.8% were women, and the mean age was 40 (SD 14.6) years. The mean HbA1c level was 9.4% (SD 2.2%), and 89.6% of the patients had HbA1c ≥7.0%. Factors independently correlated with increased HbA1c levels included: lower education, non-participation in diabetes classes/lecture during the year before, having a self-perception of poor adherence to diet and insulin, not having private medical care and not measuring the HbA1c levels in the prior year. Of note, poor adherence to diet and insulin were the independent factors most strongly associated with high levels of HbA1c (mean increment in HbA1c levels of 0.88% and 1.25%, respectively). Conclusion Poor glycaemic control, which is common among Brazilian patients with DM1, is associated with lower education, self-perception of insufficient adherence to diet and insulin and inadequate monitoring of HbA1c levels. Specific actions, particularly those targeting improving adherence to diet and insulin, may contribute to successful management of patients with DM1. PMID:29247092

Impact of demographics and disease progression on the relationship between glucose and HbA1c.

PubMed

Claussen, Anetta; Møller, Jonas B; Kristensen, Niels R; Klim, Søren; Kjellsson, Maria C; Ingwersen, Steen H; Karlsson, Mats O

2017-06-15

Several studies have shown that the relationship between mean plasma glucose (MPG) and glycated haemoglobin (HbA1c) may vary across populations. Especially race has previously been referred to shift the regression line that links MPG to HbA1c at steady-state (Herman & Cohen, 2012). To assess the influence of demographic and disease progression-related covariates on the intercept of the estimated linear MPG-HbA1c relationship in a longitudinal model. Longitudinal patient-level data from 16 late-phase trials in type 2 diabetes with a total of 8927 subjects was used to study covariates for the relationship between MPG and HbA1c. The analysed covariates included age group, BMI, gender, race, diabetes duration, and pre-trial treatment. Differences between trials were taken into account by estimating a trial-to-trial variability component. Participants included 47% females and 20% above 65years. 77% were Caucasian, 9% were Asian, 5% were Black and the remaining 9% were analysed together as other races. Estimates of the change in the intercept of the MPG-HbA1c relationship due to the mentioned covariates were determined using a longitudinal model. The analysis showed that pre-trial treatment with insulin had the most pronounced impact associated with a 0.34% higher HbA1c at a given MPG. However, race, diabetes duration and age group also had an impact on the MPG-HbA1c relationship. Our analysis shows that the relationship between MPG and HbA1c is relatively insensitive to covariates, but shows small variations across populations, which may be relevant to take into account when predicting HbA1c response based on MPG measurements in clinical trials. Copyright © 2017 Elsevier B.V. All rights reserved.

Evaluation of haemoglobin in blister fluid as an indicator of paediatric burn wound depth.

PubMed

Tanzer, Catherine; Sampson, Dayle L; Broadbent, James A; Cuttle, Leila; Kempf, Margit; Kimble, Roy M; Upton, Zee; Parker, Tony J

2015-08-01

The early and accurate assessment of burns is essential to inform patient treatment regimens; however, this first critical step in clinical practice remains a challenge for specialist burns clinicians worldwide. In this regard, protein biomarkers are a potential adjunct diagnostic tool to assist experienced clinical judgement. Free circulating haemoglobin has previously shown some promise as an indicator of burn depth in a murine animal model. Using blister fluid collected from paediatric burn patients, haemoglobin abundance was measured using semi-quantitative Western blot and immunoassays. Although a trend was observed in which haemoglobin abundance increased with burn wound severity, several patient samples deviated significantly from this trend. Further, it was found that haemoglobin concentration decreased significantly when whole cells, cell debris and fibrinous matrix was removed from the blister fluid by centrifugation; although the relationship to depth was still present. Statistical analyses showed that haemoglobin abundance in the fluid was more strongly related to the time between injury and sample collection and the time taken for spontaneous re-epithelialisation. We hypothesise that prolonged exposure to the blister fluid microenvironment may result in an increased haemoglobin abundance due to erythrocyte lysis, and delayed wound healing. Copyright © 2015 Elsevier Ltd and ISBI. All rights reserved.

HPLC-ESI-MS/MS analysis of hemoglobin peptides in tryptic digests of dried-blood spot extracts detects HbS, HbC, HbD, HbE, HbO-Arab, and HbG-Philadelphia mutations.

PubMed

Haynes, Christopher A; Guerra, Stephanie L; Fontana, Jessalyn C; DeJesús, Víctor R

2013-09-23

Hemoglobinopathies are mutations resulting in abnormal globin chain structure; some have clinically significant outcomes such as anemia or reduced lifespan. Five β-globin mutations are (c.20A>T, p.E6V), (c.19G>A, p. E6K), (c.79G>A, p.E26K), (c.364G>C, p.E121Q), and (c.364G>A, p.E121K), resulting in HbS (sickle-cell hemoglobin), HbC, HbE, HbD-Los Angeles, and HbO-Arab, respectively. One α-globin mutation is (c.[207C>G or 207C>A], p.N68K), resulting in HbG-Philadelphia. HPLC-ESI-MS/MS analysis of dried-blood spot (DBS) punches from newborns extracted with a trypsin-containing solution provides greater than 90% coverage of α-, β-, and γ-globin amino acid sequences. Because the (c.20A>T, p.E6V), (c.19G>A, p. E6K), (c.79G>A, p.E26K), (c.364G>C, p.E121Q), (c.364G>A, p.E121K), and (c.[207C>G or 207C>A], p.N68K) mutations generate globin peptides with novel amino acid sequences, detecting one of these peptides in DBS extracts is indicative of the presence of a hemoglobinopathy in the newborn. The method described here can distinguish normal β-globin peptides from the mutant HbS, HbC, HbE, HbD-Los Angeles and HbO-Arab peptides, as well as normal α-globin peptide from the mutant HbG-Philadelphia peptide, allowing the identification of unaffected heterozygotes such as HbAS, and of compound heterozygotes such as HbASG-Philadelphia. This HPLC-ESI-MS/MS analytical approach provides information that is not available from traditional hemoglobin analyses such as isoelectric focusing and HPLC-UV. It is also capable of determining the amino acid sequence of hemoglobin peptides, potentially allowing the detection of numerous hemoglobinopathies resulting from point mutations. Published by Elsevier B.V.

Complete factorial design to adjust pH and sugar concentrations in the inoculum phase of Ralstonia solanacearum to optimize P(3HB) production

PubMed Central

Alves, Mariane Igansi; Rodrigues, Amanda Ávila; Furlan, Lígia; da Silva Rodrigues, Rosane; Diaz de Oliveira, Patrícia; Vendruscolo, Claire Tondo; da Silveira Moreira, Angelita

2017-01-01

Poly(3-hydroxybutyrate) (P(3HB)) is a biodegradable plastic biopolymer that accumulates as lipophilic inclusions in the cytoplasm of some microorganisms. The biotechnological process by which P(3HB) is synthesized occurs in two phases. The first phase involves cell growth in a complex culture medium, while the second phase involves polymer accumulation in the presence of excess carbon sources. As such, the efficiency of the second phase depends on the first phase. The aim of this study was to evaluate culture media with different concentrations of sucrose and glucose and different pH values in the inoculum phase of Ralstonia solanacearum RS with the intention of identifying methods by which the biomass yield could be increased, subsequently enhancing the yield of P(3HB). The culture medium was formulated according to the experimental planning type of central composite rotational design 22. The independent variables were pH and sugar concentration (sucrose and glucose), and the dependent variables were OD600nm, dry cell weight (DCW), and P(3HB) yield. The highest cell growth, estimated by the OD600nm (20.6) and DCW (5.35) values, was obtained when sucrose was used in the culture medium at a concentration above 35 g.L-1 in combination with an acidic pH. High polymer (45%) accumulation was also achieved under these conditions. Using glucose, the best results for OD600nm (12.5) and DCW (2.74) were also obtained at acidic pH but with a sugar concentration at the minimum values evaluated. Due to the significant accumulation of polymer in the cells that were still in the growth phase, the accumulating microorganism P(3HB) Ralstonia solanacearum RS can be classified as having type II metabolism in relation to the polymer accumulation phase, which is different from other Ralstonia spp. studied until this time. PMID:28704411

Study on the interaction between typical phthalic acid esters (PAEs) and human haemoglobin (hHb) by molecular docking.

PubMed

Tan, Songwen; Wang, Donglin; Chi, Zhenxing; Li, Weiguo; Shan, Ye

2017-07-01

This work has evaluated the binding force between hHb and typcial PAEs (DMP, DEP, DPRP, DBP, DIBP, DHP and DPHP) using molecule docking technique. The DPHP with 3 aromatic rings has the strongest binding (-ΔG binding : 6.0kcalmol -1 ) than other PAEs (-ΔG binding : 2.91∼4.48kcalmol -1 ). The DMP with the lowest molecular weight has a high binding force (-ΔG binding : 4.48kcalmol -1 ), while the DHP with the highest molecular weight has the lowest binding force (-ΔG binding : 2.91kcalmol -1 ). When the length of side chain increases, the binding force trend to decrease, regarding the VDW forces and H-bonding. The lgK ow -ΔG binding plotting figure shows that a higher K ow value is accompanied by a lower binding force. The aromatic ring existed in PAEs largely increases the binding force between the hHb and the PAEs. On the other hand, the PAEs with higher number of carbon, meaning a higher hydrophobicity, can enter into the hydrophobic space of hHb centre deeper and bond to different position. The aromatic ring decreases the depth of binding position in the hydrophobic space. This work provides basic data and a theoretical method to assess the transport and accumulation of PAEs in human body, and the cytotoxicity of PAEs to hBRCs. Copyright © 2017 Elsevier B.V. All rights reserved.

Target haemoglobin to aim for with erythropoiesis-stimulating agents: a position statement by ERBP following publication of the Trial to reduce cardiovascular events with Aranesp therapy (TREAT) study.

PubMed

Locatelli, Francesco; Aljama, Pedro; Canaud, Bernard; Covic, Adrian; De Francisco, Angel; Macdougall, Iain C; Wiecek, Andrzej; Vanholder, Raymond

2010-09-01

The European Renal Best Practice (ERBP), which are issued by ERA-EDTA, are suggestions for clinical practice in areas in which evidence is lacking or weak, together with position statements on recently published randomized controlled trials, or on existing guidelines and recommendations. In 2009, the Anaemia Working Group of ERBP published its first position statement about the haemoglobin target to aim for with erythropoietin-stimulating agents (ESA) and on issues that were not covered by K-DOQI in 2006-07. This second position paper of the group follows the publication of the Trial to Reduce Cardiovascular Events with Aranesp Therapy (TREAT) Study. This multi-centre, placebo-controlled trial compared cardiovascular and renal outcomes in 4038 patients with type 2 diabetes, chronic kidney disease not on dialysis, and anaemia who were randomized to complete anaemia correction (haemoglobin target of 13 g/dL using darbepoetin alpha) or placebo (with a haemoglobin rescue value of 9 g/dL). Following the findings of the TREAT study, the Anaemia Working Group of ERBP maintains its view that 'Hb values of 11-12 g/dL should be generally sought in the CKD population without intentionally exceeding 13 g/dL' and that the doses of ESA therapy to achieve the target haemoglobin should also be considered. More caution is suggested when treating anaemia with ESA therapy in patients with type 2 diabetes not undergoing dialysis (and probably in diabetics at all CKD stages). In those with ischaemic heart disease or with a previous history of stroke, possible benefits should be weighed up against an increased risk of stroke recurrence, when deciding which Hb level to aim for. These recommendations are not intended to represent a new guideline as they are not the result of a systematic review of the evidence.

Effects of hemoglobin variants HbJ Bangkok, HbE, HbG Taipei, and HbH on analysis of glycated hemoglobin via ion-exchange high-performance liquid chromatography.

PubMed

Zhang, Xiu-Ming; Wen, Dong-Mei; Xu, Sheng-Nan; Suo, Ming-Huan; Chen, Ya-Qiong

2018-01-01

To explore the effects of HbJ Bangkok, HbE, HbG Taipei, and α-thalassemia HbH on the results of HbA1c assessment using ion-exchange high-performance liquid chromatography (IE-HPLC). We enrolled five patients in which the results of the IE-HPLC HbA1c assay were inconsistent with the average levels of FBG. We performed hemoglobin capillary (Hb) electrophoresis using whole-blood samples. We also sequenced the genes encoding Hb using dideoxy-mediated chain termination and analyzed HbA1c using borate affinity HPLC (BA-HPLC) and turbidimetric inhibition immunoassay (TINIA). Two patients had the HbJ Bangkok variant. Hb genotypes of these patients were β 41-42 /β J Bangkok and β N /β J Bangkok , and the content of HbJ Bangkok was 93.9% and 52.4%, respectively. The remaining three patients had the following: HbE (β N /β E Hb genotype, 23.6% HbE content), HbG Taipei (β N /β G Taipei Hb genotype, 39.4% HbG Taipei content), and α-thalassemia HbH (6.1% HbH content, 2.8% Hb Bart's content). In the patients with β-thalassemia and HbJ Bangkok variants, the presence of the variants interfered with the results of HbA1c analyses using IE-HPLC and TINIA; in the remaining four patients, there was interference with the results of HbA1c IE-HPLC but not with the TINIA assay. There was no interference with BA-HPLC HbA1c results. HbJ Bangkok, HbE, HbG Taipei Hb, and α-thalassemia HbH disease cause varying degrees of interference with the analysis of HbA1c using IE-HPLC. In these patients, we suggest using methods free from such interference for the analysis of HbA1c and other indicators to monitor blood glucose levels. © 2017 Wiley Periodicals, Inc.

Metabolic and Cardiovascular Ageing Indices in Relation to Glycated Haemoglobin in Healthy and Diabetic Subjects.

PubMed

Suvarna H I, Shruthi; Moodithaya, Shailaja; Sharma, Raghava

2017-01-01

Ageing is a natural phenomenon that has tremendous amount of control over normal physiological functions. Diabetes mellitus and ageing share common symptoms like stiffness and loss of functioning of tissues due to cross-liked proteins and free radicals. Glycated Haemoglobin (HbA1c) is often used as a stable cumulative index of glycemic control and has shown that even in non-diabetic adults, there is a steady increase in HbA1c levels with age. Aim of the study is to evaluate the strength of association of HbA1c with metabolic and cardiovascular ageing indices in subjects between the age group of 40 to 60 yrs. A total of 220 subjects, with (n=110) and without (n=110) diabetes were assessed for the metabolic and cardiovascular ageing indices. BMI, waist hip ratio, fat percentage, Fasting blood sugar and HbA1c were assessed as metabolic ageing indices. The cardiovascular ageing indices measured were resting heart rate, blood pressure and heart rate variability. Ageing indices were compared between subjects with and without diabetes using independent' t' test and showed that the T2DM group exhibit significant accelerated ageing as compared to that of the controls. Pearson's and partial correlation coefficient was used to assess the association of HbA1c with the ageing indices without and with controlling for chronological age, indicated that, strength of association of levels of HBA1c with cardiovascular and other metabolic indices of ageing is statistically significant. The study concludes that the tightness of glycemic control has a significant impact on the biological ageing process. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Higher haemoglobin levels and dedicated trauma admission are associated with survival after severe traumatic brain injury.

PubMed

Baltazar, Gerard Anthony; Pate, Amy J; Panigrahi, Benita; Sharp, Audrey; Smith, Michael; Chendrasekhar, Akella

2015-01-01

Prevention of secondary brain injury is a key component of acute management of patients with severe traumatic brain injury (TBI). Haemoglobin concentration may have an impact on optimization of cerebral oxygenation. Patients with TBI may best be served by an organized trauma service. The objective is to determine if haemoglobin concentration or dedicated trauma admission has an impact on outcomes after severe TBI. This study retrospectively analysed consecutive patients with severe TBI admitted to a level-I trauma centre over 3 years. Patients <16 years-old and with length of stay (LOS) <24 hours were excluded. Data were collected on demographics; injury severity; LOS; admission service; survival to discharge; and haemoglobin levels from hospital days 1-7. Data were also collected on number of transfusions of packed red blood cells. The sample was stratified based on admission service and survival to discharge. Of 147 patients (age = 54.1 ± 3.7 years), overall mortality rate was 15.4% (n = 23). Overall, non-survivors had lower daily and 7-day mean haemoglobin levels (10.7 ± 0.9 vs. 12.9 ± 0.4 g dL(-1), p < 0.001). Non-surgical admissions had lower haemoglobin levels and a higher mortality rate (28.9% vs. 12.2%, p < 0.001) compared to dedicated trauma admissions. Among patients with severe TBI, higher haemoglobin levels and maintenance as a dedicated trauma admission are associated with higher survival to discharge.

Evaluation of a New Technique for iFOBT Utilising a New Sample Collection Device with Increased Buffer Stability.

PubMed

Bruns-Toepler, Markus; Hardt, Philip

2017-07-01

The aims of the present study were: (i) Evaluate specificity and sensitivity of Hb Smart enzyme-linked immunosorbent assay (ELISA) (ScheBo Biotech) compared to colonoscopy results and (ii) assess stability of a new sample collection device containing a newly formulated buffer to extract haemoglobin using buffer and stool samples spiked with defined concentrations of haemoglobin. Stool samples were quantified with the ELISA method. The stability of haemoglobin in the extraction buffer and in native stool samples, respectively, was determined daily by ELISA during storage for 5 days at 4°C and at room temperature after addition of haemoglobin. Haemoglobin ELISA had a sensitivity of 78.4% for detection of CRC with a specificity of 98%. Haemoglobin extracted in corresponding extraction buffer demonstrated stability throughout storage for 5 days at 4°C and at room temperature. Hb Smart represents a very promising tool for large-scale screening of CRC with regard to sample handling, stability and analysis of haemoglobin in faeces. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Right Dorsolateral Frontal Lobe N-Acetyl Aspartate and Myoinositol Concentration Estimation in Type 2 Diabetes with Magnetic Resonance Spectroscopy.

PubMed

Nagothu, Rajani Santhakumari; Reddy, Yogananda Indla; Rajagopalan, Archana; Varma, Ravi

2015-07-01

Chronic hyperglycaemia in type 2 diabetes, effects the central nervous system by altering the concentrations of brain metabolites like N-acetyl aspartate (NAA) and myoinositol (mI), which are indicators of neuronal integrity and glial cell damage respectively. Dorsolateral frontal lobe is associated with aspects of cognition especially right frontal lobe is involved in episodic memory retrieval, ninety percent of the diabetic cases are type 2 in nature globally and yoga is very effective in stabilizing the brain metabolites by bringing the blood glucose levels to near or within the physiological range in type 2 diabetes. The aim of the study was to observe the effects of yogasana and pranayama on glycosilated haemoglobin (HbA1c) levels and right dorsolateral frontal cortical NAA and mI concentration in type 2 diabetic subjects. It's a case control study. Sixty eight type 2 diabetic subjects of both the sex, aged between 35-65 years are included in the study, subjects are divided in to test and control group 34 each. Test group subjects did the yogasana and pranayama for a period of 6 months, 6 days in a week, 45-60 minutes daily under the supervision of a qualified yoga teacher. Control group subjects are not on any specific exercise regimen. Both the group subjects are taking oral hypoglycaemic agents. HbA1c levels are measured using the Bio-Rad D-10™ haemoglobin A1c program and Magnetic Resonance Spectroscopy (MRS) is used in assessing the metabolite concentrations. Analysis of data was done by using unpaired t-test. P-value for HbA1c level is <0.001, which is highly significant statistically. P-value for NAA was < 0.02 and for myoinositol was < 0.01, which are statistically significant. HbA1c levels in control and test group subjects are 7.7 ± 1.84 and 6.02 ± 0.46 respectively. NAA concentrations in the right dorsolateral frontal lobe of control and test group are 1.44 ± 0.15 and 1.54 ± 0.19 respectively. The mI concentrations in the right dorsolateral

Molecular analysis of Hb Q-H disease and Hb Q-Hb E in a Singaporean family.

PubMed

Tan, J; Tay, J S; Wong, Y C; Kham, S K; Bte Abd Aziz, N; Teo, S H; Wong, H B

1995-01-01

Hb Q (alpha 74Asp-His) results from a mutation in the alpha-gene such that abnormal alpha Q-chains are synthesized. The alpha Q-chains combine with the normal Beta A-chains to form abnormal Hb alpha 2Q beta 2A (Hb Q). Hb Q-H disease is rare, and has been reported only in the Chinese. We report here a Chinese family, were the mother diagnosed with Hb Q-H disease and the father with Hb E heterozygosity and a child with Hb Q-E-thalassemia. Thalassemia screening of the mother's blood revealed a Hb level of 6.8g/dl with low MCV and MCH. Her blood film was indicative of thalassemia. Cellulose acetate electrophoresis showed Hb H and Hb Q with the absence of Hb A. Globin chain biosynthesis was carried out and alpha Q- and beta-chains were detected. Normal alpha- chains were absent. Digestion of the mother's DNA with Bam HI and Bgl II followed by hybridization with the 1.5 kb alpha-Pst probe showed a two alpha-gene deletion on one chromosome and the -alpha Q chain mutant with the -alpha 4.2 defect on the other chromosome. DNA amplification studies indicated the two-gene deletion to be of the -SEA/ defect. The patient was concluded to possess Hb Q-H disease (--SEA/-alpha 4.2Q). Cellulose acetate electrophoresis of the father's blood showed the presence of Hb A, F and E. Molecular analysis of the father's DNA confirmed an intact set of alpha-genes (alpha alpha/alpha alpha). Globin chain biosynthesis of fetal blood of their child showed gamma, beta A, beta E, alpha A and alpha Q-chains. Molecular analysis of the child's DNA showed one alpha-gene deletion, thus giving a genotype of alpha alpha/-alpha 4.2Q beta beta E.

Faecal haemoglobin concentration influences risk prediction of interval cancers resulting from inadequate colonoscopy quality: analysis of the Taiwanese Nationwide Colorectal Cancer Screening Program

PubMed Central

Chiu, Sherry Yueh-Hsia; Chuang, Shu-Ling; Chen, Sam Li-Sheng; Yen, Amy Ming-Fang; Fann, Jean Ching-Yuan; Chang, Dun-Cheng; Lee, Yi-Chia; Wu, Ming-Shiang; Chou, Chu-Kuang; Hsu, Wen-Feng; Chiou, Shu-Ti; Chiu, Han-Mo

2017-01-01

Objectives Interval colorectal cancer (CRC) after colonoscopy may affect effectiveness and cost-effectiveness of screening programmes. We aimed to investigate whether and how faecal haemoglobin concentration (FHbC) of faecal immunochemical testing (FIT) affected the risk prediction of interval cancer (IC) caused by inadequate colonoscopy quality in a FIT-based population screening programme. Design From 2004 to 2009, 29 969 subjects underwent complete colonoscopy after positive FIT in the Taiwanese Nationwide CRC Screening Program. The IC rate was traced until the end of 2012. The incidence of IC was calculated in relation to patient characteristics, endoscopy-related factors (such adenoma detection rate (ADR)) and FHbC. Poisson regression analysis was performed to assess the potential risk factors for colonoscopy IC. Results One hundred and sixty-two ICs developed after an index colonoscopy and the estimated incidence was 1.14 per 1000 person-years of observation for the entire cohort. Increased risk of IC was most remarkable in the uptake of colonoscopy in settings with ADR lower than 15% (adjusted relative risk (aRR)=3.09, 95% CI 1.55 to 6.18) and then higher FHbC (μg Hb/g faeces) (100–149: aRR=2.55, 95% CI 1.52 to 4.29, ≥150: aRR=2.74, 95% CI 1.84 to 4.09) with adjustment for older age and colorectal neoplasm detected at baseline colonoscopy. Similar findings were observed for subjects with negative index colonoscopy. Conclusions Colonoscopy ICs arising from FIT-based population screening programmes were mainly influenced by inadequate colonoscopy quality and independently predicted by FHbC that is associated with a priori chance of advanced neoplasm. This finding is helpful for future modification of screening logistics based on FHbC. PMID:26515543

Financial strain, inflammatory factors, and haemoglobin A1c levels in African American women.

PubMed

Cutrona, Carolyn E; Abraham, William T; Russell, Daniel W; Beach, Steven R H; Gibbons, Frederick X; Gerrard, Meg; Monick, Martha; Philibert, Robert

2015-09-01

Type 2 diabetes disproportionately affects African American women, a population exposed to high levels of stress, including financial strain (Centers for Disease Control & Prevention, 2011, http://www.cdc.gov/diabetes/pubs/pdf/ndfs_2011.pdf). We tested a mediational model in which chronic financial strain among African American women contributes to elevated serum inflammation markers, which, in turn, lead to increased haemoglobin A1C (HbA1c) levels and risk for type 2 diabetes. We assessed level of financial strain four times over a 10-year period and tested its effect on two serum inflammation markers, C-reactive protein (CRP) and soluble interleukin-6 receptor (sIL-6R) in year 11 of the study. We tested the inflammation markers as mediators in the association between chronic financial strain and HbA1c, an index of average blood glucose level over several months. Data were from 312 non-diabetic African American women from the Family and Community Health Study (FACHS; Cutrona et al., 2000, J. Pers. Soc. Psychol., 79, 1088). Chronic financial strain predicted circulating sIL-6R after controlling for age, BMI, health behaviours, and physical health measures. In turn, sIL-6R significantly predicted HbA1c levels. The path between chronic financial strain and HbA1c was significantly mediated by sIL-6R. Contrary to prediction, CRP was not predicted by chronic financial strain. Results support the role of inflammatory factors in mediating the effects of psychosocial stressors on risk for type 2 diabetes. Findings have implications for interventions that boost economic security and foster effective coping as well as medical interventions that reduce serum inflammation to prevent the onset of type 2 diabetes. © 2014 The British Psychological Society.

An evaluation of the HemoCue for measuring haemoglobin in field studies in Jamaica.

PubMed Central

Hudson-Thomas, M.; Bingham, K. C.; Simmons, W. K.

1994-01-01

The HemoCue system utilizes the principle of oxidation of haemoglobin to hemiglobin by sodium nitrite and the subsequent conversion of hemiglobin to hemiglobinazide by sodium azide. The reagents for these reactions are contained within a small disposable microcuvette of approximately 10 microliters in volume. A venous or capillary sample is introduced into the microcuvette by capillary action and, after reaction with the reagents, the absorbance is read in the HemoCue photometer at 565 and 880 nm. The haemoglobin concentration is then displayed as a digital reading, in either g/dl or mmol/l in 15-45 seconds. We compared haemoglobin values obtained by the HemoCue system with those from the Coulter Counter S-Plus IV in 366 pregnant women in urban Jamaica, and found a highly significant correlation (r = 0.78, P < 0.01). However, because of the convenience and ease of use of this instrument and considering the relatively high cost, we recommend it for use only as a research tool in field studies where accurate and rapid haemoglobin determinations are required. PMID:8062400

Thyroid Status in Children with Transfusion Dependent Hb-E β-Thalassaemia.

PubMed

Sharmin, T; Mollah, A H; Morshed, A A; Chowdhury, M K

2018-04-01

Despite improved haematological care, multi-endocrine dysfunction is a common complication in thalassemia. Iron overload is thought to be the most likely mechanism in thyroid dysfunction in these patients. Moreover, chronic tissue hypoxia might havedirect toxic effect on thyroid gland resulting in hypothyroidism. This study was designed to evaluate the thyroid status of children with Hb-E β-thalassemia. This cross sectional analytic study was conducted among thepatients with Hb-E β-thalassemia attending both in-patient & out-patient department of Paediatrics, Dhaka Medical College & Hospital, Dhaka, Bangladesh from April 2012 to March 2013. The children who attended inpatient and outpatient department of Paediatrics for some other illness were screened out for thalassaemia and were recruited as comparison group. Thyroid function tests (TSH & FT₄ level) were performed in both thalassaemic patients and comparison group. Serum ferritin level was also measured for assessing iron status of thalassaemic patients and their pre-transfusion Hb levels were recorded in the pre-formed data collection form. Of the 50 thalassaemia patients, 13(26%) had subclinical hypothyroidism. This proportion of subclinical hypothyroidism was significantly high, compared to that (2.5%) of non thalassaemia comparison group. Among the subclinically hypothyroid thalassaemia subjects, 8 were males and 5 were females and their mean age was 102.38±33.29 months. The mean serum ferritin levels in hypothyroid and euthyroid thalassaemia cases were 2387.87±1642.85ng/ml and 1822.95±1345.33ng/ml respectively (normal level upto 300ng/ml). This difference was not statistically significant (p=0.279); but the pre-transfusion Hb level wasfound significantly different (p=0.02) among the two groups. It was 5.57±0.98g/dl in hypothyroid & 6.37±0.09g/dl in euthyroid thalassaemic cases. Subclinical hypothyroidism was quite high among the children with transfusion dependent Hb-E β-thalassaemia. Their

HbA1c Measured in Stored Erythrocytes Is Positively Linearly Associated with Mortality in Individuals with Diabetes Mellitus

PubMed Central

Sluik, Diewertje; Boeing, Heiner; Montonen, Jukka; Kaaks, Rudolf; Lukanova, Annekatrin; Sandbaek, Annelli; Overvad, Kim; Arriola, Larraitz; Ardanaz, Eva; Saieva, Calogero; Grioni, Sara; Tumino, Rosario; Sacerdote, Carlotta; Mattiello, Amalia; Spijkerman, Annemieke M. W.; van der A, Daphne L.; Beulens, Joline W. J.; van Dieren, Susan; Nilsson, Peter M.; Groop, Leif C.; Franks, Paul W.; Rolandsson, Olov; Bueno-de-Mesquita, Bas; Nöthlings, Ute

2012-01-01

Introduction Observational studies have shown that glycated haemoglobin (HbA1c) is related to mortality, but the shape of the association is less clear. Furthermore, disease duration and medication may modify this association. This observational study explored the association between HbA1c measured in stored erythrocytes and mortality. Secondly, it was assessed whether disease duration and medication use influenced the estimates or were independently associated with mortality. Methods Within the European Prospective Investigation into Cancer and Nutrition a cohort was analysed of 4,345 individuals with a confirmed diagnosis of diabetes at enrolment. HbA1c was measured in blood samples stored up to 19 years. Multivariable Cox proportional hazard regression models for all-cause mortality investigated HbA1c in quartiles as well as per 1% increment, diabetes medication in seven categories of insulin and oral hypoglycaemic agents, and disease duration in quartiles. Results After a median follow-up of 9.3 years, 460 participants died. Higher HbA1c was associated with higher mortality: Hazard Ratio for 1%-increase was 1.11 (95% CI 1.06, 1.17). This association was linear (P-nonlinearity =0.15) and persistent across categories of medication use, disease duration, and co-morbidities. Compared with metformin, other medication types were not associated with mortality. Longer disease duration was associated with mortality, but not after adjustment for HbA1c and medication. Conclusion This prospective study showed that persons with lower HbA1c had better survival than those with higher HbA1c. The association was linear and independent of disease duration, type of medication use, and presence of co-morbidities. Any improvement of HbA1c appears to be associated with reduced mortality risk. PMID:22719972

The effect of 2,3-diphosphoglycerate on the oxygen dissociation curve of human haemoglobin.

PubMed Central

Goodford, P J; Norrington, F E; Paterson, R A; Wootton, R

1977-01-01

1. Oxygen dissociation curves for concentrated human haemoglobin solutions (1.6 mmol dm-3 in haem) have been measured by mixing known quantities of oxy- and deoxyhaemoglobin solutions and measuring the resulting partial pressure of oxygen with an oxygen electrode. 2. Observations in the presence of 2,3-diphosphoglycerate support previous conclusions derived from experiments at low haemoglobin concentrations, the validity of which has been questioned. 3. The two affinity state model of Monod, Wyman & Changeux (1965) does not fully describe the actions of 2,3-diphosphoglycerate and a model in which this allosteric effector not only binds preferentially to the T state but also lowers the oxygen affinity of this state gives an improved fit to the data. PMID:604451

Non-symbiotic haemoglobins-What's happening beyond nitric oxide scavenging?

PubMed

Hill, Robert D

2012-01-01

Non-symbiotic haemoglobins have been an active research topic for over 30 years, during which time a considerable portfolio of knowledge has accumulated relative to their chemical and molecular properties, and their presence and mode of induction in plants. While progress has been made towards understanding their physiological role, there remain a number of unanswered questions with respect to their biological function. This review attempts to update recent progress in this area and to introduce a hypothesis as to how non-symbiotic haemoglobins might participate in regulating hormone signal transduction. Advances have been made towards understanding the structural nuances that explain some of the differences in ligand association characteristics of class 1 and class 2 non-symbiotic haemoglobins. Non-symbiotic haemoglobins have been found to function in seed development and germination, flowering, root development and differentiation, abiotic stress responses, pathogen invasion and symbiotic bacterial associations. Microarray analyses under various stress conditions yield uneven results relative to non-symbiotic haemoglobin expression. Increasing evidence of the role of nitric oxide (NO) in hormone responses and the known involvement of non-symbiotic haemoglobins in scavenging NO provide opportunities for fruitful research, particularly at the cellular level. Circumstantial evidence suggests that non-symbiotic haemoglobins may have a critical function in the signal transduction pathways of auxin, ethylene, jasmonic acid, salicylic acid, cytokinin and abscisic acid. There is a strong need for research on haemoglobin gene expression at the cellular level relative to hormone signal transduction.

ARHGAP18 is a novel gene under positive natural selection that influences HbF levels in β-thalassaemia.

PubMed

He, Yunyan; Luo, Jianming; Chen, Yang; Zhou, Xiaoheng; Yu, Shanjuan; Jin, Ling; Xiao, Xuan; Jia, Siyuan; Liu, Qiang

2018-02-01

Foetal haemoglobin (HbF) plays a dominant role in ameliorating the morbidity and mortality of β-thalassaemia. A better understanding of the loci and genes involved in HbF expression would be beneficial for the treatment of β-thalassaemia major. However, the genes associated with HbF expression remain largely unknown. In this study, we first explored large-scale data sets and examined the human genome for evidence of positive natural selection to screen out single nucleotide polymorphisms (SNPs). A genetic analysis of HbF levels was conducted in a Chinese cohort of patients with β-thalassaemia to confirm the bioinformatics results. A total of 1141 subjects with β-thalassaemia were recruited. The results showed that the SNP rs11759328 in the ARHGAP18 gene was significantly associated with HbF levels (Ρ = 5.1 × 10 -4 ). ARHGAP18 belongs to the RhoGAP family and controls angiogenesis, cellular morphology and motility. Second, after determining that ARHGAP18 was highly expressed in the human K562 cell line, we used lentiviral-mediated small interfering RNA to knock down ARHGAP18 expression and subsequently assessed cell proliferation and apoptosis using cell proliferation assays and flow cytometry, respectively. ARHGAP18 downregulation in K562 cells significantly increased HBG1/2 expression and apoptosis, but proliferation was not significantly affected in vitro. Our data suggest that ARHGAP18, which was located by the SNP rs11759328 via positive selection, plays a potential role in regulating HbF expression in β-thalassaemia and may be a promising therapeutic target. Knockout studies of ARHGAP18 warrant further investigation into its aetiology in HbF.

Plasma zinc, vitamin B(12) and α-tocopherol are positively and plasma γ-tocopherol is negatively associated with Hb concentration in early pregnancy in north-west Bangladesh.

PubMed

Shamim, Abu Ahmed; Kabir, Alamgir; Merrill, Rebecca D; Ali, Hasmot; Rashid, Mahbubur; Schulze, Kerry; Labrique, Alain; West, Keith P; Christian, Parul

2013-08-01

The objective of the current analysis was to explore the association of multiple micronutrients with Hb concentration among pregnant women in a South Asian setting, a topic that has not been adequately explored. Sociodemographic, anthropometric and micronutrient status (plasma ferritin, transferrin receptor, retinol, a- and g-tocopherol, folate, vitamin B12, Zn) and Hb concentration were assessed at early pregnancy. The biochemical sub-study was nested within a double-blind, placebo-controlled, community-based vitamin A and b-carotene supplementation trial in rural north-western Bangladesh (JiVitA). All assessments were conducted before trial supplementation was initiated. A systematic sample of 285 women was selected from those enrolled in the biochemical sub-study. Seventeen per cent of women were mildly anaemic; moderate and severe anaemia was uncommon (2.1 %). a-Tocopherol, vitamin B12 and Zn deficiencies were common (43.5%, 19.7% and 14.7%, respectively); however, vitamin A, folate and Fe deficiencies were comparatively rare (7.4%, 2.8% and ,1%,respectively). Plasma Zn, vitamin B12 and a-tocopherol were positively associated and plasma g-tocopherol was negatively associated with Hb (P < 0.05) after adjustment for gestational age, inflammation status, season and nutritional status measured by mid-upper arm circumference. Among pregnant women in rural Bangladesh with minimal Fe deficiency, plasma Zn, vitamin B12, and a- and g-tocopherol concentrations were associated with Hb concentration. Appreciating the influence on Hb of micronutrients in addition to those with known associations with anaemia, such as Fe, folate, and vitamin A, is important when addressing anaemia in similar settings.

Concordance of haemoglobin A1c, blood pressure and C-reactive protein between children and their parents in Chinese households.

PubMed

Dong, F; Howard, A G; Herring, A H; Adair, L S; Thompson, A L; Popkin, B M; Aiello, A E; Zhang, B; Gordon-Larsen, P

2017-10-01

China has the world's highest diabetes prevalence, which along with hypertension and inflammation continues to grow particularly among children. Little is known about the strength of the association of these cardiometabolic risk factors between parents and their children; thus, the potential of household-based strategies to reduce risk is unknown. The objective of the study is to examine the parent-child association for haemoglobin A1c (HbA1c), blood pressure (BP) and C-reactive protein (CRP) in a large, geographically diverse Chinese sample. In 940 parent-child pairs (children aged 7-17 years) who participated in the 2009 China Health and Nutrition Survey, we measured each individual's HbA1c and CRP using fasting blood and BP. We used sex-specific random-effects linear regression to examine the parent-child association for these risk factors, accounting for within-family clustering. Child's HbA1c was positively associated with parental HbA1c. Beta coefficients ranged from 0.06 (95% CI 0.03-0.12) for father-daughter to 0.43 (95% CI 0.28-0.58) for mother-son pairs. We also detected a positive mother-daughter association for BP and positive father-child associations for CRP. The statistically significant parent-child association for HbA1c, BP and CRP in Chinese families suggests that household-based interventions could be useful for confronting the high rates of diabetes, hypertension and inflammation in China. © 2016 The Authors. Pediatric Obesity published by John Wiley & Sons, Ltd on behalf of World Obesity Federation.

Haemoglobin function in vertebrates: evolutionary changes in cellular regulation in hypoxia.

PubMed

Nikinmaa, M

2001-11-15

The evolution of erythrocytic hypoxia responses is reviewed by comparing the cellular control of haemoglobin-oxygen affinity in agnathans, teleost fish and terrestrial vertebrates. The most ancient response to hypoxic conditions appears to be an increase in cell volume, which increases the haemoglobin-oxygen affinity in lampreys. In teleost fish, an increase of cell volume in hypoxic conditions is also evident. The volume increase is coupled to an increase in erythrocyte pH. These changes are caused by an adrenergic activation of sodium/proton exchange across the erythrocyte membrane. The mechanism is important in acute hypoxia and is followed by a decrease in cellular adenosine triphosphate (ATP) and guanosine triphosphate (GTP) concentrations in continued hypoxia. In hypoxic bird embryos, the ATP levels are also reduced. The mechanisms by which hypoxia decreases cellular ATP and GTP concentrations remains unknown, although at least in bird embryos cAMP-dependent mechanisms have been implicated. In mammals, hypoxia responses appear to occur mainly via modulation of cellular organic phosphate concentrations. In moderate hypoxia, 2,3-diphosphoglycerate levels are increased as a result of alkalosis caused by increased ventilation.

Comparison of the characteristics of two hemoglobin variants, Hb D-Iran and Hb E, eluting in the Hb A2 window.

