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151.
Vivian Phan Jared Hershenson Laura Caldarera Sandra K. Larkin Kari Wheeler Ana Lucia Cortez Robin Dulman Noravy Briere Angela Lewis Frans A. Kuypers Elizabeth Yang 《Pediatric blood & cancer》2023,70(8):e30423
Background
Individuals with sickle cell anemia (SCA) exhibit decreased exercise capacity. Anemia limits oxygen-carrying capacity and affects cardiopulmonary fitness. The drug voxelotor raises hemoglobin in SCA. We hypothesized that voxelotor improves exercise capacity in youths with SCA.Methods
In a single-center, open-label, single-arm, longitudinal interventional pilot study (NCT04581356), SCA patients aged 12 and older, stably maintained on hydroxyurea, were treated with 1500 mg voxelotor daily, and performed cardiopulmonary exercise testing before (CPET#1) and after voxelotor (CPET#2). A modified Bruce Protocol was performed on a motorized treadmill, and breath-by-breath gas exchange data were collected. Peak oxygen consumption (peak VO2), anaerobic threshold, O2 pulse, VE/VCO2 slope, and time exercised were compared for each participant. The primary endpoint was change in peak VO2. Hematologic parameters were measured before each CPET. Patient Global Impression of Change (PGIC) and Clinician Global Impression of Change (CGIC) surveys were collected.Results
Ten hemoglobin SS patients aged 12–24 completed the study. All demonstrated expected hemoglobin rise, with average +1.6 g/dL (p = .003) and P50 left shift of average −11 mmHg (p < .0001) with decreased oxygen off-loading at low pO2. The change in % predicted peak VO2 from CPET#1 to CPET#2 ranged from −12.8% to +11.3%, with significant improvement of more than 5% in one subject, more than 5% decrease in five subjects, and insignificant change of less than 5% in four subjects. All 10 CGIC and seven of 10 PGIC responses were positive.Conclusion
In a plot study of 10 youths with SCA, voxelotor treatment did not improve peak VO2 in 9 out of 10 patients. 相似文献152.
Fausto Biancari Juha Saarnio Ari Mennander Linda Hypén Paulina Salminen Kari Kuttila Mikael Victorzon Camilla Böckelman Enrico Tarantino Olivier Tiffet Vesa Koivukangas Jon Arne Søreide Asgaut Viste Luigi Bonavina Halla Vidarsdóttir Tomas Gudbjartsson 《World journal of surgery》2014,38(4):902-909
Background
Recent studies have suggested that stent-grafting may improve the treatment outcome of patients with esophageal perforation, but evidence on this is still lacking.Methods
Data on 194 patients who underwent conservative (43 patients), endoclip (4 patients) stent-grafting (63 patients) or surgical treatment (84 patients) for esophageal perforation were retrieved from nine medical centers.Results
In-hospital/30-day mortality was 17.5 %. Three-year survival was 67.1 %. Age, coronary artery disease, and esophageal malignancy were independent predictors of early mortality. Chi squared automatic interaction detection analysis showed that patients without coronary artery disease, without esophageal malignancy and younger than 70 years had the lowest early mortality (4.1 %). Surgery was associated with slightly lower early mortality (conservative 23.3, endoclips 25.0 %, stent-grafting 19.0 %, surgery 13.1 %; p = 0.499). One center reported a series of more than 20 patients treated with stent-grafting which achieved an early mortality of 7.7 % (2/26 patients). Stent-grafting was associated with better survival with salvaged esophagus (conservative 76.7 %, endoclips 75.0 %, stent-grafting 77.8 %, surgery 56.0 %; p = 0.019). Propensity score adjusted analysis showed that stent-grafting achieved similar early mortality (p = 0.946), but significantly higher survival with salvaged esophagus than with surgical treatment (p = 0.001, OR 0.253, 95 % CI 0.110–0.585). Primary surgical repair was associated with somewhat lower early mortality (14.6 vs. 19.0 %; p = 0.561) and better survival with salvaged esophagus (85.4 vs. 77.8 %; p = 0.337) than stent-grafting.Conclusions
Esophageal perforation was associated with a rather high mortality rate in this all-comers population. Stent-grafting failed to decrease operative mortality, but it improved survival with salvaged esophagus. The results of one of the centers indicate that increasing experience with this less invasive procedure may possibly improve the outcome of these patients. 相似文献153.
154.
Less invasive surfactant administration methods without laryngoscopy and endotracheal catheterization include delivery via laryngeal mask airway, pharyngeal instillation, and aerosolization. These less invasive techniques are promising and have several advantages over INSURE (Intubation-Surfactant-Extubation) and thin catheter techniques. The objective of this review is to discuss the requisites, techniques, short-term outcomes, and adverse events associated with these methods. 相似文献
155.
156.
