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Clinics in Haematology Feb 1984The indications and management of blood transfusion in the haemoglobinopathies have been reviewed. The sickle cell diseases that require transfusion support are sickle... (Review)
Review
The indications and management of blood transfusion in the haemoglobinopathies have been reviewed. The sickle cell diseases that require transfusion support are sickle cell anaemia, sickle haemoglobin-C and -D diseases and sickle beta-thalassaemia. Homozygous beta-thalassaemia (Cooley's anaemia) is the major problem among the thalassaemias. The pathophysiology of the sickle cell disorders is largely based on the secondary effects of increased blood viscosity, whereas in the thalassaemias the defect is ineffective haematopoiesis. In the former the major problems occur as manifestations of vaso-occlusive crises with disseminated bone and abdominal pain, priapism, stroke and leg ulcers. Bone infarction and aseptic necrosis occur but the widespread bone changes, underdevelopment and haemochromatosis that complicate the thalassaemia are not prominent. Transfusion therapy in the sickle cell diseases is mainly episodic and is guided by the frequency of crises and the severity of vaso-occlusive complications. Partial exchange transfusion and the maintenance of haemoglobin A concentrations at 40 to 50 per cent is frequently indicated. In the thalassaemias, maintenance of haemoglobin levels is essential for normal growth and development. The problem of haemochromatosis is very serious. With hypertransfusion regimens the haemoglobin and haemotocrit are maintained above 12-13 g/dl and 35 per cent. The resulting benefit appears to be reduced blood volume, less iron turnover, and less intestinal iron absorption. The splenomegaly in these disorders is frequently associated with hypersplenism requiring well-timed splenectomy. Chronic and intensive chelation is necessary to prevent the ravages of iron overload. The availability of automated equipment for in vivo and ex vivo blood cell separation has brought new possibilities for improving the management of these haemoglobinopathies. It is feasible, but not as yet practical, to offer transfusions of neocytes (red cells with a mean age of 30 days) which have a 50 per cent longer survival than routine red cell preparations (mean age of 60 days). Neocytes can be prepared ex vivo from fresh routine blood donations using blood cell separator devices. The result is reduced transfusion requirements. A more recent suggestion for using the new technology is to remove the patient's oldest and most abnormal corpuscles on the basis of buoyant density and replacing them with neocytes . Thus the short-lived abnormal red cells would be removed before they could unload their iron. With automation it is possible to perform these procedures on an outpatient basis.
Topics: Adult; Anemia, Sickle Cell; Blood Transfusion; Bone and Bones; Child; Erythrocyte Transfusion; Erythrocytes; Exchange Transfusion, Whole Blood; Female; Hemoglobinopathies; Humans; Infant; Iron; Male; Pain Management; Pregnancy; Pregnancy Complications, Hematologic; Syndrome; Thalassemia; Transfusion Reaction
PubMed: 6373080
DOI: No ID Found -
C-Window Peaks on CE-HPLC are Extremely Rare in Northern India, and Only Infrequently Represent HbC.Indian Journal of Hematology & Blood... Jan 2018Hemoglobin C (HbC, HBB:c.19G > A) is a structural variant that has been reported rarely from India. This was a retrospective review of all high performance liquid...
Hemoglobin C (HbC, HBB:c.19G > A) is a structural variant that has been reported rarely from India. This was a retrospective review of all high performance liquid chromatography (HPLCs) submitted over a 14 year period to a tertiary care center in North India with an aim of finding hemoglobins that elute in the C-window. Of the 32,364 HPLCs screened, 6 cases showed peaks in the C-window. Of these 6 cases, only two cases contained hemoglobin C. These was one case each of HbC/β thalassemia and compound heterozygosity for HbC and HbD. There were 4 cases which showed very similar red cell indices and chromatograms with multiple peaks eluting in D-window, C-window and an additional peak with a retention time of 4.74 min. These four cases were compound heterozygous for an α chain variant HbQ-India and a β-chain variant HbD.
PubMed: 29398805
DOI: 10.1007/s12288-017-0815-y -
Journal of the Endocrine Society Oct 2022The syndrome of inappropriate antidiuresis (SIAD) with euvolemic hyponatremia may occur in patients with pulmonary tuberculosis (PTB), but little is known about the...