PubMed

Dass, Jasmita; Gupta, Aastha; Mittal, Suchi; Saraf, Amrita; Langer, Sabina; Bhargava, Manorama

2017-06-01

Cation exchange-high performance liquid chromatography (CE-HPLC) is most commonly used to evaluate hemoglobin (Hb) variants, which elute in the Hb A2 window. This study aimed to assess prevalence of an uncommon Hb variant, Hb D-Iran, and compare its red cell parameters and peak characteristics with those of Hb E that commonly elutes in the Hb A2 window. Generally, we assess abnormal Hb using CE-HPLC as the primary technique along with alkaline and acid electrophoresis. All cases with Hb A2 window >9%, as assessed by CE-HPLCs during 2009-2013, were selected. Twenty-nine cases with Hb D-Iran variant were identified-25 heterozygous, 2 homozygous, 1 compound heterozygous Hb D-Iran/β-thalassemia, and 1 Hb D-Iran/Hb D-Punjab. Overall prevalence of Hb D-Iran was 0.23%. Compared to patients with Hb E, those with Hb D-Iran had significantly higher Hb (12.1 vs. 11.3 g/dL, P =0.03), MCV (82.4 vs. 76.4 fL, P =0.0044), MCH (27.9 vs. 25.45 pg, P =0.0006), and MCHC (33.9 vs. 33.3 g/dL, P =0.0005). Amount of abnormal Hb (40.7 vs. 26.4%, P =0.0001) was significantly higher while retention time (3.56 vs. 3.70 min, P =0.0001) was significantly lower in Hb D-Iran than in Hb E. Hb D-Iran peak can be easily missed if area and retention time of the Hb A2 window are not carefully analyzed. To distinguish between variants, careful analysis of peak area and retention time is sufficient in most cases and may be further confirmed by the second technique-alkaline electrophoresis.

Both the frequency of HbA1c testing and the frequency of self-monitoring of blood glucose predict metabolic control: A multicentre analysis of 15 199 adult type 1 diabetes patients from Germany and Austria.

PubMed

Schwandt, A; Best, F; Biester, T; Grünerbel, A; Kopp, F; Krakow, D; Laimer, M; Wagner, C; Holl, R W

2017-10-01

The objective of this study was to examine the association between metabolic control and frequency of haemoglobin A 1c (HbA 1c ) measurements and of self-monitoring of blood glucose, as well as the interaction of both. Data of 15 199 adult type 1 diabetes patients registered in a standardized electronic health record (DPV) were included. To model the association between metabolic control and frequency of HbA 1c testing or of self-monitoring of blood glucose, multiple hierarchic regression models with adjustment for confounders were fitted. Tukey-Kramer test was used to adjust P values for multiple comparisons. Vuong test was used to compare non-nested models. The baseline variables of the study population were median age 19.9 [Q1; Q3: 18.4; 32.2] years and diabetes duration 10.4 [6.8; 15.7] years. Haemoglobin A 1c was 60.4 [51.5; 72.5] mmol/mol. Frequency of HbA 1c testing was 8.0 [5.0; 9.0] within 2 years, and daily self-monitoring of blood glucose frequency was 5.0 [4.0; 6.0]. After adjustment, a U-shaped association between metabolic control and frequency of HbA 1c testing was observed with lowest HbA 1c levels in the 3-monthly HbA 1c testing group. There was an inverse relationship between self-monitoring of blood glucose and HbA 1c with lower HbA 1c associated with highest frequency of testing (>6 daily measurements). Quarterly HbA 1c testing and frequent self-monitoring of blood glucose were associated with best metabolic control. The adjusted Vuong Z statistic suggests that metabolic control might be better explained by HbA 1c testing compared to self-monitoring of blood glucose (P < .0001). This research reveals the importance of quarterly clinical HbA 1c monitoring together with frequent self-monitoring of blood glucose in diabetes management to reach and maintain target HbA 1c . Copyright © 2017 John Wiley & Sons, Ltd.

New technology increases perioperative haemoglobin levels for paediatric cardiopulmonary bypass: what is the benefit?

PubMed

Thuys, Clarke; Horton, Stephen; Bennett, Martin; Augustin, Simon

2006-01-01

Increasing perioperative haemoglobin level by reducing priming volume and maintaining a safe cardiopulmonary bypass (CPB) system is the aim of every perfusionist. In this study, we have compared the two membrane oxygenators and pump systems used for paediatric bypass at the Royal Children's Hospital on a regular basis since 1988. We looked at all patients who had the Cobe VPCML (Cobe Laboratories, Denver, CO, USA) and Terumo RX-05 (Terumo Corporation, Tokyo, Japan) oxygenators used for flows from 800 mL/min up to the maximum rated flow for the respective oxygenator from January 2002 until March 2004. The VPCML refers to using only the 0.4-m2 section of the oxygenator. The pump systems used were the Stöckert CAPS (Stöckert Instrumente GmbH, Munich, Germany) and Jostra HL 30 (Jostra AB, Lund, Sweden). Changing from the VPCML to the RX-05 resulted in a 37% reduction in priming volume. The introduction of the Jostra HL 30 with a custom-designed mast system reduced the priming volume by another 15%. This change in priming volume allowed a significant increase, from 6 to 34%, in the percentage of patients who received bloodless primes, and for those patients who received blood primes, an increase in haemoglobin (Hb) on bypass from 8.2 to 9.6 g/dL, on average.

The relationship between helminth infections and low haemoglobin levels in Ethiopian children with blood type A.

PubMed

Degarege, A; Yimam, Y; Madhivanan, P; Erko, B

2017-05-01

The current study was conducted to evaluate the nature of association of ABO blood type with helminth infection and related reduction in haemoglobin concentration. Stool samples were collected from 403 school-age children attending Tikur Wuha Elementary School from February to April 2011. Helminth infection was examined using formol-ether concentration and thick Kato-Katz (two slides per stool specimen) techniques. Haemoglobin level was determined using a HemoCue machine and ABO blood type was determined using the antisera haemagglutination test. Nutritional status was assessed using height and weight measurements. Out of 403 children examined, 169, 120, 96 and 18 had blood type O, A, B and AB, respectively. The prevalences of helminth infections were 46.9% for hookworm, 24.6% for Schistosoma mansoni, 4.2% for Ascaris lumbricoides, 1.7% for Trichuris trichiura and 58.3% for any helminth species. The relative odds of infection with at least one helminth species was significantly higher among children with blood type A (adjusted odds ratio (AOR), 2.10; 95% confidence interval (CI), 1.28-3.45) or blood type B (AOR, 2.08; 95% CI, 1.22-3.56) as compared to children with blood type O. Among children infected with helminths, mean haemoglobin concentration was lower in those with blood type A than those with blood type O (β, -0.36; 95% CI, -0.72 to -0.01). The relative odds of hookworm infection (AOR, 1.78; 95% CI, 1.08-2.92) and related reduction in haemogobin levels (β, -0.45; 95% CI, -0.84 to -0.04) was higher among children with blood type A as compared to those with blood type O. Although the difference was not significant, the relative odds of S. mansoni or A. lumbricoides infections and related reduction in haemoglobin levels was also higher in children with blood type A or B as compared to children with blood type O. In conclusion, children with blood type A are associated with an increased risk of helminth, particularly hookworm, infection and related reduction

UK Renal Registry 16th annual report: chapter 10 haemoglobin, ferritin and erythropoietin amongst UK adult dialysis patients in 2012: national and centre-specific analyses.

PubMed

Rao, Anirudh; Gilg, Julie; Williams, Andrew

2013-01-01

Anaemia treatment in chronic kidney disease (CKD) patients has changed dramatically since the implementation of erythropoietin stimulating agents (ESAs) and has shifted the emphasis from treating severe anaemia in dialysis patients to preventing anaemia. The aim of this chapter is to determine the extent to which the UK Renal Association (RA) and National Institute for Health and Care Excellence (NICE) guidelines for anaemia management are met in the UK. Quarterly data were obtained for haemoglobin (Hb) and factors that influence Hb from UK renal centres for the incident and prevalent renal replacement therapy (RRT) cohorts for 2012. In the UK, in 2012, 51% of patients commenced dialysis therapy with Hb 100 g/L (median Hb 100 g/L). Of patients in the early presentation group, 54% started dialysis with Hb 100 g/L whilst 34% of patients presenting late started dialysis with Hb 100 g/L. The UK median Hb of haemodialysis (HD) patients was 112 g/L, with 82% of patients having Hb 100 g/L. The median Hb of peritoneal dialysis (PD) patients in the UK was 114 g/L, with 85% of patients having Hb 100 g/L. The median ferritin in HD patients in the UK was 431 µg/L and 95% of HD patients had a ferritin 100 µg/L. In EW&NI the median ferritin in PD patients was 285 µg/L (IQR 164-466) with 88% of PD patients having a ferritin 100 µg/L. In EW&NI the median ESA dose was higher for HD than PD patients (7,248 vs. 4,250 IU/week). The percentage of patients treated with an ESA and having Hb >120 g/L ranged between centres from 7-39% for HD and from 0-33% for PD. There was poor correlation between median Hb achieved and median ferritin and ESA usage across the EW&NI centres. There was also a significant variation between centres in the percentages of patients treated with an ESA and having Hb >120 g/L. © 2014 S. Karger AG, Basel.

Glycosylated haemoglobin: measurement and clinical use.

PubMed

Peacock, I

1984-08-01

The discovery, biochemistry, laboratory determination, and clinical application of glycosylated haemoglobins are reviewed. Sources of error are discussed in detail. No single assay method is suitable for all purposes, and in the foreseeable future generally acceptable standards and reference ranges are unlikely to be agreed. Each laboratory must establish its own. Nevertheless, the development of glycosylated haemoglobin assays is an important advance. They offer the best available means of assessing diabetic control.

Lifetime exposure to low doses of lead in rats: effect on selected parameters of carbohydrate metabolism.

PubMed

Nováková, Jaroslava; Lukačínová, Agnesa; Lovásová, Eva; Cimboláková, Iveta; Rácz, Oliver; Ništiar, František

2015-05-01

The aim of the study was to assess the effects of exposure to low doses of lead dissolved in drinking water (average daily dose of 2.2 mg kg(-1) day(-1)) on selected carbohydrate metabolism parameters in 20 wistar rats. Animals were divided into two groups - control (C) (group drinking clear water) and experimental group (Pb; group exposed to low doses of lead acetate in a concentration of 100 μmol l(-1) of drinking water). In this study, we studied the biochemical parameters (glucose, haemoglobin (Hb), glycated haemoglobin (HbA1c), lactate dehydrogenase (LDH) and amylase (AMS)) in rat blood. Glucose and Hb concentration and AMS activity decreased, LDH activity increased but HbA1c concentration levels did not change in rats exposed to lead. Our results well documented that lifetime exposure to lead affected carbohydrate metabolism of rats. Some parameters like concentration of Hb as well as activities of AMS and LDH are useful markers of intoxication of rats with lead. For the evaluation of results (e.g. AMS), not only the data at the end of the experiment should be taken into account but also the entire duration of trials (i.e. more time steps) that makes results more objective should be considered. © The Author(s) 2013.

Evaluation of the validity of a rapid method for measuring high and low haemoglobin levels in whole blood donors.

PubMed

Shahshahani, Hayedeh J; Meraat, Nahid; Mansouri, Fatemeh

2013-07-01

Haemoglobin screening methods need to be highly sensitive to detect both low and high haemoglobin levels and avoid unnecessary rejection of potential blood donors. The aim of this study was to evaluate the accuracy of measurements by HemoCue in blood donors. Three hundred and fourteen randomly selected, prospective blood donors were studied. Single fingerstick blood samples were obtained to determine the donors' haemoglobin levels by HemoCue, while venous blood samples were drawn for measurement of the haemoglobin level by both HemoCue and an automated haematology analyser as the reference method. The sensitivity, specificity, predictive values and correlation between the reference method and HemoCue were assessed. Cases with a haemoglobin concentration in the range of 12.5-17.9 g/dL were accepted for blood donation. Analysis of paired results showed that haemoglobin levels measured by HemoCue were higher than those measured by the reference method. There was a significant correlation between the reference method and HemoCue for haemoglobin levels less than 12.5 g/dL. The correlation was less strong for increasing haemoglobin levels. Linear correlation was poor for haemoglobin levels over 18 g/dL. Thirteen percent of donors, who had haemoglobin levels close to the upper limit, were unnecessarily rejected. HemoCue is suitable for screening for anaemia in blood donors. Most donors at Yazd are males and a significant percentage of them have haemoglobin values close to the upper limit for acceptance as a blood donor; since these subjects could be unnecessarily rejected on the basis of HemoCue results and testing with this method is expensive, it is recommended that qualitative methods are used for primary screening and accurate quantitative methods used in clinically suspicious cases or when qualitative methods fail.

Comparison of haemoglobin estimates using direct & indirect cyanmethaemoglobin methods.

PubMed

Bansal, Priyanka Gupta; Toteja, Gurudayal Singh; Bhatia, Neena; Gupta, Sanjeev; Kaur, Manpreet; Adhikari, Tulsi; Garg, Ashok Kumar

2016-10-01

Estimation of haemoglobin is the most widely used method to assess anaemia. Although direct cyanmethaemoglobin method is the recommended method for estimation of haemoglobin, but it may not be feasible under field conditions. Hence, the present study was undertaken to compare indirect cyanmethaemoglobin method against the conventional direct method for haemoglobin estimation. Haemoglobin levels were estimated for 888 adolescent girls aged 11-18 yr residing in an urban slum in Delhi by both direct and indirect cyanmethaemoglobin methods, and the results were compared. The mean haemoglobin levels for 888 whole blood samples estimated by direct and indirect cyanmethaemoglobin method were 116.1 ± 12.7 and 110.5 ± 12.5 g/l, respectively, with a mean difference of 5.67 g/l (95% confidence interval: 5.45 to 5.90, P<0.001); which is equivalent to 0.567 g%. The prevalence of anaemia was reported as 59.6 and 78.2 per cent by direct and indirect methods, respectively. Sensitivity and specificity of indirect cyanmethaemoglobin method were 99.2 and 56.4 per cent, respectively. Using regression analysis, prediction equation was developed for indirect haemoglobin values. The present findings revealed that indirect cyanmethaemoglobin method overestimated the prevalence of anaemia as compared to the direct method. However, if a correction factor is applied, indirect method could be successfully used for estimating true haemoglobin level. More studies should be undertaken to establish agreement and correction factor between direct and indirect cyanmethaemoglobin methods.

Hydroxyurea responses in clinically varied beta, HbE-beta thalassaemia and sickle cell anaemia patients of Eastern India.

PubMed

Chatterjee, Tridip; Chakravarty, Amit; Chakravarty, Sudipa

2018-05-01

The haematological and clinical response to hydroxyurea was estimated in HbE-beta, beta thalassaemia and sickle cell anaemia patients of Eastern India, with variable clinical severity and transfusion requirement to determine whether hydroxyurea can help these patients to maintain their steady haemoglobin level without blood transfusions. Three hundred patients (189 HbE-beta thalassaemia, 95 beta thalassaemia and 16 other haemoglobinopathies including sickle cell anaemia) were selected for hydroxyurea therapy and were followed up for 48-60 months. Results suggest significant response to hydroxyurea therapy in 19 beta and 99 HbE-beta patients in the transfusion-dependent group (GR-I). All of them became transfusion-independent while on hydroxyurea therapy. The majority of responding patients were IVS1-5(G-C) in one of their alleles in HbE-beta cases (83 out of 119). Though IVS1-5(G-C) was found to be the commonest mutation in our selected patients, the mutational background of the patients does not found to have any significant correlation with the response category towards hydroxyurea as per the results observed in our study. But, the drug works pretty well in most of the transfusion-dependent patients, as these patients were withdrawn from regular blood transfusion. At the same time, partial or no response to the drug hydroxyurea was also recorded in our study.

Pre-treatment haemoglobin and peripheral blood lymphocyte count as independent predictors of outcome in carcinoma of cervix.

PubMed

Hoskin, P J; Rojas, A M; Peiris, S N; Mullassery, V; Chong, I Y

2014-04-01

To evaluate pre-treatment haemoglobin and peripheral blood lymphocyte (PBL) counts as predictors of treatment outcome in cervix carcinoma treated with radical chemoradiation. Pre-treatment PBL counts and haemoglobin concentrations were retrieved from full blood count examinations from 111 patients who received concurrent chemoradiotherapy. Overall survival and relapse-free survival were obtained using the Kaplan-Meier method by ranking the data by median haemoglobin and PBL, singly and then in association. Their independence and significance as predictors of outcome were analysed using the Cox proportional hazard model. Survival rates were significantly higher in patients whose haemoglobin level or PBL counts were at or above the corresponding median value. At 5 years, rates of overall survival were 77% versus 41% (P = 0.0003) and 75% versus 42% (P = 0.002), when dichotomised around median haemoglobin and PBL, respectively. In multivariate and univariate analyses, both PBL and haemoglobin were independent and significant predictors for risk of death and relapse. Their predictive power was dramatically enhanced when the data were stratified into four groups by associating patients with haemoglobin ≥ median or < median with those whose PBL was ≥ or < median. Baseline PBL and haemoglobin seem to be strong, independent predictors of treatment outcome in carcinoma of the cervix, particularly if patient response is ranked using the predictors simultaneously. The hypothesis needs to be tested and, if confirmed, the markers should be used in combination to identify those at greater risk of failure who may benefit from additional therapy, with further validation in prospective trials offering treatment modification. Copyright © 2013 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Factors associated with reaching or not reaching target HbA1c after initiation of basal or premixed insulin in patients with type 2 diabetes.

PubMed

Scheen, A J; Schmitt, H; Jiang, H H; Ivanyi, T

2017-02-01

To evaluate factors associated with reaching or not reaching target glycated haemoglobin (HbA 1c ) levels by analysing the respective contributions of fasting hyperglycaemia (FHG), also referred to as basal hyperglycaemia, vs postprandial hyperglycaemia (PHG) before and after initiation of a basal or premixed insulin regimen in patients with type 2 diabetes. This post-hoc analysis of insulin-naïve patients in the DURABLE study randomised to receive either insulin glargine or insulin lispro mix 25 evaluated the percentages of patients achieving a target HbA 1c of <7.0% (<53mmol/mol) per baseline HbA 1c quartiles, and the effect of each insulin regimen on the relative contributions of PHG and FHG to overall hyperglycaemia. Patients had comparable demographic characteristics and similar HbA 1c and FHG values at baseline in each HbA 1c quartile regardless of whether they reached the target HbA 1c . The higher the HbA 1c quartile, the greater was the decrease in HbA 1c , but also the smaller the percentage of patients achieving the target HbA 1c . HbA 1c and FHG decreased more in patients reaching the target, resulting in significantly lower values at endpoint in all baseline HbA 1c quartiles with either insulin treatment. Patients not achieving the target HbA 1c had slightly higher insulin doses, but lower total hypoglycaemia rates. Smaller decreases in FHG were associated with not reaching the target HbA 1c , suggesting a need to increase basal or premixed insulin doses to achieve targeted fasting plasma glucose and improve patient response before introducing more intensive prandial insulin regimens. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

UK Renal Registry 13th Annual Report (December 2010): Chapter 9: haemoglobin, ferritin and erythropoietin amongst UK adult dialysis patients in 2009: national and centre-specific analyses.

PubMed

Gilg, Julie; Webb, Lynsey; Feest, Terry; Fogarty, Damian

2011-01-01

The UK Renal Association (RA) and National Institute for Health and Clinical Excellence (NICE) have published Clinical Practice Guidelines which include recommendations for management of anaemia in established renal failure. To determine the extent to which the guidelines for anaemia management are met in the UK. Quarterly data were obtained regarding haemoglobin (Hb) and factors that influence Hb from renal centres in England, Wales, Northern Ireland (EWNI) and the Scottish Renal Registry for the incident and prevalent renal replacement therapy (RRT) cohorts for 2009. In the UK, in 2009 55% of patients commenced dialysis therapy with Hb x10.0 g/dl (median Hb 10.2 g/dl). The median Hb of haemodialysis (HD) patients was 11.6 g/dl with an interquartile range (IQR) of 10.6 - 12.4 g/dl. Of HD patients 85% had Hb ≥ 10.0 g/dl. The median Hb of peritoneal dialysis (PD) patients in the UK was 11.7 g/dl (IQR 10.7-12.6 g/dl). Of UK PD patients, 88% had Hb ≥ 10.0 g/dl. The median ferritin in HD patients in EWNI was 441 mg/L (IQR 289-629) and 96% of HD patients had a ferritin ≥ 100 mg/L. The median ferritin in PD patients was 249 mg/L (IQR 142-412) with 86% of PD patients having a ferritin 5100 mg/L. In EWNI the mean Erythropoietin Stimulating Agent (ESA) dose was higher for HD than PD patients (9,507 vs. 6,212 IU/week). In 2009, 56% of prevalent HD patients had a Hb ≥ 10.5 and ≤ 12.5 g/dl compared with 54% in 2008 and 53% in 2007. Fifty-four percent of prevalent PD patients had a Hb ≥10.5 and ≤12.5 g/dl compared to 55% in 2008. Copyright © 2011 S. Karger AG, Basel.

Haemoglobin Fontainebleau (HBA2: c. 64G>C) in Oman: molecular and haematological characteristics and interaction with various haemoglobinopathies.

PubMed

Daar, Shahina; Al Zadjali, Shoaib; Alkindi, Salam; Wali, Yasser; Al-Rawas, Abdulhakeem; Al-Haddabi, Humood; Al-Riyami, Arwa Z

2018-04-01

To describe the laboratory features of haemoglobin Fontainebleau (Hb FB) and its interactions with various α and β globin gene mutations in the Omani population. Over a period of 10 years, a total of 94 blood samples were suspected to have an α variant on HPLC at the Sultan Qaboos University Hospital, Muscat, Oman. Molecular testing was performed using PCR based techniques to define the variant and to analyse other interacting mutations in either α or β globin genes. Of 94 subjects, molecular analysis confirmed the Hb FB variant in 55 samples (38 non-cord and 17 cord blood). A total of 36/38 non-cord samples were heterozygous for the variant, while all 17 cord blood samples were heterozygotes. A total of 43/55 individuals had a concomitant α and/or β globin gene mutation. Hb FB is the the most common α variant in the Omani population. We report the different HPLC profiles of this variant that we observed, with and without other haemoglobinopathies in non-cord and cord blood samples. This is the first report describing the HPLC profiles of this α globin chain variant on 1 year follow-up testing of cord blood samples. With careful analysis by HPLC, it is possible not only to identify Hb FB but also to predict any concomitant α and/or β globin gene mutations. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Low versus high haemoglobin concentration threshold for blood transfusion for preventing morbidity and mortality in very low birth weight infants.

PubMed

Whyte, Robin; Kirpalani, Haresh

2011-11-09

Infants of very low birth weight often receive multiple transfusions of red blood cells, usually in response to predetermined haemoglobin or haematocrit thresholds. In the absence of better indices, haemoglobin levels are imperfect but necessary guides to the need for transfusion. Chronic anaemia in premature infants may, if severe, cause apnoea, poor neurodevelopmental outcomes or poor weight gain.On the other hand, red blood cell transfusion may result in transmission of infections, circulatory or iron overload, or dysfunctional oxygen carriage and delivery. To determine if erythrocyte transfusion administered to maintain low as compared to high haemoglobin thresholds reduces mortality or morbidity in very low birth weight infants enrolled within three days of birth. Two review authors independently searched the Cochrane Central Register of Controlled Trials (The Cochrane Library) , MEDLINE,EMBASE, and conference proceedings through June 2010. We selected randomised controlled trials (RCTs) comparing the effects of early versus late, or restrictive versus liberal erythrocyte transfusion regimes in low birth weight infants applied within three days of birth, with mortality or major morbidity as outcomes.

Contemporary risk estimates of three HbA1c variables in relation to heart failure following diagnosis of type 2 diabetes

PubMed Central

Skrtic, Stanko; Cabrera, Claudia; Olsson, Marita; Schnecke, Volker; Lind, Marcus

2017-01-01

Background We evaluated the association between glycaemic control and the risk of heart failure (HF) in a contemporary cohort of persons followed after diagnosis of type 2 diabetes (T2D). Methods and results Persons with T2D diagnosed between 1998 and 2012 were retrieved from the Clinical Practice Research Data Link in the UK and followed from diagnosis until the event of HF, mortality, drop out from the database due to any other reason, or the end of the study on 1 July 2015. The association between each of three different haemoglobin A1C (HbA1c) metrics and HF was estimated using adjusted proportional hazard models. In the overall cohort (n=94 332), the increased risk for HF per 1% (10 mmol/mol) increase in HbA1c was 1.15 (95% CI 1.13 to 1.18) for updated mean HbA1c, and 1.06 (1.04 to 1.07) and 1.06 (1.04 to 1.08) for baseline HbA1c and updated latest HbA1c, respectively. When categorised, the hazard risk (HR) for the updated mean HbA1c in relation to HF became higher than for baseline and updated latest HbA1c above HbA1c levels of 9%, but did not differ at lower HbA1c levels. The updated latest variable showed an increased risk for HbA1c <6% (42 mmol/mol) of 1.16 (1.07 to 1.25), relative category 6–7%, while the HRs for updated mean and baseline HbA1c showed no such J-shaped pattern. Conclusions Hyperglycaemia is still a risk factor for HF in persons with T2D of similar magnitude as in earlier cohorts. Such a relationship exists for current glycaemic levels, at diagnosis and the overall level but the pattern differs for these variables. PMID:27647169

Effects of a diphenyl-ether herbicide, oxyfluorfen, on human BFU-E/CFU-E development and haemoglobin synthesis.

PubMed

Rio, B; Parent-Massin, D; Lautraite, S; Hoellinger, H

1997-02-01

The diphenyl-ether herbicides exert their phytotoxic activity by preventing chlorophyll formation in plants as a result of inhibition of protoporphyrinogen oxidase. This enzyme is the last step of the common pathway for chlorophyll and haem biosynthesis. The aim of this work is to determine whether herbicide inhibitors of plant protoporphyrinogen oxidase could act on the human protoporphyrinogen oxidase involved in haemoglobin synthesis and cause heamatologic diseases. Human erythroblastic progenitors (BFU-E/CFU-E: Burst Forming Unit-Erythroid and Colony Forming Unit-Erythroid) were exposed to oxyfluorfen, a diphenyl-ether herbicide in the presence of erythropoietin, and the haematoxicity evaluated in vitro by scoring the development of BFU-E/CFU-E colonies after 7 and 14 days of culture. The toxic effect on differentiation has been evaluated using four criteria: morphology, total protein, total porphyrin, and haemoglobin content. The study of BFU-E/CFU-E proliferation and differentiation showed a cytotoxic effect of oxyfluorfen only at very high concentrations. In contrast, haemoglobin synthesis can be inhibited by concentration of oxyfluorfen (10(-4) M) that have no adverse effect on cellular proliferation.

Relationship of glycated haemoglobin and reported hypoglycaemia to cardiovascular outcomes in patients with type 2 diabetes and recent acute coronary syndrome events: The EXAMINE trial.

PubMed

Heller, Simon R; Bergenstal, Richard M; White, William B; Kupfer, Stuart; Bakris, George L; Cushman, William C; Mehta, Cyrus R; Nissen, Steven E; Wilson, Craig A; Zannad, Faiez; Liu, Yuyin; Gourlie, Noah M; Cannon, Christopher P

2017-05-01

To investigate relationships between glycated haemoglobin (HbA1c) and reported hypoglycaemia and risk of major adverse cardiovascular events (MACE). The EXAMINE trial randomized 5380 patients with type 2 diabetes (T2DM) and a recent acute coronary syndrome (ACS) event, in 49 countries, to double-blind treatment with alogliptin or placebo in addition to standard of care. We used Cox proportional hazards models to analyse relationships among MACE, HbA1c levels and hypoglycaemic events. Patients randomized to alogliptin achieved lower HbA1c levels than the placebo group in all baseline HbA1c categories without differences in hypoglycaemia rates. No systematic change was found in MACE rates according to baseline HbA1c (P interaction  = 0.971) or HbA1c category at 1 month. Patients in the combined treatment groups (n = 5380) who experienced serious hypoglycaemia (n = 34) had higher MACE rates than those who did not (35.3% vs 11.4%, adjusted hazard ratio [HR] 2.42, 95% confidence interval [CI] 1.27-4.60; P = .007), although the association was less strong when analysing only events after the hypoglycaemic event (adjusted HR 1.60, 95% CI 0.80, 3.20). There were no relationships between baseline HbA1c levels or HbA1c levels after 1 month of treatment and the risk of MACE. Alogliptin improved glycaemic control without increasing hypoglycaemia. Reported events of hypoglycaemia and serious hypoglycaemia were associated with MACE. These data underscore the safety of alogliptin in improving glycaemic control in T2DM post-ACS. Further study of hypoglycaemia as an independent risk factor for MACE in patients with T2DM and coronary disease is needed. © 2017 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

Haemoglobin variants among voluntary blood donors in Jos, Nigeria: the implications on blood transfusion.

PubMed

Damulak, O D; Bolorunduro, S A; Egesie, J O; Yakubu, K; Godit, P; Smith, O A

2013-01-01

The normal haemoglobin is an efficient transporter of oxygen to the tissues and carbondioxide from tissues to the lungs for elimination. Various abnormal haemoglobin variants including, the sickle cell diseases, have been described with varying sickling tendencies. This study aimed to determine the haemoglobin variants among voluntary blood donors in Jos. Records of the age, sex, Haemoglobin level, and the haemoglobin genotype of all voluntary blood donors who donated blood at the National Blood Transfusion Service Centre, Jos, Nigeria between January 2011 and April 2012; and their haemoglobin levels and protein electrophoresis determined, were reviewed. A total of 937 blood donors, 658 (70.23%) males and 279 (29.79%) females, mean age 32.4 years, donated blood voluntarily, their haemoglobin electrophoretic patterns determined by alkaline cellulose acetate electrophoresis. Donor blood haemoglobin levels were determined by automation. Haemoglobin protein electrophoretic patterns identified among our donors were 77.70% AA, 21.88% AS, 0.22% SC, 0.11% AC and 0.11% SS. Mean haemoglobin levels of the donors according to their haemoglobin proteins electrophoretic patterns were, 150.4 +/- 12.5 gms/l for AA, 151.9 +/- 13.8 gms/l for AS and 131.1 +/- 5.0 gms/l for haemoglobin SC. Determination of haemoglobin protein electrophoretic patterns of blood unit for transfusion could enhance selective blood issuing based on recipient's haemoglobin type.

Purification, crystallization and preliminary crystallographic study of haemoglobin from camel (Camelus dromedarius): a high oxygen-affinity lowland species.

PubMed

Balasubramanian, M; Moorthy, Pon Sathya; Neelagandan, K; Ponnuswamy, M N

2009-08-01

Haemoglobin is a prototypical allosteric protein that is mainly involved in the transportation of oxygen from the lungs to tissues and of carbon dioxide back to the lungs in an intrinsically coordinated manner to maintain the viability of cells. Haemoglobin from Camelus dromedarius provides an interesting case study of adaptation to life in deserts at extremely high temperatures. An ambition to unravel the integrated structural and functional aspects of the casual survival of this animal at high temperatures led us to specifically work on this problem. The present work reports the preliminary crystallographic study of camel haemoglobin. Camel blood was collected and the haemoglobin was purified by anion-exchange chromatography and crystallized using the hanging-drop vapour-diffusion method under buffered high salt concentration using PEG 3350 as a precipitant. Intensity data were collected using a MAR 345 dtb image-plate detector system. Camel haemoglobin crystallized in the monoclinic space group P2(1), with one whole biological molecule (alpha(2)beta(2)) in the asymmetric unit and unit-cell parameters a = 52.759, b = 116.782, c = 52.807 A, beta = 120.07 degrees .

UK Renal Registry 15th annual report: Chapter 6 haemoglobin, ferritin and erythropoietin amongst UK adult dialysis patients in 2011: national and centre-specific analyses.

PubMed

Rao, Anirudh; Gilg, Julie; Williams, Andrew

2013-01-01

The UK Renal Association (RA) and National Institute for Health and Care Excellence (NICE) have published Clinical Practice Guidelines which include recommendations for management of anaemia in established renal failure. To determine the extent to which the guidelines for anaemia management are met in the UK. Quarterly data were obtained for haemoglobin (Hb) and factors that influence Hb from renal centres in England, Wales, Northern Ireland (E, W, NI) and the Scottish Renal Registry for the incident and prevalent renal replacement therapy (RRT) cohorts for 2011. In the UK, in 2011 51% of patients commenced dialysis therapy with Hb ≥10.0 g/dl (median Hb 10 g/dl). Of patients in the early presentation group, 55% started dialysis with Hb ≥10.0 g/dl whilst 37% of patients presenting late started dialysis with Hb ≥10.0 g/dl. The UK median Hb of haemodialysis (HD) patients was 11.2 g/dl with an inter-quartile range (IQR) of 10.3-12.1 g/dl. Of UK HD patients, 82% had Hb ≥10.0 g/dl. The median Hb of peritoneal dialysis (PD) patients in the UK was 11.4 g/dl (IQR 10.5-12.3 g/dl). Of UK PD patients, 85% had Hb ≥10.0 g/dl. The median ferritin in HD patients in the UK was 436 mg/L (IQR 292-625) and 96% of HD patients had a ferritin ≥100 mg/ L. In EW&NI the median ferritin in PD patients was 273 mg/ L (IQR 153-446) with 86% of PD patients having a ferritin ≥100 mg/L. In EW&NI the mean erythropoietin stimulating agent (ESA) dose was higher for HD than PD patients (8,740 vs. 6,624 IU/week). Prevalent HD and PD patients had 56% and 53% respectively within the Hb ≥10 and ≤12 g/dl target. Copyright © 2013 S. Karger AG, Basel.

Cation Homeostasis in Red Cells From Patients With Sickle Cell Disease Heterologous for HbS and HbC (HbSC Genotype)

PubMed Central

Hannemann, A.; Rees, D.C.; Tewari, S.; Gibson, J.S.

2015-01-01

Sickle cell disease (SCD) in patients of HbSC genotype is considered similar, albeit milder, to that in homozygous HbSS individuals — but with little justification. In SCD, elevated red cell cation permeability is critical as increased solute loss causes dehydration and encourages sickling. Recently, we showed that the KCl cotransporter (KCC) activity in red cells from HbSC patients correlated significantly with disease severity, but that in HbSS patients did not. Two transporters involved in red cell dehydration, the conductive channels Psickle and the Gardos channel, behaved similarly in red cells from the two genotypes, but were significantly less active in HbSC patients. By contrast, KCC activity was quantitatively greater in HbSC red cells. Results suggest that KCC is likely to have greater involvement in red cell dehydration in HbSC patients, which could explain its association with disease severity in this genotype. This work supports the hypothesis that SCD in HbSC patients is a distinct disease entity to that in HbSS patients. Results suggest the possibility of designing specific treatments of particular benefit to HbSC patients and a rationale for the development of prognostic markers, to inform early treatment of children likely to develop more severe complications of the disease. PMID:26870793

Cation Homeostasis in Red Cells From Patients With Sickle Cell Disease Heterologous for HbS and HbC (HbSC Genotype).

PubMed

Hannemann, A; Rees, D C; Tewari, S; Gibson, J S

2015-11-01

Sickle cell disease (SCD) in patients of HbSC genotype is considered similar, albeit milder, to that in homozygous HbSS individuals--but with little justification. In SCD, elevated red cell cation permeability is critical as increased solute loss causes dehydration and encourages sickling. Recently, we showed that the KCl cotransporter (KCC) activity in red cells from HbSC patients correlated significantly with disease severity, but that in HbSS patients did not. Two transporters involved in red cell dehydration, the conductive channels Psickle and the Gardos channel, behaved similarly in red cells from the two genotypes, but were significantly less active in HbSC patients. By contrast, KCC activity was quantitatively greater in HbSC red cells. Results suggest that KCC is likely to have greater involvement in red cell dehydration in HbSC patients, which could explain its association with disease severity in this genotype. This work supports the hypothesis that SCD in HbSC patients is a distinct disease entity to that in HbSS patients. Results suggest the possibility of designing specific treatments of particular benefit to HbSC patients and a rationale for the development of prognostic markers, to inform early treatment of children likely to develop more severe complications of the disease.

Clinically relevant reductions in HbA1c without hypoglycaemia: results across four studies of saxagliptin.

PubMed

Karyekar, C S; Frederich, R; Ravichandran, S

2013-08-01

In four 24-week controlled studies, the antihyperglycaemic efficacy of saxagliptin was demonstrated in patients with type 2 diabetes mellitus as add-on therapy to glyburide, a thiazolidinedione, or metformin, and when used in initial combination with metformin vs. metformin monotherapy in drug-naive patients. Data from these studies were analysed to compare the proportions of patients who achieved specific reductions from baseline in glycated haemoglobin [HbA(1c); reductions of ≥ 0.5% and ≥ 0.7% in all studies (prespecified); reductions ≥ 1.0% in the add-on studies and ≥ 1.0% to ≥ 2.5% in the initial combination study (post hoc)] for saxagliptin vs. comparator at week 24. We report overall rates of glycaemic response defined by these reductions in HbA(1c) and rates of response without experiencing hypoglycaemia. Large glycaemic response rates were higher with saxagliptin 2.5 and 5 mg/day than with comparator (HbA(1c) ≥ 1.0%, 31.7-50.3% vs. 10.3-20.0%) as add-on therapy and higher with saxagliptin 5 mg/day as initial combination with metformin than with metformin monotherapy (HbA(1c) ≥ 2.0%, 68.3% vs. 49.8%) in drug-naive patients. Addition of saxagliptin was associated with a low incidence of hypoglycaemia; overall response rates and response rates excluding patients who experienced hypoglycaemia were similar. Analysis of several demographic and baseline clinical variables revealed no consistent correlations with response to saxagliptin. Whether receiving saxagliptin as an add-on therapy to glyburide, a thiazolidinedione, or metformin or in initial combination with metformin, a greater percentage of patients achieve clinically relevant large reductions in HbA(1c) vs. comparator, with a low incidence of hypoglycaemia. © 2013 Bristol-Myers Squibb Co. International Journal of Clinical Practice published by John Wiley & Sons Ltd.

Clinically relevant reductions in HbA1c without hypoglycaemia: results across four studies of saxagliptin

PubMed Central

Karyekar, C S; Frederich, R; Ravichandran, S

2013-01-01

BackgroundIn four 24-week controlled studies, the antihyperglycaemic efficacy of saxagliptin was demonstrated in patients with type 2 diabetes mellitus as add-on therapy to glyburide, a thiazolidinedione, or metformin, and when used in initial combination with metformin vs. metformin monotherapy in drug-naive patients. MethodsData from these studies were analysed to compare the proportions of patients who achieved specific reductions from baseline in glycated haemoglobin [HbA1c; reductions of ≥ 0.5% and ≥ 0.7% in all studies (prespecified); reductions ≥ 1.0% in the add-on studies and ≥ 1.0% to ≥ 2.5% in the initial combination study (post hoc)] for saxagliptin vs. comparator at week 24. We report overall rates of glycaemic response defined by these reductions in HbA1c and rates of response without experiencing hypoglycaemia. ResultsLarge glycaemic response rates were higher with saxagliptin 2.5 and 5 mg/day than with comparator (HbA1c ≥ 1.0%, 31.7–50.3% vs. 10.3–20.0%) as add-on therapy and higher with saxagliptin 5 mg/day as initial combination with metformin than with metformin monotherapy (HbA1c ≥ 2.0%, 68.3% vs. 49.8%) in drug-naive patients. Addition of saxagliptin was associated with a low incidence of hypoglycaemia; overall response rates and response rates excluding patients who experienced hypoglycaemia were similar. Analysis of several demographic and baseline clinical variables revealed no consistent correlations with response to saxagliptin. ConclusionsWhether receiving saxagliptin as an add-on therapy to glyburide, a thiazolidinedione, or metformin or in initial combination with metformin, a greater percentage of patients achieve clinically relevant large reductions in HbA1c vs. comparator, with a low incidence of hypoglycaemia. PMID:23795975

The link between vascular deterioration and branched chain amino acids in a population with high glycated haemoglobin: the SABPA study.

