losartan-potassium and Respiratory-Insufficiency

In forensic pathology, while classical morphology remains a core procedure to investigate deaths, a spectrum of ancillary procedures has been developed and incorporated to detail the pathology. Among them, postmortem biochemistry is important to investigate the systemic pathophysiological changes involved in the dying process that cannot be detected by morphology. In addition, recent advances in molecular biology have provided a procedure to investigate genetic bases of diseases that might present with sudden death, which is called 'molecular autopsy'. Meanwhile, the practical application of RNA analyses to postmortem investigation has not been accepted due to rapid decay after death; however, recent experimental and practical studies using real-time reverse transcription-PCR have suggested that the relative quantification of mRNA transcripts can be applied in molecular pathology for postmortem investigation of deaths, which may be called 'advanced molecular autopsy'. In a broad sense, forensic molecular pathology implies applied medical sciences to investigate the genetic basis of diseases, and the pathophysiology of diseases and traumas leading to death at a biological molecular level in the context of forensic pathology. The possible applications include analyses of local pathology, including tissue injury, ischemia/hypoxia and inflammation at the site of insult or specific tissue damage from intoxication, systemic responses to violence or environmental hazards, disorders due to intoxication, and systemic pathophysiology of fatal process involving major life-support organs. A review of previous studies suggests that systematic postmortem quantitative analysis of mRNA transcripts can be established from multi-faceted aspects of molecular biology and incorporated into death investigations in forensic pathology, to support and reinforce morphological evidence.

Topics: Aging; Animals; Asphyxia; Biomarkers; Erythropoietin; Forensic Pathology; Gene Expression; Glucose Transporter Type 1; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Hypoxia-Ischemia, Brain; Immunohistochemistry; Postmortem Changes; Pulmonary Surfactant-Associated Proteins; Respiratory Insufficiency; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Shock; Specimen Handling; Vascular Endothelial Growth Factor A; Violence; Wounds and Injuries

Anemia occurs in virtually all critically ill patients receiving long-term mechanical ventilation and has been associated with increased mortality and poor outcomes. Allogeneic RBC transfusions are routinely administered to critically ill anemic patients, especially during lengthy stays in ICUs or in long-term acute care facilities. Although RBC transfusions are a physiologically rational approach to raising hemoglobin levels, they may increase the risk of complications and have been associated with higher mortality in critically ill patients. Treatment with epoetin alfa, an erythropoiesis-stimulating agent, as a means of reducing transfusion requirements has been studied in the critically ill and in patients receiving long-term mechanical ventilation. Promising results have been reported, including a potential survival benefit, although larger and more definitive studies are needed in order to establish whether raising hemoglobin levels affects clinical outcomes in patients receiving mechanical ventilation.

Topics: Anemia; Blood Banks; Comorbidity; Critical Illness; Epoetin Alfa; Erythrocyte Transfusion; Erythropoietin; Hematinics; Hemoglobins; Humans; Recombinant Proteins; Respiration, Artificial; Respiratory Insufficiency; Time Factors; Ventilator Weaning

Healthy individuals are able to tolerate profound, short-term decreases in hemoglobin levels and oxygen saturation without serious consequences, but critically ill patients in respiratory failure lack the necessary reserve capacity to preserve tissue oxygenation. The development of progressive anemia in ICU patients has led to much interest and debate about transfusion practices, yet optimal hemoglobin levels and how they should be achieved remain unclear. Animal and human studies regarding critical oxygen delivery provide the rationale for optimizing hemoglobin levels and supporting cardiovascular function during respiratory failure. Theoretically, the oxygen-carrying benefit of RBCs should hasten recovery from respiratory failure, and transfusions would therefore be expected to shorten the duration of mechanical ventilation. However, evidence to the contrary has been reported. Controversies related to transfusions and their inability to improve outcomes suggest that further research regarding transfusion alternatives is needed, especially in anemic patients with respiratory failure.

