5,099 research outputs found
Effects of isolated post-challenge hyperglycemia on mortality in American Indians: The strong heart study
No full textPURPOSE: To assess the effects of isolated post-challenge hyperglycemia (IPH) on risk of cardiovascular disease (CVD), cancer, and all-cause mortality in American Indians using longitudinal data from the Strong Heart Study. METHODS: Of 4549 American Indian women and men aged 45 to 74 years participating in the Strong Heart Study, 4304 had fasting blood measurements or oral glucose tolerance test (OGTT) data to ascertain diabetes status. At baseline and follow-up, a personal interview was conducted, and physical examinations and laboratory tests were performed. Fasting blood samples were drawn for measurement of glucose, fibrinogen, insulin, lipids, lipoproteins, creatinine, and hemoglobin A1c (HbA1c). A 75-g OGTT was performed. Five diabetes categories were defined: (i) known diabetes, (ii) newly diagnosed diabetes (fasting glucose ≥126 mg/dL and no history of diabetes or diabetes medication; ADA-new diabetes), (iii) IPH, (iv) impaired fasting glucose (≥110 - \u3c126 mg/dL; IFG), and (v) normal fasting glucose (\u3c110 mg/dL; NFG). Surveillance was initiated to determine CVD, cancer, and all-cause mortality over 9 years. RESULTS: IPH had a worse CVD risk factor profile than NFG, but IPH was associated with a better CVD risk factor profile than known diabetes or ADA-new diabetes. At follow-up, individuals with IFG had no increased risk for CVD or all-cause mortality, whereas those with ADA-new or known diabetes had significantly increased risk (RR = 1.70 and 1.40 for ADA-new diabetes, and RR = 2.87 and 2.19 for known diabetes, respectively). Those with IPH had nonsignificant elevations in risk for CVD (RR = 1.54) and all-cause (RR = 1.27) mortality. Cancer mortality was not increased in those with IFG, IPH, ADA-new diabetes, or known diabetes compared to those with NFG. CONCLUSIONS: Among American Indians 45 to 74 years of age, IPH is associated with nonsignificant elevations in total and CVD mortality. The magnitude of mortality risk associated with IPH is intermediate between diabetes and IFG. Because those with IPH are at high risk for diabetes, American Indians with IPH should be targeted for diabetes prevention. © 2003 Elsevier Science Inc. All rights reserved
TAA "Hawdon"
No full textVH-AES 'Hawdon' Douglas C-47-DL Trans Australian Airlines aircraft.Truran, Howard S.Date:195
Effects of hydroxyurea treatment on cerebral oxygenation in adult patients with sickle cell disease: An open-label pilot study
No full textBackground: In patients with sickle cell disease (SCD), cerebral oxygen saturation (rSO2) has been reported to be below normal and to increase after red blood cell transfusion. Objective: This study was designed to determine the effects of long-term and short-term hydroxyurea (HU) treatment on cerebral oxygenation in patients with SCD. Methods: This open-label pilot study was conducted at the Department of Anesthesiology and the Center for Sickle Cell Disease, College of Medicine, Howard University, Washington, DC. Adult African American outpatients with SCD and hemoglobin (Hb) genotype HbSS (homozygous sickle Hb) who were receiving long-term (\u3e6 months) HU treatment (15-30 mg/kg · d PO) or who had never received this treatment (control group) were enrolled. Patients in the treated and control groups were matched for age, sex, race, and Hb genotype. Cerebral oximetry (near-infrared spectroscopy) was performed to determine rSO2 index. In a separate analysis to determine the effects of short-term HU treatment on cerebral oxygenation, hospitalized patients with SCD and vaso-occlusive crisis (VOC)receiving long-term therapy with HU were enrolled. We performed cerebral and pulse (fingernail) oximetry to determine rSO 2index and arterial oxygen saturation (SpO2) after the administration of a single oral dose of HU (500-mg tablet) alone and againafter dosing concomitantly with inhaled oxygen. Results: The study enrolled 11 patients in the HU group (6 women, 5 men; mean [SD] age, 37 [8] years) and 20 controls (8 women, 12 men; mean [SD] age, 35 [6] years). Mean (SD) rSO2 index was significantly increased (but still low) in patients receiving long-term HU treatment compared with controls (46.1% [6.6%] vs 41.2% [7.6%]; P\u3c 0.025). Hb concentration (9.6 [1.4] g/dL vs 8.5 [1.2] g/dL; P\u3c 0.027), hematocrit (28% [3%] vs 24% [4%]; P \u3c 0.028), and mean corpuscular volume (102% [7%] vs 89% [8%]; P \u3c 0.027) also were significantly higher in the HU group compared with controls. In 8 patients with SCD and VOC (6 men, 2 women; mean [SD] age, 28 [5] years), single-dose HU, either alone or in combination with inhaled oxygen, did not significantly affect cerebral oxygenation, and SpO2 failed to correlate with rSO2 index in these patients. Conclusions: The results of this open-label pilot study in patients with SCD suggest that the low cerebral oxygenation in these patients is significantly improved but not normalized with long-term HU treatment. A single dose of HU, either alone or in combination with inhaled oxygen, did not appear to influence cerebral oxygenation in patients with VOC. Copyright © 2005 Excerpta Medica, Inc
T.A.A.
