A Czechoslovakian teenager with Hb E-β∘-thalassemia [IVS-I-1 (G → A)] complicated by the presence of an α-globin gene triplication

Summary We have examined the molecular basis of three inherited hemoglobin (Hb) disorders present in a Czechoslovakian girl with a severe, transfusion-dependent, hemolytic anemia. She is heterozygous for Hb E (on a genetic background specific for Czechoslovakian families), heterozygous for the -thalassemia (thal) allele IVS-I-1 (G A), and heterozygous for an -globin gene triplication. The combination of these three undesirable traits results in a severe chain imbalance that is the basis of the serious hemolytic disorder observed in this teenager.This study was supported in part by USPHS Research Grant HLB-41544. This is contribution 1282 from the Department of Cell and Molecular Biology at the Medical College of Georgia in Augusta     

Efficacy and safety of rupatadine in Japanese adult and adolescent patients with chronic spontaneous urticaria: A double-blind,randomized, multicenter,placebo-controlled clinical trial

Background

Rupatadine, a novel nonsedating second-generation H1-antihistamine with antiplatelet-activating factor activity, has been used in the treatment of allergic rhinitis and urticaria in European countries since 2003. However, its efficacy and safety in Japanese patients with chronic spontaneous urticaria (CSU) are unknown.

COVID-19 e Injúria Miocárdica em UTI Brasileira: Alta Incidência e Maior Risco de Mortalidade Intra-Hospitalar

BackgroundThe incidence of myocardial injury (MI) in patients with COVID-19 in Brazil and the prognostic impact of MI have not been elucidated.ObjectivesTo describe the incidence of MI in patients with COVID-19 in the intensive care unit (ICU) and to identify variables associated with its occurrence. The secondary objective was to assess high-sensitivity troponin I as a predictor of in-hospital mortality.MethodsRetrospective, observational study conducted between March and April 2020 with cases of confirmed COVID-19 admitted to the ICU. Numerical variables were compared by using Student t test or Mann-Whitney U test. The chi-square test was used for categorical variables. Multivariate analysis was performed with variables associated with MI and p<0.2 to determine predictors of MI. The ROC curve was used to determine the troponin value capable of predicting higher in-hospital mortality. Survival functions were estimated by use of the Kaplan-Meier method from the cut-off point indicated in the ROC curve.ResultsThis study assessed 61 patients (63.9% of the male sex, mean age of 66.1±15.5 years). Myocardial injury was present in 36% of the patients. Systemic arterial hypertension (HAS) [OR 1.198; 95%CI: 2.246-37.665] and body mass index (BMI) [OR 1.143; 95%CI: 1.013-1.289] were independent risk predictors. High-sensitivity troponin I >48.3 ng/mL, which was determined in the ROC curve, predicts higher in-hospital mortality [AUC 0.786; p<0.05]. Survival in the group with high-sensitivity troponin I >48.3 ng/mL was lower than that in the group with values ≤48.3 ng/dL [20.3 x 43.5 days, respectively; p<0.05].ConclusionThere was a high incidence of MI in severe COVID-19 with impact on higher in-hospital mortality. The independent risk predictors of MI were SAH and BMI. (Arq Bras Cardiol. 2020; [online].ahead print, PP.0-0)     

Insulinotropic actions of intravenous glucagon-like peptide-1 (GLP-1) [7–36 amide] in the fasting state in healthy subjects

GLP-1 (7–36 amide) stimulates insulin and suppresses glucagon secretion in normal subjects and may, in pharmacological doses, normalize hyperglycaemia in type 2 diabetic patients. It is not known whether such pharmacological doses can actually lower blood glucose to hypoglycaemic levels. Therefore, in seven normal fasting subjects, GLP-1 (7–36 amide) was infused intravenously at 0.3, 0.9 and 2.7 pmol/kg per min for 30 min each. The plasma concentration of GLP-1 (7–36 amide) increased dose-dependently, but insulin secretion (insulin, C-peptide) was stimulated only marginally. Glucagon was slightly suppressed, and plasma glucose was reduced, but not into the hypoglycaemic range. In conclusion, when plasma glucose concentrations are in the normal fasting range, GLP-1 (7–36 amide) is not able to stimulate insulin secretion to a degree that causes hypoglycaemia. This should limit the risk of hypoglycaemic responses when GLP-1 (7–36 amide) is administered in pharmacological doses to reduce hyperglycaemia in type 2 diabetic patients.     

Reduction of creatine kinase and creatine kinase-MB indexes of infarct size by intravenous verapamil

In a prospective, controlled study, 29 patients were randomly allocated to receive intravenous verapamil, 5 to 10 mg/hour, for 2 days starting at a mean of 8 hours after the onset of myocardial infarction. Twenty-five patients received no specific treatment and served as control subjects. Left ventricular (LV) filling pressure in all patients was initially less than 15 mm Hg. Age, infarct localization and hemodynamic values on admission (Swan-Ganz catheter) were comparable in both groups. Maximal creatine kinase (CK) and creatine kinase-MB (CK-MB) values were markedly lower in the verapamil group than in the control group (CK 547 vs 703 U/liter, p less than 0.05; CK-MB 51 vs 68 U/liter, p less than 0.025), as was infarct weight (48 vs 65 g-Eq, p less than 0.03; CK-MB 31 vs 49 g-Eq, p less than 0.005). Arterial blood pressure was 10% lower in the verapamil group than in the control group. Systemic vascular resistance and LV filling pressure remained unchanged. Verapamil reduced myocardial infarction size by about 30% in patients without LV failure and the arterial pressure was reduced.     