CONTEXT
The syndrome of inappropriate antidiuresis (SIAD) with euvolemic hyponatremia may occur in patients with pulmonary tuberculosis (PTB), but little is known about the clinical characteristics of SIAD-associated hyponatremia in PTB patients.
OBJECTIVE
This study aimed to investigate the frequency and risk factors of hyponatremia in PTB patients.
METHODS
In this retrospective chart review, we examined the incidence and severity of hyponatremia in PTB patients. Multivariate analysis was conducted to identify risk factors for hyponatremia in PTB patients.
RESULTS
Of the 161 patients who were screened, after excluding patients with hyperglycemia and renal failure, we enrolled and analyzed data from 113 participants. Hyponatremia occurred in 40.7% patients (<135 mEq/L). Univariate analysis revealed that the presence of hyponatremia was associated with old age, female sex, low body mass index, high glycosylated hemoglobin, C-reactive protein (CRP), and N-terminal pro-brain natriuretic peptide. Multivariable analysis indicated that hyponatremia was strongly associated with old age (odds ratio, 1.06; 95% CI, 1.03-1.09 for every 1-year age increase) and CRP values (odds ratio, 1.15; 95% CI, 1.03-1.30 for every 1-mg/dL increase in CRP). For 86 patients with blood cortisol measurements, the cortisol level was significantly high in the hyponatremia group.
CONCLUSIONS
Hyponatremia was less frequently associated with hyperglycemia, heart failure, renal failure, and other diseases that cause euvolemic hyponatremia; thus, PTB patients may have euvolemic hyponatremia due to SIAD. Administration of hypertonic saline or fluid restriction should be considered in PTB patients with hyponatremia.
PubMed: 36249414
DOI: 10.1210/jendso/bvac130 -
Biophysical Journal Oct 2008Individuals expressing hemoglobin C (beta6 Glu-->Lys) present red blood cells (RBC) with intraerythrocytic crystals that form when hemoglobin (Hb) is oxygenated. Our...
Individuals expressing hemoglobin C (beta6 Glu-->Lys) present red blood cells (RBC) with intraerythrocytic crystals that form when hemoglobin (Hb) is oxygenated. Our earlier in vitro liquid-liquid (L-L) phase separation studies demonstrated that liganded HbC exhibits a stronger net intermolecular attraction with a longer range than liganded HbS or HbA, and that L-L phase separation preceded and enhanced crystallization. We now present evidence for the role of phase separation in HbC crystallization in the RBC, and the role of the RBC membrane as a nucleation center. RBC obtained from both human homozygous HbC patients and transgenic mice expressing only human HbC were studied by bright-field and differential interference contrast video-enhanced microscopy. RBC were exposed to hypertonic NaCl solution (1.5-3%) to induce crystallization within an appropriate experimental time frame. L-L phase separation occurred inside the RBC, which in turn enhanced the formation of intraerythrocytic crystals. RBC L-L phase separation and crystallization comply with the thermodynamic and kinetics laws established through in vitro studies of phase transformations. This is the first report, to the best of our knowledge, to capture a temporal view of intraerythrocytic HbC phase separation, crystal formation, and dissolution.
Topics: Animals; Crystallization; Cytosol; Erythrocyte Membrane; Erythrocytes; Hemoglobin C; Humans; Mice; Temperature; Time Factors
PubMed: 18621841
DOI: 10.1529/biophysj.107.127324 -
Ecotoxicology and Environmental Safety Mar 2021In-vitro effects of sub-lethal concentrations of malathion, phenanthrene (Phe) and cadmium (Cd) were tested on Chironomus sancticaroli larvae in acute bioassays by...