PubMed

Mels, C M; Schutte, A E; Schutte, R; Huisman, H W; Smith, W; Fourie, C M; Kruger, R; van Rooyen, J M; Malan, N T; Malan, L

2013-12-01

Globally the prevalence of non-communicable diseases, such as hypertension and type 2 diabetes, are escalating. Metabolomic studies indicated that circulating branched chain amino acids (BCAAs) are associated with insulin resistance, coronary artery disease and increased risk for cardiovascular events. We aimed to extend the current understanding of the cardiovascular risk associated with BCAAs. We explored whether BCAAs are related to markers of cardiovascular disease in a bi-ethnic population and whether this relationship was influenced by chronic hyperglycaemia. We included 200 African and 209 Caucasian participants, and determined their ambulatory blood pressure and carotid intima-media thickness (cIMT). We analysed blood samples for glycated haemoglobin (HbA1c) and BCAAs. Participants were stratified into two groups according to their HbA1c value using the median cut-off value of 5.6%. Ambulatory BP, cIMT and BCAAs were significantly higher (all p < 0.001) in the high HbA1c group. Single regression analyses indicated significant positive associations of ambulatory blood pressure and cIMT with BCAAs (all p < 0.05) in both the groups. These associations between ambulatory systolic blood pressure (SBP) (r = 0.16, p = 0.035) and cIMT (r = 0.22, p = 0.004) with BCAAs remained in the high HbA1c group after adjusting for age, gender, ethnicity and body mass index (BMI) and were confirmed in multiple regression analyses (ambulatory SBP: R (2) = 0.17, β = 0.21, p = 0.005 and cIMT: R (2) = 0.30, β = 0.19, p = 0.003). Our results demonstrate that BCAAs are independently related to ambulatory BP and cIMT in individuals with high HbA1c levels and suggest that potential cardiovascular deterioration accompany the rise in BCAAs in conditions of hyperglycaemia.

Role of lipocalin 2 in intraventricular haemoglobin-induced brain injury

PubMed Central

Shishido, Hajime; Toyota, Yasunori; Hua, Ya; Keep, Richard F; Xi, Guohua

2016-01-01

Objective Our recent studies have shown that blood components, including haemoglobin and iron, contribute to hydrocephalus development and brain injury after intraventricular haemorrhage (IVH). The current study investigated the role of lipocalin 2 (LCN2), a protein involved in iron handling, in the ventricular dilation and neuroinflammation caused by brain injury in a mouse model of IVH. Design Female wild-type (WT) C57BL/6 mice and LCN2-deficient (LCN2−/−) mice had an intraventricular injection of haemoglobin, and control mice received an equivalent amount of saline. MRI was performed presurgery and postsurgery to measure ventricular volume and the brains were used for either immunohistochemistry or western blot. Results Ventricular dilation was observed in WT mice at 24 h after haemoglobin (25 mg/mL, 20 µL) injection (12.5±2.4 vs 8.6±1.5 mm3 in the control, p<0.01). Western blotting showed that LCN2 was significantly upregulated in the periventricular area (p<0.01). LCN2 was mainly expressed in astrocytes, whereas the LCN2 receptor was detected in astrocytes, microglia/macrophages and neurons. Haemoglobin-induced ventricle dilation and glia activation were less in LCN2−/− mice (p<0.01). Injection of high-dose haemoglobin (50 mg/mL) resulted in lower mortality in LCN2−/− mice (27% vs 86% in WT; p<0.05). Conclusions Intraventricular haemoglobin caused LCN2 upregulation and ventricular dilation. Haemoglobin resulted in lower mortality and less ventricular dilation in LCN2−/− mice. These results suggest that LCN2 has a role in haemoglobin-induced brain injury and may be a therapeutic target for IVH. PMID:28959462

Hb variants in Korea: effect on HbA1c using five routine methods.

PubMed

Yun, Yeo-Min; Ji, Misuk; Ko, Dae-Hyun; Chun, Sail; Kwon, Gye Cheol; Lee, Kyunghoon; Song, Sang Hoon; Seong, Moon Woo; Park, Sung Sup; Song, Junghan

2017-07-26

Quantification of glycated hemoglobin (HbA1c) is a challenge in patients with hemoglobin (Hb) variants. We evaluated the impact of various Hb variants on five routine HbA1c assays by comparing with the IFCC reference measurement procedure (RMP). Whole blood samples showing warning flags or no results on routine HPLC HbA1c assays were confirmed for Hb variants and were submitted to HbA1c quantification using Sebia Capillarys 2 Flex Piercing, Roche Tina-quant HbA1c Gen. 2, Bio-Rad Variant II Turbo 2.0, ADAMS HA-8180, Tosoh G8 standard mode, and IFCC RMP using LC-MS. Among 114 samples, the most common variants were Hb G-Coushatta (n=47), Queens (n=41), Ube-4 (n=11), Chad (n=4), Yamagata (n=4), G-His-Tsou (n=2), G-Taipei (n=1), Fort de France (n=1), Hoshida (n=1), and two novel variants (Hb α-globin, HBA 52 Gly>Cys and Hb β-globin, HBB 146 His>Asn). In terms of control samples, all the result of HbA1c were "acceptable", within the criteria of ±7% compared to IFCC RMP target values. However, percentage of "unacceptable" results of samples with Hb variants were 16% for Capillarys 2, 7% for Tina-quant, 51% for Variant II Turbo 2.0, 95% for G8 standard mode, and 89% for HA-8180. The Capillarys 2 and HA-8180 assay did not provide the results in 5 and 40 samples with Hb variants, respectively. HbA1c results from five routine assays in patients with relatively common Hb variants in Korea showed various degrees of bias compared to those of IFCC RMP. Therefore, laboratories should be aware of the limitation of their methods with respect to interference from Hb variants found commonly in their local population and suggest an alternative HbA1c quantification method.

Prevalence of high HbA1c levels in Brazilian adolescents: The Study of Cardiovascular Risk in Adolescents.

PubMed

de Cássia Lima Fernandes, Rita; Teló, Gabriela H; Cureau, Felipe V; Barufaldi, Laura A; Kuschnir, Maria Cristina C; Schaan, Beatriz D; Szklo, Moyses; Bloch, Katia V

2017-03-01

To evaluate the prevalence of elevated glycated haemoglobin (HbA1c) levels in a population of adolescents participating in the Study of Cardiovascular Risk in Adolescents. This is a school-based cross-sectional study based on a complex sample of adolescents 12-17years old representative at the national and macro-regional levels and for each Brazilian state capital. Blood was collected in schools and then evaluated in a single laboratory. HbA1c levels were considered elevated if ⩾5.7% (39mmol/mol) and were analyzed according to sex, age, macro-region, type of school, skin color, and nutritional status. Data from 37,804 adolescents were analyzed. The mean level of HbA1c was 5.4% (95%CI 5.4-5.4) (36mmol/mol [95%CI 36-36]), and 20.5% (95%CI 19.1-22.0) of adolescents presented values ⩾5.7% (⩾39mmol/mol). Among males, 23.6% (95%CI 21.8-25.6) showed elevated HbA1c levels compared to 17.5% (95%CI 15.9-19.2) observed in females. The prevalence of elevated levels of HbA1c was higher in adolescents with black skin color (27.6%; 95%CI 23.2-32.4) vs. white skin color (16.9%; 95%CI 15.4-18.5), and higher in those who studied in public schools (21.6%; 95%CI 20.0-23.4) vs. private schools (16.7%; 95%CI 14.7-19.0). Among obese adolescents, 29.7% (95%CI 25.4-34.3) had elevated levels of HbA1c, compared to 19.3% (95%CI 18.0-20.7) in normal weight students and 19.7% (95%CI 17.1-22.6) in overweight adolescents. Obese male adolescents of lower socioeconomic status had a higher prevalence of elevated HbA1c levels. Our findings highlight the importance of focusing on this high risk group for interventions to prevent diabetes. Copyright © 2017 Elsevier B.V. All rights reserved.

Carboxyhaemoglobin: a possible reference material for haemoglobin assay.

PubMed Central

Rideout, J M; Louderback, A

1982-01-01

The inter- and intralaboratory quality control of haemoglobin estimation in remote laboratories requires a more rugged control haemolysate than is commercially available. The stabilities of oxyhaemoglobin and carboxyhaemoglobin forms of an ethanediol-containing haemolysate were studied over a three-year period. From the results obtained, carboxyhaemoglobin under nitrogen is proposed as a possible candidate reference material for haemoglobin assay. PMID:7068921

Haematological and electrophoretic characterisation of β-thalassaemia in Yunnan province of Southwestern China

PubMed Central

Zhang, Jie; He, Jing; Mao, Xiaoqin; Zeng, Xiaohong; Chen, Hong; Su, Jie; Zhu, Baosheng

2017-01-01

Objectives β-Thalassaemia is widely found in Southwestern China. Characterisation of β-thalassaemia can improve screening and prenatal diagnosis for at-risk populations. Design A retrospective study. Methods In this study, the levels of haemoglobin alpha 2 (HbA2) and haemoglobin alpha (HbA) were analysed by gender for a total of 15 067 subjects screened by capillary electrophoresis. The cut-off value with the highest accuracy was established to identify β-thalassaemia in 723 patients suspected to have this disease. Haematological and electrophoretic characterisation of eight common types of β-thalassaemia were analysed in 486 β-thalassaemia subjects. Results HbA levels were significantly higher in men than in women, but there was no significant difference on HbA2 levels. A new cut-off value for the diagnosis of β-thalassaemia (HbA2≥4.0%) with the highest accuracy was proposed for the studied populations. Haemoglobin (Hb) was significantly higher in men compared with women (p<0.05), whereas no statistically significant differences were found for mean cell volume (MCV), mean cell haemoglobin (MCH), HbA and HbA2. The haemoglobin E (HbE) group showed comparatively higher values for haematological indices (Hb, MCV and MCH) than the other genotypes in heterozygous β-thalassaemia groups (p<0.05), and −28 (A>G) (HBB (β-globin):c.−78A>C) had significantly higher HbA2 values compared with other β-thalassaemia. Conclusions Ethnic groups have diversified β-globin gene mutations and considerable haematological variations. Our study will lay the foundation for screening programmes and clinical management of thalassaemia in Southwestern China. PMID:28143837

Noninvasive methods for haemoglobin screening in prospective blood donors.

PubMed

Belardinelli, A; Benni, M; Tazzari, P L; Pagliaro, P

2013-08-01

The haemoglobin level of prospective blood donors is usually performed on blood obtained by from the finger pulp by fingerstick with a lancet and filling a capillary tube with a sample. New noninvasive methods are now available for rapid, noninvasive predonation haemoglobin screening. Prospective blood donors at our blood centre were tested, in two different trials, as follows: by the NBM 200 (OrSense) test (n = 445 donors) and by the Pronto-7 (Masimo) test (n = 463 donors). The haemoglobin values of each trial and the haemoglobin of finger pulp blood obtained by fingerstick with a lancet (HemoCue) were compared with the haemoglobin values obtained from a venous sample on a Cell Counter (Beckman Coulter). Comparison of Beckman Coulter Cell Counter and OrSense and results showed a bias of 0.29 g/dl, the standard deviation of the differences (SDD) of 0.98 and 95% limits of agreement from -1.64 to 2.21, using Bland and Altman statistical methodology. Comparison of Masimo and Beckman Coulter Cell Counter results showed a bias of -0.53 g/dl, SDD of 1.04 and 95% limits of agreement from -2.57 to 1.51. Cumulative analysis of all 908 donors, as tested by the usual fingerstick test showed a bias of 0.83 g/dl, SDD of 0.70 and 95% limits of agreement from -0.54 to 2.20 compared with the Coulter Cell Counter. Compared with the Coulter Counter, the specificity of the methods was 99.5% for fingerstick, 97% for OrSense and 83% for Massimo, and the sensitivity was 99, 98 and 93%, respectively. Analysis of finger pulp blood by either direct sampling by fingerstick and Hemocue, or by noninvasive haemoglobin tests does not replicate the results of cell counter analysis of venous samples. Compared with fingerstick, noninvasive haemoglobin tests eliminate pain and reduce stress, but have a lower level of specificity and sensitivity. © 2013 International Society of Blood Transfusion.

Contemporary risk estimates of three HbA1c variables in relation to heart failure following diagnosis of type 2 diabetes.

PubMed

Skrtic, Stanko; Cabrera, Claudia; Olsson, Marita; Schnecke, Volker; Lind, Marcus

2017-03-01

We evaluated the association between glycaemic control and the risk of heart failure (HF) in a contemporary cohort of persons followed after diagnosis of type 2 diabetes (T2D). Persons with T2D diagnosed between 1998 and 2012 were retrieved from the Clinical Practice Research Data Link in the UK and followed from diagnosis until the event of HF, mortality, drop out from the database due to any other reason, or the end of the study on 1 July 2015. The association between each of three different haemoglobin A 1C (HbA 1c ) metrics and HF was estimated using adjusted proportional hazard models. In the overall cohort (n=94 332), the increased risk for HF per 1% (10 mmol/mol) increase in HbA 1c was 1.15 (95% CI 1.13 to 1.18) for updated mean HbA 1c , and 1.06 (1.04 to 1.07) and 1.06 (1.04 to 1.08) for baseline HbA 1c and updated latest HbA 1c , respectively. When categorised, the hazard risk (HR) for the updated mean HbA 1c in relation to HF became higher than for baseline and updated latest HbA 1c above HbA 1c levels of 9%, but did not differ at lower HbA 1c levels. The updated latest variable showed an increased risk for HbA 1c <6% (42 mmol/mol) of 1.16 (1.07 to 1.25), relative category 6-7%, while the HRs for updated mean and baseline HbA 1c showed no such J-shaped pattern. Hyperglycaemia is still a risk factor for HF in persons with T2D of similar magnitude as in earlier cohorts. Such a relationship exists for current glycaemic levels, at diagnosis and the overall level but the pattern differs for these variables. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Evaluation of haemoglobin (erythrogen): for improved somatic embryogenesis and plant regeneration in cotton (Gossypium hirsutum L. cv. SVPR 2).

PubMed

Ganesan, M; Jayabalan, N

2004-10-01

Somatic embryogenesis in cotton (Gossypium hirsutum L.) is accelerated when the plant regeneration medium is supplemented with haemoglobin (erythrogen). In cotton SVPR 2 lines, a higher frequency of embryoid formation was observed when the medium contained 400 mg/l haemoglobin. Fresh weight of the callus, rate of embryoid induction, number of embryoids formed and the percentage of plant regeneration from somatic embryos were increased. Among the two different cultivars tested, MCU 11 showed no response to the presence of haemoglobin when compared to SVPR 2, and embryogenic callus formation was completely absent in the former. Medium containing MS salts, 100 mg/l myo-inositol , 0.3 mg/l thiamine-HCL, 0.3 mg/l Picloram (PIC), 0.1 mg/l kinetin and 400 mg/l haemoglobin effected a better response with respect to embryogenic callus induction. After 8 weeks of culture, a high frequency of embryoid induction was observed on medium containing MS basal salts, 100 mg/l myo-inositol, 0.3 mg/l PIC , 0.1 mg/l isopentenyl adenine, 1.0 g/l NH4NO3 and 400 mg/l haemoglobin. Plant regeneration was observed in 75.8% of the mature somatic embryos, and whole plant regeneration was achieved within 6-7 months of culture. The regenerated plantlets were fertile and similar to in vivo-grown, seed-derived plants except that they were phenotypically smaller. A positive influence of haemoglobin was observed at concentrations up to 400 mg/l at all stages of somatic embryogenesis. The increase in the levels of antioxidant enzyme activities, for example superoxide dismutase and peroxidase, indicated the presence of excess oxygen uptake and the stressed condition of the plant tissues that arose from haemoglobin supplementation. This increased oxygen uptake and haemoglobin-mediated stress appeared to accelerate somatic embryogenesis in cotton.

[Introduction of capillary glycosylated haemoglobin determination in a Primary Care Health Area: Multicentre study of the evolution of patients with type 2 diabetes mellitus].

PubMed

Núñez-Sánchez, M Á; Cervantes-Cuesta, M Á; Brocal-Ibañez, P; Salmeron-Arjona, E; León-Martínez, L P; Cerezo-Sanmartin, M

The aim of this study was to evaluate the efficiency of a joint intervention that included educational components, self-assessment, and information to optimise diabetes control through the introduction of instant capillary glycosylated haemoglobin (HbA1c) determination in Primary Care. A multicentre prospective descriptive study was carried out over 3years in 10Primary Care Centres of the Area VII Murcia East. At the end of the study there were 804 patients with type 2 diabetes (DM2). Patients were divided into 4 groups based on initial values of HbA1c, and if changes in their treatment were needed. HbA1c, body mass index, and blood pressure were monitored. A financial assessment was also performed on the impact of the implementation of a protocol to measure instant capillary RESULTS: A significant reduction was observed in HbA1c values. The initial HbA1c mean value was 7.4±1.4%, which decreased to a final value of 6.9±1.0% (P<.001). At the end of the study, 71.4% of patients included reached diabetic control objectives. In addition, the financial assessment demonstrated that the implementation of this diabetes control system led to a decrease of the 24.7% in spending on glucose strips after the first year of study in Area VII Murcia Health Service. The introduction of capillary HbA1c determination in Primary Care has demonstrated to improve diabetes control and the efficiency of the health personnel. Furthermore, a reduction in the health costs of patients with DM2 was also shown. Copyright © 2016 SECA. Publicado por Elsevier España, S.L.U. All rights reserved.

Nitric oxide-fixation by non-symbiotic haemoglobin proteins in Arabidopsis thaliana under N-limited conditions.

PubMed

Kuruthukulangarakoola, Gitto Thomas; Zhang, Jiangli; Albert, Andreas; Winkler, Barbro; Lang, Hans; Buegger, Franz; Gaupels, Frank; Heller, Werner; Michalke, Bernhard; Sarioglu, Hakan; Schnitzler, Jörg-Peter; Hebelstrup, Kim Henrik; Durner, Jörg; Lindermayr, Christian

2017-01-01

Nitric oxide (NO) is an important signalling molecule that is involved in many different physiological processes in plants. Here, we report about a NO-fixing mechanism in Arabidopsis, which allows the fixation of atmospheric NO into nitrogen metabolism. We fumigated Arabidopsis plants cultivated in soil or as hydroponic cultures during the whole growing period with up to 3 ppmv of NO gas. Transcriptomic, proteomic and metabolomic analyses were used to identify non-symbiotic haemoglobin proteins as key components of the NO-fixing process. Overexpressing non-symbiotic haemoglobin 1 or 2 genes resulted in fourfold higher nitrate levels in these plants compared with NO-treated wild-type. Correspondingly, rosettes size and weight, vegetative shoot thickness and seed yield were 25, 40, 30, and 50% higher, respectively, than in wild-type plants. Fumigation with 250 ppbv 15 NO confirmed the importance of non-symbiotic haemoglobin 1 and 2 for the NO-fixation pathway, and we calculated a daily uptake for non-symbiotic haemoglobin 2 overexpressing plants of 250 mg N/kg dry weight. This mechanism is probably important under conditions with limited N supply via the soil. Moreover, the plant-based NO uptake lowers the concentration of insanitary atmospheric NOx, and in this context, NO-fixation can be beneficial to air quality. © 2016 The Authors Plant, Cell & Environment Published by John Wiley & Sons Ltd.

An evaluation of the Diamat HPLC analyser for simultaneous determination of haemoglobins A2 and F

PubMed Central

Carpinelli, Assunta; Majavacca, Rita; Cantu'-Rajnoldi, Angelo; Garatti, Massimo; Paleari, Renata; Ferrari, Maurizio; Agape, Vittorio; Maccioni, Liliana; Pisano, Sandra; Galanello, Renzo

1989-01-01

The authors describe a modification of the instrumental parameters of the Diamat fully automated HPLC system for Hb A2 assay (Bio-Rad Laboratories, Milan, Italy) in order to obtain simultaneous determination of Hb A2 and Hb F. Hb A2 and Hb F measurements are reproducible (within-run CV 2.6%, with Hb A22.7%; 5.1%, with Hb F 1.3%) and accurate (from a comparison with two microchromatographic techniques for Hb A2: r = 0.9639 and 0.9755; with two alkali denaturation procedures for Hb F: r = 0.9990 and 0.9952; with radial immunodiffusion, r = 0.9877). Assay linearity has been confirmed for Hb A2 concentrations between 0 and 6.0%, and for Hb F between 0 and 60%. The data obtained from the analysis of some pathological samples for Hb Bart's, Hb H, Hb J Sardegna, Hb Lepore and Hb S are in agreement with cellulose acetate electrophoresis analysis. The Hb A2 reference intervals for normals (N = 597) and Beta-thalassemia carriers (N = 200) are respectively (95% limits) 2.02-3.27 and 3.92-5.90 in % units. Hb F values measured in normals (N = 968), in β-thal carriers (N = 302) and in δβ-thal carriers (N =3) have been found to be consistent with the usual diagnostic parameters. Some minor limitations emerged: the most relevant concerns Hb A1c, which is overestimated with respect to a reference method (y = 1.217x + 0.16; N = 79; r = 0.9235). A probable interference from labile fractions is responsible for this Hb A1c inaccuracy. PMID:18925255

A Cross-Reactive Monoclonal Antibody to Nematode Haemoglobin Enhances Protective Immune Responses to Nippostrongylus brasiliensis

PubMed Central

Nieuwenhuizen, Natalie E.; Meter, Jeanne M.; Horsnell, William G.; Hoving, J. Claire; Fick, Lizette; Sharp, Michael F.; Darby, Matthew G.; Parihar, Suraj P.; Brombacher, Frank; Lopata, Andreas L.

2013-01-01

Background Nematode secreted haemoglobins have unusually high affinity for oxygen and possess nitric oxide deoxygenase, and catalase activity thought to be important in protection against host immune responses to infection. In this study, we generated a monoclonal antibody (48Eg) against haemoglobin of the nematode Anisakis pegreffii, and aimed to characterize cross-reactivity of 4E8g against haemoglobins of different nematodes and its potential to mediate protective immunity against a murine hookworm infection. Methodology/Principal Findings Immunoprecipitation was used to isolate the 4E8g-binding antigen in Anisakis and Ascaris extracts, which were identified as haemoglobins by peptide mass fingerprinting and MS/MS. Immunological cross-reactivity was also demonstrated with haemoglobin of the rodent hookworm N. brasiliensis. Immunogenicity of nematode haemoglobin in mice and humans was tested by immunoblotting. Anisakis haemoglobin was recognized by IgG and IgE antibodies of Anisakis-infected mice, while Ascaris haemoglobin was recognized by IgG but not IgE antibodies in mouse and human sera. Sequencing of Anisakis haemoglobin revealed high similarity to haemoglobin of a related marine nematode, Psuedoterranova decipiens, which lacks the four –HKEE repeats of Ascaris haemoglobin important in octamer assembly. The localization of haemoglobin in the different parasites was examined by immunohistochemistry and associated with the excretory-secretary ducts in Anisakis, Ascaris and N. brasiliensis. Anisakis haemoglobin was strongly expressed in the L3 stage, unlike Ascaris haemoglobin, which is reportedly mainly expressed in adult worms. Passive immunization of mice with 4E8g prior to infection with N. brasiliensis enhanced protective Th2 immunity and led to a significant decrease in worm burdens. Conclusion The monoclonal antibody 4E8g targets haemoglobin in broadly equivalent anatomical locations in parasitic nematodes and enhances host immunity to a hookworm

A cross-reactive monoclonal antibody to nematode haemoglobin enhances protective immune responses to Nippostrongylus brasiliensis.

PubMed

Nieuwenhuizen, Natalie E; Meter, Jeanne M; Horsnell, William G; Hoving, J Claire; Fick, Lizette; Sharp, Michael F; Darby, Matthew G; Parihar, Suraj P; Brombacher, Frank; Lopata, Andreas L

2013-01-01

Nematode secreted haemoglobins have unusually high affinity for oxygen and possess nitric oxide deoxygenase, and catalase activity thought to be important in protection against host immune responses to infection. In this study, we generated a monoclonal antibody (48Eg) against haemoglobin of the nematode Anisakis pegreffii, and aimed to characterize cross-reactivity of 4E8g against haemoglobins of different nematodes and its potential to mediate protective immunity against a murine hookworm infection. Immunoprecipitation was used to isolate the 4E8g-binding antigen in Anisakis and Ascaris extracts, which were identified as haemoglobins by peptide mass fingerprinting and MS/MS. Immunological cross-reactivity was also demonstrated with haemoglobin of the rodent hookworm N. brasiliensis. Immunogenicity of nematode haemoglobin in mice and humans was tested by immunoblotting. Anisakis haemoglobin was recognized by IgG and IgE antibodies of Anisakis-infected mice, while Ascaris haemoglobin was recognized by IgG but not IgE antibodies in mouse and human sera. Sequencing of Anisakis haemoglobin revealed high similarity to haemoglobin of a related marine nematode, Psuedoterranova decipiens, which lacks the four -HKEE repeats of Ascaris haemoglobin important in octamer assembly. The localization of haemoglobin in the different parasites was examined by immunohistochemistry and associated with the excretory-secretary ducts in Anisakis, Ascaris and N. brasiliensis. Anisakis haemoglobin was strongly expressed in the L3 stage, unlike Ascaris haemoglobin, which is reportedly mainly expressed in adult worms. Passive immunization of mice with 4E8g prior to infection with N. brasiliensis enhanced protective Th2 immunity and led to a significant decrease in worm burdens. The monoclonal antibody 4E8g targets haemoglobin in broadly equivalent anatomical locations in parasitic nematodes and enhances host immunity to a hookworm infection.

Association between maternal haemoglobin and stillbirth: a cohort study among a multi-ethnic population in England.

PubMed

Nair, Manisha; Churchill, David; Robinson, Susan; Nelson-Piercy, Cathy; Stanworth, Simon J; Knight, Marian

2017-12-01

The study objectives were to examine the association of maternal haemoglobin with stillbirth and perinatal death in a multi-ethnic population in England. We conducted a retrospective cohort analysis using anonymised maternity data from 14 001 women with singleton pregnancies ≥24 weeks' gestation giving birth between 2013 and 2015 in two hospitals - the Royal Wolverhampton NHS Trust and Guy's and St Thomas' NHS Foundation Trust. Multivariable logistic regression analyses were undertaken to analyse the associations between maternal haemoglobin at first visit and at 28 weeks with stillbirth and perinatal death, adjusting for 11 other risk factors. Results showed that 46% of the study population had anaemia (haemoglobin <110 g/l) at some point during their pregnancy. The risk of stillbirth and perinatal death decreased linearly per unit increase in haemoglobin concentration at first visit (adjusted odds ratio [aOR] stillbirth = 0·70, 95% confidence interval [CI] 0·58-0·85, aOR perinatal death = 0·71, 95% CI 0·60-0·84) and at 28 weeks (aOR stillbirth = 0·83, 95% CI 0·66-1·04; aOR perinatal death = 0·86, 95%CI 0·67-1·12). Compared with women with haemoglobin ≥110 g/l, the risk of stillbirth and perinatal death was five- and three-fold higher in women with moderate-severe anaemia (haemoglobin <100 g/l) at first visit and 28 weeks, respectively. These findings have clinical and public health importance. © 2017 The Authors. British Journal of Haematology published by John Wiley & Sons Ltd.

Glaucoma diagnostic capacity of optic nerve head haemoglobin measures compared with spectral domain OCT and HRT III confocal tomography.

PubMed

Mendez-Hernandez, Carmen; Rodriguez-Uña, Ignacio; Gonzalez-de-la Rosa, Manuel; Arribas-Pardo, Paula; Garcia-Feijoo, Julian

2016-11-01

The computer program laguna onhe determines optic nerve head haemoglobin (ONH Hb) on retinal photographs based on detecting colour differences. This study compares the diagnostic capacity of Laguna ONhE with that of spectral domain optical coherence tomography (OCT) and confocal tomography (HRT III). In a prospective, observational, cross-sectional study, glaucomatous (n = 66) and healthy (n = 52) eyes were examined by Spectralis OCT, HRT III and Laguna ONhE. The following Laguna ONhE variables were determined: ONH Hb across the vertical disc diameter (8&20 Hb), estimated cup-disc ratio (C/D) and the glaucoma discriminant function (GDF), which combines the slope of Hb amount with the mean in 8&20 Hb. The three diagnostic methods were compared by calculating areas under ROC curves (AUCs). Correlations between variables were assessed through Spearman's rho coefficient. Areas under ROC curves (AUCs) were 0.785 (95% CI: 0.700-0.863) for GDF, 0.807 (95% CI: 0.730-0.883) for OCT retinal nerve fibre layer thickness (OCT-RNFL) and 0.714 (95% CI: 0.618-0.810) and 0.721 (95% CI: 0.628-0.815) for the HRT III variable GPS (glaucoma probability score) and vertical C/D ratio, respectively. Glaucoma discriminant function (GDF) was correlated with OCT-RNFL (0.587, p 0.001; 0.507, p 0.045; and -0.119, p 0.713 for mild, moderate and advanced glaucoma, respectively), mostly so with inferior OCT-RNFL (0.622; p < 0.001). Glaucoma discriminant function (GDF)-HRT III correlations were lower (rim area 0.471, p < 0.0001; rim/disc area 0.426, p < 0.0001; vertical C/D -0.413, p < 0.0001; GPS -0.408, p < 0.0001; rim volume 0.341, p < 0.0001). Similar diagnostic power was observed for Laguna ONhE, Spectralis OCT and HRT III. © 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Haematological and electrophoretic characterisation of β-thalassaemia in Yunnan province of Southwestern China.

PubMed

Zhang, Jie; He, Jing; Mao, Xiaoqin; Zeng, Xiaohong; Chen, Hong; Su, Jie; Zhu, Baosheng

2017-01-31

β-Thalassaemia is widely found in Southwestern China. Characterisation of β-thalassaemia can improve screening and prenatal diagnosis for at-risk populations. A retrospective study. In this study, the levels of haemoglobin alpha 2 (HbA 2 ) and haemoglobin alpha (HbA) were analysed by gender for a total of 15 067 subjects screened by capillary electrophoresis. The cut-off value with the highest accuracy was established to identify β-thalassaemia in 723 patients suspected to have this disease. Haematological and electrophoretic characterisation of eight common types of β-thalassaemia were analysed in 486 β-thalassaemia subjects. HbA levels were significantly higher in men than in women, but there was no significant difference on HbA 2 levels. A new cut-off value for the diagnosis of β-thalassaemia (HbA 2 ≥4.0%) with the highest accuracy was proposed for the studied populations. Haemoglobin (Hb) was significantly higher in men compared with women (p<0.05), whereas no statistically significant differences were found for mean cell volume (MCV), mean cell haemoglobin (MCH), HbA and HbA 2 . The haemoglobin E (HbE) group showed comparatively higher values for haematological indices (Hb, MCV and MCH) than the other genotypes in heterozygous β-thalassaemia groups (p<0.05), and -28 (A>G) (HBB (β-globin):c.-78A>C) had significantly higher HbA 2 values compared with other β-thalassaemia. Ethnic groups have diversified β-globin gene mutations and considerable haematological variations. Our study will lay the foundation for screening programmes and clinical management of thalassaemia in Southwestern China. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Hepcidin plasma levels are not associated with changes in haemoglobin in early rheumatoid arthritis patients.

PubMed

Østgård, R D; Glerup, H; Jurik, A G; Kragstrup, T W; Stengaard-Pedersen, K; Hetland, M L; Hørslev-Petersen, K; Junker, P; Deleuran, B W

2017-11-01

A reduction in haemoglobin level is a frequent complication among rheumatoid arthritis (RA) patients. Hepcidin has been linked to disturbed erythropoiesis. The objective of this study was to investigate the longitudinal changes in hepcidin in patients with early RA. Hepcidin plasma concentrations were measured by enzyme-linked immunosorbent assay in patients with early RA (n = 80) and healthy volunteers (HV, n = 40). Haemoglobin and other iron-related proteins were also measured. At baseline, all patients had active disease and were treatment naïve. Patients were treated with disease-modifying anti-rheumatic drugs (DMARDs) and with additional adalimumab (ADA, n = 42) or placebo (PLA, n = 38) during 52 weeks, using a treat-to-target strategy, aiming for a 28-joint Disease Activity Score (DAS28) < 3.2. At baseline, hepcidin levels [median (interquartile range)] were 9.7 ng/mL (5.2-19.4 ng/mL) in DMARD + ADA and 11.3 ng/mL (5.9-19.1 ng/mL) in DMARD + PLA. Both were significantly higher than seen in HV (6.0 ng/mL (3.3-9.3 ng/mL) (p < 0.001). After 12 months, both treatment regimens resulted in normalization of hepcidin. DAS28 correlated with hepcidin at baseline (r = 0.48, p < 0.001). No correlation was observed between levels of haemoglobin and hepcidin at baseline or during the 52 week follow-up. No change in haemoglobin levels was seen as a function of hepcidin changes. In a mixed statistical model, no single factor was connected with the regulation of haemoglobin in early RA. The changes in hepcidin were not associated with changes in haemoglobin levels. Thus, hepcidin could not be used as a prognostic marker in patients with early RA.

Estimation of the quantum efficiency of the photodissociation of HbO2 and HbCO

NASA Astrophysics Data System (ADS)

Gisbrecht, A. I.; Mamilov, S. A.; Esman, S. S.; Asimov, M. M.

2016-01-01

The paper presents our results on the study of the efficiency of inter-fractional changes in hemoglobin molecules depending on the laser radiation parameters. The evaluation of the quantum efficiency of light interaction in vivo with oxyhemoglobin (HbO2) and carboxyhemoglobin (HbCO) in the blood at wavelengths for 525 and 605 nm is presented. The photodissociation yield of 11% for HbO2 and 79% for HbCO are measured at the wavelength of 525 nm and 10 % for HbO2 and 76 % for HbCO at a wavelength of 605 nm. Thus, the quantum yield of photodissociation of the HbCO is considerably higher, which ensures high efficiency of photodecomposition of the HbCO in the blood. The obtained results can be used in the clinical phototherapy practice for effective treatment of CO poisoning.

A pilot study of an HbA1c chairside screening protocol for diabetes in patients with chronic periodontitis: the dental hygienist's role.

PubMed

Bossart, M; Calley, K H; Gurenlian, J R; Mason, B; Ferguson, R E; Peterson, T

2016-05-01

To assess effectiveness, convenience and cost of point-of-care diabetes screenings performed by a dental hygienist for patients with periodontitis, using a diabetes risk questionnaire, periodontal findings and a glycosylated haemoglobin (HbA1c) analyser. A purposive sample of 50 participants with periodontitis, never diagnosed with diabetes, reporting ≥one diabetes risk factor, were administered an HbA1c test. Spearman's correlation measured relationships between HbA1c and diabetes risk test scores, numbers of missing teeth, percentage of deep pockets ≥5 mm and percentage of bleeding sites (BOP). Cost and time were assessed. Analyses used 0.05 alpha levels. Thirty-two per cent (n = 16) of participants presented HbA1c values indicating prediabetes; one HbA1c value indicated type 2 diabetes, totalling 34% (N = 17). No relationships existed between HbA1c values and diabetes risk scores (rs = 0.153; P = 0.144), numbers of missing teeth (r = 0.190; P = 0.093), percentage of deep pockets (rs = -0.048; P = 0.370) or percentage of BOP sites (rs = 0.066, P = 0.324). Direct cost for each HbA1c was $9US, excluding follow-up medical diagnosis. Mean screening time including patient education was 14 min (SD = 6.2). Fifty-three per cent (n = 9 of 17) of participants with elevated HbA1c values contacted their primary healthcare provider within 2 weeks as recommended. Point-of-care HbA1c screenings by dental hygienists were effective and convenient for identifying undiagnosed prediabetes and provide opportunity for interprofessional patient care; cost or lack of dental insurance may inhibit implementation. Identification of patients at risk for diabetes requires further evaluation. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

HbA1c below 7% as the goal of glucose control fails to maximize the cardiovascular benefits: a meta-analysis.

PubMed

Wang, Pin; Huang, Rong; Lu, Sen; Xia, Wenqing; Sun, Haixia; Sun, Jie; Cai, Rongrong; Wang, Shaohua

2015-09-22

Whether lowering glycosylated haemoglobin (HbA1c) level below 7.0% improves macro-vascular outcomes in diabetes remains unclear. Here, we aimed to assess the effect of relatively tight glucose control resulting in a follow-up HbA1c level of less or more than 7.0% on cardiovascular outcomes in diabetic patients. We systematically searched Medline, Web of science and Cochrane Library for prospective randomized controlled trials published between Jan 1, 1996 and July 1, 2015 that recorded cardiovascular outcome trials of glucose-lowering drugs or strategies in patients with type 2 diabetes mellitus. Data from 15 studies involving 88,266 diabetic patients with 4142 events of non-fatal myocardial infarction, 6997 of major cardiovascular events, 3517 of heart failure, 6849 of all-cause mortality, 2084 of non-fatal stroke, 3816 of cardiovascular death were included. A 7% reduction of major cardiovascular events was observed only when relatively tight glucose control resulted in a follow-up HbA1c level above 7.0% (OR 0.93, 95% CI 0.88-0.98; I(2) = 33%), however, the patients can benefit from reduction incidence of non-fatal myocardial infarction only when the follow-up HbA1c value below 7.0% (OR 0.85, 95% CI 0.74-0.96). Apart from the HbA1c value above 7.0% (OR 1.22, 95% CI 1.06-1.40), the application of thiazolidinediones (OR 1.39, 95% CI 1.14-1.69) also increased the risk of heart failure, while the gliptins shows neutral effects to heart failure (OR 1.14, 95% CI 0.97-1.34). Relatively tight glucose control has some cardiovascular benefits. HbA1c below 7.0% as the goal to maximize the cardiovascular benefits remains suspended.

Prevalence of anaemia in pregnant women during the last trimester: consequense for birth weight.

PubMed

Demmouche, A; Lazrag, A; Moulessehoul, S

2011-04-01

Iron deficiency continues to be one of the most prevalent single-nutrient deficiencies in the world. The current study aimed to estimate the prevalence of iron deficiency anemia (IDA) among pregnant women who attend Antenatal Care Centers in Sidi Bel Abbes, Algeria. The effect of anaemia on infant birth weight was also examined. The study was conducted during the period March-Mai, 2010 and the sample consisted of 207 pregnant women (in the third trimesters) in the age group (17-41) years. The subjects were not taking iron, folate or vitamin B12 supplements at the time of the study. Blood samples were collected from each pregnant woman and a questionnaire was completed at the time of blood collection. A series of determinations was conducted to determine hemoglobin concentration (Hb); packed cell volume (PCV); corpuscular hemoglobin concentration (MCHC), corpuscular volume (MCV). The effect of anemia on the weight of new born babies was examined by calculating the correlation coefficient of birth weight and hematological indexes. The overall prevalence of anemia was found to be 46.86%. According to the severity anemia was 36.08% mild, 49.48% moderate and 14.43% severe anemia. The mean values (+/- SD) of haematological indexes were as follows: Hb 9.00 +/- 1.57 g/dl; PCV 27 +/- 5.37%; mean corpuscular haemoglobin concentration (MCHC) 33.75 +/- 2.69 g/dl and mean corpuscular volume (MCV) 75.7 +/- 10.4 fl. The results have shown that 46.39% of the subjects had MCV values less than standard value of 75 fl suggesting a microcytic anemia. The mean haemoglobin concentration was 9 +/- 1.57 g/dl while the mean birth weight was 3201.54 +/- 566.71 g. There was a not significant correlation between the Hb level and the birth weight of the infants (r = 0.28, p > 0.05). The prevalence of low birth weight was 9.2%. There was no statistically significant haemoglobin concentration /foetal birth weight difference among the various hemoglobin concentration (Chi square test = 0.34, p

Evaluation of high performance liquid chromatography (HPLC) pattern and prevalence of beta-thalassaemia trait among sickle cell disease patients in Lagos, Nigeria.