Maternal and child health workforce profile and density in China since 1949: a systematic review

Background

Routine sources of information on the maternal and child health workforce in China are without clear definition and categorisation. The aim of the study was to systematically review all the evidence on China's maternal and child health workforce profile (ie, level of education, training, qualification, and professional title), and determine the density of the maternal and child health workforce.

HIV infection-associated immune activation occurs by two distinct pathways that differentially affect CD4 and CD8 T cells

HIV infection is characterized by a brisk immune activation that plays an important role in the CD4 depletion and immune dysfunction of patients with AIDS. The mechanism underlying this activation is poorly understood. In the current study, we tested the hypothesis that this activation is the net product of two distinct pathways: the inflammatory response to HIV infection and the homeostatic response to CD4 T cell depletion. Using ex vivo BrdU incorporation of PBMCs from 284 patients with different stages of HIV infection, we found that CD4 proliferation was better predicted by the combination of CD4 depletion and HIV viral load (R² = 0.375, P < 0.001) than by either parameter alone (CD4 T cell counts, R² = 0.202, P < 0.001; HIV viremia, R² = 0.302, P < 0.001). Interestingly, CD8 T cell proliferation could be predicted by HIV RNA levels alone (R² = 0.334, P < 0.001) and this predictive value increased only slightly (R² = 0.346, P < 0.001) when CD4 T cell depletion was taken into account. Consistent with the hypothesis that CD4 T cell proliferation is driven by IL-7 as a homeostatic response to CD4 T cell depletion, levels of phosphorylated STAT-5 were found to be elevated in naive subsets of CD4 and CD8 T cells from patients with HIV infection and in the central memory subset of CD4 T cells. Taken together these data demonstrate that at least two different pathways lead to immune activation of T cells in patients with HIV infection and these pathways differentially influence CD4 and CD8 T cell subsets.     

Mast cells derived from human induced pluripotent stem cells are useful for allergen tests

Background

Several methods have been developed to detect allergen-specific IgE in sera. The passive IgE sensitization assay using human IgE receptor-expressing rat cell line RBL-2H3 is a powerful tool to detect biologically active allergen-specific IgE in serum samples. However, one disadvantage is that RBL-2H3 cells are vulnerable to high concentrations of human sera. Only a few human cultured cell lines are easily applicable to the passive IgE sensitization assay. However, the use of human induced pluripotent stem cells (iPSCs) to generate human mast cells (MCs) has not yet been reported.

Assessment of the American Heart Association's “Life's simple 7” score in French-speaking adults from Québec

Background and aimsThe “Life's Simple 7” (LS7) metrics were developed by the American Heart Association (AHA) to assess and promote cardiovascular health in the American population. The purpose of this study was to assess the overall cardiovascular health of French-speaking adults from the Province of Quebec using the LS7 score.Methods and resultsA total of 777 age and sex-representative participants of five different administrative regions in the Province of Quebec (387 men and 390 women; mean age ± SEM: 41.9 ± 0.1 years) were included in these analyses. Metrics of the LS7 score (smoking, physical activity, diet, body mass index, blood pressure, fasting total cholesterol and blood glucose) were analysed to generate a final score ranging from 0 to 7.Only 0.5% of participants met all criteria for ideal cardiovascular health. The diet metric showed the lowest prevalence of “ideal” scores (4.8%) whereas not smoking was the metric with the highest prevalence (88.1%). Women had a higher LS7 score than men, while age and education level (negative and positive association, respectively; p < 0.0001) were also associated with the LS7 score.ConclusionConsistent with studies conducted among other populations, very few French-speaking adults from the Province of Quebec achieve an ideal cardiovascular health. These data indicate that further public health efforts aimed at promoting the LS7 metrics, focusing primarily on diet, are urgently needed. Specific groups, including older adults and those with lower levels of education, should be targeted when developing cardiovascular health promotion interventions.     

Surgical technique and results of intrapancreatic bile duct resection for hilar malignancy (with video)

Background

Hilar malignancy can occasionally be associated with high grade dysplasia (HGD) adjacent to invasive malignancy. For patients with HGD extending into the intrapancreatic bile duct, the authors adopted intrapancreatic bile duct resection (IP-BDR). The aims of this study were to compare the incidence of clinically relevant postoperative pancreatic fistula (CR-POPF), distal R0 resection and local recurrence within the distal bile duct remnant for patients undergoing extrahepatic bile duct resection without pancreaticoduodenectomy (with or without IP-BDR).