51 research outputs found
In Vitro Erythropoiesis at Different pO2 Induces Adaptations That Are Independent of Prior Systemic Exposure to Hypoxia
Hypoxia is associated with increased erythropoietin (EPO) release to drive erythropoiesis.
At high altitude, EPO levels first increase and then decrease, although erythropoiesis remains elevated
at a stable level. The roles of hypoxia and related EPO adjustments are not fully understood, which
has contributed to the formulation of the theory of neocytolysis. We aimed to evaluate the role
of oxygen exclusively on erythropoiesis, comparing in vitro erythroid differentiation performed
at atmospheric oxygen, a lower oxygen concentration (three percent oxygen) and with cultures of
erythroid precursors isolated from peripheral blood after a 19-day sojourn at high altitude (3450 m).
Results highlight an accelerated erythroid maturation at low oxygen and more concave morphology
of reticulocytes. No differences in deformability were observed in the formed reticulocytes in the
tested conditions. Moreover, hematopoietic stem and progenitor cells isolated from blood affected by
hypoxia at high altitude did not result in different erythroid development, suggesting no retention of a
high-altitude signature but rather an immediate adaptation to oxygen concentration. This adaptation
was observed during in vitro erythropoiesis at three percent oxygen by a significantly increased
glycolytic metabolic profile. These hypoxia-induced effects on in vitro erythropoiesis fail to provide
an intrinsic explanation of the concept of neocytolysis
In Vitro Erythropoiesis at Different pO2 Induces Adaptations That Are Independent of Prior Systemic Exposure to Hypoxia
Hypoxia is associated with increased erythropoietin (EPO) release to drive erythropoiesis. At high altitude, EPO levels first increase and then decrease, although erythropoiesis remains elevated at a stable level. The roles of hypoxia and related EPO adjustments are not fully understood, which has contributed to the formulation of the theory of neocytolysis. We aimed to evaluate the role of oxygen exclusively on erythropoiesis, comparing in vitro erythroid differentiation performed at atmospheric oxygen, a lower oxygen concentration (three percent oxygen) and with cultures of erythroid precursors isolated from peripheral blood after a 19-day sojourn at high altitude (3450 m). Results highlight an accelerated erythroid maturation at low oxygen and more concave morphology of reticulocytes. No differences in deformability were observed in the formed reticulocytes in the tested conditions. Moreover, hematopoietic stem and progenitor cells isolated from blood affected by hypoxia at high altitude did not result in different erythroid development, suggesting no retention of a high-altitude signature but rather an immediate adaptation to oxygen concentration. This adaptation was observed during in vitro erythropoiesis at three percent oxygen by a significantly increased glycolytic metabolic profile. These hypoxia-induced effects on in vitro erythropoiesis fail to provide an intrinsic explanation of the concept of neocytolysis
Routinely measuring symptom burden and health-related quality of life in dialysis patients: first results from the Dutch registry of patient-reported outcome measures
Background. The use of patient-reported outcome measures (PROMS) is becoming increasingly important in healthcare. However, incorporation of PROMS into routine nephrological care is challenging. This study describes the first experience with PROMS in Dutch routine dialysis care.Methods. A pilot study was conducted in dialysis patients in 16 centres. Patients were invited to complete PROMS at baseline and 3 and 6 months. PROMS consisted of the 12-item short-form and Dialysis Symptom Index to assess health-related quality of life (HRQoL) and symptom burden. Response rates, HRQoL and symptom burden scores were analysed. Qualitative research methods were used to gain insight into patients' views on using PROMS in clinical practice.Results. In total, 512 patients (36%) completed 908 PROMS (24%) across three time points. Response rates varied from 6 to 70% among centres. Mean scores for physical and mental HRQoL were 35.6 [standard deviation (SD) 10.2] and 47.7 (SD 10.6), respectively. Patients experienced on average 10.8 (SD 6.1) symptoms with a symptom burden score of 30.7 (SD 22.0). Only 1-3% of the variation in PROM scores can be explained by differences between centres. Patients perceived discussing their HRQoL and symptom scores as insightful and valuable. Individual feedback on results was considered crucial.Conclusions. The first results show low average response rates with high variability among centres. Dialysis patients experienced a high symptom burden and poor HRQoL. Using PROMs at the individual patient level is suitable and may improve patient-professional communication and shared decision making. Further research is needed to investigate how the collection and the use of PROMs can be successfully integrated into routine care to improve healthcare quality and outcomes.Clinical epidemiolog
An exploratory study of perinatal hair cortisol concentrations in mother–infant dyads with severe psychiatric disorders versus healthy controls
Background
Maternal psychopathology during pregnancy is associated with
negative outcomes in offspring. Increased placental transfer of
maternal cortisol may contribute to mediate this association.