PubMed

Adeyemo, Titilope; Ojewunmi, Oyesola; Oyetunji, Ajoke

2014-01-01

Sickle cell disease (SCD) is the most common inherited disorder of haemoglobin worldwide. This study evaluated the chromatographic patterns and red blood cell indices of sickle cell patients to determine the co-inheritance of other haemoglobin(Hb) variants and β-thalassaemia trait. Red cell indices, blood film, sickle solubility test, Hb electrophoresis using alkaline cellulose acetate membrane, and chromatographic patterns using Bio Rad HPLC Variant II were evaluated for 180 subjects. Based on low MCV <76fL and MCH<25 pg, in the presence of elevated A₂ >4.0% on HPLC and Hb variants eluting outside the S and C windows, at least four haemoglobin phenotypes (SS: 87.7%; SC: 1.1%; SD Punjab: 0.6%; Sβ-thalassemia: 10.6%) were identified. Mean Hb F% was 8.1±5.1 (median 7.65) for Hb SS and 6.03±5.2 (median 3.9) for Hb Sβ-thalassemia trait. Majority of Hb SS (69.1%) had Hb F% less than 10 while 27.6% had 10-19.9 and 3.2% had ≥ 20. Mean Hb F% was higher in female Hb SS (9.55±5.09; mean age 7.4±3.8 years) than the males (7.63±4.80; mean age 6.9±3.8 years) (P=0.02). A borderline significant negative correlation between age and Hb F levels among Hb SS subjects (r= -0.169 P=0.038) was also observed. Our data suggests that α and β- thalassaemia traits, and other haemoglobin variants co-exist frequently with SCD in our population.

Comparison of the Current Diagnostic Criterion of HbA1c with Fasting and 2-Hour Plasma Glucose Concentration

PubMed Central

Karnchanasorn, Rudruidee; Huang, Jean; Feng, Wei; Chuang, Lee-Ming

2016-01-01

To determine the effectiveness of hemoglobin A1c (HbA1c) ≥ 6.5% in diagnosing diabetes compared to fasting plasma glucose (FPG) ≥ 126 mg/dL and 2-hour plasma glucose (2hPG) ≥ 200 mg/dL in a previously undiagnosed diabetic cohort, we included 5,764 adult subjects without established diabetes for whom HbA1c, FPG, 2hPG, and BMI measurements were collected. Compared to the FPG criterion, the sensitivity of HbA1c ≥ 6.5% was only 43.3% (106 subjects). Compared to the 2hPG criterion, the sensitivity of HbA1c ≥ 6.5% was only 28.1% (110 subjects). Patients who were diabetic using 2hPG criterion but had HbA1c < 6.5% were more likely to be older (64 ± 15 versus 60 ± 15 years old, P = 0.01, mean ± STD), female (53.2% versus 38.2%, P = 0.008), leaner (29.7 ± 6.1 versus 33.0 ± 6.6 kg/m2, P = 0.000005), and less likely to be current smokers (18.1% versus 29.1%, P = 0.02) as compared to those with HbA1c ≥ 6.5%. The diagnostic agreement in the clinical setting revealed the current HbA1c ≥ 6.5% is less likely to detect diabetes than those defined by FPG and 2hPG. HbA1c ≥ 6.5% detects less than 50% of diabetic patients defined by FPG and less than 30% of diabetic patients defined by 2hPG. When the diagnosis of diabetes is in doubt by HbA1c, FPG and/or 2hPG should be obtained. PMID:27597979

Identification of rare and novel deletions that cause (δβ)0-thalassaemia and hereditary persistence of foetal haemoglobin in Indian population.

PubMed

Mayuranathan, Thiyagaraj; Rayabaram, Janakiram; Das, Reena; Arora, Neeraj; Edison, Eunice S; Chandy, Mammen; Srivastava, Alok; Velayudhan, Shaji R

2014-06-01

Hereditary persistence of foetal haemoglobin (HPFH) and (δβ)(0) -thalassaemia are conditions caused by large deletions that involve δ- and β-globin genes in the β-globin cluster, and they are characterized by increased haemoglobin (HbF) levels in adults. Significant phenotypic diversity is observed between the different mutations that cause these conditions. Molecular characterization of these deletions is important for accurate molecular diagnosis, and they will also provide the information on the cis-acting genetic regulatory elements present in the β-globin cluster. We performed gap-PCR, multiplex ligation-dependent probe amplification (MLPA), quantitative fluorescent multiplex PCR (QF-MPCR) and DNA sequencing to detect and characterize the deletions in the β-globin cluster. We characterized six different deletions resulting in (δβ)(0) -thalassaemia or HPFH in 51 unrelated families. With the help of multiple genetic tools, we performed comprehensive genetic analysis of HPFH and (δβ)(0) -thalassaemia in Indian population and could define the molecular basis of these conditions in this population. We also identified two novel HPFH mutations, 49.98 kb (HPFH-9) and 86.7 kb (HPFH-10) deletions, in this population. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Prevalence of haemoglobinopathies in 34,030 healthy adults in Tehran, Iran.

PubMed

Ashtiani, M T H; Monajemzadeh, M; Sina, A H; Berenji, F; Abdollahi, M; Said, M G; Alam, M

2009-10-01

Haemoglobinopathies are a group of inherited disorders of haemoglobin synthesis. Their frequency varies considerably with geographic location and ethnic group. To establish the prevalence of haemoglobinopathies in a mainly healthy Iranian population. All files of the haematology unit of the Boghrat laboratory over a period of 10 years (1998-2007) were analysed in relation to the age, sex, full blood count, haemoglobin electrophoresis results, high performance liquid chromatography (HPLC) findings, and iron profile of healthy subjects referred for consultation before marriage. Other tests were performed if indicated. There were 34,030 files; 13,432 (39.5%) were for men, and 20,567 (60.4%) for women. 0.74% of subjects (255) showed a haemoglobinopathy. The distribution of variant haemoglobins in these 255 subjects was: Hb D 75.67% (193 cases), Hb S 4.7%, Hb E 3.13%, Hb O-Arab 1.96% and Hb Lepore 0.39%. A fast haemoglobin was found in 4.71% of subjects. Of the subjects tested, 13.2% (4478) had beta-thalassaemia minor, 0.2% (52) beta-thalassaemia intermedia and 0.1% (30) beta-thalassaemia major. In comparison with other parts of world, there is a different pattern of haemoglobinopathy with a high prevalence of Hb D, which appears to be Hb D Iran.

Purification, crystallization and preliminary crystallographic study of low oxygen-affinity haemoglobin from cat (Felis silvestris catus) in two different crystal forms.

PubMed

Balasubramanian, M; Moorthy, Pon Sathya; Neelagandan, K; Ponnuswamy, M N

2009-03-01

Haemoglobin is a metalloprotein which plays a major role in the transportation of oxygen from the lungs to tissues and of carbon dioxide back to the lungs. The present work reports the preliminary crystallographic study of low oxygen-affinity haemoglobin from cat in different crystal forms. Cat blood was collected, purified by anion-exchange chromatography and crystallized in two different conditions by the hanging-drop vapour-diffusion method under unbuffered low-salt and buffered high-salt concentrations using PEG 3350 as a precipitant. Intensity data were collected using MAR345 and MAR345dtb image-plate detector systems. Cat haemoglobin crystallizes in monoclinic and orthorhombic crystal forms with one and two whole biological molecules (alpha(2)beta(2)), respectively, in the asymmetric unit.

Patterns of type 2 diabetes monitoring in rural towns: How does frequency of HbA1c and lipid testing compare with existing guidelines?

PubMed

Paul, Christine L; Piterman, Leon; Shaw, Jonathan E; Kirby, Catherine; Barker, Daniel; Robinson, Jennifer; Forshaw, Kristy L; Sikaris, Kenneth A; Bisquera, Alessandra; Sanson-Fisher, Robert W

2016-12-01

To indicate levels of monitoring of type 2 diabetes in rural and regional Australia by examining patterns of glycated haemoglobin (HbA1c) and blood lipid testing. Retrospective analysis of pathology services data from twenty regional and rural towns in eastern Australia over 24 months. Of 13 105 individuals who had either a single HbA1c result ≥7.0% (53 mmol mol -1 ); or two or more HbA1c tests within the study period. Frequency of testing of HbA1c and blood lipids (cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol and triglycerides) were compared with guideline recommendations. About 58.3% of patients did not have the recommended 6-monthly HbA1c tests and 30.6% did not have annual lipid testing. For those who did not receive tests at the recommended interval, the mean between-test interval was 10.5 months (95% CI = 7.5-13.5) rather than 6 months for HbA1c testing; and 15.7 (95% CI = 13.3-18.1) months rather than annually for blood lipids. For those with at least one out-of-range test result, 77% of patients failed to receive a follow-up HbA1c test and 86.5% failed to receive a follow-up blood lipid test within the recommended 3 months. Patients less than 50 years of age, living in a more remote area and with poor diabetes control were less likely to have testing at the recommended intervals (P < 0.0001). Although poor diabetes testing is not limited to rural areas, more intensive diabetes monitoring is likely to be needed for patients living in non-metropolitan areas, particularly for some subgroups. © 2016 National Rural Health Alliance Inc.

Circulation kinetics and organ distribution of Hb-vesicles developed as a red blood cell substitute.

PubMed

Sou, Keitaro; Klipper, Robert; Goins, Beth; Tsuchida, Eishun; Phillips, William T

2005-02-01

Phospholipid vesicles encapsulating concentrated human hemoglobin (Hb-vesicles, HbV), also known as liposomes, have a membrane structure similar to that of red blood cells (RBCs). These vesicles circulate in the bloodstream as an oxygen carrier, and their circulatory half-life times (t(1/2)) and biodistribution are fundamental characteristics required for representation of their efficacy and safety as a RBC substitute. Herein, we report the pharmacokinetics of HbV and empty vesicles (EV) that do not contain Hb, in rats and rabbits to evaluate the potential of HbV as a RBC substitute. The samples were labeled with technetium-99m and then intravenously infused into animals at 14 ml/kg to measure the kinetics of HbV elimination from blood and distribution to the organs. The t(1/2) values were 34.8 and 62.6 h for HbV and 29.3 and 57.3 h for EV in rats and rabbits, respectively. At 48 h after infusion, the liver, bone marrow, and spleen of both rats and rabbits had significant concentrations of HbV and EV, and the percentages of the infused dose in these three organs were closely correlated to the circulatory half-life times in elimination phase (t(1/2beta)). Furthermore, the milligrams of HbV per gram of tissue correlated well between rats and rabbits, suggesting that the balance between organ weight and body weight is a fundamental factor determining the pharmacokinetics of HbV. This factor could be used to estimate the biodistribution and the circulation time of HbV in humans, which is estimated to be equal to that in rabbit.

The Hb A variant (beta73 Asp-->Leu) disrupts Hb S polymerization by a novel mechanism.

PubMed

Adachi, Kazuhiko; Ding, Min; Surrey, Saul; Rotter, Maria; Aprelev, Alexey; Zakharov, Mikhail; Weng, Weijun; Ferrone, Frank A

2006-09-22

Polymerization of a 1:1 mixture of hemoglobin S (Hb S) and the artificial mutant HbAbeta73Leu produces a dramatic morphological change in the polymer domains in 1.0 M phosphate buffer that are a characteristic feature of polymer formation. Instead of feathery domains with quasi 2-fold symmetry that characterize polymerization of Hb S and all previously known mixtures such as Hb A/S and Hb F/S mixtures, these domains are compact structures of quasi-spherical symmetry. Solubility of Hb S/Abeta73Leu mixtures was similar to that of Hb S/F mixtures. Kinetics of polymerization indicated that homogeneous nucleation rates of Hb S/Abeta73Leu mixtures were the same as those of Hb S/F mixtures, while exponential polymer growth (B) of Hb S/Abeta73Leu mixtures were about three times slower than those of Hb S/F mixtures. Differential interference contrast (DIC) image analysis also showed that fibers in the mixture appear to elongate between three and five times more slowly than in equivalent Hb S/F mixtures by direct measurements of exponential growth of mass of polymer in a domain. We propose that these results of Hb S/Abeta73Leu mixtures arise from a non-productive binding of the hybrid species of this mixture to the end of the growing polymer. This "cap" prohibits growth of polymers, but by nature is temporary, so that the net effect is a lowered growth rate of polymers. Such a cap is consistent with known features of the structure of the Hb S polymer. Domains would be more spherulitic because slower growth provides more opportunity for fiber bending to spread domains from their initial 2-fold symmetry. Moreover, since monomer depletion proceeds more slowly in this mixture, more homogeneous nucleation events occur, and the resulting gel has a far more granular character than normally seen in mixtures of non-polymerizing hemoglobins with Hb S. This mixture is likely to be less stiff than polymerized mixtures of other hybrids such as Hb S with HbF, potentially providing a novel

Characterization of HbWRKY1, a WRKY transcription factor from Hevea brasiliensis that negatively regulates HbSRPP.

PubMed

Wang, Ying; Guo, Dong; Li, Hui-Liang; Peng, Shi-Qing

2013-10-01

Small rubber particle protein (SRPP) is a major component of Hevea brasiliensis (H. brasiliensis) latex, which is involved in natural rubber (NR) biosynthesis. However, little information is available on the regulation of SRPP gene (HbSRPP) expression. To study the transcriptional regulation of HbSRPP, the yeast one-hybrid experiment was performed to screen the latex cDNA library using the HbSRPP promoter as bait. One cDNA that encodes the WRKY transcription factor, designated as HbWRKY1, was isolated from H. brasiliensis. HbWRKY1 contains a 1437 bp open reading frame that encodes 478 amino acids. The deduced HbWRKY1 protein was predicted to possess two conserved WRKY domains and a C2H2 zinc-finger motif. HbWRKY1 was expressed at different levels, with the highest transcription in the flower, followed by the bark, latex, and leaf. Furthermore, the co-expression of pHbSRP::GUS with CaMV35S::HbWRKY1 significantly decreased the GUS activity in transgenic tobacco, indicating that HbWRKY1 significantly suppressed the HbSRPP promoter. These results suggested that HbWRKY1 maybe a negative transcription regulator of HbSRPP involved in NR biosynthesis in H. brasiliensis. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Probing the diphosphoglycerate binding pocket of HbA and HbPresbyterian (beta 108Asn --> Lys).

PubMed

Gottfried, D S; Manjula, B N; Malavalli, A; Acharya, A S; Friedman, J M

1999-08-31

HbPresbyterian (beta 108Asn --> Lys, HbP) contains an additional positive charge (per alpha beta dimer) in the middle of the central cavity and exhibits a lower oxygen affinity than wild-type HbA in the presence of chloride. However, very little is known about the molecular origins of its altered functional properties. In this study, we have focused on the beta beta cleft of the Hb tetramer. Recently, we developed an approach for quantifying the ligand binding affinity to the beta-end of the Hb central cavity using fluorescent analogues of the natural allosteric effector 2, 3-diphosphoglycerate (DPG) [Gottfried, D. S., et al. (1997) J. Biol. Chem. 272, 1571-1578]. Time-correlated single-photon counting fluorescence lifetime studies were used to assess the binding of pyrenetetrasulfonate to both HbA and HbP in the deoxy and CO ligation states under acidic and neutral pH conditions. Both the native and mutant proteins bind the probe at a weak binding site and a strong binding site; in all cases, the binding to HbP was stronger than to HbA. The most striking finding was that for HbA the binding affinity varies as follows: deoxy (pH 6.35) > deoxy (pH 7.20) > CO (pH 6.35); however, the binding to HbP is independent of ligation or pH. The mutant oxy protein also hydrolyzes p-nitrophenyl acetate, through a reversible acyl-imidazole pathway linked to the His residues of the beta beta cleft, at a considerably higher rate than does HbA. This implies a perturbation of the microenvironment of these residues at the DPG binding pocket. Structural consequences due to the presence of the new positive charge in the middle of the central cavity have been transmitted to the beta beta cleft of the protein, even in its liganded conformation. This is consistent with a newly described quaternary state (B) for liganded HbPresbyterian and an associated change in the allosteric control mechanism.

Performance of glycated haemoglobin (HbA1c) as a screening test for diabetes and impaired glucose tolerance (IGT) in a high risk population--the Brazilian Xavante Indians.

PubMed

Franco, L J; Dal Fabbro, A L; Martinez, E Z; Sartorelli, D S; Silva, A S; Soares, L P; Franco, L F; Kuhn, P C; Vieira-Filho, J P B; Moisés, R S

2014-11-01

To examine the properties of HbA1c to detect diabetes and IGT in adult Brazilian Xavante Indians, a high risk population for diabetes. The survey was carried out between October 2010 and January 2012 and based on a 75 g oral glucose tolerance test (OGTT). Basal and 2h capillary glycaemia were measured by HemoCue Glucose 201+; HbA1c using an automated high-performance liquid chromatography analyzer (Tosoh G7). 630 individuals aged ≥ 20 years were examined and 80 had a previous diagnosis of diabetes. Sensitivity, specificity and accuracy for HbA1c ≥ 6.5% (≥ 48 mmol/mol) were 71.3%, 90.5% and 87.2%. The areas under the ROC curve (AUC) was 0.88 (95%CI: 0.83-0.93). To identify IGT, HbA1c values between 5.7% and 6.4% (39-47 mmol/mol) presented sensitivity, specificity and accuracy of 87.2%, 24.7% and 51.4%, with an AUC of 0.62 (95%CI: 0.57-0.67). The ADA/WHO proposed cut-off of 6.5% (48 mmol/mol) for HbA1c was adequate to detect diabetes among the Xavante. However, the performance of the ADA proposed cut-off points for pre-diabetes, when used to detect IGT was inadequate and should not be recommended. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Routine Iron Supplementation and Anaemia by Third Trimester in a Nigerian Hospital.

PubMed

Adanikin, Abiodun I; Awoleke, Jacob O; Olofinbiyi, Babatunde A; Adanikin, Pipeloluwa O; Ogundare, Omobolanle R

2015-10-01

Anaemia in pregnancy is associated with adverse maternal and fetal outcome. Unfortunately, in developing countries its prevalence has continued to rise. To improve the situation, iron supplement is routinely prescribed during pregnancy. We therefore examine the impact of the intervention as being currently practised in our clinical setting. In total, 255 prenatal clinic attendees who had more than 8 weeks of prescribed iron supplements were sampled. Data was obtained on their socio-demographic features, haemoglobin concentration at booking, compliance with iron supplements and third trimester haemoglobin value. Observed iron supplementation compliance rate was 184(72.2%). There was a significant drop in mean haemoglobin (Hb) concentration between the two time points (booking Hb: 32.56±2.99; third trimester Hb: 31.67±3.01; mean diff: 0.89±3.04; t = 4.673; 95% CI= 0.52-1.27; p= <0.001). Anaemia increased from 132(51.8%) to 150(58.8%) by the third trimester. Increase in anaemia occurred in both iron-compliant and non-compliant groups. Non-compliance however had higher odds of predicting anaemia by the third trimester (OR: 1.83; 95% CI: 1.03-3.26; p: 0.04). Although iron supplementation is still a good intervention in developing countries, it is not sufficient to reduce overall prevalence of anaemia by the third trimester. There is a need to look beyond the approach and reinforce the importance of better feeding practices, food fortification and reduced frequency of pregnancies.

HbMADS4, a MADS-box Transcription Factor from Hevea brasiliensis, Negatively Regulates HbSRPP.

PubMed

Li, Hui-Liang; Wei, Li-Ran; Guo, Dong; Wang, Ying; Zhu, Jia-Hong; Chen, Xiong-Ting; Peng, Shi-Qing

2016-01-01

In plants MADS-box transcription factors (TFs) play important roles in growth and development. However, no plant MADS-box gene has been identified to have a function related to secondary metabolites regulation. Here, a MADS-box TF gene, designated as HbMADS4 , was isolated from Hevea brasiliensis by the yeast one-hybrid experiment to screen the latex cDNA library using the promoter of the gene encoding H. brasiliensis small rubber particle protein (HbSRPP) as bait. HbMADS4 was 984-bp containing 633-bp open reading frame encoding a deduced protein of 230 amino acid residues with a typical conserved MADS-box motif at the N terminus. HbMADS4 was preferentially expressed in the latex, but little expression was detected in the leaves, flowers, and roots. Its expression was inducible by methyl jasmonate and ethylene. Furthermore, transient over-expression and over-expression of HbMADS4 in transgenic tobacco plants significantly suppressed the activity of the HbSRP promoter. Altogether, it is proposed that HbMADS4 is a negative regulator of HbSRPP which participates in the biosynthesis of natural rubber.

Cross-sectional comparison of point-of-care with laboratory HbA1c in detecting diabetes in real-world remote Aboriginal settings

PubMed Central

Marley, Julia V; Oh, May S; Hadgraft, Nyssa; Singleton, Sally; Isaacs, Kim; Atkinson, David

2015-01-01

Objectives To determine if point-of-care (POC) glycated haemoglobin (HbA1c) is sufficiently accurate in real-world remote settings to predict or exclude the diagnosis of diabetes based on laboratory HbA1c measurements. Design Cross-sectional study comparing POC capillary HbA1c results with corresponding venous HbA1c levels measured in a reference laboratory. Participants Aboriginal patients ≥15 years old who were due for diabetes screening at the participating clinics were invited to participate. Two hundred and fifty-five Aboriginal participants were enrolled and 241 were included in the analysis. Setting 6 primary healthcare sites in the remote Kimberley region of Western Australia from September 2011 to November 2013. Main outcome measures Concordance and mean differences between POC capillary blood HbA1c measurement and laboratory measurement of venous blood HbA1c level; POC capillary blood HbA1c equivalence value for screening for diabetes or a high risk of developing diabetes; sensitivity, specificity and positive-predictive value for diagnosing and screening for diabetes; barriers to conducting POC testing. Results Concordance between POC and laboratory results was good (ρ=0.88, p<0.001). The mean difference was −0.15% (95% limits of agreement, −0.67% to 0.36%). POC HbA1c measurements ≥6.5%, 48 mmol/mol had a specificity of 98.2% and sensitivity of 73.7% for laboratory measurements ≥6.5%. The POC equivalence value for screening for diabetes or a high risk of developing diabetes was ≥5.7%, 39 mmol/mol (sensitivity, 91%; specificity, 76.7% for laboratory measurements ≥6.0%, 42 mmol/mol). Staff trained by other clinic staff ‘on the job’ performed as well as people with formal accredited training. Staff reported difficulty in maintaining formal accreditation. Conclusions POC HbA1c testing is sufficiently accurate to be a useful component in screening for, and diagnosing, diabetes in remote communities. Limited local training is

The binding of carbon dioxide by horse haemoglobin

PubMed Central

Kilmartin, J. V.; Rossi-Bernardi, L.

1971-01-01

1. Three modified horse haemoglobins have been prepared: (i) αc2βc2, in which both the α-amino groups of the α- and β-chains have reacted with cyanate, (ii) αc2β2, in which the α-amino groups of the α-chains have reacted with cyanate, and (iii) α2βc2, in which the two α-amino groups of the β-chain have reacted with cyanate. 2. The values of n (the Hill constant) for αc2βc2, α2βc2 and αc2β2 were (respectively) 2.5, 2.0 and 2.6, indicating the presence of co-operative interactions between the haem groups for all derivatives. 3. In the alkaline pH range (about pH8.0) all the derivatives show the same charge as normal haemoglobin whereas in the acid pH range (about pH6.0) αc2βc2 differs by four protonic charges and αc2β2, α2βc2 by two protonic charges from normal haemoglobin, indicating that the expected number of ionizing groups have been removed. 4. αc2β2 and αc2βc2 show a 25% decrease in the alkaline Bohr effect, in contrast with α2βc2, which has the same Bohr effect as normal haemoglobin. 5. The deoxy form of αc2βc2 does not bind more CO2 than the oxy form of αc2βc2, whereas αc2β2 and α2βc2 show intermediate binding. 6. The results reported confirm the hypothesis that, under physiological conditions, haemoglobin binds CO2 through the four terminal α-amino groups and that the two terminal α-amino groups of α-chains are involved in the Bohr effect. ImagesPLATE 1 PMID:5166592

Evaluation of two-step haemoglobin screening with HemoCue for blood donor qualification in mobile collection sites.

PubMed

Gómez-Simón, A; Plaza, E M; Torregrosa, J M; Ferrer-Marín, F; Sánchez-Guiu, I; Vicente, V; Lozano, M L; Rivera, J

2014-11-01

Inaccuracy of fingerstick haemoglobin compromises donor's health and losses blood donations. We evaluated the benefit of double haemoglobin screening with HemoCue. Blood donors underwent fingerstick screening by HemoCue and were driven for donation if capillary haemoglobin was within the regulatory range. Those failing were drawn venous blood and donated if their venous haemoglobin determined with HemoCue was acceptable. Of 276 605 donor clinic visits, 10 011 (3·6%) were assessed by two-step haemoglobin screening using HemoCue, because of low (n = 9444) or high (n = 567) capillary haemoglobin. Among these, 2561 (25·6%) were deemed eligible [recovered donations]. The recovery rate was 23·8% and 55·0% among donors presenting with low and high capillary haemoglobin, respectively. In both categories of attempted donations, capillary and venous haemoglobin with HemoCue correlated significantly in recovered donors (R(2)  ≈ 0·5-0·7) but not in deferred visits (R(2)  < 0·15). Venous haemoglobin with HemoCue and by haematological analyzer significantly correlated in all donations attempts (R(2)  ≈ 0·7). Donors presenting with low capillary haemoglobin showed small bias between capillary and venous haemoglobin by HemoCue (-2·4 ± 6·2 g/l), fingerstick haemoglobin and venous haemoglobin with counter (1·3 ± 7·3 g/l), and venous haemoglobin with HemoCue and counter (3·7 ± 3·9 g/l). This bias was slightly greater in donors with high capillary haemoglobin (-7·5 ± 7·8, 13·7 ± 7·5, and 6·2 ± 7·5, respectively). Double haemoglobin screening by HemoCue reached an accuracy of 87·3% for qualifying donors presenting with low fingerstick haemoglobin. Double haemoglobin measurement with HemoCue [fingerstick and venous blood if required] is feasible and allows a significant recovery of blood donations. © 2014 International Society of Blood Transfusion.

Detection of haemoglobins with abnormal oxygen affinity by single blood gas analysis and 2,3-diphosphoglycerate measurement.

PubMed

Guerrini, G; Morabito, A; Samaja, M

2000-10-01

The aim is to determine if a single measurement of blood 2,3-diphosphoglycerate combined with gas analysis (pH, PCO2, PO2 and saturation) can identify the cause of an altered blood-oxygen affinity: the presence of an abnormal haemoglobin or a red cell disorder. The population (n=94) was divided into healthy controls (A, n=14), carriers of red cell disorders (B, n=72) and carriers of high oxygen affinity haemoglobins (C, n=8). Those variables were measured both in samples equilibrated at selected PCO2 and PO2 and in venous blood. In the univariable approach applied to equilibrated samples, we correctly identified C subjects in 93.6% or 96.8% of the cases depending on the selected variable, the standard P50 (PO2 at which 50% of haemoglobin is oxygenated) or a composite variable calculated from the above measurements. After introducing the haemoglobin concentration as a further discriminating variable, the A and B subjects were correctly identified in 91.9% or 94.2% of the cases, respectively. These figures become 93.0% or 86.1%, and 93.7% or 94.9% of the cases when using direct readings from venous blood, thereby avoiding the blood equilibration step. This test is feasible also in blood samples stored at 4 degrees C for 48 h, or at room temperature for 8 h.

Prospective evaluation of haemoglobin oxygen saturation at rest and after exercise in paediatric sickle cell disease patients

PubMed Central

Campbell, Andrew; Minniti, Caterina P.; Nouraie, Mehdi; Arteta, Manuel; Rana, Sohail; Onyekwere, Onyinye; Sable, Craig; Ensing, Gregory; Dham, Niti; Luchtman-Jones, Lori; Kato, Gregory J.; Gladwin, Mark T.; Castro, Oswaldo L.; Gordeuk, Victor R.

2009-01-01

Summary Low steady state haemoglobin oxygen saturation in patients with sickle cell anaemia has been associated with the degree of anaemia and haemolysis. How much pulmonary dysfunction contributes to low saturation is not clear. In a prospective study of children and adolescents with sickle cell disease aged 3–20 years at steady state and matched controls, 52% of 391 patients versus 24% of 63 controls had steady state oxygen saturation <99% (P < 0·0001), 9% of patients versus no controls had saturation <95% (P = 0·008) and 8% of patients versus no controls had exercise-induced reduction in saturation ≥3%. Decreasing haemoglobin concentration (P ≤ 0·001) and increasing haemolysis (P ≤ 0·003) but not pulmonary function tests were independent predictors of both lower steady-state saturation and exercise-induced reduction in saturation. Neither history of stroke nor history of acute chest syndrome was significantly associated with lower steady-state oxygen saturation or exercise-induced reduction in saturation. Tricuspid regurgitation velocity was higher in patients with lower steady state haemoglobin oxygen saturation (P = 0·003) and with greater decline in oxygen saturation during the six-minute walk (P = 0·022). In conclusion, lower haemoglobin oxygen saturation is independently associated with increasing degrees of anaemia and haemolysis but not pulmonary function abnormalities among children and adolescents with sickle cell disease. PMID:19694721

In vivo real time non invasive monitoring of brain penetration of chemicals with near-infrared spectroscopy: Concomitant PK/PD analysis.

PubMed

Crespi, Francesco; Cattini, Stefano; Donini, Maurizio; Bandera, Andrea; Rovati, Luigi

2016-01-30

Near-infrared spectroscopy (NIRS) is a non-invasive technique that monitors changes in oxygenation of haemoglobin. The absorption spectra of near-infrared light differ for the oxygenation-deoxygenation states of haemoglobin (oxygenate (HbO2) and deoxygenate (Hb), respectively) so that these two states can be directly monitored. Different methodologies report different basal values of HbO2 and Hb absolute concentrations in brain. Here, we attempt to calculate basal HbO2 levels in rat CNS via evaluation of the influence of exogenous oxygen or exogenous carbon dioxide on the NIRS parameters measured in vivo. Furthermore the possibility that changes of haemoglobin oxygenation in rat brain as measured by NIRS might be a useful index of brain penetration of chemical entities has been investigated. Different compounds from different chemical classes were selected on the basis of parallel ex vivo and in vivo pharmacokinetic (PK/PD) studies of brain penetration and overall pharmacokinetic profile. It appeared that NIRS might contribute to assess brain penetration of chemical entities, i.e. significant changes in NIRS signals could be related to brain exposure, conversely the lack of significant changes in relevant NIRS parameters could be indicative of low brain exposure. This work is proposing a further innovation on NIRS preclinical applications i.e. a "chemical" NIRS [chNIRS] approach for determining penetration of drugs in animal brain. Therefore, chNIRS could became a non invasive methodology for studies on neurobiological processes and psychiatric diseases in preclinical but also a translational strategy from preclinical to clinical investigations. Copyright © 2015 Elsevier B.V. All rights reserved.

Haemoglobin responses to transfusion in severe iron deficiency anaemia: potential impact of gastrointestinal disorders.

PubMed

Bosch, X; Montori, E; Guerra-García, M; Costa-Rodríguez, J; Quintanilla, M H; Tolosa-Chapasian, P E; Moreno, P; Guasch, N; López-Soto, A

2017-04-01

Red blood cell (RBC) transfusion may be justified in iron deficiency anaemia (IDA) when an increase in oxygen delivery is needed, as sometimes occurs in subjects with haemoglobin <8·0 mg/dL, serious comorbidities or at risk of cardiovascular instability. Earlier investigations showed that some patients with severe IDA requiring transfusion had lower than expected post-transfusion haemoglobin levels with poorer clinical outcomes than other patients. After hypothesizing that haemoglobin responses to transfusion were different and that the underlying gastrointestinal (GI) disorders causing IDA could be a confounder explaining this association, these responses were analysed in a prospective cohort of IDA adults referred for outpatient GI investigation. Transfused patients with proven IDA, baseline haemoglobin at referral <9·0 g/dL and no extraintestinal bleeding were eligible. To assess a homogeneous population, only GI disorders known to cause occult bleeding were considered. Haemoglobin increments per 100 mL of RBCs were investigated. In total, 2818 patients were enrolled over 10·5 years. On multivariable regression, diffuse angiodysplasias and GI cancer independently predicted for reduced increments in post-transfusion haemoglobin [adjusted regression coefficients: -0·082 (95% confidence interval, -0·093 to -0·072) and -0·073 (95% confidence interval, -0·081 to -0·066), respectively, P < 0·001 in both]. Haemoglobin responses in the remaining bleeding disorders were adequate and agreed with the principle that one RBC unit increases the haemoglobin an average of 1 g/dL. The potential differential impact of GI disorders on changes in haemoglobin levels after RBC transfusion could be useful for transfusing physicians, especially for diagnostic purposes. © 2017 International Society of Blood Transfusion.

Evaluation of sample stability for a quantitative faecal immunochemical test and comparison of two sample collection approaches.

PubMed

Mellen, Samantha; de Ferrars, Maria; Chapman, Claire; Bevan, Sarah; Turvill, James; Turnock, Daniel

2018-01-01

Background Faecal immunochemical testing is increasingly being used to triage symptomatic patients for suspected colorectal cancer. However, there are limited data on the effect of preanalytical factors on faecal haemoglobin when measured by faecal immunochemical testing. The aim of this work was to evaluate the stability of faecal haemoglobin in faeces and to compare two methods of faecal haemoglobin sampling for faecal immunochemical testing. Methods Six patients provided faeces for faecal haemoglobin measurement which were transferred into specialized collection devices at baseline and at 1, 2, 3 and 7 days after storage at either room temperature or 4°C. A total of 137 patients returned both faeces transferred into the specialized collection device and faeces in a standard collection pot. A quantitative immunoturbidometric method was used to measure faecal haemoglobin and results were compared categorically. Discrepant results were assessed against diagnosis. Results Faecal haemoglobin concentration declined rapidly within a day of storage at room temperature but results remained ≥10 μg Hb/g faeces in 5/6 patients after two days. A faecal haemoglobin result ≥10 μg Hb/g faeces was obtained in 4/6 patients after storage for seven days at 4°C. Results obtained when patients used specialized collection devices were significantly different from results obtained when faeces was transferred into the specialized collection device in the laboratory. Conclusion There is considerable heterogeneity in the sample stability of faecal haemoglobin; therefore, samples should be transferred rapidly into specialized collection devices to prevent false-negative results. Use of collection devices by patients can lead to false-positive results compared with their use in a laboratory.

Local descriptive norms for overweight/obesity and physical inactivity, features of the built environment, and 10-year change in glycosylated haemoglobin in an Australian population-based biomedical cohort.

PubMed

Carroll, Suzanne J; Paquet, Catherine; Howard, Natasha J; Coffee, Neil T; Taylor, Anne W; Niyonsenga, Theo; Daniel, Mark

2016-10-01

Descriptive norms vary between places. Spatial variation in health-related descriptive norms may predict individual-level health outcomes. Such relationships have rarely been investigated. This study assessed 10-year change in glycosylated haemoglobin (HbA1c) in relation to local descriptive norms for overweight/obesity (n = 1890) and physical inactivity (n = 1906) in models accounting for features of the built environment. HbA1c was measured three times over 10 years for a population-based biomedical cohort of adults in Adelaide, South Australia. Environmental exposures were expressed for cohort participants using 1600 m road-network buffers centred on participants' residential address. Local descriptive norms (prevalence of overweight/obesity [body mass index ≥25 kg/m(2)] and of physical inactivity [<150 min/week]) were aggregated from responses to a separate geocoded population survey. Built environment measures were public open space (POS) availability (proportion of buffer area) and walkability. Separate sets of multilevel models analysed different predictors of 10-year change in HbA1c. Each model featured one local descriptive norm and one built environment variable with area-level education and individual-level covariates (age, sex, employment status, education, marital status, and smoking status). Interactions between local descriptive norms and built environment measures were assessed. HbA1c increased over time. POS availability and local descriptive norms for overweight/obesity and physical inactivity were each associated with greater rates of HbA1c increase. Greater walkability was associated with a reduced rate of HbA1c increase, and reduced the influence of the overweight/obesity norm on the rate of increase in HbA1c. Local descriptive health-related norms and features of the built environment predict 10-year change in HbA1c. The impact of local descriptive norms can vary according to built environment features. Little researched thus far

Impact of nutrition education on knowledge and haemoglobin status of hill women in Uttarakhand State of India.

PubMed

Upadhyay, S; Kumar, A R; Raghuvanshi, R S; Singh, B B

2011-12-01

This study aimed to examine the impact of the use of single vs. combination of media on nutritional knowledge and haemoglobin status of women in a rural hill area in Uttarakhand State, India. Women from three villages were selected randomly and divided into three groups namely, print media group (n = 59), multimedia group (n = 53) and control group (n = 111). The print media group was exposed to nutrition education through the use of calendars on anaemia for 60 days; the multimedia group was given nutrition education through a combination of media including calendars, video films, and group discussions for 60 days. At pre-exposure stage, 62.7% of the women in the print media group, 67.9% of the multimedia group, and 66.7% of the control group had a low nutrition knowledge level. After exposure, the print media group and the multimedia group showed a significant rise in nutrition knowledge, with the multimedia group scoring significantly higher than the print media group. Overall, 69.1% of the women were anaemic with mean haemoglobin concentration of 10.74 +/- 0.86 g/dl. A non-significant rise in mean haemoglobin concentrations in the experimental groups was found at post-exposure stage. Calendars and video films are effective in increasing nutrition knowledge of illiterate hill women. Use of mass media programmes of longer duration should be encouraged to combat the nutritional problems of rural communities.

Assessment of tissue oxygenation of periodontal inflammation in smokers using optical spectroscopy.

PubMed

Liu, Kan-Zhi; Duarte, Poliana Mendes; Santos, Vanessa Renata; Xiang, Xiaoming; Xu, Minqi; Miranda, Tamires Szeremeske; Fermiano, Daiane; Gonçalves, Tiago Eduardo Dias; Sowa, Micheal G

2014-04-01

We have recently developed a periodontal diagnostic tool that was validated in non-smokers with periodontitis. Tobacco smoking is a recognized risk factor for periodontal diseases that can mask gingival bleeding and lead to a false negative diagnosis. Therefore, the purpose of current study is to further validate this instrument in smokers with periodontal diseases. Using a portable optical near-infrared spectrometer, optical spectra were obtained, processed and evaluated from healthy (n = 108), gingivitis (n = 100), and periodontitis (n = 79) sites of 54 systemically healthy smokers. A modified Beer-Lambert unmixing model that incorporates a non-parametric scattering loss function was used to determine the relative contribution of deoxygenated haemoglobin (Hb) and oxygenated haemoglobin (HbO2 ) to the overall spectrum. The balance between tissue oxygen delivery and utilization in periodontal tissues was then assessed. Tissue oxygen saturation was significantly decreased in the gingivitis (p = 0.016) and periodontitis (p = 0.007) sites, compared to the healthy sites. There was a trend towards increased concentration of Hb and decreased concentration of HbO2 from healthy to diseased sites, without statistical significance (p > 0.05). Optical spectroscopy can determine tissue oxygenation profiles of healthy and diseased sites in smokers. The spectral profile of periodontal sites in smokers generally resembles those from non-smoking patients. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Erratum to: Blood HbO2 and HbCO2 dissociation curves at varied O2, CO2, pH, 2,3-DPG and temperature levels.