In-vitro effects of sub-lethal concentrations of malathion, phenanthrene (Phe) and cadmium (Cd) were tested on Chironomus sancticaroli larvae in acute bioassays by measuring biochemical and molecular parameters. Malathion was evaluated at 0.001, 0.0564 and 0.1006 mg L; Phe at 0.0025, 1.25 and 2.44 mg L; and Cd at 0.001, 3.2 and 7.4 mg L. The recovery test carried out at the highest concentration of each compound showed that survival of larvae exposed to Phe ranged from 4% to 5%, while the effects of malathion and Cd were irreversible, not allowing the emergence of adults. Results showed that malathion and Cd inhibited AChE, EST-α and ES-β activities at the two highest concentrations. Phe at 0.0025, 1.25 and 2.44 mg L; and Cd at 3.2 and 7.4 mg L inhibited glutathione S-transferase activity. Oxidative stress was exclusively induced by the lowest concentration of malathion considering SOD activity once CAT was unaffected by the stressors. Lipid peroxidation was registered exclusively by malathion at the two highest concentrations, and total hemoglobin content was only reduced by Cd at the two highest concentrations. The relationship among biochemical results, examined using the PCA, evidenced that malathion and Cd concentrations were clustered into two groups, while Phe only formed one group. Four hemoglobin genes of C. sancticaroli were tested for the first time in this species, with Hemoglobin-C being upregulated by malathion. The toxicity ranking was malathion > Phe > Cd, while biochemical and molecular results showed the order malathion > Cd > Phe. Our results highlight the importance of combining different markers to understand the effects of the diverse compounds in aquatic organisms.
Topics: Animals; Biological Assay; Cadmium; Chironomidae; Larva; Lipid Peroxidation; Malathion; Oxidative Stress; Phenanthrenes; Water Pollutants, Chemical
PubMed: 33482495
DOI: 10.1016/j.ecoenv.2021.111953 -
PloS One Jun 2009Hemoglobin C differs from normal hemoglobin A by a glutamate-to-lysine substitution at position 6 of beta globin and is oxidatively unstable. Compared to homozygous AA...
BACKGROUND
Hemoglobin C differs from normal hemoglobin A by a glutamate-to-lysine substitution at position 6 of beta globin and is oxidatively unstable. Compared to homozygous AA erythrocytes, homozygous CC erythrocytes contain higher levels of membrane-associated hemichromes and more extensively clustered band 3 proteins. These findings suggest that CC erythrocytes have a different membrane matrix than AA erythrocytes.
METHODOLOGY AND FINDINGS
We found that AA and CC erythrocytes differ in their membrane lipid composition, and that a subset of CC erythrocytes expresses increased levels of externalized phosphatidylserine. Detergent membrane analyses for raft marker proteins indicated that CC erythrocyte membranes are more resistant to detergent solubilization. These data suggest that membrane raft organization is modified in CC erythrocytes. In addition, the average zeta potential (a measure of surface electrochemical potential) of CC erythrocytes was approximately 2 mV lower than that of AA erythrocytes, indicating that substantial rearrangements occur in the membrane matrix of CC erythrocytes. We were able to recapitulate this low zeta potential phenotype in AA erythrocytes by treating them with NaNO(2) to oxidize hemoglobin A molecules and increase levels of membrane-associated hemichromes.
CONCLUSION
Our data support the possibility that increased hemichrome deposition and altered lipid composition induce molecular rearrangements in CC erythrocyte membranes, resulting in a unique membrane structure.
Topics: Detergents; Electrochemistry; Electrophoresis, Polyacrylamide Gel; Erythrocytes; Flow Cytometry; Glutamates; Hemoglobin C; Homozygote; Humans; Lipids; Lysine; Membrane Lipids; Oxygen; Phenotype
PubMed: 19503809
DOI: 10.1371/journal.pone.0005828 -
JAMA Network Open Nov 2022To optimize palliative care in patients with cancer who are in their last year of life, timely and accurate prognostication is needed. However, available instruments for...
IMPORTANCE
To optimize palliative care in patients with cancer who are in their last year of life, timely and accurate prognostication is needed. However, available instruments for prognostication, such as the surprise question ("Would I be surprised if this patient died in the next year?") and various prediction models using clinical variables, are not well validated or lack discriminative ability.
OBJECTIVE
To develop and validate a prediction model to calculate the 1-year risk of death among patients with advanced cancer.