Hair cortisol concentrations (HCCs) appear to be a good biomarker of long-term prenatal stress exposure. Little is known
about the associations between severe maternal psychopathology and perinatal infant HCCs.
Aims
We assessed HCCs in the perinatal period in mother–infant
dyads with and without severe psychiatric disorders.
Method
We examined group differences in HCCs of mother–infant dyads
(n = 18) subjected to severe maternal psychiatric disorders versus healthy control dyads (n = 27). We assessed the correlation
of HCCs between mother and infant within both groups, and the
association between current maternal symptoms and HCCs in
patient dyads.
Results
Median (interquartile range) and distribution of HCC differed in
patients compared with control mothers (U = 468.5, P = 0.03).
HCCs in infants of patients did not differ from control infants
(U = 250.0, P = 0.67). Subsequently, we found that HCCs within
healthy control dyads were correlated (n = 27, r 0.55 (0.14),
P = 0.003), but were not within patient dyads (n = 18, r 0.082
(0.13), P = 0.746). HCCs in infants of patients showed a positive
correlation with maternal symptoms (n = 16, r = 0.63 (0.06),
P = 0.008).
Conclusions
These preliminary findings suggest that infant HCC reflect perinatal stress exposure. In infants, these early differences could
influence lifetime hypothalamic–pituitary–adrenal axis functioning, which might be associated with increased susceptibility to
later disease
Serum proteomics reveals hemophagocytic lymphohistiocytosis-like phenotype in a subset of patients with multisystem inflammatory syndrome in children
Children with Multisystem Inflammatory Syndrome in Children (MIS-C) can present with thrombocytopenia, which is a key feature of hemophagocytic lymphohistiocytosis (HLH). We hypothesized that thrombocytopenic MIS-C patients have more features of HLH. Clinical characteristics and routine laboratory parameters were collected from 228 MIS-C patients, of whom 85 (37%) were thrombocytopenic. Thrombocytopenic patients had increased ferritin levels; reduced leukocyte subsets; and elevated levels of ASAT and ALAT. Soluble IL-2RA was higher in thrombocytopenic children than in non-thrombocytopenic children. T-cell activation, TNF-alpha and IFN-gamma signaling markers were inversely correlated with thrombocyte levels, consistent with a more pronounced cytokine storm syndrome. Thrombocytopenia was not associated with severity of MIS-C and no pathogenic variants were identified in HLH-related genes. This suggests that thrombocytopenia in MIS-C is not a feature of a more severe disease phenotype, but the consequence of a distinct hyperinflammatory immunopathological process in a subset of children.</p
Serum proteomics reveals hemophagocytic lymphohistiocytosis-like phenotype in a subset of patients with multisystem inflammatory syndrome in children
Children with Multisystem Inflammatory Syndrome in Children (MIS-C) can present with thrombocytopenia, which is a key feature of hemophagocytic lymphohistiocytosis (HLH). We hypothesized that thrombocytopenic MIS-C patients have more features of HLH. Clinical characteristics and routine laboratory parameters were collected from 228 MIS-C patients, of whom 85 (37%) were thrombocytopenic. Thrombocytopenic patients had increased ferritin levels; reduced leukocyte subsets; and elevated levels of ASAT and ALAT. Soluble IL-2RA was higher in thrombocytopenic children than in non-thrombocytopenic children. T-cell activation, TNF-alpha and IFN-gamma signaling markers were inversely correlated with thrombocyte levels, consistent with a more pronounced cytokine storm syndrome. Thrombocytopenia was not associated with severity of MIS-C and no pathogenic variants were identified in HLH-related genes. This suggests that thrombocytopenia in MIS-C is not a feature of a more severe disease phenotype, but the consequence of a distinct hyperinflammatory immunopathological process in a subset of children.</p
Four screening instruments for frailty in older patients with and without cancer: a diagnostic study
Geriatric screening tools are of limited value to predict decline in functional status and quality of life: results of a cohort study
Practical Recommendations for Long-term Management of Modifiable Risks in Kidney and Liver Transplant Recipients
Sirolimus and proteinuria in kidney transplantation
Contains fulltext :
140170.pdf (publisher's version ) (Open Access)19 mei 2015Promotores : Hoitsma, A.J., Wetzels, J.F.M
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