No full textVH-AES "Hawdon" Douglas C-47-DL, Trans Australian Airlines aircraft.Truran, Howard S.Date:195
Deoxygenated sickle hemoglobin. Modulation of its solubility by 2,3-diphosphoglycerate and other allosteric polyanions
No full textThe effects of 2,3-diphosphoglycerate (DPG) and other allosteric polyanions of the phosphate or sulfate ester class (inositol hexaphosphate (IHP), ATP, pyridoxamine-5\u27-phosphate (PMP), and inositol hexasulfate (IHS)) on the solubility of deoxyhemoglobin S, and the oxygen affinity of Hb A were evaluated. Their effects on the saturation concentration (c(sat)) indicated promotion of gelation in each case, according to the following order of molar effectiveness: IHP \u3e IHS \u3e DPG \u3e ATP \u3e\u3e PMP. Four polybasic carboxylic acids (benzenetricarboxylate (trimesic acid), benzenetetracarboxylate (BTC), benzenepentacarboxylate (BPC), and benzenehexacarboxylate (BHC)) were evaluated as well. Their order of molar effectiveness was: BHC \u3e BPC \u3e BTC \u3e\u3e trimesic acid. Both classes of polyanions influenced oxygen affinity in the same order as solubility. Overall, a good correlation existed between the negative charges of these nine allosteric polyanions at neutral pH and their effects on solubility and oxygen affinity. Because of its possible role in the pathophysiology of sickle cell disease, the effect of DPG on c(sat) was examined over the pH range 6.5-7.6. While a decrease in c(sat) was observed for DPG-saturated deoxyhemoglobin S throughout this range, the decrement observed in the physiological pH range (1.8 g/dl) was somewhat lower than that below neutral pH (3.0 g/dl); in either case the sickling tendency of SS red cells would be enhanced. Inasmuch as the intracellular concentration of DPG in sickle cell anemia may be elevated as much as 2-fold, maneuvers aimed at its reduction could be therapeutically beneficial
Effect of Hydroxyurea on Mortality and Morbidity in Adult Sickle Cell Anemia: Risks and Benefits Up to 9 Years of Treatment
No full textContext: Hydroxyurea increases levels of fetal hemoglobin (HbF) and decreases morbidity from vaso-occlusive complications in patients with sickle cell anemia (SCA). High HbF levels reduce morbidity and mortality. Objective: To determine whether hydroxyurea attenuates mortality in patients with SCA. Design: Long-term observational follow-up study of mortality in patients with SCA who originally participated in the randomized, double-blind, placebo-controlled Multicenter Study of Hydroxyurea in Sickle Cell Anemia (MSH), conducted in 1992-1995, to determine if hydroxyurea reduces vaso-occlusive events. In the MSH Patients\u27 Follow-up, conducted in 1996-2001, patients could continue, stop, or start hydroxyurea. Data were collected during the trial and in the follow-up period. Setting: Inpatients and outpatients in 21 sickle cell referral centers in the United States and Canada. Patients: Two-hundred ninety-nine adult patients with frequent painful episodes enrolled in the follow-up. Follow-up data through May 2001 were complete for 233 patients. Intervention: In the MSH, patients were randomly assigned to receive hydroxyurea (n=152) or placebo (n=147). Main Outcome Measures: Mortality, HbF levels, painful episodes, acute chest syndrome, and blood cell counts, The randomized trial was not designed to detect specified differences in mortality. Results: Seventy-five of the original 299 patients died, 28% from pulmonary disease. Patients with reticulocyte counts less than 250000/mm3 and hemoglobin levels lower than 9 g/dL had increased mortality (P=.002). Cumulative mortality at 9 years was 28% when HbF levels were lower than 0.5 g/ dL after the trial was completed compared with 15% when HbF levels were 0.5 g/ dL or higher (P=.03). Individuals who had acute chest syndrome during