PubMed

Dash, Ranjan K; Bassingthwaighte, James B

2010-04-01

New mathematical model equations for O(2) and CO(2) saturations of hemoglobin (S(HbO)(2) and S(HbCO)(2) are developed here from the equilibrium binding of O(2) and CO(2) with hemoglobin inside RBCs. They are in the form of an invertible Hill-type equation with the apparent Hill coefficients KHbO(2) and KHbCO(2) in the expressions for SHbO(2) and SHbCO(2) dependent on the levels of O(2) and CO(2) partial pressures (P(O)(2) and P(CO)(2)), pH, 2,3-DPG concentration, and temperature in blood. The invertibility of these new equations allows PO(2) and PCO(2) to be computed efficiently from S(HbO)(2) and S(HbCO)(2) and vice versa. The oxyhemoglobin (HbO(2)) and carbamino-hemoglobin (HbCO(2)) dissociation curves computed from these equations are in good agreement with the published experimental and theoretical curves in the literature. The model solutions describe that, at standard physiological conditions, the hemoglobin is about 97.2% saturated by O(2) and the amino group of hemoglobin is about 13.1% saturated by CO(2). The O(2) and CO(2) content in whole blood are also calculated here from the gas solubilities, hematocrits, and the new formulas for S(HbO)(2) and S(HbCO)(2). Because of the mathematical simplicity and invertibility, these new formulas can be conveniently used in the modeling of simultaneous transport and exchange of O(2) and CO(2) in the alveoli-blood and blood-tissue exchange systems.

Global standardisation of HbA1c.

PubMed

Lai, Leslie C

2008-12-01

HbA1c is used for assessing glycaemic control in patients with diabetes. It is also used for treatment goals and as a target for therapeutic intervention. The Direct Control and Complications Trial in the USA showed that HbA1c can be used to predict the risk of complications. Hence, it is important for HbA1c assays to be standardised. The National Glycohemoglobin Standardization Program (NGSP) in the USA was formed in 1996 so that HbA1c results from different laboratories would be comparable to those reported in the DCCT study. There were also HbA1c standardisation programmes in Sweden and Japan. These three standardisation programmes are, in fact, direct comparison methods (DCMs), and yield different HbA1c results. In 1994, the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) established a Working Group on Standardisation of HbA1c. This working group has developed a global HbA1c reference system with very much improved intra-assay and inter-assay coefficients of variation. Recommendations have been made to report HbA1c results as IFCC-HbA1c values in SI units (mmol HbA1c/mol Hb) and NGSP-HbA1c (%) as well as estimated average glucose (eAG), once a tight relationship has been shown to exist between eAG and HbA1c.

Familial congenital cyanosis caused by Hb-MYantai(α-76 GAC → TAC, Asp → Tyr)

PubMed Central

2010-01-01

Methemoglobin (Hb-M) is a rare hemoglobinopathy in China. We hereby report on a family living in Yantai, East China, with congenital cyanosis due to Hb-M mutation. The proband, a 65-year-old female, presented 63% oxygen saturation. Both Hb-M concentration and arterial oxygen saturation remained unchanged, even following intravenous treatment with methylene blue. There was also no change in blood-color (chocolate-brown) after adding 0.1% KCN. A fast-moving band (Hb-X) in hemolysates was found by cellulose acetate electrophoresis, the Hb-X/Hb-A ratio exceeding 10%. GT transition at 131nt of exon 2, although present in one of the α2 -globin alleles, was not found in α1 -globin alleles as a whole. This mutation leads to the aspartic acid to tyrosine substitution (Asp76Tyr). In this family, the novel mutation in the α2 -globin gene resulted in a rare form of congenital cyanosis due to Hb-M. This hemoglobin was named Hb-M Yantai . PMID:21637412

HB Puerta del Sol [HBA1:c.148A>C], HB Valdecilla [HBA2:c.3G>T], HB Gran Vía [HBA2:c.98T>G], HB Macarena [HBA2:c.358C>T] and HB El Retiro [HBA2:c.364_366dupGTG]: description of five new hemoglobinopathies.

PubMed

de la Fuente-Gonzalo, Félix; Nieto, Jorge M; Velasco, Diego; Cela, Elena; Pérez, Germán; Fernández-Teijeiro, Ana; Escudero, Antonio; Villegas, Ana; González-Fernández, Fernando A; Ropero, Paloma

2016-04-01

Structural hemoglobinopathies do not usually have a clinical impact, but they can interfere with the analytical determination of some parameters, such as the glycated hemoglobin in diabetic patients. Thalassemias represent a serious health problem in areas where their incidence is high. The defects in the post-translational modifications produce hyper-unstable hemoglobin that is not detected by most of electrophoretic or chromatographic methods that are available so far. We studied seven patients who belong to six unrelated families. The first two families were studied because they had peak abnormal hemoglobin (Hb) during routine analytical assays. The other four families were studied because they had microcytosis and hypochromia with normal HbA2 and HbF without iron deficiency. HbA2 and F quantification and abnormal Hb separation were performed by chromatographic and electrophoretic methods. The molecular characterization was performed using specific sequencing. The Hb Puerta del Sol presents electrophoretic mobility and elution in HPLC that is different from HbA and similar to HbS. The electrophoretic and chromatographic profiles of the four other variants are normal and do not show any anomalies, and their identification was only possible with sequencing. Some variants, such as Hb Valdecilla, Hb Gran Vía, Hb Macarena and Hb El Retiro, have significant clinical impact when they are associated with other forms of α-thalassemia, which could lead to more serious forms of this group of pathologies as for HbH disease. Therefore, it is important to maintain an adequate program for screening these diseases in countries where the prevalence is high to prevent the occurrence of severe forms.

Purification, crystallization and preliminary X-ray analysis of haemoglobin from ostrich (Struthio camelus).

PubMed

Sundaresan, S S; Ramesh, P; Sivakumar, K; Ponnuswamy, M N

2009-07-01

Haemoglobin is a tetrameric protein that carries oxygen from the lungs to tissues and carbon dioxide from tissues back to the lungs. The oxygen-binding properties of haemoglobin are regulated through the binding of allosteric effectors. The respiratory system of avian species is unique and complex in nature when compared with that of mammals. In avian species, inositol pentaphosphate (inositol-P(5)) is present in the erythrocytes of the adult and is thought to be the major factor responsible for the relatively high oxygen affinity of the whole blood. The ostrich (Struthio camelus) is a large flightless bird which contains inositol tetrakisphosphate (inositol-P(4)) in its erythrocytes and its whole blood oxygen affinity is higher. Efforts have been made to explore the structure-function relationship of ostrich haemoglobin. Ostrich haemoglobin was purified using ion-exchange chromatography. Haemoglobin crystals were grown by the hanging-drop vapour-diffusion method using PEG 3350 as the precipitant in 50 mM phosphate buffer pH 7.2. Data were collected using a MAR345 image-plate detector system. The crystals of ostrich haemoglobin diffracted to 2.2 A resolution. They belonged to the orthorhombic space group P2(1)2(1)2(1) with one whole biological molecule in the asymmetric unit; the unit-cell parameters were a = 80.93, b = 81.68, c = 102.05 A.

Reflectance spectroscopy can quantify cutaneous haemoglobin oxygenation by oxygen uptake from the atmosphere after epidermal barrier disruption.

PubMed

Heise, H M; Lampen, P; Stücker, M

2003-11-01

The supply of oxygen to the viable skin tissue within the upper layers is not only secured by the cutaneous blood vascular system, but to a significant part also by oxygen diffusion from the atmosphere through the horny layer. The aim of this study was to examine whether changes in haemoglobin oxygenation can be observed within the isolated perfused bovine udder skin used as a skin model by removing the upper horny layer by adhesive tape stripping. Diffuse reflectance spectroscopy in the visible spectral range was used for non-invasive characterisation of haemoglobin oxygenation in skin under in vitro conditions. Mid-infrared attenuated total reflectance spectroscopy was employed for analysing the surface layer of the stratum corneum with respect to keratin, water and lipid components. Skin barrier disruption was achieved by repeated stripping of superficial corneocyte layers by adhesive tape. Significant changes in skin haemoglobin oxygenation were observed for skin areas with reduced lipid concentration and a reduced stratum corneum layer, as determined from the quantitative evaluation of the diffuse reflectance skin spectra. The result can be interpreted as an increase of oxygen diffusion after the removal of the upper horny layer.

Haemoglobin recovery among HIV-1 infected patients on zidovudine-based antiretroviral therapy and other regimens in north-central Nigeria.

PubMed

Parrish, Deidra D; Blevins, Meridith; Megazzini, Karen M; Shepherd, Bryan E; Mohammed, Mukhtar Y; Wester, C William; Vermund, Sten H; Aliyu, Muktar H

2014-04-01

We conducted a study to assess trends in haemoglobin recovery among HIV-infected patients initiated on zidovudine-based combination antiretroviral therapy (cART) stratified by baseline haemoglobin level. Haemoglobin data from non-pregnant adult patients initiating cART in rural north-central Nigeria between June 2009 and May 2011 were analysed using a linear mixed effects model to assess the interaction between time, zidovudine-containing regimen and baseline haemoglobin level on the outcome of subsequent haemoglobin level. Best-fit curves were created for baseline haemoglobin in the 10th, 25th, 75th and 90th percentiles. We included 313 patients with 736 measures of haemoglobin in the analysis (239 on zidovudine and 74 on non-zidovudine-containing regimens). Median haemoglobin increased over time in both groups, with differences in haemoglobin response over time related to baseline haemoglobin levels and zidovudine use (p = 0.003). The groups of patients on zidovudine at the 10th and 90th percentiles had downward sloping curves while all other groups had upward trending haemoglobin levels. Although haemoglobin levels increased overall for patients on zidovudine-containing regimens, for those in the 10th and 90th percentiles haemoglobin levels trended downward over time. These results have implications for decisions regarding when to initiate, switch from or avoid the use of zidovudine.

Influence of smoking and diet on glycated haemoglobin and 'pre-diabetes' categorisation: a cross-sectional analysis.

PubMed

Vlassopoulos, Antonis; Lean, Michael E J; Combet, Emilie

2013-10-26

The new HbA1c criteria for diagnosis of pre-diabetes have been criticised for misdiagnosis. It is possible that some elevation of HbA1c is not driven by hyperglycaemia. This study assesses associations of HbA1c, commonly assumed to relate solely to glucose concentration, with (i) smoking, a major source of reactive oxygen species (ROS) and (ii) fruit & vegetables consumption associated with improved redox status. One-way ANOVA, Chi-squared and multivariate linear regressions, adjusted for all known confounders were used to explore associations of HbA1c with self-reported smoking status and fruit & vegetables consumptions in the Scottish Health Surveys 2003-2010, among individuals without known diabetes and HbA1c < 6.5%. Compared to non-smokers (n = 2831), smokers (n = 1457) were younger, consumed less fruit & vegetables, had lower physical activity levels, lower BMI, higher HbA1c and CRP (p < 0.05). HbA1c was higher in smokers by 0.25 SDs (0.08%), and 0.38 SDs higher (0.14%) in heavy smokers (>20 cigarettes/day) than non-smokers (p < 0.001 both). Smokers were twice as likely to have HbA1c in the 'pre-diabetic' range (5.7-6.4%) (p < 0.001, adj.model). Pre-diabetes and low grade inflammation did not affect the associations. For every extra 80 g vegetable portion consumed, HbA1c was 0.03 SDs (0.01%) lower (p = 0.02), but fruit consumption did not impact on HbA1c, within the low range of consumptions in this population. This study adds evidence to relate smoking (an oxidative stress proxy) with protein glycation in normoglycaemic subjects, with implications for individuals exposed to ROS and for epidemiological interpretation of HbA1c.

Design of a tissue oxygenation monitor and verification on human skin

NASA Astrophysics Data System (ADS)

Liu, Hongyuan; Kohl-Bareis, Matthias; Huang, Xiabing

2011-07-01

We report the design of a tissue oxygen and temperature monitor. The non-invasive, fibre based device monitors tissue haemoglobin (Hb) and oxygen saturation (SO2) and is based on white-light reflectance spectroscopy.Visible light with wavelengths in the 500 - 650nm range is utilized. The spectroscopic algorithm takes into account the tissue scattering and melanin absorption for the calculation of tissue haemoglobin concentration and oxygen saturation. The monitor can probe superficial layers of tissue with a high spatial resolution (mm3) and a high temporal resolution (40 Hz). It provides an accurate measurement with the accuracy of SO2 at 2 % and high reliability with less than 2 % variation of continuous SO2 measurement over 12 hours. It can also form a modular system when used in conjunction with a laser Doppler monitor, enabling simultaneous measurements of Hb, SO2 and blood flow. We found experimentally that the influence of the source-detector separation on the haemoglobin parameters is small. This finding is discussed by Monte Carlo simulations for the depth sensitivity profile. The influence of probe pressure and the skin pigmentation on the measurement parameters are assessed before in vivo experimental data is presented. The combination with laser Doppler flowmetry demonstrates the importance of a measurement of both the haemoglobin and the blood flow parameters for a full description of blood tissue perfusion. This is discussed in experimental data on human skin during cuff occlusion and after hyperemisation by a pharmacological cream. Strong correlation is observed between tissue oxygen (Hb and SO2) and blood flow measurements.

A potent anti-HB-EGF monoclonal antibody inhibits cancer cell proliferation and multiple angiogenic activities of HB-EGF.

PubMed

Sato, Shuji; Drake, Andrew W; Tsuji, Isamu; Fan, Jinhong

2012-01-01

Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a member of the epidermal growth factor family and has a variety of physiological and pathological functions. Modulation of HB-EGF activity might have a therapeutic potential in the oncology area. We explored the therapeutic possibilities by characterizing the in vitro biological activity of anti-HB-EGF monoclonal antibody Y-142. EGF receptor (EGFR) ligand and species specificities of Y-142 were tested. Neutralizing activities of Y-142 against HB-EGF were evaluated in EGFR and ERBB4 signaling. Biological activities of Y-142 were assessed in cancer cell proliferation and angiogenesis assays and compared with the anti-EGFR antibody cetuximab, the HB-EGF inhibitor CRM197, and the anti-vascular endothelial growth factor (VEGF) antibody bevacizumab. The binding epitope was determined with alanine scanning. Y-142 recognized HB-EGF as well as the EGFR ligand amphiregulin, and bound specifically to human HB-EGF, but not to rodent HB-EGF. In addition, Y-142 neutralized HB-EGF-induced phosphorylation of EGFR and ERBB4, and blocked their downstream ERK1/2 and AKT signaling. We also found that Y-142 inhibited HB-EGF-induced cancer cell proliferation, endothelial cell proliferation, tube formation, and VEGF production more effectively than cetuximab and CRM197 and that Y-142 was superior to bevacizumab in the inhibition of HB-EGF-induced tube formation. Six amino acids in the EGF-like domain were identified as the Y-142 binding epitope. Among the six amino acids, the combination of F115 and Y123 determined the amphiregulin cross-reactivity and that F115 accounted for the species selectivity. Furthermore, it was suggested that the potent neutralizing activity of Y-142 was derived from its recognition of R142 and Y123 and its high affinity to HB-EGF. Y-142 has a potent HB-EGF neutralizing activity that modulates multiple biological activities of HB-EGF including cancer cell proliferation and angiogenic

Effects of a healthier snack on snacking habits and glycated Hb (HbA1c): a 6-week intervention study.

PubMed

Yan, Mary R; Parsons, Andrew; Whalley, Gillian A; Rush, Elaine C

2016-12-01

Dietary behaviour modification may change eating habits and reduce the impact of poor nutrition. This study aimed to evaluate the effects of daily consumption of a healthier snack bar on snacking habits and glycated Hb (HbA1c) within a 6-week intervention. In all, twenty-eight participants were randomly allocated to two groups to either consume the bars as the main snack for 6 weeks (n 14) or receipt of the bars was delayed for 6 weeks (n 14) following a stepped-wedge design. All participants had HbA1c concentrations measured at weeks -1, 0, 4, 6, 10 and 12. A short dietary habits questionnaire was self-completed at weeks 0, 6 and 12. Participants consumed the bars they received instead of other snacks, and found that the healthier snack bar was acceptable as part of their daily dietary pattern. Over the 12 weeks, there was a significant reduction in intake of biscuits, cakes and pies (approximately 2 servings/week, P<0·05) in both groups. Fruit juice intake was reduced (approximately 1 serving/week, P=0·029) in the first group. In all, twenty participants (71·4 %) experienced a decrease (n 15) or no change (n 5) in HbA1c (range 0-4 mmol/mol), whereas eight participants experienced an increase in HbA1c (range 0·5-2·5 mmol/mol). There was high compliance with the healthier snack intervention and a trend towards a favourable effect on glucose homoeostasis. Habitual snacking behaviour has the potential to be improved through changes in the food supply, and in the longer term may reduce the impact of poor nutrition on public health.

Increased blood carboxyhaemoglobin concentrations in inflammatory pulmonary diseases

PubMed Central

Yasuda, H; Yamaya, M; Yanai, M; Ohrui, T; Sasaki, H

2002-01-01

Background: Exhaled carbon monoxide has been reported to increase in inflammatory pulmonary diseases and to be correlated with blood carboxyhaemoglobin (Hb-CO) concentration. A study was undertaken to determine whether arterial blood Hb-CO increases in patients with inflammatory pulmonary diseases. Methods: The Hb-CO concentration in arterial blood was measured with a spectrophotometer in 34 normal control subjects, 24 patients with bronchial asthma, 52 patients with pneumonia, and 21 patients with idiopathic pulmonary fibrosis (IPF). Results: The mean (SE) Hb-CO concentrations in patients with bronchial asthma during exacerbations (n=24, 1.05 (0.05)%), with pneumonia at the onset of illness (n=52, 1.08 (0.06)%), and with IPF (n=21, 1.03 (0.09)%) were significantly higher than those in control subjects (n=34, 0.60 (0.07)%) (mean difference 0.45% (95% confidence interval (CI) 0.23 to 0.67), p<0.01 in patients with bronchial asthma, mean difference 0.48% (95% CI 0.35 to 0.60), p<0.0001 in patients with pneumonia, and mean difference 0.43% (95% CI 0.26 to 0.61) p<0.001 in patients with IPF). In 20 patients with bronchial asthma the Hb-CO concentration decreased after 3 weeks of treatment with oral glucocorticoids (p<0.001). In 20 patients with pneumonia the Hb-CO concentration had decreased after 3 weeks when patients showed evidence of clinical improvement (p<0.001). The values of C-reactive protein (CRP), an acute phase protein, correlated with Hb-CO concentrations in patients with pneumonia (r=0.74, p<0.0001) and in those with IPF (r=0.46, p<0.01). In patients with bronchial asthma changes in Hb-CO concentrations were significantly correlated with those in forced expiratory volume in 1 second (FEV1) after 3 weeks (r=0.67, p<0.01). Exhaled carbon monoxide (CO) concentrations were correlated with Hb-CO concentrations (n=33, r=0.80, p<0.0001). Conclusions: Hb-CO concentrations are increased in inflammatory pulmonary diseases including bronchial asthma, pneumonia, and

Verification of a novel point-of-care HbA1c device in real world clinical practice by comparison to three high performance liquid chromatography instruments.

PubMed

Wang, Yufei; Peng, Wei; Tang, Junling; Dong, Lu; Gu, Chengchen; Zhang, Xin; Zhou, Jian; Jia, Weiping

2018-06-15

A real world clinical study was designed and conducted to evaluate the performance of a novel point-of-care device for determination of glycated haemoglobin A 1c (HbA 1c ), A1C EZ 2.0, in daily clinical practice. Five hundred and fourteen subjects were included in this study, and divided into three groups. HbA 1c was measured by A1C EZ 2.0 and three different high performance liquid chromatography (HPLC) devices: Bio-Rad Variant II Turbo, Tosoh HLC-723 G8 and Premier Hb9210 separately. Precision of A1C EZ 2.0 was also evaluated. Results obtained from A1C EZ 2.0 and all HPLC devices are correlated. Passing-Bablok regression analysis shows the equation of A1C EZ 2.0 results against the mean of HPLC devices with corresponding 95% confidence intervals (95% CI) for the intercept and slope is y = 0.10 (- 0.17 to 0.10) + 1.00 (1.00 to 1.04) x. Bland-Altman difference plot shows that the mean relative difference between A1C EZ 2.0 and Variant II Turbo, G8, Hb9210 and all HPLC results is 2.5%, 0.6%, 0.4% and 1.1%, respectively. In addition, 121 pairs of results determined by using both venous and capillary blood prove that the difference of two kinds of blood sample causes no notable variation when measured by A1C EZ 2.0. Precision study gives 2.3% and 1.9% of total coefficient of variation for normal and abnormal HbA 1c sample in A1C EZ 2.0. HbA 1c values measured by A1C EZ 2.0 were in good accordance with the results obtained with the reference HPLC devices.

Proficiency testing of Hb A1c: a 4-year experience in Taiwan and the Asian Pacific region.

PubMed

Shiesh, Shu-Chu; Wiedmeyer, Hsiao-Mei; Kao, Jau-Tsuen; Vasikaran, Samuel D; Lopez, Joseph B

2009-10-01

The correlation between hemoglobin A(1c) (Hb A(1c)) and risk for complications in diabetic patients heightens the need to measure Hb A(1c) with accuracy. We evaluated the current performance for measuring Hb A(1c) in the Asian and Pacific region by examining data submitted by laboratories participating in the Taiwan proficiency-testing program. Five fresh-pooled blood samples were sent to participating laboratories twice each year. The results were evaluated against target values assigned by the National Glycohemoglobin Standardization Program network laboratories; a passing criterion of +/-7% of the target value was used. Measurement uncertainty at Hb A(1c) concentrations of 7.0% and 8.0% were determined. A total of 276 laboratories from 11 countries took part in the Hb A(1c) survey. At the Hb A(1c) concentrations tested method-specific interlaboratory imprecision (CVs) were 1.1%-13.9% in 2005, 1.3%-10.1% in 2006, 1.2%-8.2% in 2007, and 1.1%-6.1% in 2008. Differences between target values and median values from the commonly used methods ranged from -0.24% to 0.22% Hb A(1c) in 2008. In 2005 83% of laboratories passed the survey, and in 2008 93% passed. At 7.0% Hb A(1c), measurement uncertainty was on average 0.49% Hb A(1c). The use of accuracy-based proficiency testing with stringent quality criteria has improved the performance of Hb A(1c) testing in the Asian and Pacific laboratories during the 4 years of assessment.

Acquisition of haemoglobin-bound iron by strains of the Actinobacillus minor/"porcitonsillarum" complex.

PubMed

Arya, Gitanjali; Niven, Donald F

2011-03-24

Members of the Actinobacillus minor/"porcitonsillarum" complex are common inhabitants of the swine respiratory tract. Although avirulent or of low virulence for pigs, these organisms, like pathogens, do grow in vivo and must, therefore, be able to acquire iron within the host. Here, we investigated the abilities of six members of the A. minor/"porcitonsillarum" complex to acquire iron from transferrin and various haemoglobins. Using growth assays, all six strains were shown to acquire iron from porcine, bovine and human haemoglobins but not from porcine transferrin. Analyses of whole genome sequences revealed that A. minor strains NM305(T) and 202, unlike the swine-pathogenic actinobacilli, A. pleuropneumoniae and A. suis, lack not only the transferrin-binding protein genes, tbpA and tbpB, but also the haemoglobin-binding protein gene, hgbA. Strains NM305(T) and 202, however, were found to possess other putative haemin/haemoglobin-binding protein genes that were predicted to encode mature proteins of ∼ 72 and ∼ 75 kDa, respectively. An affinity procedure based on haemin-agarose allowed the isolation of ∼ 65 and ∼ 67 kDa iron-repressible outer membrane polypeptides from membranes derived from strains NM305(T) and 202, respectively, and mass spectrometry revealed that these polypeptides were the products of the putative haemin/haemoglobin-binding protein genes. PCR approaches allowed the amplification and sequencing of homologues of both haemin/haemoglobin-binding protein genes from each of the other four strains, strains 33PN and 7ATS of the A. minor/"porcitonsillarum" complex and "A. porcitonsillarum" strains 9953L55 and 0347, suggesting that such proteins are involved in the utilization of haemoglobin-bound iron, presumably as surface receptors, by all six strains investigated. Copyright © 2010 Elsevier B.V. All rights reserved.

Affect school and script analysis versus basic body awareness therapy in the treatment of psychological symptoms in patients with diabetes and high HbA1c concentrations: two study protocols for two randomized controlled trials.

PubMed

Melin, Eva O; Svensson, Ralph; Gustavsson, Sven-Åke; Winberg, Agneta; Denward-Olah, Ewa; Landin-Olsson, Mona; Thulesius, Hans O

2016-04-27

Depression is linked with alexithymia, anxiety, high HbA1c concentrations, disturbances of cortisol secretion, increased prevalence of diabetes complications and all-cause mortality. The psycho-educational method 'affect school with script analysis' and the mind-body therapy 'basic body awareness treatment' will be trialled in patients with diabetes, high HbA1c concentrations and psychological symptoms. The primary outcome measure is change in symptoms of depression. Secondary outcome measures are changes in HbA1c concentrations, midnight salivary cortisol concentration, symptoms of alexithymia, anxiety, self-image measures, use of antidepressants, incidence of diabetes complications and mortality. Two studies will be performed. Study I is an open-labeled parallel-group study with a two-arm randomized controlled trial design. Patients are randomized to either affect school with script analysis or to basic body awareness treatment. According to power calculations, 64 persons are required in each intervention arm at the last follow-up session. Patients with type 1 or type 2 diabetes were recruited from one hospital diabetes outpatient clinic in 2009. The trial will be completed in 2016. Study II is a multicentre open-labeled parallel-group three-arm randomized controlled trial. Patients will be randomized to affect school with script analysis, to basic body awareness treatment, or to treatment as usual. Power calculations show that 70 persons are required in each arm at the last follow-up session. Patients with type 2 diabetes will be recruited from primary care. This study will start in 2016 and finish in 2023. For both studies, the inclusion criteria are: HbA1c concentration ≥62.5 mmol/mol; depression, alexithymia, anxiety or a negative self-image; age 18-59 years; and diabetes duration ≥1 year. The exclusion criteria are pregnancy, severe comorbidities, cognitive deficiencies or inadequate Swedish. Depression, anxiety, alexithymia and self-image are assessed

Evolution, Three-Dimensional Model and Localization of Truncated Hemoglobin PttTrHb of Hybrid Aspen

PubMed Central

Dumont, Estelle; Jokipii-Lukkari, Soile; Parkash, Vimal; Vuosku, Jaana; Sundström, Robin; Nymalm, Yvonne; Sutela, Suvi; Taskinen, Katariina; Kallio, Pauli T.; Salminen, Tiina A.; Häggman, Hely

2014-01-01

Thus far, research on plant hemoglobins (Hbs) has mainly concentrated on symbiotic and non-symbiotic Hbs, and information on truncated Hbs (TrHbs) is scarce. The aim of this study was to examine the origin, structure and localization of the truncated Hb (PttTrHb) of hybrid aspen (Populus tremula L. × tremuloides Michx.), the model system of tree biology. Additionally, we studied the PttTrHb expression in relation to non-symbiotic class1 Hb gene (PttHb1) using RNAi-silenced hybrid aspen lines. Both the phylogenetic analysis and the three-dimensional (3D) model of PttTrHb supported the view that plant TrHbs evolved vertically from a bacterial TrHb. The 3D model suggested that PttTrHb adopts a 2-on-2 sandwich of α-helices and has a Bacillus subtilis -like ligand-binding pocket in which E11Gln and B10Tyr form hydrogen bonds to a ligand. However, due to differences in tunnel cavity and gate residue (E7Ala), it might not show similar ligand-binding kinetics as in Bs-HbO (E7Thr). The immunolocalization showed that PttTrHb protein was present in roots, stems as well as leaves of in vitro -grown hybrid aspens. In mature organs, PttTrHb was predominantly found in the vascular bundles and specifically at the site of lateral root formation, overlapping consistently with areas of nitric oxide (NO) production in plants. Furthermore, the NO donor sodium nitroprusside treatment increased the amount of PttTrHb in stems. The observed PttTrHb localization suggests that PttTrHb plays a role in the NO metabolism. PMID:24520401

Comparison between electrically evoked and voluntary isometric contractions for biceps brachii muscle oxidative metabolism using near-infrared spectroscopy.

PubMed

Muthalib, Makii; Jubeau, Marc; Millet, Guillaume Y; Maffiuletti, Nicola A; Nosaka, Kazunori

2009-09-01

This study compared voluntary (VOL) and electrically evoked isometric contractions by muscle stimulation (EMS) for changes in biceps brachii muscle oxygenation (tissue oxygenation index, DeltaTOI) and total haemoglobin concentration (DeltatHb = oxygenated haemoglobin + deoxygenated haemoglobin) determined by near-infrared spectroscopy. Twelve men performed EMS with one arm followed 24 h later by VOL with the contralateral arm, consisting of 30 repeated (1-s contraction, 1-s relaxation) isometric contractions at 30% of maximal voluntary contraction (MVC) for the first 60 s, and maximal intensity contractions thereafter (MVC for VOL and maximal tolerable current at 30 Hz for EMS) until MVC decreased approximately 30% of pre-exercise MVC. During the 30 contractions at 30% MVC, DeltaTOI decrease was significantly (P < 0.05) greater and DeltatHb was significantly (P < 0.05) lower for EMS than VOL, suggesting that the metabolic demand for oxygen in EMS is greater than VOL at the same torque level. However, during maximal intensity contractions, although EMS torque (approximately 40% of VOL) was significantly (P < 0.05) lower than VOL, DeltaTOI was similar and tHb was significantly (P < 0.05) lower for EMS than VOL towards the end, without significant differences between the two sessions in the recovery period. It is concluded that the oxygen demand of the activated biceps brachii muscle in EMS is comparable to VOL at maximal intensity.

Microvascular responses to (hyper-)gravitational stress by short-arm human centrifuge: arteriolar vasoconstriction and venous pooling.

PubMed

Habazettl, H; Stahn, Alexander; Nitsche, Andrea; Nordine, Michael; Pries, A R; Gunga, H-C; Opatz, O

2016-01-01

We hypothesized that lower body microvessels are particularly challenged during exposure to gravity and hypergravity leading to failure of resistance vessels to withstand excessive transmural pressure during hypergravitation and gravitation-dependent microvascular blood pooling. Using a short-arm human centrifuge (SAHC), 12 subjects were exposed to +1Gz, +2Gz and +1Gz, all at foot level, for 4 min each. Laser Doppler imaging and near-infrared spectroscopy were used to measure skin perfusion and tissue haemoglobin concentrations, respectively. Pretibial skin perfusion decreased by 19% during +1Gz and remained at this level during +2Gz. In the dilated area, skin perfusion increased by 24 and 35% during +1Gz and +2Gz, respectively. In the upper arm, oxygenated haemoglobin (Hb) decreased, while deoxy Hb increased with little change in total Hb. In the calf muscle, O2Hb and deoxy Hb increased, resulting in total Hb increase by 7.5 ± 1.4 and 26.6 ± 2.6 µmol/L at +1Gz and +2Gz, respectively. The dynamics of Hb increase suggests a fast and a slow component. Despite transmural pressures well beyond the upper myogenic control limit, intact lower body resistance vessels withstand these pressures up to +2Gz, suggesting that myogenic control may contribute only little to increased vascular resistance. The fast component of increasing total Hb indicates microvascular blood pooling contributing to soft tissue capacitance. Future research will have to address possible alterations of these acute adaptations to gravity after deconditioning by exposure to micro-g.

Diagnosing anaemia in pregnancy in rural clinics: assessing the potential of the Haemoglobin Colour Scale.

PubMed Central

van den Broek, N. R.; Ntonya, C.; Mhango, E.; White, S. A.

1999-01-01

Anaemia in pregnancy is a common and severe problem in many developing countries. Because of lack of resources and staff motivation, screening for anaemia is often solely by clinical examination of the conjunctiva or is not carried out at all. A new colour scale for the estimation of haemoglobin concentration has been developed by WHO. The present study compares the results obtained using the new colour scale on 729 women visiting rural antenatal clinics in Malawi with those obtained by HemoCue haemoglobinometer and electronic Coulter Counter and with the assessment of anaemia by clinical examination of the conjunctiva. Sensitivity using the colour scale was consistently better than for conjunctival inspection alone and interobserver agreement and agreement with Coulter Counter measurements was good. The Haemoglobin Colour Scale is simple to use, well accepted, cheap and gives immediate results. It shows considerable potential for use in screening for anaemia in antenatal clinics in settings where resources are limited. PMID:10063656

Diagnosing anaemia in pregnancy in rural clinics: assessing the potential of the Haemoglobin Colour Scale.

PubMed

van den Broek, N R; Ntonya, C; Mhango, E; White, S A

1999-01-01

Anaemia in pregnancy is a common and severe problem in many developing countries. Because of lack of resources and staff motivation, screening for anaemia is often solely by clinical examination of the conjunctiva or is not carried out at all. A new colour scale for the estimation of haemoglobin concentration has been developed by WHO. The present study compares the results obtained using the new colour scale on 729 women visiting rural antenatal clinics in Malawi with those obtained by HemoCue haemoglobinometer and electronic Coulter Counter and with the assessment of anaemia by clinical examination of the conjunctiva. Sensitivity using the colour scale was consistently better than for conjunctival inspection alone and interobserver agreement and agreement with Coulter Counter measurements was good. The Haemoglobin Colour Scale is simple to use, well accepted, cheap and gives immediate results. It shows considerable potential for use in screening for anaemia in antenatal clinics in settings where resources are limited.

Modified formulation of CPDA for storage of whole blood, and of SAGM for storage of red blood cells, to maintain the concentration of 2,3-diphosphoglycerate.

PubMed

Kurup, P A; Arun, P; Gayathri, N S; Dhanya, C R; Indu, A R

2003-11-01

A dramatic decrease in the level of 2,3-diphosphoglycerate (2,3-DPG) takes place during the storage of whole blood (WB) in CPDA (citrate-phosphate-dextrose-adenine) and a similar decrease occurs during the storage of red blood cells (RBCs) in SAGM (saline-adenine-glucose-mannitol). The aim of the present study was to prevent this decrease by modifying CPDA and SAGM. The pH of WB anticoagulant or RBC preservative solution was maintained at 7.6 by autoclaving the dextrose solution separately, by incorporating ascorbic acid and nicotinic acid into both CPDA and SAGM (to produce modified CPDA and SAGM solutions), and by reducing the concentration of adenine and adding citrate to the modified SAGM solution. The concentration of 2,3-DPG in WB after 28 days of storage in modified CPDA, and in RBCs stored in modified SAGM, was compared with that in WB or RBCs stored in unmodified solutions. The initial 2,3-DPG levels were maintained after 28 days in the modified formulations [10.63 +/- 2.58 microM/g of haemoglobin (Hb) in the case of modified CPDA and 12.07 +/- 1.47 microM/g of Hb in the case of modified SAGM], whereas in standard CPDA and SAGM solutions, the concentration of 2,3-DPG decreased to very low levels (0.86 +/- 0.97 microM/g Hb for CPDA and 0.12 +/- 0.008 for SAGM). Our modification in the formulation of CPDA or SAGM is effective in arresting the dramatic decrease in the level of 2,3-DPG that occurs during storage of WB and RBCs in unmodified solutions.

Clinical characteristics of type 2 diabetes patients with discordance between HbA1c and fasting plasma glucose in the real world: An analysis of the ORBIT study.

PubMed

Shu, Hua; Lu, Juming; Zhang, Puhong; Zhu, Dongshan; Li, Xian; Ji, Jiachao; Zhao, Fang; Ji, Linong

2018-05-01

We aimed to determine the clinical characteristics of type 2 diabetes patients on basal insulin therapy with inadequate glucose control due to discordance between glycated haemoglobin (HbA 1c ) and fasting plasma glucose (FPG) in the real world. This was a retrospective analysis of data from the ORBIT study in China. Clinical characteristics of patients with discordance between HbA 1c and FPG at baseline and at the end of 6 months of follow-up were analysed using multinomial logistic regression in 4 study groups divided by HbA 1c and FPG. Overall, of 6721 patients initiated on basal insulin, 853 achieved HbA 1c  < 7% but FPG ≥ 7 mmol/L (group 2), while 997 had FPG < 7 mmol/L but HbA 1c  ≥ 7% (group 3) at the end of follow-up. Patients in group 3 had a longer duration of type 2 diabetes compared with those in group 2 (7.22 ± 5.30 vs 6.00 ± 4.80 y, P < .05). Patients on glargine (32.90%) or detemir (36.88%) treatment accounted for a higher proportion of patients with both HbA 1c and FPG controlled than those on neutral protamine Hagedorn therapy (23.45%; P < .05). Per the multinomial logistic analysis, higher frequency of self-monitoring of blood glucose (SMBG) and use of glargine or detemir therapy were significantly inversely associated with risk of discordance between HbA 1c and FPG, while dose of insulin was a risk factor for discordance at the end of follow-up (all P < .05). Patients treated with insulin analogues (glargine or detemir), instead of neutral protamine Hagedorn, and with more frequent SMBG are more likely to exhibit concordance between HbA 1c and FPG. Copyright © 2018 John Wiley & Sons, Ltd.

Relationship between Hb and HbA1c in Japanese adults: an analysis of the 2009 Japan Society of Ningen Dock database.

PubMed

Takahashi, Eiko; Moriyama, Kengo; Yamakado, Minoru

2014-06-01

We investigated the effect of Hb on HbA1c levels in 265,427 Japanese individuals. The divergence between fasting plasma glucose (FPG) and HbA1c levels increased with lower Hb, resulting in HbA1c levels that were higher in relation to than the FPG levels. Similarly, the correlation between FPG and HbA1c levels, stratified by Hb, weakened as Hb decreased. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Maternal haemoglobin levels and cardio-metabolic risk factors in childhood: the Generation R study.

PubMed

Welten, M; Gaillard, R; Hofman, A; de Jonge, L L; Jaddoe, V W V

2015-05-01

To assess whether variations in maternal haemoglobin levels during pregnancy are associated with cardio-metabolic risk factors in school age children. Population-based prospective cohort study. Rotterdam, The Netherlands, 2002-2012. Mothers and children (n = 5002) participating in the Generation R Study. We obtained maternal haemoglobin levels during early pregnancy (median gestational age 14.6 weeks [95% range 10.3, 25.3]) from venous blood samples. Maternal anaemia and elevated haemoglobin levels were based on World Health Organization criteria. We measured childhood cardio-metabolic risk factors at age 6 years. Cardio-metabolic risk factors included body mass index, total fat mass percentage, android/gynoid fat mass ratio, systolic and diastolic blood pressure, left ventricular mass, and blood levels of cholesterol, insulin and C-peptide. Maternal haemoglobin levels were not associated with childhood body mass index, total fat mass percentage, android/gynoid fat mass ratio, systolic blood pressure, cholesterol or insulin levels. Compared with children with normal maternal haemoglobin levels, children from anaemic mothers had slightly higher diastolic blood pressures (difference 0.70 mmHg, 95% CI 0.12, 1.29) and lower C-peptide levels (difference factor 0.93, 95% CI 0.88, 0.98), and children of mothers with elevated haemoglobin levels had lower left ventricular masses (difference -1.08 g, 95% CI -1.88, -0.29). These associations attenuated after adjustment for multiple testing and were not consistent within linear models. These results do not strongly support the hypothesis that variations in maternal haemoglobin levels during pregnancy influence cardio-metabolic risk factors in childhood. © 2014 Royal College of Obstetricians and Gynaecologists.

Effects of a low-radiotoxicity uranium salt (uranyl acetate) on biochemical and hematological parameters of the catfish, Clarias gariepinus

NASA Astrophysics Data System (ADS)

Al-Ghanim, Khalid A.; Ahmad, Zubair; Al-Kahem Al-Balawi, Hmoud F.; Al-Misned, Fahad; Maboob, Shahid; Suliman, El-Amin M.