Targeted deletion of histidine decarboxylase gene in mice increases bone formation and protects against ovariectomy-induced bone loss 总被引:7,自引:0,他引:7
Fitzpatrick LA Buzas E Gagne TJ Nagy A Horvath C Ferencz V Mester A Kari B Ruan M Falus A Barsony J 《Proceedings of the National Academy of Sciences of the United States of America》2003,100(10):6027-6032
Targeted disruption of the histidine decarboxylase gene (HDC(-/-)), the only histamine-synthesizing enzyme, led to a histamine-deficient mice characterized by undetectable tissue histamine levels, impaired gastric acid secretion, impaired passive cutaneous anaphylaxis, and decreased mast cell degranulation. We used this model to study the role of histamine in bone physiology. Compared with WT mice, HDC(-/-) mice receiving a histamine-free diet had increased bone mineral density, increased cortical bone thickness, higher rate of bone formation, and a marked decrease in osteoclasts. After ovariectomy, cortical and trabecular bone loss was reduced by 50% in HDC(-/-) mice compared with WT. Histamine deficiency protected the skeleton from osteoporosis directly, by inhibiting osteoclastogenesis, and indirectly, by increasing calcitriol synthesis. Quantitative RT-PCR showed elevated 25-hydroxyvitamin D-1alpha-hydroxylase and markedly decreased 25-hydroxyvitamin D-24-hydroxylase mRNA levels. Serum parameters confirming this indirect effect included elevated calcitriol, phosphorus, alkaline phosphatase, and receptor activator of NF-kappaB ligand concentrations, and suppressed parathyroid hormone concentrations in HDC(-/-) mice compared with WT mice. After ovariectomy, histamine-deficient mice were protected from bone loss by the combination of increased bone formation and reduced bone resorption. 相似文献
157.
Strategies for Mapping and Identifying Quantitative Trait Loci Specifying Behavioral Responses to Alcohol 总被引:3,自引:0,他引:3
Kari J. Buck 《Alcoholism, clinical and experimental research》1995,19(4):795-801
Most responses to alcohol in both humans and animals are heritable, and this genetic sensitivity to ethanol is determined by multiple genes. However, the number of genes, their identities, and just how they determine susceptibility to the actions of alcohol are unknown. Herein, we describe a multistage strategy for mapping quantitative trait loci (QTLs) using recombinant inbred strains and F2 mice. Precise mapping of the chromosome positions of these QTLs should increase our understanding of the genetic causes for individual differences in behavioral sensitivity to alcohol by (1) identifying genomic markers associated with sensitivity to alcohol, (2) allowing the genes specifying behavior to be cloned by position, and (3) elucidating "candidate" genes demonstrating linkage to markers associated with behavioral responses to alcohol. Syntenic conservation between the mouse and human genomes should facilitate the eventual mapping and cloning of human homologs of these QTLs. Ultimately, cloning of these genes may allow the development of gene therapies or other therapeutic interventions for management or prevention of alcoholism and alcohol abuse. 相似文献
158.
Huang P Kraja AT Tang W Hunt SC North KE Lewis CE Devereux RB de Simone G Arnett DK Rice T Rao DC 《Journal of hypertension》2008,26(7):1360-1366
BACKGROUND: Metabolic syndrome and its risk factors are predictors of cardiovascular events. Metabolic syndrome is also directly associated with echocardiographic phenotypes. METHODS: The current study is the first to investigate the factors associated with both metabolic syndrome risk factors and echocardiographic phenotypes and assess their heritability. Multivariate factor analysis was performed on 15 traits in 1393 African-Americans and 1133 whites, as well as stratified by type 2 diabetes mellitus status. RESULTS: Factor analysis with varimax rotation established four to five latent factors across ethnicities and diabetes mellitus stratifications. Among metabolic syndrome risk factors, blood pressure was the most highly correlated with cardiac traits. The factor domains, in the order of the proportion of variance explained, were 'left ventricle wall thickness', 'left ventricle geometry', 'blood pressure', 'BMI-insulin', and 'lipid-insulin'. Factor analysis without any rotation identified special (cross domain) metabolic syndrome-echocardiographic factors, 'blood pressure-left ventricle geometry' and 'blood pressure-left ventricle dimension-wall thickness' in whites. Fifty to 57% of the total original risk factor variance was explained by the latent factors. Heritability was highest for BMI-insulin (37-53%), lowest for 'blood pressure' factors (15-27%), and intermediate for metabolic syndrome-echocardiographic factors. CONCLUSION: These latent factors identified can be utilized as summary phenotypes in epidemiological, linkage, and association studies. 相似文献
159.
160.
Lindholm MG Aldershvile J Sundgreen C Jørgensen E Saunamäki K Boesgaard S 《European journal of heart failure》2003,5(1):73-79
BACKGROUND: Five to 10% of patients with acute myocardial infarction develop cardiogenic shock and the majority of these patients are expected to die within the first few weeks. In this study, we review our recent experience in the management of patients with cardiogenic shock complicating MI and examine the effect of early invasive revascularisation on mortality. METHODS: Thirty-six consecutive patients who developed cardiogenic shock less than 48 h after MI were retrospectively evaluated and divided into two treatment groups. One group received early invasive revascularisation (n=24) and the other group had no early invasive revascularisation, but received similar conventional intensive care medical treatment (n=12). RESULTS: Baseline characteristics and hemodynamic variables were similar in both groups. Apart from invasive revascularisation and the use of intra aortic balloon counterpulsation (IABP), treatment strategies did not differ between the two groups. Thirty-day mortality was 21% in the revascularised group of patients and 58% in the non-revascularised group (P<0.05). CONCLUSIONS: Our data support previous observations suggesting that an aggressive treatment strategy including early invasive revascularisation and IABP is associated with improved short and long-term survival in patients with cardiogenic shock. Since early revascularisation appears safe with a considerable treatment benefit, this approach must be considered in patients with short shock duration early after MI. 相似文献