the trial had 32% mortality compared with 18% of individuals without acute chest syndrome (P=.02). Patients with 3 or more painful episodes per year during the trial had 27% mortality compared with 17% of patients with less frequent episodes (P=.06). Taking hydroxyurea was associated with a 40% reduction in mortality (P=.04) in this observational follow-up with self-selected treatment. There were 3 cases of cancer, 1 fatal. Conclusions: Adult patients taking hydroxyurea for frequent painful sickle cell episodes appear to have reduced mortality after 9 of years follow-up. Survival was related to HbF levels and frequency of vaso-occlusive events. Whether indications for hydroxyurea treatment should be expanded is unknown
2,3-Diphosphoglycerate and intracellular pH as interdependent determinants of the physiologic solubility of deoxyhemoglobin S
No full textWe have established that 2,3-diphosphoglycerate (2,3-DPG) content and intracellular pH exert separate, but interdependent, effects on the equilibrium solubility (c(sat)) of deoxyhemoglobin S (deoxy-Hb S) that act in concert to modulate intraerythrocytic polymer formation. In a nonphysiologic c(sat) assay system, a steep dependence of c(sat) on pH in the physiologic range 7.0 to 7.6 was shown for both stripped (Hb) and DPG-saturated deoxy-Hb S (Hb-DPG). The solubility-pH profile for Hb under near-physiologic buffer conditions also showed that c(sat) increased steeply in the same pH range (6.8 to 7.6). The effect of 2,3-DPG on c(sat) under near-physiologic conditions was evaluated separately. At pH 7.20, the pH of the human red blood cell, c(sat) values for Hb and Hb-DPG were 19.56 ± 0.14 and 17.95 ± 0.45 g/dL, respectively, indicating that the solubility of Hb-DPG is lower than that of Hb by 8.2% ± 2.3%. Thus, binding of 2.3-DPG in the β-cleft promotes the polymerization of deoxy-Hb S, the ultimate determinant of cell sickling. Furthermore, because of the abnormal Bohr effect of sickle blood (approximately double that of normal blood), the intracellular pH of deoxygenated sickle erythrocytes should be ~0.28 pH unit higher than that of oxygenated cells (ie, 7.41 v 7.13). At the higher pH, the corresponding c(sat) for Hb-DPG is 20.22 g/dL, which is the best estimate of the intrinsic solubility of T-state Hb S under conditions that approximate closely those of Ph, temperature, ionic strength, and 2,3-DPG saturation in the fully desaturated sickle erythrocyte
Clinical Characteristics and Predictors of Mortality in Minority Patients Hospitalized with COVID-19 Infection
No full textObjectives: To identify the early mortality predictors in minority patients hospitalized with coronavirus disease 2019 (COVID-19). Design: Demographics, presenting characteristics, admission laboratory data, ICU admission, and mortality data were collected from 200 consecutively hospitalized patients with COVID-19. Results: The mean (SD) age was 58.9 (15.1) years, 121(60.5%) were men, 143 (71.5%) were African Americans, and 33 (16.5%) were Latino. Common presenting symptoms were cough 130 (65.0%), shortness of breath 129 (64.5%), and fever 121 (60.5%). One or more comorbid illness occurred in 171 (85.5%) and common comorbidities were hypertension (130 (65.2%)), diabetes (100 (50.0%)) and chronic kidney disease (60 (30.0%)). Of the 200 patients, 71 (35.5%) were treated in the ICU, 47 (24.2%) received mechanical ventilation, 45 (22.5%) died, and 155(77.5%) patients discharged home alive. The non-survivors were significantly older and had elevated markers of inflammation, coagulation, and acute organ damage on presentation. Age ≥ 65 years (odds ratio (OR), 3.78; 95% CI, 1.74–8.22; P =.001), lactate dehydrogenase level \u3e 400 IU/L (OR, 9.1; 95% CI, 2.97–28.1; p \u3c 0.001), C-reactive protein \u3e 20 mg/dl (OR, 5.56; 95%CI, 1.84–16.8; p \u3c 