2016-01-01

Specimens of Clarias gariepinus were treated with lethal (70, 75, 80, 85, 90, and 95 mg/L) and sub-lethal concentrations (8, 12 and 16 mg/L) of uranyl acetate, a low-radiotoxicity uranium salt. The LC 50 value was registered as 81.45 mg/L. The protein and glycogen concentrations in liver and muscles were decreased in the fish exposed to sub-lethal concentrations. The red blood cell (RBC) and white blood cell (WBC) counts, haemoglobin (Hb) concentration and haematocrit (Hct) values were decreased. Different blood indices like mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH) and mean corpuscular haemoglobin concentration (MCHC) were negatively affected. Level of plasma glucose was elevated whereas protein was decreased. The level of calcium concentration (Ca) was declined in the blood of exposed fish whereas magnesium (Mg) remains unchanged. The activity level of glutamic-oxaloacetic transaminase (GOT) and glutamic-pyruvic transaminase (GPT) was elevated in exposed fish. These effects were more pronounced in the last period of exposure and in higher concentrations. Results of the present study indicate that uranyl acetate has adverse effects on Clarias gariepinus and causes changes in the biochemical and hematological parameters of the fish.

[Frequency of hemoglobin abnormalities and hemoglobinopathies in Mozambique peoples (comparison between leprosy and non-leprosy subjects].

PubMed

Nowicki, L; Behnken, L; Martin, H

1975-11-01

In 588 bloodsamples of negride natives from Moçambique, preferably Chuabo and Macua, haemoglobin analyses were performed. In 21 cases an increase of Hb A2 was found, indicating the presence of heterozygous beta-thalassaemia, in one case the changes in Hb-analysis were typical for beta-delta-thalassaemia, 18 samples could be shown to contain Hb S, typical for the heterozygous sickle cell trait. Futhermore in 7 cases Hb A2' was found. In two bloodsamples haemoglobin variants were observed, which according to their electrophoretical mobility were assumed to represent Hb D in one case, and Hb G in the other. In the Chuabo population the frequency of the thalassaemia gene was found to be more than twice as high as in the Macua population. In non-lepers Hb S was observed with a remarkable higher incidence than in lepers.

HbA1c presents low sensitivity as a post-pregnancy screening test for both diabetes and prediabetes in Greek women with history of gestational diabetes mellitus.

PubMed

Apostolakis, Michael; Paschou, Stavroula A; Zapanti, Evangelia; Sarantopoulou, Vasiliki; Vasileiou, Vasiliki; Anastasiou, Eleni

2018-06-11

Women with a history of gestational diabetes mellitus (GDM) are at increased risk for type 2 diabetes (T2D). It is thus recommended that an oral glucose tolerance test (OGTT) be performed after delivery. Recently, the use of glycated haemoglobin A1c (HbA1c) has been proposed as a simpler and faster method to diagnose glucose disorders. The aim of this study was to investigate whether HbA1c measurement can replace OGTT in the detection of prediabetes and T2D in women with a history of GDM. We studied 1336 women (35.3 ± 5.8 years old) with a history of GDM 16.6 ± 28.2 months after delivery. All women were evaluated through an OGTT and a simultaneous HbA1c measurement. American Diabetes Association (ADA) criteria were used for the assessment of glucose disorders. Sensitivity and specificity of HbA1c were measured for the prediction of T2D and prediabetes, while Cohen's coefficient of agreement (k) was calculated. ROC analysis was performed to evaluate the sensitivity and specificity of HbA1c. Based on OGTT, 725 women (54.3%) were normal, 406 (30.4%) presented impaired fasting glucose (IFG), 48 (3.6%) impaired glucose tolerance (IGT), 74 (5.5%) combined IFG+IGT, and 83 presented with T2D (6.2%). By contrast, using HbA1c as a screening test, 1150 women (94.1%) were normal, while 49 (4.0%) had prediabetes and 23 (1.9%) T2D. Sensitivity of HbA1c for the diagnosis of prediabetes was 5.3% in comparison to OGTT, specificity was 99.2%, while for the diagnosis of T2D, the percentages were 29.6 and 100%, respectively. The consistency in classifying impaired glucose tolerance between HbA1c and OGTT was 59.7%. Cohen's coefficient of agreement was k = 0.116, indicating slight agreement. Performing a ROC curve, the optimal value of distinctive ability of HbA1c was 4.6% in the case of prediabetes, while for diabetes, it was 5.5%. This study provided evidence that HbA1c can identify fewer women with prediabetes and T2D than OGTT, indicating that HbA1c cannot be

Borderline maintenance of erythrocyte 2,3-diphosphoglycerate concentrations in normoxic type 1 (insulin dependent) diabetic subjects.

PubMed

Story, C J; Roberts, A P; Ryall, R G

1986-02-01

Erythrocyte 2,3-diphosphoglycerate and haemoglobin A1c concentrations were measured in 26 clinically normoxic patients with type 1 (insulin dependent) diabetes mellitus. The concentration of 2,3-diphosphoglycerate theoretically required to maintain normal erythrocyte oxygen delivery function in each subject was calculated and compared with the measured concentrations. In the majority of diabetic patients 2,3-diphosphoglycerate concentrations were sufficient to keep the erythrocyte oxygen dissociation curve within the normal range under otherwise normal blood conditions. There was, however, a minority of patients in which this was not true. It is concluded that the increased erythrocyte 2,3-diphosphoglycerate concentrations in clinically normoxic diabetic subjects are generally less than compensatory for the effect of haemoglobin A1c formation on the haemoglobin-oxygen dissociation curve.

Purification, crystallization and preliminary X-ray diffraction studies on avian haemoglobin from pigeon (Columba livia).

PubMed

Sathya Moorthy, Pon; Neelagandan, K; Balasubramanian, M; Ponnuswamy, M N

2009-02-01

Haemoglobin is a physiologically significant metalloprotein that is involved in the exchange of gases for sustaining life. The respiratory system of birds is unique and complex compared with that of mammals. Many investigations of avian haemoglobins have revealed the presence of inositol pentaphosphate (IP5), a principal allosteric effector that is involved in regulation of their function. Structural investigations of avian haemoglobins are presently not adequate to explain their function. Efforts have been made in this direction in order to understand the oxygen-binding affinity involved in adapting to hypoxia in avian haemoglobins. Fresh whole blood was collected from pigeon (Columba livia) and purified using a DEAE cellulose anion-exchange chromatographic column. Crystallization of pigeon haemoglobin was accomplished using the hanging-drop vapour-diffusion method using PEG 3350 as a precipitant in 50 mM sodium acetate buffer pH 5.5 with 1 M NaCl. Data collection was carried out using a MAR345 image-plate detector system. The crystals diffracted to 2 A resolution. Pigeon haemoglobin crystallizes in a triclinic space group, with two whole biological molecules in the asymmetric unit and with unit-cell parameters a = 55.005, b = 65.528, c = 104.370 A, alpha = 78.742, beta = 89.819, gamma = 65.320 degrees .

Validation and determination of a reference interval for canine HbA1c using an immunoturbidimetric assay.

PubMed

Goemans, Anne F; Spence, Susanna J; Ramsey, Ian K

2017-06-01

Hemoglobin A1c (HbA1c) provides a reliable measure of glycemic control over 2-3 months in human diabetes mellitus. In dogs, presence of HbA1c has been demonstrated, but there are no validated commercial assays. The purpose of the study was to validate a commercially available automated immunoturbidimetric assay for canine HbA1c and determine an RI in a hospital population. The specificity of the assay was assessed by inducing glycosylation in vitro using isolated canine hemoglobin, repeatability by measuring canine samples 5 times in succession, long term inter-assay imprecision by measuring supplied control materials, stability using samples stored at 4°C over 5 days and -20°C over 8 weeks, linearity by mixing samples of known HbA1c in differing proportions, and the effect of anticoagulants with paired samples. An RI was determined using EDTA-anticoagulated blood samples from 60 nondiabetic hospitalized animals of various ages and breeds. Hemoglobin A1c was also measured in 10 diabetic dogs. The concentration of HbA1c increased proportionally with glucose concentration in vitro. For repeat measurements, the CV was 4.08% (range 1.16-6.10%). Samples were stable for 5 days at 4°C. The assay was linear within the assessed range. Heparin- and EDTA-anticoagulated blood provided comparable results. The RI for HbA1c was 9-18.5 mmol/mol. There was no apparent effect of age or breed on HbA1c. In diabetic dogs, HbA1c ranged from 14 to 48 mmol/mol. The assay provides a reliable method for canine HbA1c measurement with good analytic performance. © 2017 American Society for Veterinary Clinical Pathology.

Expected outcomes from topical haemoglobin spray in non-healing and worsening venous leg ulcers.

PubMed

Arenberger, P; Elg, F; Petyt, J; Cutting, K

2015-05-01

To evaluate the effect of topical haemoglobin spray on treatment response and wound-closure rates in patients with chronic venous leg ulcers. A linear regression model was used to forecast healing outcomes over a 12-month period. Simulated data were taken from normal distributions based on post-hoc analysis of a 72-patient study in non-healing and worsening wounds (36 patients receiving standard care and 36 receiving standard care plus topical haemoglobin spray). Using a simulated 25,000 'patients' from each group, the proportion of wound closure over time was projected. Simulation results predicted a 55% wound closure rate at six months in the haemoglobin group, compared with 4% in the standard care group. Over a 12-month simulation period, a 43% overall reduction in wound burden was predicted. With the haemoglobin spray, 85% of wounds were expected to heal in 12 months, compared with 13% in the standard care group. Topical haemoglobin spray promises a more effective treatment for chronic venous leg ulcers than standard care alone in wounds that are non-healing or worsening. Further research is required to validate these predictions and to identify achievable outcomes in other chronic wound types.

NITRATE CONVERSION OF HB-LINE REILLEXTM HPQ RESIN

DOE Office of Scientific and Technical Information (OSTI.GOV)

Steimke, J.; Williams, M.; Steeper, T.

Reillex{trademark} HPQ ion exchange resin is used by HB Line to remove plutonium from aqueous streams. Reillex{trademark} HPQ resin currently available from Vertellus Specialties LLC is a chloride ionic form, which can cause stress corrosion cracking in stainless steels. Therefore, HB Line Engineering requested that Savannah River National Laboratory (SRNL) convert resin from chloride form to nitrate form in the Engineering Development Laboratory (EDL). To perform this task, SRNL treated two batches of resin in 2012. The first batch of resin from Reilly Industries Batch 80302MA was initially treated at SRNL in 2001 to remove chloride. This batch of resin,more » nominally 30 liters, has been stored wet in carboys since that time until being retreated in 2012. The second batch of resin from Batch 23408 consisted of 50 kg of new resin purchased from Vertellus Specialties in 2012. Both batches were treated in a column designed to convert resin using downflow of 1.0 M sodium nitrate solution through the resin bed followed by rinsing with deionized water. Both batches were analyzed for chloride concentration, before and after treatment, using Neutron Activation Analysis (NAA). The resin specification [Werling, 2003] states the total chlorine and chloride concentration shall be less than 250 ppm. The resin condition for measuring this concentration is not specified; however, in service the resin would always be fully wet. Measurements in SRNL showed that changing from oven dry resin to fully wet resin, with liquid in the particle interstices but no supernatant, increases the total weight by a factor of at least three. Therefore, concentration of chlorine or chloride expressed as parts per million (ppm) decreases by a factor of three. Therefore, SRNL recommends measuring chlorine concentration on an oven dry basis, then dividing by three to estimate chloride concentration in the fully wet condition. Chloride concentration in the first batch (No.80302MA) was nearly the

Long-term effect of dietary fibre intake on glycosylated haemoglobin A1c level and glycaemic control status among Chinese patients with type 2 diabetes mellitus.

PubMed

Yang, Luxi; Shu, Le; Jiang, Junyi; Qiu, Hua; Zhao, Genming; Zhou, Yi; Jiang, Qingwu; Sun, Qiao; Qin, Guoyou; Wu, Hongyan; Yang, Liming; Ruan, Xiaonan; Xu, Wang Hong

2014-08-01

Dietary fibre has been linked to lower levels of glycosylated haemoglobin A1c (HbA1c) among diabetes patients. The present study aimed to evaluate the long-term effect of dietary fibre on HbA1c levels among Chinese patients with type 2 diabetes mellitus. Two cross-sectional surveys were conducted in 2006 and 2011, with the second one being a repeat survey on a sub-sample from the initial one. In both surveys, an in-person interview was conducted to collect information on demographic characteristics and lifestyles following a similar protocol. Dietary intake was assessed with a validated FFQ. Anthropometric measures and biochemical assays were performed at the interview. Communities in Pudong New Area of Shanghai, China. Chinese patients (n 934) with type 2 diabetes mellitus. An inverse association was observed between dietary fibre and glycaemic status indicated by HbA1c level in both surveys, although it was significant only in the first survey. Among 497 patients participating in both surveys, dietary fibre intake at the first survey was inversely associated with uncontrolled glycaemic status at the second survey, with adjusted odds ratios across the tertiles of intake being 1·00, 0·72 (95 % CI 0·43, 1·21) and 0·58 (95 % CI 0·34, 0·99; P trend = 0·048). The change in fibre intake was slightly associated with glycaemic status, with each increase in tertile scores of intake linked to a 0·138 % (β = -0·138; 95 % CI -0·002, 0·278) decrease in HbA1c value and a 19 % (OR = 0·81; 95 % CI 0·65, 1·02) reduced risk of uncontrolled glycaemic status at the second survey. Dietary fibre may have a long-term beneficial effect on HbA1c level among Chinese diabetes patients.

HbA1c as a predictor of diabetes after gestational diabetes mellitus.

PubMed

Claesson, Rickard; Ignell, Claes; Shaat, Nael; Berntorp, Kerstin

2017-02-01

We wanted to investigate third-trimester HbA1c as a predictor of diabetes after gestational diabetes mellitus (GDM). Women with GDM were followed up prospectively for five years from pregnancy to detect the development of diabetes. The ability of HbA1c to predict diabetes was evaluated with receiver-operating characteristic (ROC) curves and logistic regression analysis. By five years, 73 of 196 women had been diagnosed with diabetes. An optimal cut-off point for HbA1c of 36mmol/mol (5.4%) could predict diabetes with 45% sensitivity and 92% specificity. For HbA1c ≥39mmol/mol (≥5.7%), sensitivity, specificity, and positive predictive value were 30%, 97%, and 91%, respectively. In logistic regression analysis, adjusting for the diagnostic glucose concentration during pregnancy, HbA1c levels in the upper quartile (≥36mmol/mol) were associated with a 5.5-fold increased risk of diabetes. Third-trimester HbA1c levels in the pre-diabetes range revealed women with post-partum diabetes with high specificity and high positive predictive value. HbA1c testing could be used as a strategy to select high-risk women for lifestyle interventions aimed at prevention of diabetes starting during pregnancy. The results should encourage further validation in other populations using new diagnostic criteria for GDM. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Risk factors and consequences of maternal anaemia and elevated haemoglobin levels during pregnancy: a population-based prospective cohort study.

PubMed

Gaillard, Romy; Eilers, Paul H C; Yassine, Siham; Hofman, Albert; Steegers, Eric A P; Jaddoe, Vincent W V

2014-05-01

To determine sociodemographic and life style-related risk factors and trimester specific maternal, placental, and fetal consequences of maternal anaemia and elevated haemoglobin levels in pregnancy. In a population-based prospective cohort study of 7317 mothers, we measured haemoglobin levels in early pregnancy [gestational age median 14.4 weeks (inter-quartile-range 12.5-17.5)]. Anaemia (haemoglobin ≤11 g/dl) and elevated haemoglobin levels (haemoglobin ≥13.2 g/dl) were defined according to the WHO criteria. Maternal blood pressure, placental function and fetal growth were measured in each trimester. Data on gestational hypertensive disorders and birth outcomes was collected from hospitals. Older maternal age, higher body mass index, primiparity and European descent were associated with higher haemoglobin levels (P < 0.05). Elevated haemoglobin levels were associated with increased systolic and diastolic blood pressure throughout pregnancy (mean differences 5.1 mmHg, 95% confidence interval [CI] 3.8, 6.5 and 4.1 mmHg, 95% CI 3.0, 5.2, respectively) and with a higher risk of third trimester uterine artery notching (RR 1.3, 95% CI 1.0, 1.7). As compared with maternal normal haemoglobin levels, not anaemia, but elevated haemoglobin levels were associated with fetal head circumference, length, and weight growth restriction from third trimester onwards (P < 0.05). Elevated haemoglobin levels were associated with increased risks of gestational hypertensive disorders (RR 1.4, 95% CI 1.1, 1.8) and adverse birth outcomes (RR 1.4, 95% CI 1.1, 1.7). In a low-risk population, various sociodemographic and life style factors affect haemoglobin levels during pregnancy. Elevated haemoglobin levels are associated with increased risks of maternal, placental, and fetal complications. © 2014 John Wiley & Sons Ltd.

Liposomes as potential masking agents in sport doping. Part 2: Detection of liposome-entrapped haemoglobin by flow cytofluorimetry.

PubMed

Esposito, Simone; Colicchia, Sonia; de la Torre, Xavier; Donati, Francesco; Mazzarino, Monica; Botrè, Francesco

2017-02-01

This work presents an analytical procedure for the identification and characterization of liposome-entrapped haemoglobins, based on flow cytofluorimetry. Flow cytofluorimetric detection is carried out following labelling by two distinct fluorescent reagents, an anti-haemoglobin antibody, fluorescein isothiocyanate conjugated, and an anti-poly(ethylene glycol) antibody, streptavidin-phycoerythrin conjugated. This experimental strategy allows the detection of liposome-entrapped haemoglobins in aqueous media, including plasma; the efficacy of the proposed approach has been verified on whole blood samples added with the liposomal formulation (ex-vivo). Additionally, the proposed technique allows the characterization of several key parameters in the study of liposomal haemoglobins, including, for instance (1) the determination of the degree of haemoglobin entrapment by liposomes; (2) the poly(ethylene glycol) insertion efficiency; and (3) the evaluation of liposome-entrapped haemoglobins stability following storage at 4 °C, allowing to follow both the process of haemoglobin loss from liposomes and the liposome degradation. The procedure is proposed for the detection and characterization of liposome-entrapped haemoglobin formulations to control their misuse in sport, but is also suggested for further applications in biological and clinical laboratory investigations. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

A nomogram to estimate the HbA1c response to different DPP-4 inhibitors in type 2 diabetes: a systematic review and meta-analysis of 98 trials with 24 163 patients

PubMed Central

Esposito, Katherine; Chiodini, Paolo; Maiorino, Maria Ida; Capuano, Annalisa; Cozzolino, Domenico; Petrizzo, Michela; Bellastella, Giuseppe; Giugliano, Dario

2015-01-01

Objectives To develop a nomogram for estimating the glycated haemoglobin (HbA1c) response to different dipeptidyl peptidase-4 (DPP-4) inhibitors in type 2 diabetes. Design A systematic review and meta-analysis of randomised controlled trials (RCTs) of DPP-4 inhibitors (vildagliptin, sitagliptin, saxagliptin, linagliptin and alogliptin) on HbA1c were conducted. Electronic searches were carried out up to December 2013. Trials were included if they were carried out on participants with type 2 diabetes, lasted at least 12 weeks, included at least 30 participants and had a final assessment of HbA1c. A random effect model was used to pool data. A nomogram was used to represent results of the metaregression model. Participants Adults with type 2 diabetes. Interventions Any DPP-4 inhibitor (vildagliptin, sitagliptin, saxagliptin, linagliptin or alogliptin). Outcome measures The HbA1c response to each DPP-4 inhibitor within 1 year of therapy. Results We screened 928 citations and reviewed 98 articles reporting 98 RCTs with 100 arms in 24 163 participants. There were 26 arms with vildagliptin, 37 with sitagliptin, 13 with saxagliptin, 13 with linagliptin and 11 with alogliptin. For all 100 arms, the mean baseline HbA1c value was 8.05% (64 mmol/mol); the decrease of HbA1c from baseline was −0.77% (95% CI −0.82 to −0.72%), with high heterogeneity (I2=96%). Multivariable metaregression model that included baseline HbA1c, type of DPP-4 inhibitor and fasting glucose explained 58% of variance between studies, with no significant interaction between them. Other factors, including age, previous diabetes drugs and duration of treatment added low predictive power (<1%). The nomogram estimates the absolute HbA1c reduction from baseline using the type of DPP-4 inhibitor, baseline values of HbA1c and fasting glucose. Conclusions Baseline HbA1c level and fasting glucose explain most of the variance in HbA1c change in response to DPP-4 inhibitors: each increase of 1.0% units

Purification, crystallization and preliminary X-ray diffraction studies on avian haemoglobin from pigeon (Columba livia)

PubMed Central

Sathya Moorthy, Pon.; Neelagandan, K.; Balasubramanian, M.; Ponnuswamy, M. N.

2009-01-01

Haemoglobin is a physiologically significant metalloprotein that is involved in the exchange of gases for sustaining life. The respiratory system of birds is unique and complex compared with that of mammals. Many investigations of avian haemoglobins have revealed the presence of inositol pentaphosphate (IP5), a principal allosteric effector that is involved in regulation of their function. Structural investigations of avian haemoglobins are presently not adequate to explain their function. Efforts have been made in this direction in order to understand the oxygen-binding affinity involved in adapting to hypoxia in avian haemoglobins. Fresh whole blood was collected from pigeon (Columba livia) and purified using a DEAE cellulose anion-exchange chromatographic column. Crystallization of pigeon haemoglobin was accomplished using the hanging-drop vapour-diffusion method using PEG 3350 as a precipitant in 50 mM sodium acetate buffer pH 5.5 with 1 M NaCl. Data collection was carried out using a MAR345 image-plate detector system. The crystals diffracted to 2 Å resolution. Pigeon haemoglobin crystallizes in a triclinic space group, with two whole biological molecules in the asymmetric unit and with unit-cell parameters a = 55.005, b = 65.528, c = 104.370 Å, α = 78.742, β = 89.819, γ = 65.320°. PMID:19194000

Effects of exenatide twice daily, exenatide once weekly or insulin in patients with type 2 diabetes and baseline HbA1c ≥10.0%: Two pooled analyses including 20 randomised controlled trials.

PubMed

Busch, Robert S; Ruggles, James; Han, Jenny; Hardy, Elise

2017-12-01

Patients with advanced type 2 diabetes (T2D) and high glycated haemoglobin (HbA1c) values can be difficult to treat because of their severe metabolic disease. This pooled analysis examined the treatment effects of exenatide twice daily (BID), exenatide once weekly (QW) and insulin in patients with high baseline HbA1c (≥10.0%). This post hoc analysis used pooled data from 12 and 8 randomised controlled trials of exenatide BID and exenatide QW, respectively. Patients with T2D who completed at least 24 weeks of treatment with exenatide BID, exenatide QW or insulin (insulin glargine, insulin detemir or insulin aspart) were categorised by baseline HbA1c. Patients with HbA1c ≥10.0% were included in the analysis. Both exenatide and insulin reduced HbA1c (mean ± SE reduction: -2.0% ± 0.2% [exenatide] and -2.1% ± 0.2% [insulin] in the exenatide BID studies, and -2.6% ± 0.1% [exenatide] and -2.1% ± 0.2% [insulin] in the exenatide QW studies; all P < .001). Body weight decreased with exenatide and increased with insulin. Systolic blood pressure decreased with exenatide QW. Insulin dose increased over the course of treatment. The most common adverse events with exenatide were gastrointestinal. Insulin was associated with some hypoglycaemia risk. Hypoglycaemia events occurred infrequently with exenatide when given without sulphonylureas. For patients with high HbA1c, treatment with exenatide or insulin both improved glycaemic control. Given the associated weight loss and low risk of hypoglycaemia, exenatide may be a suitable alternative to treatment with insulin in certain patients with T2D and high HbA1c. © 2017 John Wiley & Sons Ltd.

Low-grade inflammation is associated with lower haemoglobin levels in healthy individuals: results from the Danish blood donor study.

PubMed

Kotzé, S R; Pedersen, O B; Petersen, M S; Sørensen, E; Thørner, L W; Sørensen, C J; Rigas, A S; Hjalgrim, H; Rostgaard, K; Ullum, H; Erikstrup, C

2016-08-01

Chronic inflammation can lead to anaemia of chronic disease due to the sequestration of iron caused by inflammatory cytokines and the protein hepcidin. However, the effect of low-grade inflammation (LGI) on haemoglobin among healthy individuals is not known. This study examines the effect of LGI on haemoglobin among Danish blood donors. We performed multivariable linear regression to assess the effect of LGI (i.e. high-sensitivity C-reactive protein above 3 mg/l but below 10 mg/l) on haemoglobin in 17 322 Danish blood donors. We also performed multivariable logistic regression to evaluate the effect of LGI on the risk of having low haemoglobin (below the 10th percentile among men and women, respectively). We adjusted for donation activity, age, sex, low ferritin, oral contraceptives and menopause. All analyses were stratified by current smoking status. LGI was associated with lower haemoglobin (0·08 mm lower [0·12 g/dl], 95% confidence interval (CI): -0·11-0·05) and increased risk of low haemoglobin (OR = 1·22, 95% CI: 1·05-1·43) in non-smokers. Conversely, LGI was associated with higher haemoglobin in smokers (0·12 mm [0·19 g/dl], 95% CI: 0·06-0·18). In this first study of LGI and haemoglobin in healthy individuals, there was a negative association between LGI and haemoglobin in non-smokers. The association was positive in smokers, probably because smoking leads to both increased inflammation and increased haemoglobin through CO exposure. © 2016 International Society of Blood Transfusion.

Investigation of local heterogeneity of hbO2 and hb in working dog heart in situ under isovolemic hemodilution and critical coronary stenosis

NASA Astrophysics Data System (ADS)

Krug, Alfons; Kessler, Manfred D.; Khuri, Raja; Lust, Robert; Chitwood, Randolph

1996-12-01

A tissue spectrophotometer (EMPHO II) working with 70 micrometer micro lightguide sensors enables recording of spectra in the visible wavelength range (500 - 630 nm). During an initial period arterial hypoxia and hyperoxia were induced on working dog heart by mechanical ventilation with oxygen fractions (fiO2) of 0.1 and 0.5. Under these conditions the effects of low and high fiO2 on oxygenation distribution of intracapillary hemoglobin were investigated. In the second part of the experiment the relation between systemic hematocrit, local hemoglobin concentration, local hemoglobin oxygenation and the oxygen regulation mechanism were studied in detail. In the final part of the experiment the effect of critical coronary stenosis on hb and hbO2 was measured. Critical stenosis was achieved by partial clamping of the left anterior coronary artery (LAD).

Measurement of HbA1c in multicentre diabetes trials - should blood samples be tested locally or sent to a central laboratory: an agreement analysis.

PubMed

Arch, Barbara N; Blair, Joanne; McKay, Andrew; Gregory, John W; Newland, Paul; Gamble, Carrol

2016-10-24

Glycated haemoglobin (HbA1c) is an important outcome measure in diabetes clinical trials. For multicentre designs, HbA1c can be measured locally at participating centres or by sending blood samples to a central laboratory. This study analyses the agreement between local and central measurements, using 1-year follow-up data collected in a multicentre randomised controlled trial (RCT) of newly diagnosed children with type I diabetes. HbA1c measurements were routinely analysed both locally and centrally at baseline and then at 3, 6, 9 and 12 months and the data reported in mmol/mol. Agreement was assessed by calculating the bias and 95 % limits of agreement, using the Bland-Altman analysis method. A predetermined benchmark for clinically acceptable margin of error between measurements was subjectively set as ±10 % for HbA1c. The percentage of pairs of measurements that were classified as clinically acceptable was calculated. Descriptive statistics were used to examine the agreement within centres. Treatment group was not considered. Five hundred and ninety pairs of measurement, representing 255 children and 15 trial centres across four follow-up time points, were compared. There was no significant bias: local measurements were an average of 0.16 mmol/mol (SD = 4.5, 95 % CI -0.2 to 0.5) higher than central. The 95 % limits of agreement were -8.6 to 9.0 mmol/mol (local minus central). Eighty percent of local measurements were within ±10 % of corresponding central measurements. Some trial centres were more varied in the differences observed between local and central measurements: IQRs ranging from 3 to 9 mmol/mol; none indicated systematic bias. Variation in agreement between HbA1c measurements was greater than had been expected although no overall bias was detected and standard deviations were similar. Discrepancies were present across all participating centres. These findings have implications for the comparison of standards of clinical care between centres

Effects of α-thalassaemia mutations on the haematological parameters of β-thalassaemia carriers.

PubMed

Saleh-Gohari, Nasrollah; Khademi Bami, Maryam; Nikbakht, Roya; Karimi-Maleh, Hassan

2015-07-01

Thalassaemia is a haemoglobin disorder caused by a reduction in, or a complete absence of, the production of α- or β-globin genes. Detection of β-thalassaemia carriers is the first step in the prenatal diagnosis of the disease and is based primarily on the differences between levels of blood cell indices. Since co-inheritance of β- and α-thalassaemia mutations modulates the haematological parameters of heterozygote β-thalassaemia indices, understanding the influence of this interaction is helpful for identification of disease carriers. To determine the effects of α-thalassaemia mutations on the haematological parameters of β-thalassaemia carriers. We used gap-PCR and amplification refractory mutation system techniques to find any α- and/or β-thalassaemia mutations in 270 subjects who were suspected to be thalassaemia carriers. The mean values of the haematological parameters in α, β-thalassaemia and β-thalassaemia carriers were compared. Significant differences in mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH) and HbA2 were found between the two groups. Patients who were α, β-thalassaemia carriers had higher mean values of MCV and MCH, whereas HbA2 levels were higher in simple β-thalassaemia. No marked differences were found in mean cell haemoglobin (Hb) concentration and Hb blood cell indices. The value of MCV, MCH and HbA2 were significantly different between α,β-thalassaemia and simple β-thalassaemia in men and women, but the mean values of Hb in the two groups differed markedly only in men. We conclude that co-inheritance of α- and β-thalassaemia mutations may result in misdiagnosis of β-thalassaemia carriers. Therefore, in genetic counselling of patients with a near-normal range of blood cell indices the possibility that they may carry α, β-thalassaemia mutations must be considered. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

The fecal hemoglobin concentration, age and sex test score: Development and external validation of a simple prediction tool for colorectal cancer detection in symptomatic patients.

PubMed

Cubiella, Joaquín; Digby, Jayne; Rodríguez-Alonso, Lorena; Vega, Pablo; Salve, María; Díaz-Ondina, Marta; Strachan, Judith A; Mowat, Craig; McDonald, Paula J; Carey, Francis A; Godber, Ian M; Younes, Hakim Ben; Rodriguez-Moranta, Francisco; Quintero, Enrique; Álvarez-Sánchez, Victoria; Fernández-Bañares, Fernando; Boadas, Jaume; Campo, Rafel; Bujanda, Luis; Garayoa, Ana; Ferrandez, Ángel; Piñol, Virginia; Rodríguez-Alcalde, Daniel; Guardiola, Jordi; Steele, Robert J C; Fraser, Callum G

2017-05-15

Prediction models for colorectal cancer (CRC) detection in symptomatic patients, based on easily obtainable variables such as fecal haemoglobin concentration (f-Hb), age and sex, may simplify CRC diagnosis. We developed, and then externally validated, a multivariable prediction model, the FAST Score, with data from five diagnostic test accuracy studies that evaluated quantitative fecal immunochemical tests in symptomatic patients referred for colonoscopy. The diagnostic accuracy of the Score in derivation and validation cohorts was compared statistically with the area under the curve (AUC) and the Chi-square test. 1,572 and 3,976 patients were examined in these cohorts, respectively. For CRC, the odds ratio (OR) of the variables included in the Score were: age (years): 1.03 (95% confidence intervals (CI): 1.02-1.05), male sex: 1.6 (95% CI: 1.1-2.3) and f-Hb (0-<20 µg Hb/g feces): 2.0 (95% CI: 0.7-5.5), (20-<200 µg Hb/g): 16.8 (95% CI: 6.6-42.0), ≥200 µg Hb/g: 65.7 (95% CI: 26.3-164.1). The AUC for CRC detection was 0.88 (95% CI: 0.85-0.90) in the derivation and 0.91 (95% CI: 0.90-093; p = 0.005) in the validation cohort. At the two Score thresholds with 90% (4.50) and 99% (2.12) sensitivity for CRC, the Score had equivalent sensitivity, although the specificity was higher in the validation cohort (p < 0.001). Accordingly, the validation cohort was divided into three groups: high (21.4% of the cohort, positive predictive value-PPV: 21.7%), intermediate (59.8%, PPV: 0.9%) and low (18.8%, PPV: 0.0%) risk for CRC. The FAST Score is an easy to calculate prediction tool, highly accurate for CRC detection in symptomatic patients. © 2017 UICC.

Inherited haemoglobin disorders: an increasing global health problem.

PubMed Central

Weatherall, D. J.; Clegg, J. B.

2001-01-01

Despite major advances in our understanding of the molecular pathology, pathophysiology, and control and management of the inherited disorders of haemoglobin, thousands of infants and children with these diseases are dying through lack of appropriate medical care. This problem will undoubtedly increase over the next 20 years because, as the result of a reduction in childhood mortality due to infection and malnutrition, more babies with haemoglobin disorders will survive to present for treatment. Although WHO and various voluntary agencies have tried to disseminate information about these diseases, they are rarely mentioned as being sufficiently important to be included in setting health care priorities for the future. It takes considerable time to establish expertise in developing programmes for the control and management of these conditions, and the lessons learned in developed countries will need to be transmitted to those countries in which they occur at a high frequency. PMID:11545326

Association of pre-pregnancy BMI and postpartum weight retention with postpartum HbA1c among women with Type 1 diabetes

PubMed Central

Huang, T.; Brown, F. M.; Curran, A.; James-Todd, T.

2015-01-01

Aim To examine the association of pre-pregnancy BMI and postpartum weight retention with postpartum HbA1c levels in women with Type 1 diabetes. Methods We longitudinally evaluated 136 women with Type 1 diabetes who received prenatal and postpartum care through the Joslin Diabetes Center’s Diabetes and Pregnancy Program between 2004 and 2009. Weight, BMI and HbA1c concentration were assessed before the index pregnancy and repeatedly monitored after delivery until 12 months postpartum. We used a linear mixed model to assess the association of postpartum HbA1c with pre-pregnancy BMI and postpartum weight retention. Results The mean HbA1c concentration increased from 49 mmol/mol (6.6%) at 6 weeks postpartum to 58 mmol/mol (7.5%) by 10 months postpartum, a level similar to the mean pre-pregnancy HbA1c concentration. Postpartum weight retention showed a linearly decreasing trend of 0.06 kg/week (P<0.0001), with −0.1 kg average postpartum weight retention by 1 year postpartum. Compared with women with a pre-pregnancy BMI≥25 kg/m2, women with a lower pre-pregnancy BMI maintained a 3.4 mmol/mol (0.31%) lower HbA1c concentration, after adjusting for several sociodemographic, reproductive and diabetes-related factors (P=0.03). There was a suggestion of a time-varying positive association between HbA1c and postpartum weight retention, with the most significant difference of 3.7 mmol/mol (0.34%; P=0.05) at 30 weeks postpartum among women with postpartum weight retention ≥5 kg vs those with postpartum weight retention <5 kg. Conclusions Pre-pregnancy BMI and postpartum weight retention were positively associated with HbA1c during the first postpartum year in women with Type 1 diabetes. Interventions to modify the behaviours associated with these body weight factors before pregnancy and after delivery may help women with Type 1 diabetes maintain good glycaemic control after pregnancy. PMID:25346003

Near-infrared oxymeter biosensor prototype for non-invasive in vivo analysis of rat brain oxygenation: effects of drugs of abuse

NASA Astrophysics Data System (ADS)

Crespi, F.; Donini, M.; Bandera, A.; Congestri, F.; Formenti, F.; Sonntag, V.; Heidbreder, C.; Rovati, L.

2006-07-01

The feasibility of non-invasive analysis of brain activities was studied in the attempt to overcome the major limitation of actual in vivo methodologies, i.e. invasiveness. Optic fibre probes were used as the optical head of a novel, highly sensitive near-infrared continuous wave spectroscopy (CW-NIR) instrument. This prototype was designed for non-invasive analysis of the two main forms of haemoglobin: oxy-haemoglobin (HbO2) and deoxy-haemoglobin (Hb), chromophores present in biological tissues. It was tested in peripheral tissue (human gastrocnemius muscle) and then reset to perform the measurement on rat brain. In animal studies, the optical head was firmly placed using stereotaxic apparatus upon the sagittal line of the head of anaesthetized adult rats, without any surgery. Then pharmacological treatments with saline (300 µl s.c.) amphetamine (2 mg kg-1) or nicotine (0.4 mg kg-1) were performed. Within 10-20 min amphetamine substantially increased HbO2 and reduced Hb control levels. Nicotine produced a rapid initial increase followed by a decrease in HbO2. In contrast to amphetamine, nicotine treatment also reduced Hb and blood volume. These results support the capacity of our CW-NIR prototype to measure non-invasively HbO2 and Hb levels in the rat brain, that are markers of the degree of tissue oxygenation, thus providing an index of blood levels and therefore of brain metabolism.

Association of napping and night-time sleep with impaired glucose regulation, insulin resistance and glycated haemoglobin in Chinese middle-aged adults with no diabetes: a cross-sectional study

PubMed Central

Baoying, Huang; Hongjie, Chen; Changsheng, Qiu; Peijian, Wu; Qingfei, Lin; Yinghua, Lin; Huibin, Huang; Jixing, Liang; Liantao, Li; Ling, Chen; Kaka, Tang; Zichun, Chen; Lixiang, Lin; Jieli, Lu; Yufang, Bi; Guang, Ning; Penli, Zhu; Junping, Wen; Gang, Chen

2014-01-01

Objective To assess associations between napping and night-time sleep duration with impaired glucose regulation, insulin resistance (IR) and glycated haemoglobin (HbA1c). Design Cross-sectional study. Setting Fujian Province, China, from June 2011 to January 2012. Participants This study enrolled 9028 participants aged 40–65 years. Data of 7568 participants with no diabetes were included for analysis. Type 2 diabetes was defined applying WHO criteria. Outcome measures Participants’ daytime napping and night-time sleep duration data were collected using a standardised self-reported Chinese-language questionnaire about sleep frequency and quality. Anthropometric and laboratory parameters were also measured. IR was defined as a HOMA-IR index value >2.50. ORs and 95% CIs were derived from multivariate logistic regression models. Results Participants (mean age 51.1±7.0 years) included 3060 males and 4508 females with average night-time sleep of 7.9 h. A higher proportion of males napped than females. After adjustment for potential confounders, ORs for HbA1c >6.0% were 1.28 and 1.26 for those napping ≤1 h and >1 h (p=0.002 and p=0.018), respectively. Statistically significant differences in IR between nappers and non-nappers were only marginal clinically. Odds for HbA1c >6.0% were significantly lower in participants with longer night-time sleep durations than in the reference group (>8 h vs 6–8 h). Odds for IR were significantly lower in participants whose night-time sleep hours deviated from the reference group (<6 h, >8 h vs 6–8 h) Conclusions Chinese middle-aged adults with no diabetes who napped had higher HbA1c and IR; those with shorter night-time sleep durations had increased HbA1c. Night-time sleep hours that are either <6 or >8 tend to be associated with lower odds for IR. Further studies are necessary to determine the underlying clinical significance and mechanisms behind these associations. PMID:25056969

Effects of photobiomodulation therapy (pulsed LASER 904 nm) on muscle oxygenation and performance in exercise-induced skeletal muscle fatigue in young women: a pilot study

NASA Astrophysics Data System (ADS)

Oliveira, Murilo X.; Toma, Renata L.; Jones, Brett J. L.; Cyprien, Thomas P.; Tier, Matthew R.; Wallace, Cameron A.; Renno, Ana C. M.; Sabapathy, Surendran; Laakso, E.-Liisa

2017-02-01

Photobiomodulation therapy (PBMt) has been used to increase muscle performance and improve recovery when applied before exercise. We aimed to evaluate the effects of PBMt using LASER on muscle oxygenation and performance. The study was a randomized, participant and assessor-blinded, within-subject crossover trial with placebo control to test the viability of the methods. Five physically active young women were randomly assigned to either placebo, or active PBMt (12 diode cluster probe; 904 nm; 60 mW; 250 Hz; 43.2 J per site, 129.6 J total) in contact over rectus femoris (RF) muscle of the dominant limb immediately before an isokinetic fatigue protocol. A one-week wash-out period preceded cross-over. Electromyography and isokinetic performance measures were evaluated. Absolute concentrations of deoxygenated haemoglobin and myoglobin (deoxy[Hb + Mb]) of the RF, an index of local microvascular fractional O2 extraction, was monitored continuously by near-infrared spectroscopy (NIRS). Total haemoglobin concentration as an indicator of microvascular haematocrit was calculated as the sum of the deoxy[Hb + Mb] and oxy[Hb + Mb] signals. PBMt pre-conditioning reduced time to peak torque when compared to placebo (P<0.05). PBMt resulted in a noticeably reduced trend in deoxy[Hb + Mb] during exercise compared to placebo (P>0.05). PBMt before exercise improves indicators of muscle performance, potentially by increasing local matching of bulk and microvascular O2 delivery relative to skeletal muscle O2 utilisation. Further work is required to understand the effect of PBMt on haemodynamic and metabolic characteristics of muscle.