DESIGN, SETTING, AND PARTICIPANTS
This multicenter prospective prognostic study was performed in the general oncology inpatient and outpatient clinics of 6 hospitals in the Netherlands. A total of 867 patients were enrolled between June 2 and November 22, 2017, and followed up for 1 year. The primary analyses were performed from October 9 to 25, 2019, with the most recent analyses performed from June 19 to 22, 2022. Cox proportional hazards regression analysis was used to develop a prediction model including 3 categories of candidate predictors: clinician responses to the surprise question, patient clinical characteristics, and patient laboratory values. Data on race and ethnicity were not collected because most patients were expected to be of White race and Dutch ethnicity, and race and ethnicity were not considered as prognostic factors. The models' discriminative ability was assessed using internal-external validation by study hospital and measured using the C statistic. Patients 18 years and older with locally advanced or metastatic cancer were eligible. Patients with hematologic cancer were excluded.
MAIN OUTCOMES AND MEASURES
The risk of death by 1 year.
RESULTS
Among 867 patients, the median age was 66 years (IQR, 56-72 years), and 411 individuals (47.4%) were male. The 1-year mortality rate was 41.6% (361 patients). Three prediction models with increasing complexity were developed: (1) a simple model including the surprise question, (2) a clinical model including the surprise question and clinical characteristics (age, cancer type prognosis, visceral metastases, brain metastases, Eastern Cooperative Oncology Group performance status, weight loss, pain, and dyspnea), and (3) an extended model including the surprise question, clinical characteristics, and laboratory values (hemoglobin, C-reactive protein, and serum albumin). The pooled C statistic was 0.69 (95% CI, 0.67-0.71) for the simple model, 0.76 (95% CI, 0.73-0.78) for the clinical model, and 0.78 (95% CI, 0.76-0.80) for the extended model. A nomogram and web-based calculator were developed to support clinicians in adequately caring for patients with advanced cancer.
CONCLUSIONS AND RELEVANCE
In this study, a prediction model including the surprise question, clinical characteristics, and laboratory values had better discriminative ability in predicting death among patients with advanced cancer than models including the surprise question, clinical characteristics, or laboratory values alone. The nomogram and web-based calculator developed for this study can be used by clinicians to identify patients who may benefit from palliative care and advance care planning. Further exploration of the feasibility and external validity of the model is needed.
Topics: Humans; Male; Aged; Female; Models, Statistical; Prospective Studies; Prognosis; Palliative Care; Neoplasms, Second Primary; Brain Neoplasms
PubMed: 36449290
DOI: 10.1001/jamanetworkopen.2022.44350 -
The Journal of Biological Chemistry Sep 2011Recent crystallographic studies suggested that fully liganded human hemoglobin can adopt multiple quaternary conformations that include the two previously solved relaxed...
Recent crystallographic studies suggested that fully liganded human hemoglobin can adopt multiple quaternary conformations that include the two previously solved relaxed conformations, R and R2, whereas fully unliganded deoxyhemoglobin may adopt only one T (tense) quaternary conformation. An important unanswered question is whether R, R2, and other relaxed quaternary conformations represent different physiological states with different oxygen affinities. Here, we answer this question by showing the oxygen equilibrium curves of single crystals of human hemoglobin in the R and R2 state. In this study, we have used a naturally occurring mutant hemoglobin C (β6 Glu→Lys) to stabilize the R and R2 crystals. Additionally, we have refined the x-ray crystal structure of carbonmonoxyhemoglobin C, in the R and R2 state, to 1.4 and 1.8 Å resolution, respectively, to compare precisely the structures of both types of relaxed states. Despite the large quaternary structural difference between the R and R2 state, both crystals exhibit similar noncooperative oxygen equilibrium curves with a very high affinity for oxygen, comparable with the fourth oxygen equilibrium constant (K(4)) of human hemoglobin in solution. One small difference is that the R2 crystals have an oxygen affinity that is 2-3 times higher than that of the R crystals. These results demonstrate that the functional difference between the two typical relaxed quaternary conformations is small and physiologically less important, indicating that these relaxed conformations simply reflect a structural polymorphism of a high affinity relaxed state.
Topics: Absorption; Amino Acid Substitution; Carboxyhemoglobin; Crystallography, X-Ray; Heme; Hemoglobin C; Humans; Models, Molecular; Oxygen; Protein Structure, Quaternary; Spectrum Analysis; Stereoisomerism
PubMed: 21816820
DOI: 10.1074/jbc.M111.266056 -
Frontiers in Endocrinology 2023This study evaluated the effect of continuous glucose monitoring (CGM) versus self-monitored blood glucose (SMGB) in gestational diabetes mellitus (GDM) with hemoglobin... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
This study evaluated the effect of continuous glucose monitoring (CGM) versus self-monitored blood glucose (SMGB) in gestational diabetes mellitus (GDM) with hemoglobin A1c (HbA1c) <6%.