Topics: Anemia; Animals; Cell Hypoxia; Comorbidity; Critical Illness; Erythrocyte Transfusion; Erythropoietin; Humans; Oxygen; Oxygen Consumption; Respiration, Artificial; Respiratory Insufficiency; Risk Factors

Critically ill children with bronchiolitis often require red blood cell transfusions. Anemia normally results in increased circulating erythropoietin concentrations; however, critical illness has been associated with a blunted erythropoietin response. Treatment with erythropoietin decreases the need for red blood cell transfusion in several disease states. We hypothesized that critically ill children with bronchiolitis and anemia would have a circulating erythropoietin deficiency and that treatment with exogenous erythropoietin would increase reticulocyte count and hematocrit and reduce red blood cell transfusion requirements.. Randomized, blinded, placebo-controlled trial.. Children's hospital.. Critically ill children with bronchiolitis, anemia, and respiratory failure. Anemia was defined as a hematocrit >2 SD below normal for age.. Patients were randomized to one of two groups. In the erythropoietin group, patients received daily intravenous erythropoietin. In the control group, patients received daily intravenous placebo. Both groups were treated with elemental iron.. Blood for complete blood count, reticulocyte count, and ferritin and erythropoietin concentration was obtained at admission and discharge. Red blood cell transfusions were administered to patients with a persistent oxygen requirement and a hematocrit of <25%. Outcome variables included number of red blood cell transfusions, change in reticulocyte count, ferritin values, and circulating erythropoietin values between groups. Forty-four patients completed the study (mean 3.1 +/- 0.6 months), with a baseline hematocrit of 27.6 +/- 0.5%, ventilator days of 8.2 +/- 0.6, and pediatric intensive care unit length of stay of 9.8 +/- 0.6 days. There were no significant baseline demographic differences between the control and erythropoietin groups. Ten of 22 (45%) children in the erythropoietin group required red blood cell transfusion compared with 11 of 22 (50%) in the control group (p = nonsignificant). The increase in reticulocyte count was greater in the erythropoietin group compared with the control group (2.1 +/- 0.3% to 4.7 +/- 0.7%, p = .003 vs. 2.1 +/- 0.3% to 2.7 +/- 0.5%, p = nonsignificant).. Despite a favorable reticulocyte and circulating erythropoietin response, red blood cell transfusion requirements were not significantly diminished by erythropoietin treatment in children with bronchiolitis and respiratory failure. Erythropoietin cannot be routinely recommended for this patient population.

Topics: Anemia; Blood Transfusion; Bronchiolitis; Chi-Square Distribution; Critical Illness; Erythropoietin; Female; Humans; Infant; Male; Respiratory Insufficiency; Treatment Outcome

Erythropoietin (EPO) controls red cell production. Hypoxaemia, reduced blood oxygen-carrying capacity and increased affinity of haemoglobin (Hb) for oxygen are the primary stimuli for EPO secretion. The effect of hyperoxaemia (arterial oxygen tension (Pa,O2) > 13.3 kPa) on EPO secretion has not been thoroughly studied and is not fully understood. The primary purpose of this study was to evaluate EPO production in patients with acute respiratory failure as well as to determine the effect of hyperoxaemia on EPO secretion in patients with and without anaemia. A prospective clinical study was carried out in a 14-bed general (medical and surgical) intensive care unit in a university hospital. Twenty-one patients with acute or acute on chronic respiratory failure, requiring mechanical ventilation, were included in this study. The patients were divided into two groups; group I comprised patients who developed anaemia, and group II patients who did not. EPO levels and haematological parameters were measured in venous blood under three oxygenation conditions: hypoxaemia, hyperoxaemia and normoxaemia. All patients exhibited high EPO levels during hypoxaemia (mean value 108.7 +/- 27 mU.mL-1 (+/- SD)). During hyperoxaemia, EPO levels decreased in both groups (mean value 21.6 +/- 15.2 mU.mL-1 in group I, 36.8 +/- 19 mU.mL-1 in group II). During normoxaemia, EPO levels increased again in group I patients, but in group II patients EPO production remained stable. In conclusion, hyperoxaemia inhibits erythropoietin secretion in spite of anaemia and low arterial oxygen tension. Hyperoxaemia may be a contributing factor to anaemia in intensive care unit patients under oxygen therapy.

Topics: Adult; Aged; Analysis of Variance; Anemia; Blood Gas Analysis; Erythropoietin; Female; Humans; Hyperoxia; Linear Models; Lung Diseases, Obstructive; Male; Middle Aged; Monitoring, Physiologic; Prospective Studies; Pulmonary Gas Exchange; Respiration, Artificial; Respiratory Insufficiency; Sensitivity and Specificity

Haemolytic anaemia is a well-recognised but rare complication of heart-valve prostheses. The authors report a case of an 80-year-old woman with severe haemolytic anaemia previously treated with valvuloplasty and annuloplasty without rings. To our knowledge, no cases of haemolysis have been described with this type of surgery.