0.001), ferritin \u3e 2000 ng/ml (OR, 5.42; 95%CI, 1.63–17.9; p = 0.006), creatinine kinase \u3e 1000 iu/l (OR, 3.57; 95% CI, 1.23 10.3; p = 0.019), procalcitonin \u3e 2.5 ng/ml (OR, 4.21; 95% CI, 1.47–12.0; p = 0.007), D-dimer level \u3e 3.0 μg/ml (OR,10.9; 95% CI, 3.33–36.2; p = \u3c 0.001), creatinine \u3e 2 mg/dl (OR, 4.5; 95% CI, 1.29–15.8; P = 0.018) at admission were associated independently with increases risk of in-hospital mortality. Conclusion: Patients of advanced age that present with elevated biomarkers of inflammation, coagulation, and end-organ damage were at higher risk of mortality
Preoperative Albumin, Transferrin, and Total Lymphocyte Count as Risk Markers for Postoperative Complications After Total Joint Arthroplasty: A Systematic Review
No full textINTRODUCTION: The purpose of this systematic review is to identify whether poor nutrition, as defined by the more commonly used markers of low albumin, low transferrin, or low total lymphocyte count (TLC), leads to more postoperative complications. We hypothesized that it may be possible to identify the levels of these laboratory values at which point total joint arthroplasty (TJA) may be ill advised. To this end, we analyzed the available literature regarding links between these three variables on postoperative complications after TJA. METHODS: This systematic review was done in two parts: (1) In the first part, we reviewed the most commonly used malnutrition marker, albumin. (2) In the second part, we reviewed TLC and transferrin. We accessed PubMed, EMBASE, and Cochrane Library using relevant keywords to this study. The biostatistics were visualized using a random-effects forest plot. We compared data from all articles with sufficient data on patients with complications (ie, cases) and patients without complications (ie, noncases) among the two groups, malnourished and normal nutrition, from albumin, transferrin, and TLC data. RESULTS: A meta-analysis of seven large-scale articles detailing the complications of albumin led to an all-cause relative risk increase of 1.93 when operating with hypoalbuminemia. This means that in the studies detailed enough to incorporate in this pooled analysis, operating on elective TJAs with low albumin is associated with a 93% increase in all measured complications. In the largest studies, analysis of transferrin levels for the most common complications revealed a relative risk increase of 2.52 when operating on patients with low transferrin levels. There were not enough subjects to do a biostatistical analysis in articles using TLC as the definition of malnutrition. CONCLUSION: The focus is on the trends rather than absolutes. As shown in Table 1, whether the albumin cutoff for albumin was 3.0 g/dL, 3.5 g/dL, or 3.9 g/dL, the trend remains the same. Because low albumin before TJAs tends to increase complications, it is recommended to incorporate albumin levels in preoperative workups. Many patients with hip and knee arthritis undergo months of conservative management (eg, physical therapy and corticosteroid injections) before considering surgery, and it would be wise to optimize their nutritional status in this period to minimize the risk of perioperative complications. The physician should use these data to provide informed consent of the increased risk to patients planning to undergo TJAs with elevated malnutrition markers. Because this research is retrospective in nature, albumin should be studied prospectively in hypoalbuminemic and normoalbuminemic patients and their postoperative outcomes should be measured. Regarding transferrin and TLC, future research should help elucidate their predictive value and determine the value of preoperatively optimizing them and their effect in mitigating postoperative complications
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