METHODS
From January 2019 to February 2021, 154 GDM patients with HbA1c<6% at 24-28 gestational weeks were recruited and assigned randomly to either SMBG only or CGM in addition to SMBG, with 77 participants in each group. CGM was used in combination with fingertip blood glucose monitoring every four weeks until antepartum in the CGM group, while in the SMBG group, fingertip blood glucose monitoring was applied. The CGM metrics were evaluated after 8 weeks, HbA1c levels before delivery, gestational weight gain (GWG), adverse pregnancy outcomes and CGM medical costs were compared between the two groups.
RESULTS
Compared with patients in the SMBG group, the CGM group patients had similar times in range (TIRs) after 8 weeks (100.00% (93.75-100.00%) versus 99.14% (90.97-100.00%), =0.183) and HbA1c levels before delivery (5.31 ± 0.06% versus 5.35 ± 0.06%, =0.599). The proportion with GWG within recommendations was higher in the CGM group (59.7% versus 40.3%, =0.046), and the newborn birth weight was lower (3123.79 ± 369.58 g versus 3291.56 ± 386.59 g, =0.015). There were no significant differences in prenatal or obstetric outcomes, e.g., cesarean delivery rate, hypertensive disorders, preterm births, macrosomia, hyperbilirubinemia, neonatal hypoglycemia, respiratory distress, and neonatal intensive care unit admission >24 h, between the two groups. Considering glucose monitoring, SMBG group patients showed a lower cost than CGM group patients.
CONCLUSIONS
For GDM patients with HbA1c<6%, regular SMBG is a more economical blood glucose monitoring method and can achieve a similar performance in glycemic control as CGM, while CGM is beneficial for ideal GWG.
Topics: Adult; Female; Humans; Pregnancy; Blood Glucose; Blood Glucose Self-Monitoring; Diabetes, Gestational; Glycated Hemoglobin; Glycemic Control; Hemoglobin C; Gestational Weight Gain
PubMed: 37152928
DOI: 10.3389/fendo.2023.1174239 -
Frontiers in Physiology 2022We propose a method to perform simultaneous measurements of percutaneous arterial oxygen saturation ( ), tissue oxygen saturation ( ), pulse rate (), and respiratory...
We propose a method to perform simultaneous measurements of percutaneous arterial oxygen saturation ( ), tissue oxygen saturation ( ), pulse rate (), and respiratory rate () in real-time, using a digital red-green-blue (RGB) camera. Concentrations of oxygenated hemoglobin ( ), deoxygenated hemoglobin ( ), total hemoglobin ( ), and were estimated from videos of the human face using a method based on a tissue-like light transport model of the skin. The photoplethysmogram (PPG) signals are extracted from the temporal fluctuations in , , and using a finite impulse response (FIR) filter (low and high cut-off frequencies of 0.7 and 3 Hz, respectively). The is calculated from the PPG signal for . The ratio of pulse wave amplitude for and that for are associated with the reference value of measured by a commercially available pulse oximeter, which provides an empirical formula to estimate from videos. The respiration-dependent oscillation in was extracted from another FIR filter (low and high cut-off frequencies of 0.05 and 0.5 Hz, respectively) and used to calculate the . experiments with human volunteers while varying the fraction of inspired oxygen were performed to evaluate the comparability of the proposed method with commercially available devices. The Bland-Altman analysis showed that the mean bias for , , , and were -1.4 (bpm), -1.2(rpm), 0.5 (%), and -3.0 (%), respectively. The precisions for , , , and were ±3.1 (bpm), ±3.5 (rpm), ±4.3 (%), and ±4.8 (%), respectively. The resulting precision and RMSE for were pretty close to the clinical accuracy requirement. The accuracy of the is considered a little less accurate than clinical requirements. This is the first demonstration of a low-cost RGB camera-based method for contactless simultaneous measurements of the heart rate, percutaneous arterial oxygen saturation, and tissue oxygen saturation in real-time.
PubMed: 36200058
DOI: 10.3389/fphys.2022.933397