Topics: Aged, 80 and over; Anemia, Hemolytic; Atrial Fibrillation; Diagnosis, Differential; Echocardiography; Echocardiography, Transesophageal; Erythrocyte Indices; Erythrocyte Transfusion; Erythropoietin; Female; Hematocrit; Hemoglobinometry; Humans; Mitral Valve Annuloplasty; Mitral Valve Insufficiency; Postoperative Complications; Psychotic Disorders; Recombinant Proteins; Respiratory Insufficiency; Suture Techniques; Ultrasonography, Doppler, Color

In order to determine the initial values and dynamic changes of EPO (erythropoietin) after therapy, 57 consecutively presenting, typical COPD (chronic obstructive pulmonary disease) patients with chronic hypoxia and acute exacerbated serum EPO levels were serially measured. Initial mean EPO levels were slightly above the normal range (41.4 +/- 83.5 units/l), but in the majority of patients the initial EPO levels were significantly reduced. Following the correction of hypoxaemia, mean EPO levels decreased to 14.1 +/- 16.9 units/l (P=0.0093). However, not all COPD patients showed this pattern; in an important subset of patients (36.8%), who had initially lower EPO levels and lower erythrocyte count, EPO levels were significantly increased (by more than 60%; P=0.0028) on the second day of treatment, despite correction of the hypoxaemia. This finding was unexpected and paradoxical when compared with physiological studies addressing the same issue. The data presented support previous reports of variable EPO levels in severely hypoxic COPD patients and suggest that the haematological response is already hampered at an early stage, at the level of EPO production, and much less likely at later steps in the haemopoietic response by failure to respond to elevated EPO levels. Our data are consistent with recent discoveries that the O2 sensing and regulation of EPO production is a complex process in which multiple factors, including cytokines and therapeutic agents, play a role by enhancing or inhibiting the response. We believe that further studies on this clinical condition are complementary to basic physiological research and may help to elucidate the role of cytokines and other individual factors in complex clinical hypoxic situations.

Topics: Acute Disease; Aged; Carbon Dioxide; Erythropoietin; Female; Hemoglobins; Humans; Hypoxia; Male; Middle Aged; Oxygen; Partial Pressure; Prospective Studies; Pulmonary Disease, Chronic Obstructive; Respiratory Insufficiency

Topics: Anemia; Bronchiolitis; Critical Illness; Erythropoietin; Humans; Infant; Respiratory Insufficiency

Topics: Anemia; Arthritis, Rheumatoid; Coma; Critical Care; Erythrocyte Transfusion; Erythropoietin; Female; Hemoglobins; Humans; Middle Aged; Recombinant Proteins; Respiratory Insufficiency

It was revealed during examination of 91 patients with chronic nonspecific lung diseases for the blood titers of erythropoietin, erythrocytic chalones, erythrocyte hemolysis products and medium molecules that in the stage I respiratory failure, there were no material changes in the titres of erythrocyte hemolysis products, erythropoietin and medium molecules, whereas the titer of erythrocytic chalones appeared to be high. Stage III of the disease was also marked by no changes in the titer of erythrocyte hemolysis products. However, the titers of erythropoietin and medium molecules rose whereas the titer of erythrocytic chalones was reduced. In the stage II respiratory failure, the above enumerated factors of humoral regulation of erythropoiesis appeared similar to those in stage I. These data evidence that different compensatory reactions to hypoxia associated with chronic respiratory failure are implicated at the molecular, cellular and systemic levels. The up-to-date treatment and diagnostic process is not feasible, provided these reactions are not taken into consideration.

Topics: Adaptation, Physiological; Adult; Aged; Bronchitis; Chronic Disease; Erythrocytes; Erythropoiesis; Erythropoietin; Female; Growth Inhibitors; Humans; Male; Middle Aged; Neurotransmitter Agents; Respiratory Insufficiency

Topics: Aged; Arteries; Blood Gas Analysis; Erythrocytes; Erythropoietin; Heart Failure; Hematocrit; Humans; Hypoxia; Leukocyte Count; Lung Diseases; Middle Aged; Pulmonary Embolism; Pulmonary Fibrosis; Respiratory Insufficiency; Reticulocytes