Changes in blood gas transport of altitude native soccer players near sea-level and sea-level native soccer players at altitude (ISA3600).

PubMed

Wachsmuth, Nadine; Kley, Marlen; Spielvogel, Hilde; Aughey, Robert J; Gore, Christopher J; Bourdon, Pitre C; Hammond, Kristal; Sargent, Charli; Roach, Gregory D; Sanchez, Rudy Soria; Claros, Jesus C Jimenez; Schmidt, Walter F; Garvican-Lewis, Laura A

2013-12-01

The optimal strategy for soccer teams playing at altitude is not known, that is, 'fly-in, fly-out' versus short-term acclimatisation. Here, we document changes in blood gas and vascular volumes of sea-level (Australian, n=20) and altitude (Bolivian, n=19) native soccer players at 3600 m. Haemoglobin-oxygen saturation (Hb-sO₂), arterial oxygen content (CaO₂), haemoglobin mass (Hbmass), blood volume (BV) and blood gas concentrations were measured before descent (Bolivians only), together with aerobic fitness (via Yo-YoIR1), near sea-level, after ascent and during 13 days at 3600 m. At baseline, haemoglobin concentration [Hb] and Hbmass were higher in Bolivians (mean ± SD; 18.2 ± 1.0 g/dL, 12.8 ± 0.8 g/kg) than Australians (15.0 ± 0.9 g/dL, 11.6 ± 0.7 g/kg; both p ≤ 0.001). Near sea-level, [Hb] of Bolivians decreased to 16.6 ± 0.9 g/dL, but normalised upon return to 3600 m; Hbmass was constant regardless of altitude. In Australians, [Hb] increased after 12 days at 3600 m to 17.3 ± 1.0 g/dL; Hbmass increased by 3.0 ± 2.7% (p ≤ 0.01). BV decreased in both teams at altitude by ∼400 mL. Arterial partial pressure for oxygen (PaO₂), Hb-sO₂ and CaO₂ of both teams decreased within 2 h of arrival at 3600 m (p ≤ 0.001) but increased over the following days, with CaO₂ overcompensated in Australians (+1.7 ± 1.2 mL/100 mL; p ≤ 0.001). Yo-YoIR1 was lower on the 3rd versus 10th day at altitude and was significantly related to CaO₂. The marked drop in PaO₂ and CaO₂ observed after ascent does not support the 'fly-in, fly-out' approach for soccer teams to play immediately after arrival at altitude. Although short-term acclimatisation was sufficient for Australians to stabilise their CaO₂ (mostly due to loss of plasma volume), 12 days appears insufficient to reach chronic levels of adaption.

Beyond HbA1c.

PubMed

Bloomgarden, Zachary

2017-12-01

It can scarcely be denied that the supreme goal of all theory is to make the irreducible basic elements as simple and as few as possible without having to surrender the adequate representation of a single datum of experience. The diaTribe Foundation convened a meeting on the topic of glycemic outcomes beyond HbA1c on 21 July 2017, in Bethesda (MD, USA), focusing on potential uses of continuous glucose monitoring (CGM). Understanding patterns of glycemia in people with diabetes has long been a focus of approaches to improving treatment, and over the past few years this has become an available modality for clinical practice. Glucose levels are not the only biologic parameters affecting HbA1c levels; HbA1c changes with anemia or, more subtly, with changes in rates of erythrocyte turnover not reflected in hemoglobin levels outside the normal range. Renal disease often is associated with lower HbA1c than would be predicted based on an individual's glycemic levels. Furthermore, HbA1c levels tend to increase with age and are higher in some ethnic groups; for example, people of African ethnicity have higher HbA1c levels than people of Northern European descent. Indeed, we have argued that even as a measure of mean glycemia HbA1c is inherently imprecise. Overall, for some 20% of people with diabetes, HbA1c levels are substantially higher, or substantially lower, than those that would be predicted from mean blood glucose levels. If one recognizes that HbA1c is, at best, a partial measure of mean glycemic exposure, one must surely accept that HbA1c does not reflect variability within a day, from day to day, and from period to period. Many glucose-lowering medicines, particularly the sulfonylureas and insulin, cause hypoglycemia, with consequent negative effects on quality of life and patient-reported outcomes, as well as association with weight gain and adverse macrovascular outcome; hypoglycemia will, of course, not be captured by HbA1c measurement. Based on these

Could the erythrocyte indices or serum ferritin predict the therapeutic response to a trial with oral iron during pregnancy? Results from the Accuracy study for Maternal Anaemia diagnosis (AMA).

PubMed

Bresani Salvi, Cristiane Campello; Braga, Maria Cynthia; Figueirôa, José Natal; Batista Filho, Malaquias

2016-08-12

Treatment of maternal iron-deficiency anaemia can reduce risks of prematurity and low birth weight; hence a reliable diagnosis of maternal iron needs is critical. However, erythrocyte indices and serum ferritin have shown a weak correlation with iron status during pregnancy. This study verified the accuracy of those tests to predict the responsiveness to a therapeutic test with oral iron as reference standard for iron deficiency in pregnant women. A prospective diagnostic study phase 3 was conducted in a single prenatal care center in Northeast Brazil. Between August 2011 and October 2012 a consecutive sampling included 187 women in their 2(nd)-3(rd) trimesters of low-risk pregnancy and having anaemia (haemoglobin <11.0 g/dL). Until December 2012, 139 women completed a trial with daily pills of ferrous sulfate (40 mg of iron), during 23 to 125 days. Haemoglobin (Hb), other erythrocyte indices and ferritin (index-tests) were assessed pre-treatment by automated analyzers. Hb was performed also post-treatment to assess the therapeutic response by its post-pretreatment differences. We estimated sensitivity (Se), specificity (Sp), predictive values (PV), likelihood ratios (LR), diagnostic Odds Ratio (OR), area under Receiver Operating Characteristic curve (AUC), accuracy ratio and agreement coefficient of the index-tests against an increase of at least 0.55 Hb Z-score (reference standard test). We calculated the Z-scores according to the reference population from Centers for Disease Control and Prevention. Hb had a mean increase of 0.24 Z-score after 30 iron pills (p 0.013). All index-tests demonstrated PV- above 70 %, PV+ around 40 %, LR around 1.0, and AUC of 0.5 to 0.6. Hb and haematocrit had Se of 50 % (95 % CI 40 to 70); and Sp of 59 % (95 % CI 43 to 74) and 47 % (95 % CI 38 to 57), respectively. Ferritin, Mean Corpuscular Volume, Mean Corpuscular Haemoglobin, Mean Corpuscular Haemoglobin Concentration and Red blood cell Distribution Width had Se below 40�

Associations between local descriptive norms for overweight/obesity and insufficient fruit intake, individual-level diet, and 10-year change in body mass index and glycosylated haemoglobin in an Australian cohort.

PubMed

Carroll, Suzanne J; Niyonsenga, Theo; Coffee, Neil T; Taylor, Anne W; Daniel, Mark

2018-05-18

Descriptive norms (what other people do) relate to individual-level dietary behaviour and health outcome including overweight and obesity. Descriptive norms vary across residential areas but the impact of spatial variation in norms on individual-level diet and health is poorly understood. This study assessed spatial associations between local descriptive norms for overweight/obesity and insufficient fruit intake (spatially-specific local prevalence), and individual-level dietary intakes (fruit, vegetable and sugary drinks) and 10-year change in body mass index (BMI) and glycosylated haemoglobin (HbA 1c ). HbA 1c and BMI were clinically measured three times over 10 years for a population-based adult cohort (n = 4056) in Adelaide, South Australia. Local descriptive norms for both overweight/obesity and insufficient fruit intake specific to each cohort participant were calculated as the prevalence of these factors, constructed from geocoded population surveillance data aggregated for 1600 m road-network buffers centred on cohort participants' residential addresses. Latent growth models estimated the effect of local descriptive norms on dietary behaviours and change in HbA 1c and BMI, accounting for spatial clustering and covariates (individual-level age, sex, smoking status, employment and education, and area-level median household income). Local descriptive overweight/obesity norms were associated with individual-level fruit intake (inversely) and sugary drink consumption (positively), and worsening HbA 1c and BMI. Spatially-specific local norms for insufficient fruit intake were associated with individual-level fruit intake (inversely) and sugary drink consumption (positively) and worsening HbA 1c but not change in BMI. Individual-level fruit and vegetable intakes were not associated with change in HbA 1c or BMI. Sugary drink consumption was also not associated with change in HbA 1c but rather with increasing BMI. Adverse local descriptive norms for overweight

Study of helminthiasis in pregnancy and its correlation with haemoglobin level.

PubMed

K, Shrinivas; Radhika; R, Sreelatha; K, Kavitha

2014-10-01

To study types of worm infestation in pregnancy and to correlate helminthiasis with haemoglobin level in antenatal women presenting in 2nd and 3rd trimester. This prospective cross sectional hospital based study conducted at Vanivilas hospital attached to Bangalore medical college, over a period of sixmonths. Study included 500 pregnant women attending antenatal opd in 2nd and 3rd trimester, selected by systematic random sampling method. Parasitic examination and haemoglobin estimation done respectively with Stool and blood samples collected from study group. Presence of parasites was correlated with haemoglobin percentage. Helminthiasis was found in 62 women (12.4%). All infected women had single type helminth infection. Ascariasis was more commonly found than hookworm (10% Vs 2.4%). Anaemia of various degrees was found in 88.7% of women with helminthiasis as compared to 56.4% women without worm infestation (p-value <0.05). Helminthiasis is a significant burden in pregnancy and it is associated with anaemia. Hence, the policy of universal administration of anthelminthic drug in pregnancy after first trimester, as recommended by WHO should be practically enforced besides health education.

Clinical course of dengue in patients with thalassaemia.

PubMed

Natesirinilkul, Rungrote; Tantiworawit, Adisak; Charoenkwan, Pimlak

2013-02-01

Dengue and thalassaemia are prevalent in tropical regions. Thalassaemia patients with dengue present with atypical clinical manifestations and may experience more severe disease and complications. To investigate the clinical manifestations and outcome in thalassaemia patients with dengue. Medical records of thalassaemia patients aged from birth to 18 years with serologically-confirmed dengue who were admitted to Chiang Mai University Hospital, Thailand from January 2005 to December 2010 were reviewed retrospectively. Clinical presentation, laboratory results and outcome were analysed. Twenty patients were included and their mean (SD) age was 13·6 (3·1) years. Patients were as follows: haemoglobin H (HbH)/Hb Constant Spring disease 7, HbH disease 3, HbH disease/HbE trait one, beta-thalassaemia/HbE disease 7, beta-thalassaemia/HbS disease one and unspecified thalassaemia one. Four patients had primary and the others secondary dengue. Five patients (25%) had severe dengue, three with severe liver involvement, one with a massive upper gastro-intestinal haemorrhage and one with acute interstitial nephritis, raised creatinine and seizures. Nineteen patients required red cells transfusions. All made a full recovery. Almost all patients presented with haemoglobin lower than baseline. While mean (SD) haemoglobin at baseline was 8·2 (1·6) g/dl, mean (SD) haemoglobin on admission was 6·4 (1·6) g/dl. Median maximum AST and ALT levels were 359 (range 42-5344) and 81 (12-1846) units/L, respectively. Thalassaemia patients with dengue present with anaemia rather than haemoconcentration. Most patients have markedly increased AST levels in relation to ALT, and severe dengue, especially severe liver involvement, is common. In patients with thalassaemia, awareness of the atypical manifestations should aid early recognition of dengue.

Racial variations in booking haemoglobin of primigravidae in Malaysia: a prospective study

PubMed Central

2013-01-01

Background Variations in racial haemoglobin had been previously described in multiple studies locally and abroad. This study was conducted to quantify the differences in haemoglobin of booking primigravidae amongst the three major races in Malaysia at the antenatal clinic of University Malaya Medical Centre, Kuala Lumpur. Findings One year prospective study of booking full blood count sample of primigravidae taken in one centre was conducted. Multiple comparative analyses of the booking haemoglobin were performed using the One-way ANOVA comparative mean test in each trimester. 622 primigravidae without any known history of haematological disorders were recruited into the study. The mean haemoglobin for the Indian race was the lowest compared to the two other races in the second and the third trimesters, and it was found to be statistically significant lower (p- value 0.001) than the Malay race in the second trimester. It was also found that the Indian race had a significantly higher incidence of moderate to severe anaemia (p- value: 0.029). The prevalence of anaemia in our study population is also significantly higher in the Indian population (p- value: 0.01). Conclusions The findings from this study have established that there is racial preponderance to anaemia in pregnancy. The Indian race is at a higher risk of having anaemia in pregnancy particularly in the second trimester. PMID:23634656

HbA1c Alone Is a Poor Indicator of Cardiometabolic Risk in Middle-Aged Subjects with Pre-Diabetes but Is Suitable for Type 2 Diabetes Diagnosis: A Cross-Sectional Study

PubMed Central

Millar, Seán R.; Perry, Ivan J.; Phillips, Catherine M.

2015-01-01

Objectives Glycated haemoglobin A1c (HbA1c) measurement is recommended as an alternative to fasting plasma glucose (FPG) for the diagnosis of pre-diabetes and type 2 diabetes. However, evidence suggests discordance between HbA1c and FPG. In this study we examine a range of metabolic risk features, pro-inflammatory cytokines, acute-phase response proteins, coagulation factors and white blood cell counts to determine which assay more accurately identifies individuals at increased cardiometabolic risk. Materials and Methods This was a cross-sectional study involving a random sample of 2,047 men and women aged 46-73 years. Binary and multinomial logistic regression were employed to examine risk feature associations with pre-diabetes [either HbA1c levels 5.7-6.4% (39-46 mmol/mol) or impaired FPG levels 5.6-6.9 mmol/l] and type 2 diabetes [either HbA1c levels >6.5% (>48 mmol/mol) or FPG levels >7.0 mmol/l]. Receiver operating characteristic curve analysis was used to evaluate the ability of HbA1c to discriminate pre-diabetes and diabetes defined by FPG. Results Stronger associations with diabetes-related phenotypes were observed in pre-diabetic subjects diagnosed by FPG compared to those detected by HbA1c. Individuals with type 2 diabetes exhibited cardiometabolic profiles that were broadly similar according to diagnosis by either assay. Pre-diabetic participants classified by both assays displayed a more pro-inflammatory, pro-atherogenic, hypertensive and insulin resistant profile. Odds ratios of having three or more metabolic syndrome features were also noticeably increased (OR: 4.0, 95% CI: 2.8-5.8) when compared to subjects diagnosed by either HbA1c (OR: 1.4, 95% CI: 1.2-1.8) or FPG (OR: 3.0, 95% CI: 1.7-5.1) separately. Conclusions In middle-aged Caucasian-Europeans, HbA1c alone is a poor indicator of cardiometabolic risk but is suitable for diagnosing diabetes. Combined use of HbA1c and FPG may be of additional benefit for detecting individuals at highest odds of

Red cell 2,3-diphosphoglycerate levels in children with hereditary haemolytic anaemias.

PubMed

Haidas, S; Zannos-Mariolea, L; Matsaniotis, N

1975-12-01

The role of red cell 2,3-diphosphoglycerate (2,3-DPG) in increasing the availability of haemoglobin oxygen in neonatal jaundice and hereditary haemolytic anaemias was investigated. Measurements of 2,3-DPG were carried out on 58 normal children and six normal adults, 18 full-term newborns with neonatal jaundice and 57 cases (51 children and six adults) with hereditary haemolytic anaemias. In normal children and adults, with a mean haemoglobin of 12.69 g/dl, mean 2,3-DPG was 14.90 mumol/g Hb. In jaundiced newborns with a mean haemoglobin of 16.04 g/dl mean 2,3-DPG levels were 14.51 mumol/g Hb, i.e. normal. 2,3-DPG levels were increased in patients with beta-thalassaemia major, alpha-thalassaemia, sickle-cell disease, favism, hereditary spherocytosis and in heterozygotes for beta-thalassaemia with increased haemoglobin F. In heterozygotes for beta-thalassaemia with increased haemoglobin A2 only and in sickle cell trait 2,3-DPG levels were normal.

Group Medical Visits (GMVs) in primary care: an RCT of group-based versus individual appointments to reduce HbA1c in older people

PubMed Central

Khan, Karim M; Windt, Adriaan; Davis, Jennifer C; Dawes, Martin; Liu-Ambrose, Teresa; Madden, Ken; Marra, Carlo A; Housden, Laura; Hoppmann, Christiane; Adams, David J

2015-01-01

Introduction Type 2 diabetes mellitus (T2DM) affects more than 1.1 million Canadians aged ≥65 years. Group Medical Visits are an emerging health service delivery method. Recent systematic reviews show that they can significantly reduce glycated haemoglobin (HbA1c) levels, but Group Visits have not been evaluated within primary care. We intend to determine the clinical effectiveness, quality of life and economic implications of Group Medical Visits within a primary care setting for older people with T2DM. Methods and analysis A 2-year proof-of-concept, single-blinded (measurement team) randomised control trial to test the efficacy of Group Medical Visits in an urban Canadian primary care setting. Participants ≥65 years old with T2DM (N=128) will be equally randomised to either eight groups of eight patients each (Group Medical Visits; Intervention) or to Individual visits (Standard Care; Controls). Those administering cointerventions are not blinded to group assignment. Our sample size is based on estimates of variance (±1.4% for HbA1c) and effect size (0.9/1.4=0.6) from the literature and from our own preliminary data. Forty participants per group will provide a β likelihood of 0.80, assuming an α of 0.05. A conservative estimation of an effect size of 0.7/1.4 changes the N in the power calculation to 59 per group. Hence, we aim to enrol 64 participants in each study arm. We will use intention-to-treat analysis and compare mean HbA1c (% glycosylated HbA1c) (primary outcome) of Intervention/Control participants at 12 months, 24 months and 1 year postintervention on selected clinical, patient-rated and economic measures. Trial registration number NCT02002143. PMID:26169803

Relating oxygen partial pressure, saturation and content: the haemoglobin-oxygen dissociation curve.

PubMed

Collins, Julie-Ann; Rudenski, Aram; Gibson, John; Howard, Luke; O'Driscoll, Ronan

2015-09-01

The delivery of oxygen by arterial blood to the tissues of the body has a number of critical determinants including blood oxygen concentration (content), saturation (S O2 ) and partial pressure, haemoglobin concentration and cardiac output, including its distribution. The haemoglobin-oxygen dissociation curve, a graphical representation of the relationship between oxygen satur-ation and oxygen partial pressure helps us to understand some of the principles underpinning this process. Historically this curve was derived from very limited data based on blood samples from small numbers of healthy subjects which were manipulated in vitro and ultimately determined by equations such as those described by Severinghaus in 1979. In a study of 3524 clinical specimens, we found that this equation estimated the S O2 in blood from patients with normal pH and S O2 >70% with remarkable accuracy and, to our knowledge, this is the first large-scale validation of this equation using clinical samples. Oxygen saturation by pulse oximetry (S pO2 ) is nowadays the standard clinical method for assessing arterial oxygen saturation, providing a convenient, pain-free means of continuously assessing oxygenation, provided the interpreting clinician is aware of important limitations. The use of pulse oximetry reduces the need for arterial blood gas analysis (S aO2 ) as many patients who are not at risk of hypercapnic respiratory failure or metabolic acidosis and have acceptable S pO2 do not necessarily require blood gas analysis. While arterial sampling remains the gold-standard method of assessing ventilation and oxygenation, in those patients in whom blood gas analysis is indicated, arterialised capillary samples also have a valuable role in patient care. The clinical role of venous blood gases however remains less well defined.

Cardiovascular and metabolic adaptations in horses competing in cross-country events.

PubMed

Muñoz, A; Riber, C; Santisteban, R; Rubio, M D; Agüera, E I; Castejón, F M

1999-01-01

The cardiovascular and metabolic response to two cross-country events (CC*: preliminary level and CC*** advanced level) were analysed in 8 male eventing horses (4 Anglo-Hunter and 4 Anglo-Arabian). This study focused on the establishment of the main metabolic pathways involved in the muscle energy resynthesis during the competitions. Heart rate (HR) was recorded throughout the CC events. Jugular venous blood samples were withdrawn before the warm-up period, immediately after the competitions and at 5 and 10 min in the recuperation period. The following haematological parameters were studied: red blood cells (RBC), packed cell volume (PCV), haemoglobin concentration (Hb), mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH), mean corpuscular haemoglobin concentration (MCHC), white blood cells (WBC), and number and percentages of lymphocytes (LYM) and granulocytes and monocytes (GRAN). One fraction of blood was centrifuged and, in plasma, lactate (LA), total plasma protein (TPP) and the rate of LA disappearance were determined. The competitions induced significant increases in RBC, Hb, PCV, MCV and TPP. Plasma LA response exceeded the anaerobic threshold of 4 mmol/l, reaching a maximum level of 13.3 mmol/l. HR ranged from 140 to more than 200 bpm, peaking at 230 bpm, revealing a limitation in the oxygen supply to the working muscles. It was concluded that muscle energy resynthesis during a CC event is provided both through oxidative processes and glycolysis with LA formation. Therefore, both stamina and power exercises are required for eventing horses.

[About the HbA1c in the elderly].

PubMed

Farcet, Anaïs; Delalande, Géraldine; Oliver, Charles; Retornaz, Frédérique

2016-03-01

HbA1c product of non enzymatic glycation of HbA increases in relation with the mean blood glucose level during the former 2-3 months. HbA1c levels are correlated with the development of diabetic complications and HbA1c assessment is now the gold standard for evaluation of diabetes control. HbA1c level should not be higher than 7% to avoid these complications. However, in aged peoples, the objectives of diabetes control vary according to their health status. It must be good with HbA1c lower than 7-7.5% in healthy subjects and more relax in subjects with symptoms of frailty and risks of non perceived and self corrected hypoglycemia. Under these conditions, HbA1c values lower than 8 to 9% are advised. Nevertheless, hypoglycemia episodes may occur in patients with high HbA1c and capillary glucose follow-up is necessary for detection of such complications.

A new approach for the carbon monoxide (CO) exposure diagnosis: measurement of total CO in human blood versus carboxyhemoglobin (HbCO).

PubMed

Varlet, Vincent; De Croutte, Emma Lagroy; Augsburger, Marc; Mangin, Patrice

2013-07-01

The aim of the study is to present the application of a headspace-gas chromatography-mass spectrometry (HS-GC-MS) method for the determination of the carbon monoxide (CO) blood concentration and to compare it with carboxyhemoglobin (HbCO) saturation. In postmortem cases, the HbCO measured by spectrophotometry frequently leads to inaccurate results due to inadequate samples or analyses. The true role of CO intoxication in the death of a person could be misclassified. The estimation of HbCO from HS-GC-MS CO measurements provides helpful information by determining the total CO levels (CO linked to hemoglobin (HbCO) and CO dissociated from hemoglobin). The CO concentrations were converted in HbCO saturation levels to define cutoff blood CO values. CO limits were defined as less than 1 μmol/mL for living persons, less than 1.5 μmol/mL for dead persons without CO exposure, and greater than 3 μmol/mL for dead persons with clear CO poisoning. © 2013 American Academy of Forensic Sciences.

Molecular Characterisation of α- and β-Thalassaemia among Indigenous Senoi Orang Asli Communities in Peninsular Malaysia.

PubMed

Koh, Danny Xuan Rong; Raja Sabudin, Raja Zahratul Azma; Mohd Yusoff, Malisa; Hussin, Noor Hamidah; Ahmad, Rahimah; Othman, Ainoon; Ismail, Endom

2017-09-01

Thalassaemia is a public health problem in Malaysia, with each ethnic group having their own common mutations. However, there is a lack on data on the prevalence and common mutations among the indigenous people. This cross-sectional study was performed to determine the common mutations of α- and β-thalassaemia among the subethnic groups of Senoi, the largest Orang Asli group in Peninsular Malaysia. Blood samples collected from six Senoi subethnic groups were analysed for full blood count and haemoglobin analysis (HbAn). Samples with abnormal findings were then screened for α- and β-globin gene mutations. Out of the 752 samples collected, 255 showed abnormal HbAn results, and 122 cases showing abnormal red cell indices with normal HbAn findings were subjected to molecular screening. DNA analysis revealed a mixture of α- and β-globin gene mutations with 25 concomitant cases. The types of gene abnormalities detected for α-thalassaemia were termination codon (T>C) Hb CS (α CS α), Cd59 (G>A) haemoglobin Adana (Hb Adana) (α Cd59 α), initiation codon (ATG>A-G) (α IniCd α), two-gene deletion (- SEA ), and single-gene 3.7-kb deletion (-α 3.7 ). For β-thalassaemia, there were Cd26 (G>A) Hb E (β E ), Cd19 (A>G) Haemoglobin Malay (Hb Malay) (β Cd19 ), and IVS 1-5 (G>C) (β IVS 1-5 ). © 2017 John Wiley & Sons Ltd/University College London.

HbA1c and the Prediction of Type 2 Diabetes in Children and Adults.

PubMed

Vijayakumar, Pavithra; Nelson, Robert G; Hanson, Robert L; Knowler, William C; Sinha, Madhumita

2017-01-01

Long-term data validating glycated hemoglobin (HbA 1c ) in assessing the risk of type 2 diabetes in children are limited. HbA 1c , fasting plasma glucose (FPG), and 2-h postload plasma glucose (2hPG) concentrations were measured in a longitudinal study of American Indians to determine their utility in predicting incident diabetes, all of which is thought to be type 2 in this population. Incident diabetes (FPG ≥126 mg/dL [7.0 mmol/L], 2hPG ≥200 mg/dL [11.1 mmol/L], HbA 1c ≥6.5% [8 mmol/mol], or clinical diagnosis) was determined in 2,095 children without diabetes ages 10-19 years monitored through age 39, and in 2,005 adults ages 20-39 monitored through age 59. Areas under the receiver operating characteristic (ROC) curve for HbA 1c , FPG, and 2hPG in predicting diabetes within 10 years were compared. During long-term follow-up of children and adolescents who did not initially have diabetes, the incidence rate of subsequent diabetes was fourfold (in boys) as high and more than sevenfold (in girls) as high in those with HbA 1c ≥5.7% as in those with HbA 1c ≤5.3%-greater rate ratios than experienced by adults in the same HbA 1c categories. Analyses of ROCs revealed no significant differences between HbA 1c , FPG, and 2hPG in sensitivity and specificity for identifying children and adolescents who later developed diabetes. HbA 1c is a useful predictor of diabetes risk in children and can be used to identify prediabetes in children with other type 2 diabetes risk factors with the same predictive value as FPG and 2hPG. © 2017 by the American Diabetes Association.

Awareness and distribution of ABO, Rhesus blood groups and haemoglobin phenotypes among medical undergraduates in a Nigerian university.

PubMed

Akingbola, T S; Yuguda, S; Akinyemi, O O; Olomu, S

2016-09-01

In the past two decades the Nigerian government and religious organisations have put more emphasis on knowing the haemoglobin electrophoresis of school children and intending couples respectively. Knowledge of the distribution of blood groups and haemoglobin electrophoretic patterns among young people is vital for the prevention of haemoglobinopathies in the population and for providing effective blood banking services. Therefore, this study was designed to assess the frequency and awareness of blood group and haemoglobinphenotypes among a new set of fourth year clinical medical and dental students of the University of Ibadan, Nigeria. Data, including socio-demographics, self- reported blood group and haemoglobin phenotypes, were obtained from 155 students using a self-administered questionnaire. The ABO, Rhesus (Rh) blood groups and haemoglobin electrophoresis were determined by the tile (slide) technique and cellulose acetate at alkaline phrespectively. Only 43.9% of the participants knew their blood groups while less than a third (29.7%) knew their haemoglobin phenotypes. knowledge of both their blood groups and haemoglobin phenotypes was documented in as low as 20.6% of the respondents. The frequency of haemoglobin AA, AS, AC and. CC were 78.0%, 16.8%, 3.9% and 1.3% respectively. Similarly, the distribution of blood groups were: 0 RhD positive - 47.8%;0 RhD negative- 1.9%;ARhD positive- 21.9%; A RhD negative - 1.3%; B RhD positive - 23.2%; B RhD negative -1.3% and AB RhD positive - 2.6%. No participant was AB RhD negative. Participants who bad previously donated blood and those who were females were more likely to know their blood groups and haemoglobin phenotypes respectively (p<0.05). Awareness of blood groups and haemoglobin phenotypes among the medical and dental students was poor. Documentation and routine screening for haemoglobinphenotypes as well as blood grouping, accompanied by appropriate counseling should be institutionalised in Nigeriantertiary

Excess body weight affects HbA1c progression irrespective of baseline HbA1c levels in Japanese individuals: a longitudinal retrospective study.

PubMed

Nakajima, Kei; Suwa, Kaname

2015-01-01

Obese individuals with normal HbA1c levels and low-body-weight individuals with high-normal HbA1c levels are frequently encountered in clinical settings, but the effects of these phenotypes on the onset of diabetes are poorly understood. Therefore, we addressed this issue in a longitudinal study. We analyzed clinical parameters, including body mass index (BMI) and HbA1c levels, in 5325 non-diabetic Japanese people aged 20-75 years who underwent four medical checkups between 1999 (baseline) and 2007. The subjects were then classified into six baseline BMI categories, each of which was divided into two HbA1c groups, resulting in a total of 12 groups. In 405 obese subjects with a normal baseline HbA1c (BMI ≥ 27.0 kg/m(2), HbA1c 5.2-5.6%), the mean HbA1c level increased during the study period, and 50.9% developed prediabetes/diabetes. In contrast, in 77 low-body-weight subjects with a high-normal baseline HbA1c (BMI ≤ 18.9 kg/m(2), HbA1c 5.7-6.4%), the mean HbA1c level remained constant. Similar changes occurred in the other groups during the study, resulting in a linear increase in HbA1c levels with increasing BMI. Our results suggest that approximately half of the obese individuals with HbA1c in the normal range develop prediabetes or diabetes within 8 years, whereas low-body-weight individuals with high-normal HbA1c are less likely to exhibit worsening in glycemia. Thus, excess body weight may be the primary therapeutic target to prevent the early onset of diabetes, regardless of the individual's HbA1c.

Use of topical haemoglobin on sloughy wounds in the community setting.

PubMed

Bateman, Sharon Dawn

2015-09-01

This evaluation aimed to determine whether the use of a haemoglobin spray solution expedited sloughy wound healing. A descriptive evaluation was undertaken within a community setting exploring 25 patients presenting with sloughy healing and non-healing wounds, and the effects of 8 topically administered haemoglobin treatments over a 4-week period. Standard wound cleansing and dressing management were continued, with no changes to pre-evaluation regimens, and care being provided by the patients themselves or by a carer. Data were collected weekly with regard to primary outcomes of slough reduction, wound surface area reduction, patient ease of use (self-care), and overall product experience. At 4 weeks, all wounds demonstrated positive measured endpoints of slough elimination and continued wound-size reduction. Patients and carers found the product easy to use (self-caring) with an overall positive wound care experience. The administration of a haemoglobin spray solution on patients presenting with sloughy wounds resulted in positive healing outcomes of slough elimination and wound reduction alongside positive self-care and product satisfaction. Continued evaluation is recommended to build upon the evidence of this form of treatment.

The practical application of reflectance spectrophotometry for the demonstration of haemoglobin and its degradation in bruises

PubMed Central

Hughes, V K; Ellis, P S; Burt, T; Langlois, N E I

2004-01-01

Aims: To develop a non-invasive method to demonstrate the presence of haemoglobin and its degradation products in bruises in live human subjects for the purposes of objectively assisting in the determination of the age of a bruise. Methods: The cuvette holder unit of a Cary 100 Bio UV-Visible Spectrophotometer was replaced with the manufacture’s fibre optic cable and optical reflectance probe. The probe was placed on the skin surface. The absorption spectrum from 780 to 380 nm was collected and transformed into the first derivative. Calculation of the first derivative permits absorption attributed to haemoglobin degradation (primarily to bilirubin, but also haemosiderin) to be separated from absorption by haemoglobin. First derivative and colorimetry values, expressed as CIEL*a*b data, were derived from scans of 50 bruises. Results: The fibre optic cable and probe allowed the spectrophotometer to collect reproducible absorption spectra of bruises in the skin of living subjects. A bruise at three days has greater negative first derivative values at 480 and 490 nm than does a fresh bruise, indicating the local degradation of haemoglobin. Correlation between the first derivative and the CIEL*a*b “b” values in a series of bruises indicates that the yellow colour in a bruise is proportional to the amount of local haemoglobin breakdown. Conclusion: The ability to demonstrate the presence of haemoglobin and measure its degradation in bruises in living human subjects by a non-invasive method has not been described previously, and may be of use in the objective ageing of bruises for forensic purposes. PMID:15047735

Pregnancy outcome in patients with sickle cell disease in the UK--a national cohort study comparing sickle cell anaemia (HbSS) with HbSC disease.

PubMed

Oteng-Ntim, Eugene; Ayensah, Benjamin; Knight, Marian; Howard, Jo

2015-04-01

We describe the findings from a national study of maternal and fetal outcomes of pregnancy in women with sickle cell disease (SCD). Data were collected via the United Kingdom Obstetric Surveillance System between 1 February 2010 and 31 January 2011 from 109 women, of whom 51 (46·8%) had HbSS and 44 (40·4%) had HbSC. Data included antenatal, maternal and fetal outcomes. Comparisons were made between women with HbSS and HbSC. Incidence of complications were acute pain (57%), blood transfusion (26%), urinary tract infection (UTI; 12%) and critical care unit admission (23%) and these were all more common in women with HbSS than HbSC. There was no difference in the incidence of acute chest syndrome, hypertension and venous thromboembolism between HbSS and HbSC. Women with HbSS were more likely to deliver at <37 weeks gestation (P = 0·01) and their babies were more likely to have reduced birth weight. Delivery at <34 weeks was increased in both HbSS and HbSC women (5·9% vs. 4·6%) compared to national data. This study confirms a high rate of maternal and fetal complications in mothers with SCD, even in women with HbSC, which has previously been considered to have a more benign phenotype in pregnancy. © 2014 John Wiley & Sons Ltd.

Hydrogen ion titrations of the anodic and cathodic haemoglobin components of the European eel Anguilla anguilla.

PubMed

Brauner, C J; Weber, R E

1998-09-01

H+ titrations were conducted on the separated haemoglobin components of eel Anguilla anguilla in both the oxygenated and deoxygenated states. In anodic haemoglobin, the addition of GTP, and to a lesser extent C1-, increased the magnitude of the Haldane effect and shifted its maximum value into the in vivo pH range. Of the 22 histidine residues in the anodic component, only approximately seven were titratable, presumably the beta-chain residues at positions 41, 97, 109 and 146 (helical positions C7, FG4, G11 and HC3, respectively). In cathodic haemoglobin, a small negative Haldane effect was observed at pH values between 6.8 and 8.5 which disappeared in the presence of GTP (molar ratio 3:1 GTP:haemoglobin tetramer). GTP had virtually no effect on the buffer value at fixed oxygenation status, and the lowest buffer value was observed at in vivo pH values. No titratable histidine residues were observed in the cathodic component, indicating that all 14 histidines in this component are buried. We conclude that the anodic component, which constitutes two-thirds of the haemoglobin in the eel, plays the predominant role in CO2 transport and pH homeostasis in vivo.

Anaemia, iron deficiency and a common polymorphism of iron-regulation, TMPRSS6 rs855791, in Rwandan children.

PubMed

Danquah, Ina; Gahutu, Jean-Bosco; Zeile, Irene; Musemakweri, Andre; Mockenhaupt, Frank P

2014-01-01

Anaemia in children living in sub-Saharan Africa is common, but its causes are diverse. In 545 children below 5 years of age from rural southern Rwanda, we assessed the role of iron deficiency (ID) and of the TMPRSS6 736(V) (rs855791) allele, known to reduce iron status and haemoglobin (Hb) levels, in anaemia and Hb concentrations. Anaemia (Hb <11 g/dl) was present in 34.4% of the children and ID (ferritin <12 ng/ml) in 17.6%. The TMPRSS6 736(V) allele was uncommon (allele frequency, 0.096) and not associated with ID. In multivariate analysis, ID was positively associated with anaemia (adjusted odds ratio, 1.67) to an extent comparable with α(+) -thalassaemia, breastfeeding, inflammation and low household income, but the odds were substantially higher in Plasmodium falciparum infection (adjusted odds ratio, 10.3). These findings were verified in a multivariate analysis of Hb concentrations. The TMPRSS6 736(V) allele only tended to be associated with low Hb levels. TMPRSS6 736(V) is comparatively rare among Rwandan children and may only slightly contribute to low Hb concentrations. Preventable causes of anaemia, notably ID and P. falciparum infection, largely outweigh its impact and need to be addressed to improve the haematological status of children in the study area. © 2013 John Wiley & Sons Ltd.

Unmasking Hb Paksé (codon 142, TAA>TAT, α2) and its combinations in patients also carrying Hb Constant Spring (codon 142, TAA>CAA, α2) in northern Thailand.

PubMed

Pornprasert, Sakorn; Panyasai, Sitthichai; Treesuwan, Kallayanee

2012-01-01

The incidence of Hb Paksé (codon 142, TAA>TAT, α2) might have been underestimated due to misidentifying some cases as Hb Constant Spring (Hb CS, codon 142, TAA>CAA, α2) since both abnormal hemoglobins (Hbs) migrate to the same position on Hb electrophoresis or chromatography. Multiplex asymmetric allele-specific polymerase chain reaction (PCR) for identification of Hb CS and Hb Paksé, and a real-time PCR (ReTi-PCR) with SYBR Green1 high resolution melting (HRM) analysis, for detection of the α-thalassemia-1 (α-thal-1) Southeast Asian (- -(SEA)/) type deletion, were performed on 114 blood samples collected from subjects who lived in northern Thailand. These samples were previously identified as carrying Hb CS by capillary electrophoresis (CE) or high performance liquid chromatography (HPLC). Five out of 114 (4.4%) samples were found to carry Hb Paksé with four different genotypes including Hb Paksé trait, compound Hb CS/Hb Paksé, Hb H-Hb Paksé disease and Hb H-Hb Paksé-Hb E disease. These results suggested that Hb Paksé and its various combinations can be misidentified as Hb CS. Although the clinical symptoms of Hb Paksé and Hb CS are similar, to prevent erroneous epidemiological data on Hb CS as well as underestimating the prevalence of Hb Paksé in northern Thailand, DNA analysis is recommended to be performed in all cases when peaks of Hb CS/Hb Paksé are detected on CE or HPLC.

Comparability of HbA1c and lipids measured with dried blood spot versus venous samples: a systematic review and meta-analysis

PubMed Central

2014-01-01

Background Levels of haemoglobin A1c (HbA1c) and blood lipids are important determinants of risk in patients with diabetes. Standard analysis methods based upon venous blood samples can be logistically challenging in resource-poor settings where much of the diabetes epidemic is occurring. Dried blood spots (DBS) provide a simple alternative method for sample collection but the comparability of data from analyses based on DBS is not well established. Methods We conducted a systematic review and meta-analysis to define the association of findings for HbA1c and blood lipids for analyses based upon standard methods compared to DBS. The Cochrane, Embase and Medline databases were searched for relevant reports and summary regression lines were estimated. Results 705 abstracts were found by the initial electronic search with 6 further reports identified by manual review of the full papers. 16 studies provided data for one or more outcomes of interest. There was a close agreement between the results for HbA1c assays based on venous and DBS samples (DBS = 0.9858venous + 0.3809), except for assays based upon affinity chromatography. Significant adjustment was required for assays of total cholesterol (DBS = 0.6807venous + 1.151) but results for triglycerides (DBS = 0.9557venous + 0.1427) were directly comparable. Conclusions For HbA1c and selected blood lipids, assays based on DBS samples are clearly associated with assays based on standard venous samples. There are, however, significant uncertainties about the nature of these associations and there is a need for standardisation of the sample collection, transportation, storage and analysis methods before the technique can be considered mainstream. This should be a research priority because better elucidation of metabolic risks in resource poor settings, where venous sampling is infeasible, will be key to addressing the global epidemic of cardiovascular diseases. PMID:25045323

Transfusion associated peak in hb HPLC chromatogram - a case report.

PubMed

Jain, Sonal; Dass, Jasmita; Pati, Hara Prasad

2012-01-01

High performance liquid chromatography (HPLC) and electrophoresis are commonly used to diagnose various hemoglobinopathies. However, insufficient information about the transfusion history can lead to unexpected and confusing results. We are reporting a case of Juvenile myelomonocytic leukemia (JMML) in which HbHPLC was done to quantify fetal hemoglobin (HbF). The chromatogram showed elevated HbF along with a peak in the HbD window. A transfusion acquired peak was suspected based on the unexpectedly low percentage of HbD and was subsequently confirmed using parental HbHPLC.

Can the Afinion HbA1c Point-of-Care instrument be an alternative method for the Tosoh G8 in the case of Hb-Tacoma?

PubMed

Lenters-Westra, Erna; Strunk, Annuska; Campbell, Paul; Slingerland, Robbert J

2017-02-01

Hb-variant interference when reporting HbA1c has been an ongoing challenge since HbA1c was introduced to monitor patients with diabetes mellitus. Most Hb-variants show an abnormal chromatogram when cation-exchange HPLC is used for the determination of HbA1c. Unfortunately, the Tosoh G8 generates what appears to be normal chromatogram in the presence of Hb-Tacoma, yielding a falsely high HbA1c value. The primary aim of the study was to investigate if the Afinion HbA1c point-of-care (POC) instrument could be used as an alternative method for the Tosoh G8 when testing for HbA1c in the presence of Hb-Tacoma. Whole blood samples were collected in K 2 EDTA tubes from individuals homozygous for HbA (n = 40) and heterozygous for Hb-Tacoma (n = 20). Samples were then immediately analyzed with the Afinion POC instrument. After analysis, aliquots of each sample were frozen at -80 °C. The frozen samples were shipped on dry ice to the European Reference Laboratory for Glycohemoglobin (ERL) and analyzed with three International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) and National Glycohemoglobin Standardization Program (NGSP) Secondary Reference Measurement Procedures (SRMPs). The Premier Hb9210 was used as the reference method. When compared to the reference method, samples with Hb-Tacoma yielded mean relative differences of 31.8% on the Tosoh G8, 21.5% on the Roche Tina-quant Gen. 2 and 16.8% on the Afinion. The Afinion cannot be used as an alternative method for the Tosoh G8 when testing for HbA1c in the presence of Hb-Tacoma.

Serum Iron and Haemoglobin Estimation in Oral Submucous Fibrosis and Iron Deficiency Anaemia: A Diagnostic Approach.

PubMed

Bhardwaj, Divya; Dinkar, Ajit D; Satoskar, Sujata K; Desai, Sapna Raut

2016-12-01

Oral Submucous Fibrosis (OSMF) is a premalignant condition with potential malignant behaviour characterized by juxta-epithelial fibrosis of the oral cavity. In the process of collagen synthesis, iron gets utilized, by the hydroxylation of proline and lysine, leading to decreased serum iron levels. The trace element like iron is receiving much attention in the detection of oral cancer and precancerous condition like OSMF as it was found to be significantly altered in these conditions. The aim of this study was to compare the haemoglobin and serum iron values of OSMF subjects with that of iron deficiency anaemia subjects. Total of 120 subjects were included, 40 subjects with the OSMF, 40 with the iron deficiency anemia without tobacco chewing habit, 40 healthy control subjects without OSMF and iron deficiency anaemia. A total of 5ml of venous blood was withdrawn from all the subjects and serum iron and haemoglobin levels were estimated for all the subjects. Estimation of iron was done using Ferrozine method and haemoglobin by Sahli's method. The statistical method applied were Kruskal Wallis, Mann Whitney and Pearson correlation coefficient test. There was a statistically significant difference in serum iron and haemoglobin level in all three groups (p<0.05). The serum iron level was lowest in OSMF group and haemoglobin was lowest in iron deficiency anaemia group. A progressive decrease in serum iron and haemoglobin levels from Stage I of OSMF to the Stage IV of OSMF was also observed. The iron deficiency anaemia group was not found to be suffering from OSMF in the absence of areca-nut or tobacco chewing habits, but OSMF patients with chewing habits were found to be suffering from iron deficiency anaemia. There is a progressive decrease in serum iron and haemoglobin levels from Stage I of OSMF to the Stage IV of OSMF so it can be used as an auxillary test in assessment of prognosis of the disease.

Serum Iron and Haemoglobin Estimation in Oral Submucous Fibrosis and Iron Deficiency Anaemia: A Diagnostic Approach

PubMed Central

Dinkar, Ajit D; Satoskar, Sujata K; Desai, Sapna Raut

2016-01-01

Introduction Oral Submucous Fibrosis (OSMF) is a premalignant condition with potential malignant behaviour characterized by juxta-epithelial fibrosis of the oral cavity. In the process of collagen synthesis, iron gets utilized, by the hydroxylation of proline and lysine, leading to decreased serum iron levels. The trace element like iron is receiving much attention in the detection of oral cancer and precancerous condition like OSMF as it was found to be significantly altered in these conditions. Aim The aim of this study was to compare the haemoglobin and serum iron values of OSMF subjects with that of iron deficiency anaemia subjects. Materials and Methods Total of 120 subjects were included, 40 subjects with the OSMF, 40 with the iron deficiency anemia without tobacco chewing habit, 40 healthy control subjects without OSMF and iron deficiency anaemia. A total of 5ml of venous blood was withdrawn from all the subjects and serum iron and haemoglobin levels were estimated for all the subjects. Estimation of iron was done using Ferrozine method and haemoglobin by Sahli’s method. The statistical method applied were Kruskal Wallis, Mann Whitney and Pearson correlation coefficient test. Results There was a statistically significant difference in serum iron and haemoglobin level in all three groups (p<0.05). The serum iron level was lowest in OSMF group and haemoglobin was lowest in iron deficiency anaemia group. A progressive decrease in serum iron and haemoglobin levels from Stage I of OSMF to the Stage IV of OSMF was also observed. The iron deficiency anaemia group was not found to be suffering from OSMF in the absence of areca-nut or tobacco chewing habits, but OSMF patients with chewing habits were found to be suffering from iron deficiency anaemia. Conclusion There is a progressive decrease in serum iron and haemoglobin levels from Stage I of OSMF to the Stage IV of OSMF so it can be used as an auxillary test in assessment of prognosis of the disease. PMID

HB-Line Plutonium Oxide Data Collection Strategy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Watkins, R.; Varble, J.; Jordan, J.

2015-05-26

HB-Line and H-Canyon will handle and process plutonium material to produce plutonium oxide for feed to the Mixed Oxide Fuel Fabrication Facility (MFFF). However, the plutonium oxide product will not be transferred to the MFFF directly from HB-Line until it is packaged into a qualified DOE-STD-3013-2012 container. In the interim, HB-Line will load plutonium oxide into an inner, filtered can. The inner can will be placed in a filtered bag, which will be loaded into a filtered outer can. The outer can will be loaded into a certified 9975 with getter assembly in compliance with onsite transportation requirement, for subsequentmore » storage and transfer to the K-Area Complex (KAC). After DOE-STD-3013-2012 container packaging capabilities are established, the product will be returned to HB-Line to be packaged into a qualified DOE-STD-3013-2012 container. To support the transfer of plutonium oxide to KAC and then eventually to MFFF, various material and packaging data will have to be collected and retained. In addition, data from initial HB-Line processing operations will be needed to support future DOE-STD-3013-2012 qualification as amended by the HB-Line DOE Standard equivalency. As production increases, the volume of data to collect will increase. The HB-Line data collected will be in the form of paper copies and electronic media. Paper copy data will, at a minimum, consist of facility procedures, nonconformance reports (NCRs), and DCS print outs. Electronic data will be in the form of Adobe portable document formats (PDFs). Collecting all the required data for each plutonium oxide can will be no small effort for HB-Line, and will become more challenging once the maximum annual oxide production throughput is achieved due to the sheer volume of data to be collected. The majority of the data collected will be in the form of facility procedures, DCS print outs, and laboratory results. To facilitate complete collection of this data, a traveler form will be developed

Effects of α-Thalassemia on HbA1c Measurement.

PubMed

Xu, Anping; Ji, Ling; Chen, Weidong; Xia, Yong; Zhou, Yu

2016-11-01

α-Thalassemia is a benign condition that is often present in patients with diabetes mellitus. Here, we evaluated the effects of different genotypes α-thalassemia on HbA 1c measurement. A total of 189 samples from nondiabetic patients were analyzed. HbA 1c analysis was performed by ion-exchange high-performance liquid chromatography, boronate affinity HPLC, immunoassay, and capillary electrophoresis. Fasting glucose, fructosamin, and HbA 2 were also performed. All samples were confirmed by genotyping for thalassemia. In patients with two or three functional α-genes, HbA 1c values were not significantly different from those of controls (P > 0.05); however, in individuals with α-thalassemia with one functional α-gene (i.e., HbH disease), HbA 1c levels were significantly different from those of controls (P < 0.01). HbA 1c values were significantly lower in individuals with HbH disease than in control individuals and patients in the other two α-thalassemia groups. For patients with HbH disease, there were no significant differences in the four HbA 1c measurement systems (P > 0.05). In this study, HbA 1c values in samples from individuals with two or three functional α-genes basically reflected the normal mean blood glucose level, while those in samples from individuals with one functional α-gene did not. © 2016 Wiley Periodicals, Inc.

Simple diagnosis of HbA1c using the dual-plasmonic platform integrated with LSPR and SERS

NASA Astrophysics Data System (ADS)

Heo, Nam Su; Kwak, Cheol Hwan; Lee, Hoomin; Kim, Dongjoo; Lee, Sunmook; Kim, Gi-bum; Kwon, Soonjo; Kim, Woo Sik; Huh, Yun Suk

2017-07-01

A plasmonic active chip was designed with a transparent polymer film self-assembled with gold nanoparticles (AuNPs). In this study, we demonstrated the feasibility and sensitivity of biosensors by employing a plasmonic resonance technique. AuNPs are widely used as biosensing probes because they facilitate stable immobilization of biomolecules. Transparent polymer film facilitated measurement of changes in absorbance via transmitted light and analysis of Raman scattering via scattered light. The cysteine rich protein G and anti-HbA1c were sequentially conjugated to self-assembled AuNPs on the transparent polymer film to detect a target protein. HbA1c, which is used as an indicator for diabetes diagnosis, was selected for target protein detection. We confirmed the linearly increased absorbance values with increasing HbA1c level (3.19-14.0%) by LSPR detection. We also verified the linear increase in SERS intensity as the concentration of anti-Hb increased from 10 ng mL-1 to 1 μg mL-1 by analyzing the SERS spectra of Cy3 labeled anti-Hb added substrates.

Hb Dartmouth (HBA2: c.200T>C): An α2-Globin Gene Associated with Hb H Disease in One Homozygous Patient.

PubMed

Farashi, Samaneh; Faramarzi Garous, Negin; Ashki, Mehri; Vakili, Shadi; Zeinali, Fatemah; Imanian, Hashem; Azarkeivan, Azita; Najmabadi, Hossein

2015-01-01

Hb H (β4) disease is caused by deletion or inactivation of three out of four α-globin genes. A high incidence of Hb H disease has been reported all over the world. There is a wide spectrum of phenotypic presentations, from clinically asymptomatic to having significant hepatosplenomegaly and requiring occasional or even regular blood transfusions, even more severe anemia, Hb Bart's (γ4) hydrops fetalis syndrome that can cause death in the affected fetuses late in gestation. We here present a case who was diagnosed with Hb H disease that represents a new genotype for this hereditary disorder. Hb Dartmouth is a variant caused by a missense mutation at codon 66 of the α2-globin gene (HBA2: c.200T>C), resulting in the substitution of leucine by proline. We here emphasize the importance of this point mutation involving Hb H disease and also the necessity for prenatal diagnosis (PND) for those who carry this point mutation in the heterozygous state.

An intriguing high performance liquid chromatogram of a double heterozygosity for Hb Q-India/Hb D-Punjab.

PubMed

Badyal, Rama Kumari; Chhabra, Sanjeev; Sharma, Prashant; Das, Reena

2014-01-01

Cation exchange high performance liquid chromatography (HPLC) is commonly utilized as the first method of screening for thalassemias and hemoglobinopathies worldwide. This method of diagnosis requires knowledge of the clinical background and complete blood counts as well as skill and experience in interpreting the sometimes complex results produced. An asymptomatic 27-year-old pregnant North Indian woman was found to have a highly unusual chromatographic pattern with multiple unexpected peaks during routine antenatal screening. Most concerning was a C-window peak as Hb C (HBB: c.19G>A) is rare in ethnic Asian Indian populations. Cellulose acetate electrophoresis at alkaline pH (8.6) and parental screening were performed. These revealed the correct diagnosis to be a double heterozygosity for Hb Q-India (HBA1: c.193G>C) (an uncommon asymptomatic α-globin chain variant) plus Hb D-Punjab (HBB: c.364G>C) (a β-globin chain variant that is common in this region and is asymptomatic in the heterozygous state). The unexpected C-window peak was the hybrid of the abnormal α-Q-India and β-D-Punjab globin chains. Another small peak was explained as a variant Hb A2 formed by the combination of α-Q-India and δ-globin chains. Hematopathologists should be cognizant of the complex pattern resulting from coinheritance of both α- and β-globin structural variants. Second-line testing and parental testing are invaluable in resolving unknown peaks, especially if rare or unexpected variants are being considered. Although both Hb Q-India and Hb D-Punjab are relatively common in northwestern India, to the best of our knowledge, only two recent reports describe a total of three cases of such diagnostically puzzling coinheritance.

Association of napping and night-time sleep with impaired glucose regulation, insulin resistance and glycated haemoglobin in Chinese middle-aged adults with no diabetes: a cross-sectional study.

PubMed

Baoying, Huang; Hongjie, Chen; Changsheng, Qiu; Peijian, Wu; Qingfei, Lin; Yinghua, Lin; Huibin, Huang; Jixing, Liang; Liantao, Li; Ling, Chen; Kaka, Tang; Zichun, Chen; Lixiang, Lin; Jieli, Lu; Yufang, Bi; Guang, Ning; Penli, Zhu; Junping, Wen; Gang, Chen

2014-07-23

To assess associations between napping and night-time sleep duration with impaired glucose regulation, insulin resistance (IR) and glycated haemoglobin (HbA1c). Cross-sectional study. Fujian Province, China, from June 2011 to January 2012. This study enrolled 9028 participants aged 40-65 years. Data of 7568 participants with no diabetes were included for analysis. Type 2 diabetes was defined applying WHO criteria. Participants' daytime napping and night-time sleep duration data were collected using a standardised self-reported Chinese-language questionnaire about sleep frequency and quality. Anthropometric and laboratory parameters were also measured. IR was defined as a HOMA-IR index value >2.50. ORs and 95% CIs were derived from multivariate logistic regression models. Participants (mean age 51.1±7.0 years) included 3060 males and 4508 females with average night-time sleep of 7.9 h. A higher proportion of males napped than females. After adjustment for potential confounders, ORs for HbA1c >6.0% were 1.28 and 1.26 for those napping ≤1 h and >1 h (p=0.002 and p=0.018), respectively. Statistically significant differences in IR between nappers and non-nappers were only marginal clinically. Odds for HbA1c >6.0% were significantly lower in participants with longer night-time sleep durations than in the reference group (>8 h vs 6-8 h). Odds for IR were significantly lower in participants whose night-time sleep hours deviated from the reference group (<6 h, >8 h vs 6-8 h) Chinese middle-aged adults with no diabetes who napped had higher HbA1c and IR; those with shorter night-time sleep durations had increased HbA1c. Night-time sleep hours that are either <6 or >8 tend to be associated with lower odds for IR. Further studies are necessary to determine the underlying clinical significance and mechanisms behind these associations. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go

HbA1c and the Prediction of Type 2 Diabetes in Children and Adults

PubMed Central

Vijayakumar, Pavithra; Nelson, Robert G.; Hanson, Robert L.; Knowler, William C.

2017-01-01

OBJECTIVE Long-term data validating glycated hemoglobin (HbA1c) in assessing the risk of type 2 diabetes in children are limited. HbA1c, fasting plasma glucose (FPG), and 2-h postload plasma glucose (2hPG) concentrations were measured in a longitudinal study of American Indians to determine their utility in predicting incident diabetes, all of which is thought to be type 2 in this population. RESEARCH DESIGN AND METHODS Incident diabetes (FPG ≥126 mg/dL [7.0 mmol/L], 2hPG ≥200 mg/dL [11.1 mmol/L], HbA1c ≥6.5% [8 mmol/mol], or clinical diagnosis) was determined in 2,095 children without diabetes ages 10–19 years monitored through age 39, and in 2,005 adults ages 20–39 monitored through age 59. Areas under the receiver operating characteristic (ROC) curve for HbA1c, FPG, and 2hPG in predicting diabetes within 10 years were compared. RESULTS During long-term follow-up of children and adolescents who did not initially have diabetes, the incidence rate of subsequent diabetes was fourfold (in boys) as high and more than sevenfold (in girls) as high in those with HbA1c ≥5.7% as in those with HbA1c ≤5.3%—greater rate ratios than experienced by adults in the same HbA1c categories. Analyses of ROCs revealed no significant differences between HbA1c, FPG, and 2hPG in sensitivity and specificity for identifying children and adolescents who later developed diabetes. CONCLUSIONS HbA1c is a useful predictor of diabetes risk in children and can be used to identify prediabetes in children with other type 2 diabetes risk factors with the same predictive value as FPG and 2hPG. PMID:27810987

Comparative genome-wide analysis and evolutionary history of haemoglobin-processing and haem detoxification enzymes in malarial parasites.

PubMed

Ponsuwanna, Patrath; Kochakarn, Theerarat; Bunditvorapoom, Duangkamon; Kümpornsin, Krittikorn; Otto, Thomas D; Ridenour, Chase; Chotivanich, Kesinee; Wilairat, Prapon; White, Nicholas J; Miotto, Olivo; Chookajorn, Thanat

2016-01-29

Malaria parasites have evolved a series of intricate mechanisms to survive and propagate within host red blood cells. Intra-erythrocytic parasitism requires these organisms to digest haemoglobin and detoxify iron-bound haem. These tasks are executed by haemoglobin-specific proteases and haem biocrystallization factors that are components of a large multi-subunit complex. Since haemoglobin processing machineries are functionally and genetically linked to the modes of action and resistance mechanisms of several anti-malarial drugs, an understanding of their evolutionary history is important for drug development and drug resistance prevention. Maximum likelihood trees of genetic repertoires encoding haemoglobin processing machineries within Plasmodium species, and with the representatives of Apicomplexan species with various host tropisms, were created. Genetic variants were mapped onto existing three-dimensional structures. Genome-wide single nucleotide polymorphism data were used to analyse the selective pressure and the effect of these mutations at the structural level. Recent expansions in the falcipain and plasmepsin repertoires are unique to human malaria parasites especially in the Plasmodium falciparum and P. reichenowi lineage. Expansion of haemoglobin-specific plasmepsins occurred after the separation event of Plasmodium species, but the other members of the plasmepsin family were evolutionarily conserved with one copy for each sub-group in every Apicomplexan species. Haemoglobin-specific falcipains are separated from invasion-related falcipain, and their expansions within one specific locus arose independently in both P. falciparum and P. vivax lineages. Gene conversion between P. falciparum falcipain 2A and 2B was observed in artemisinin-resistant strains. Comparison between the numbers of non-synonymous and synonymous mutations suggests a strong selective pressure at falcipain and plasmepsin genes. The locations of amino acid changes from non

Brain RVD-haemopressin, a haemoglobin-derived peptide, inhibits bombesin-induced central activation of adrenomedullary outflow in the rat.

PubMed

Tanaka, Kenjiro; Shimizu, Takahiro; Yanagita, Toshihiko; Nemoto, Takayuki; Nakamura, Kumiko; Taniuchi, Keisuke; Dimitriadis, Fotios; Yokotani, Kunihiko; Saito, Motoaki

2014-01-01

Haemopressin and RVD-haemopressin, derived from the haemoglobin α-chain, are bioactive peptides found in brain and are ligands for cannabinoid CB1 receptors. Activation of brain CB1 receptors inhibited the secretion of adrenal catecholamines (noradrenaline and adrenaline) induced by i.c.v. bombesin in the rat. Here, we investigated the effects of two haemoglobin-derived peptides on this bombesin-induced response Anaesthetised male Wistar rats were pretreated with either haemoglobin-derived peptide, given i.c.v., 30 min before i.c.v. bombesin and plasma catecholamines were subsequently measured electrochemically after HPLC. Direct effects of bombesin on secretion of adrenal catecholamines were examined using bovine adrenal chromaffin cells. Furthermore, activation of haemoglobin α-positive spinally projecting neurons in the rat hypothalamic paraventricular nucleus (PVN, a regulatory centre of central adrenomedullary outflow) after i.c.v. bombesin was assessed by immunohistochemical techniques. Bombesin given i.c.v. dose-dependently elevated plasma catecholamines whereas incubation with bombesin had no effect on spontaneous and nicotine-induced secretion of catecholamines from chromaffin cells. The bombesin-induced increase in catecholamines was inhibited by pretreatment with i.c.v. RVD-haemopressin (CB1 receptor agonist) but not after pretreatment with haemopressin (CB1 receptor inverse agonist). Bombesin activated haemoglobin α-positive spinally projecting neurons in the PVN. The haemoglobin-derived peptide RVD-haemopressin in the brain plays an inhibitory role in bombesin-induced activation of central adrenomedullary outflow via brain CB1 receptors in the rat. These findings provide basic information for the therapeutic use of haemoglobin-derived peptides in the modulation of central adrenomedullary outflow. © 2013 The British Pharmacological Society.

Comparison between capillary electrophoresis and high performance liquid chromatography for detection and quantification of Hb constant spring [Hb CS; α142, Term→Gln (TAA>CAA IN α2)].

PubMed

Waneesorn, Jarurin; Panyasai, Sitthichai; Kongthai, Kanyakan; Singboottra, Panthong; Pornprasert, Sakorn

2011-01-01

Hb Constant Spring [Hb CS; α142, Term→Gln (TAA>CAA in α2)] is often missed by routine laboratory testing since its mRNA as well as gene product are unstable and presented at a low level in peripheral blood. This study aimed to analyze the efficacy of capillary electrophoresis (CE) and high performance liquid chromatography (HPLC) for detecting and quantifying Hb CS in 19 heterozygotes and 14 homozygotes with Hb CS as well as 10 Hb H-CS disease subjects who were detected by molecular analysis. In the CE electrophoregram, Hb CS was seen at zone 2 and was observed in all samples, while the chromatogram of Hb CS peaks was found in 26.32% heterozygotes, 42.86% homozygotes and 90% Hb H-CS disease subjects, respectively. In addition, the Hb CS levels in each group of subjects quantified by CE were significantly higher than those quantified by HPLC. Based on the CE method, the lowest Hb CS level was found in the heterozygotes, whereas the highest level was found in the Hb H-CS disease patients. Therefore, the CE method was superior to the HPLC method for detecting Hb CS. Furthermore, the level of Hb CS quantified by CE proved useful in screening heterozygotes and homozygotes with Hb CS as well as Hb H-CS disease.

Life on the edge: O2 binding in Atlantic cod red blood cells near their southern distribution limit is not sensitive to temperature or haemoglobin genotype

PubMed Central

Barlow, Samantha L.; Metcalfe, Julian; Righton, David A.

2017-01-01

ABSTRACT Atlantic cod are a commercially important species believed to be threatened by warming seas near their southern, equatorward upper thermal edge of distribution. Limitations to circulatory O2 transport, in particular cardiac output, and the geographic distribution of functionally different haemoglobin (Hb) genotypes have separately been suggested to play a role in setting thermal tolerance in this species. The present study assessed the thermal sensitivity of O2 binding in Atlantic cod red blood cells with different Hb genotypes near their upper thermal distribution limit and modelled its consequences for the arterio-venous O2 saturation difference, Sa–vO2, another major determinant of circulatory O2 supply rate. The results showed statistically indistinguishable red blood cell O2 binding between the three HbI genotypes in wild-caught Atlantic cod from the Irish Sea (53° N). Red blood cells had an unusually low O2 affinity, with reduced or even reversed thermal sensitivity between pH 7.4 and 7.9, and 5.0 and 20.0°C. This was paired with strongly pH-dependent affinity and cooperativity of red blood cell O2 binding (Bohr and Root effects). Modelling of Sa–vO2 at physiological pH, temperature and O2 partial pressures revealed a substantial capacity for increases in Sa–vO2 to meet rising tissue O2 demands at 5.0 and 12.5°C, but not at 20°C. Furthermore, there was no evidence for an increase of maximal Sa–vO2 with temperature. It is suggested that Atlantic cod at such high temperatures may solely depend on increases in cardiac output and blood O2 capacity, or thermal acclimatisation of metabolic rate, for matching circulatory O2 supply to tissue demand. PMID:28148818

Life on the edge: O2 binding in Atlantic cod red blood cells near their southern distribution limit is not sensitive to temperature or haemoglobin genotype.

PubMed

Barlow, Samantha L; Metcalfe, Julian; Righton, David A; Berenbrink, Michael

2017-02-01

Atlantic cod are a commercially important species believed to be threatened by warming seas near their southern, equatorward upper thermal edge of distribution. Limitations to circulatory O 2 transport, in particular cardiac output, and the geographic distribution of functionally different haemoglobin (Hb) genotypes have separately been suggested to play a role in setting thermal tolerance in this species. The present study assessed the thermal sensitivity of O 2 binding in Atlantic cod red blood cells with different Hb genotypes near their upper thermal distribution limit and modelled its consequences for the arterio-venous O 2 saturation difference, Sa-v O 2 , another major determinant of circulatory O 2 supply rate. The results showed statistically indistinguishable red blood cell O 2 binding between the three HbI genotypes in wild-caught Atlantic cod from the Irish Sea (53° N). Red blood cells had an unusually low O 2 affinity, with reduced or even reversed thermal sensitivity between pH 7.4 and 7.9, and 5.0 and 20.0°C. This was paired with strongly pH-dependent affinity and cooperativity of red blood cell O 2 binding (Bohr and Root effects). Modelling of Sa-v O 2  at physiological pH, temperature and O 2 partial pressures revealed a substantial capacity for increases in Sa-v O 2  to meet rising tissue O 2 demands at 5.0 and 12.5°C, but not at 20°C. Furthermore, there was no evidence for an increase of maximal Sa-v O 2  with temperature. It is suggested that Atlantic cod at such high temperatures may solely depend on increases in cardiac output and blood O 2 capacity, or thermal acclimatisation of metabolic rate, for matching circulatory O 2 supply to tissue demand. © 2017. Published by The Company of Biologists Ltd.

Maternal Hemoglobin Concentration during Gestation and Risk of Anemia in Infancy: Secondary Analysis of a Randomized Controlled Trial

PubMed Central

Zhang, Yiting; Jin, Lei; Liu, Jian-meng; Ye, Rongwei; Ren, Aiguo

2016-01-01

Objective To examine the relationship between maternal hemoglobin (Hb) concentration and the risk of anemia in infancy. Study design This analysis included 17,193 women who entered the trial when they were 20 years of age or older, no more than 20 weeks of gestation, had mild or no anemia, and delivered singleton live births. Maternal Hb concentrations were measured in the first trimester and during 24-28 weeks of gestation; infant Hb concentrations were measured at 5-7 months and 11-13 months of life. The associations between maternal Hb concentrations and infant Hb concentrations were examined. Results Maternal Hb concentrations measured during 24-28 weeks of gestation, but not in the first trimester, were correlated with infant Hb concentrations measured at either of the two post-partum periods. The risk of infant anemia at 5-7 months increased when maternal Hb concentration was ≤109 g/L during 24-28 weeks of gestation ([AOR: 1.95, 95% CI: 1.59-2.40] and 11-13 months [AOR: 1.72, 95% CI: 1.36-2.18]); whereas the risk of anemia during 5-7 months as well as 11-13 months in infancy decreased when maternal Hb level at 24-28 weeks of gestation was 120-129 g/L (AOR for 5-7 months: 0.74, 95% CI: 0.64-0.85; AOR for 11-13 months: 0.72, 95% CI: 0.61-0.85) or ≥130 g/L (AOR for 5-7 months: 0.75, 95% CI: 0.63-0.90; AOR for 11-13 months: 0.89, 95% CI: 0.73-1.08). Conclusion Low maternal Hb concentration during 24-28 weeks of gestation was associated with an increased risk of anemia in infancy, whereas high maternal Hb concentration was associated with a reduced risk of anemia. PMID:27263403

Preoperative haemoglobin cut-off values for the prediction of post-operative transfusion in total knee arthroplasty.

PubMed

Yeh, Jared Ze Yang; Chen, Jerry Yongqiang; Bin Abd Razak, Hamid Rahmatullah; Loh, Bryan Huai Gu; Hao, Ying; Yew, Andy Khye Soon; Chia, Shi-Lu; Lo, Ngai Nung; Yeo, Seng Jin

2016-10-01

The purpose of this study is to determine preoperative haemoglobin cut-off values that could accurately predict post-operative transfusion outcome in patients undergoing primary unilateral total knee arthroplasty (TKA). This will allow surgeons to provide selective preoperative type and screen to only patients at high risk of transfusion. A total of 1457 patients diagnosed with osteoarthritis and underwent primary unilateral TKA between January 2012 and December 2014 were retrospectively reviewed. Logistic regression analyses were applied to identify factors that could predict transfusion outcome. A total of 37 patients (2.5 %) were transfused postoperatively. Univariate analysis revealed preoperative haemoglobin (p < 0.001), age (p < 0.001), preoperative haematocrit (p < 0.001), and preoperative creatinine (p < 0.001) to be significant predictors. In the multivariate analysis with patients dichotomised at 70 years of age, preoperative haemoglobin remained significant with adjusted odds ratio of 0.33. Receiver operating characteristic curve identified the preoperative haemoglobin cut-off values to be 12.4 g/dL (AUC = 0.86, sensitivity = 87.5 %, specificity = 77.2 %) and 12.1 g/dL (AUC = 0.85, sensitivity = 69.2 %, specificity = 87.1 %) for age above and below 70, respectively. The authors recommend preoperative haemoglobin cut-off values of 12.4 g/dL for age above 70 and 12.1 g/dL for age below 70 to be used to predict post-operative transfusion requirements in TKA. To maximise the utilisation of blood resources, the authors recommend that only patients with haemoglobin level below the cut-off should receive routine preoperative type and screen before TKA. IV.

Molecular Cloning of HbPR-1 Gene from Rubber Tree, Expression of HbPR-1 Gene in Nicotiana benthamiana and Its Inhibition of Phytophthora palmivora

PubMed Central

Khunjan, Uraiwan; Ekchaweng, Kitiya; Panrat, Tanate; Tian, Miaoying; Churngchow, Nunta

2016-01-01

This is the first report to present a full-length cDNA (designated HbPR-1) encoding a putative basic HbPR-1 protein from rubber tree (Hevea brasiliensis) treated with salicylic acid. It was characterized and also expressed in Nicotiana benthamiana using Agrobacterium-mediated transient gene expression system in order to investigate the role of HbPR-1 gene in rubber tree against its oomycete pathogen Phytopthora palmivora and to produce recombinant HbPR-1 protein for microbial inhibition test. The HbPR-1 cDNA was 647 bp long and contained an open reading frame of 492 nucleotides encoding 163 amino acid residues with a predicted molecular mass of 17,681 Da and an isoelectric point (pI) of 8.56, demonstrating that HbPR-1 protein belongs to the basic PR-1 type. The predicted 3D structure of HbPR-1 was composed of four α-helices, three β-sheets, seven strands, and one junction loop. Expression and purification of recombinant HbPR-1 protein were successful using Agrobacterium-mediated transient expression and one-step of affinity chromatography. Heterologous expression of HbPR-1 in N. benthamiana reduced necrosis areas which were inoculated with P. palmivora zoospores, indicating that the expressed HbPR-1 protein played an important role in plant resistance to pathogens. The purified recombinant HbPR-1 protein was found to inhibit 64% of P. palmivora zoospore germination on a water agar plate compared with control, suggesting that it was an antimicrobial protein against P. palmivora. PMID:27337148

A Protein Diet Score, Including Plant and Animal Protein, Investigating the Association with HbA1c and eGFR—The PREVIEW Project

PubMed Central

Mikkilä, Vera; Raitakari, Olli T.; Hutri-Kähönen, Nina; Dragsted, Lars O.; Poppitt, Sally D.; Silvestre, Marta P.; Feskens, Edith J.M.

2017-01-01

Higher-protein diets have been advocated for body-weight regulation for the past few decades. However, the potential health risks of these diets are still uncertain. We aimed to develop a protein score based on the quantity and source of protein, and to examine the association of the score with glycated haemoglobin (HbA1c) and estimated glomerular filtration rate (eGFR). Analyses were based on three population studies included in the PREVIEW project (PREVention of diabetes through lifestyle Intervention and population studies in Europe and around the World): NQplus, Lifelines, and the Young Finns Study. Cross-sectional data from food-frequency questionnaires (n = 76,777 subjects) were used to develop a protein score consisting of two components: 1) percentage of energy from total protein, and 2) plant to animal protein ratio. An inverse association between protein score and HbA1c (slope −0.02 ± 0.01 mmol/mol, p < 0.001) was seen in Lifelines. We found a positive association between the protein score and eGFR in Lifelines (slope 0.17 ± 0.02 mL/min/1.73 m2, p < 0.0001). Protein scoring might be a useful tool to assess both the effect of quantity and source of protein on health parameters. Further studies are needed to validate this newly developed protein score. PMID:28714926

A Protein Diet Score, Including Plant and Animal Protein, Investigating the Association with HbA1c and eGFR-The PREVIEW Project.

PubMed

Møller, Grith; Sluik, Diewertje; Ritz, Christian; Mikkilä, Vera; Raitakari, Olli T; Hutri-Kähönen, Nina; Dragsted, Lars O; Larsen, Thomas M; Poppitt, Sally D; Silvestre, Marta P; Feskens, Edith J M; Brand-Miller, Jennie; Raben, Anne

2017-07-17

Higher-protein diets have been advocated for body-weight regulation for the past few decades. However, the potential health risks of these diets are still uncertain. We aimed to develop a protein score based on the quantity and source of protein, and to examine the association of the score with glycated haemoglobin (HbA1c) and estimated glomerular filtration rate (eGFR). Analyses were based on three population studies included in the PREVIEW project (PREVention of diabetes through lifestyle Intervention and population studies in Europe and around the World): NQplus, Lifelines, and the Young Finns Study. Cross-sectional data from food-frequency questionnaires ( n = 76,777 subjects) were used to develop a protein score consisting of two components: 1) percentage of energy from total protein, and 2) plant to animal protein ratio. An inverse association between protein score and HbA1c (slope -0.02 ± 0.01 mmol/mol, p < 0.001) was seen in Lifelines. We found a positive association between the protein score and eGFR in Lifelines (slope 0.17 ± 0.02 mL/min/1.73 m², p < 0.0001). Protein scoring might be a useful tool to assess both the effect of quantity and source of protein on health parameters. Further studies are needed to validate this newly developed protein score.

Current Status of HbA1c Biosensors

PubMed Central

Lin, Hua; Yi, Jun

2017-01-01

Glycated hemoglobin (HbA1c) is formed via non-enzymatic glycosylation reactions at the α–amino group of βVal1 residues in the tetrameric Hb, and it can reflect the ambient glycemic level over the past two to three months. A variety of HbA1c detection methods, including chromatography, immunoassay, enzymatic measurement, electrochemical sensor and capillary electrophoresis have been developed and used in research laboratories and in clinics as well. In this review, we summarize the current status of HbA1c biosensors based on the recognition of the sugar moiety on the protein and also their applications in the whole blood sample measurements. PMID:28777351

Interaction of Hb South Florida (codon 1; GTG-->ATG) and HbE, with beta-thalassemia (IVS1-1; G-->A): expression of different clinical phenotypes.

PubMed

Tan, Jin-Ai Mary Anne; Tan, Kim-Lian; Omar, Khairul Zaman; Chan, Lee-Lee; Wee, Yong-Chui; George, Elizabeth

2009-09-01

Interactions of different hemoglobin variants with thalassemia alleles can result in various clinical phenotypes. HbE-beta-thalassemia generally manifests with severe anemia where individuals exhibit beta-thalassemia major with regular blood transfusions or beta-thalassemia intermedia with periodic blood transfusions. This study presents a unique Malay family with three beta-globin gene defects-HbE, Hb South Florida, and IVS1-1 (G-->A). HbE activates a cryptic splice site that produces non-functional mRNAs. Hb South Florida is a rare beta-hemoglobin variant, and its interactions with other beta-thalassemia alleles have not been reported. IVS1-1 is a Mediterranean mutation that affects mRNA processing giving rise to beta(o)-thalassemia. Fifteen mutations along the beta-globin gene complex were analyzed using the amplification refractory mutation system. Hb South Florida was identified by direct sequencing using genomic DNA. The affected child with HbE/IVS1-1 produced a beta-thalassemia major phenotype. Compound heterozygosity for Hb South Florida/IVS1-1 produced a beta-thalassemia carrier phenotype in the mother.

Novel haemoglobin-derived antimicrobial peptides from chicken (Gallus gallus) blood: purification, structural aspects and biological activity.

PubMed

Vasilchenko, A S; Rogozhin, E A; Vasilchenko, A V; Kartashova, O L; Sycheva, M V

2016-12-01

To purify and characterize antimicrobial peptides derived from the acid extract of Gallus gallus blood cells. Two polypeptides (i.e. CHb-1 and CHb-2) with antibacterial activity were detected in the acidic extract of blood cells from chicken (G. gallus). The isolated peptides that possessed a potent antibacterial activity were purified using a two-step chromatography procedure that involved solid-phase extraction of a total protein/peptide extract followed by thin fractionation by reversed-phase high performance liquid chromatography (RP-HPLC). The molecular masses of the purified peptides were similar and were 4824·4 and 4825·2 Da, which have been measured by matrix-assisted laser desorption/ionization mass spectrometry (MALDI TOF MS). Their amino acid sequences were determined by Edman degradation and showed that the peptides were fully identical to the two fragments of G. gallus α-haemoglobin localized into different subunits (A and D respectively). The peptides were active in micromolar concentrations against Gram-negative Escherichia coli K12 TG1. Using the 1-N-phenylnaphthylamine, the FITC-dextran labelled probes and the live/dead staining allowed to show the hemocidin mode of action and estimate the pore size. In this study, for the first time, α-haemoglobin from chicken (G. gallus) has been investigated as a donor of the two high homologous native peptide fragments that possess potent antibacterial activity in vitro. These are membrane-active peptides and their mechanism of action against E. coli involves a toroidal pore formation. The obtained results expand the perception of the role of haemoglobin in a living system, describing it as a source of multifunction substances. Additionally, the data presented in this paper may contribute to the development of new, cost-effective, antimicrobial agents. © 2016 The Society for Applied Microbiology.