Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0020672 (hypothermia)
 17,327 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Analysis of blood product use after cardiac operations reveals that a few patients (< or = 20%) consume the majority of blood products (> 80%). The risk factors that predispose a minority of patients to excessive blood use include patient-related factors, transfusion practices, drug-related causes, and procedure-related factors. Multivariate studies suggest that patient age and red blood cell volume are independent patient-related variables that predict excessive blood product transfusion after cardiac procedures. Other factors include preoperative aspirin ingestion, type of operation, over- or underutilization of heparin during cardiopulmonary bypass, failure to correct hypothermia after cardiopulmonary bypass, and physician overtransfusion. A survey of the currently available blood conservation techniques reveals 5 that stand out as reliable methods: 1) high-dose aprotinin therapy, 2) preoperative erythropoietin therapy when time permits adequate dosage before operation, 3) hemodilution by harvest of whole blood immediately before cardiopulmonary bypass, 4) autologous predonation of blood, and 5) salvage of oxygenator blood after cardiopulmonary bypass. Other methods, such as the use of epsilon-aminocaproic acid or desmopressin, cell saving devices, reinfusion of shed mediastinal blood, and hemofiltration have been reported to be less reliable and may even be harmful in some high-risk patients. Consideration of the available data allows formulation of a 4-pronged plan for limiting excessive blood transfusion after surgery: 1) recognize the causes of excessive transfusion, including the importance of red blood cell volume, type of procedure being performed, preoperative aspirin ingestion, etc.; 2) establish a quality management program, including a survey of transfusion practices that emphasizes physician education and availability of real-time laboratory testing to guide transfusion therapy; 3) adopt a multimodal approach using institution-proven techniques; and 4) continually reassess blood product use and analyze the cost-benefits of blood conservation interventions.
 ...
PMID:Limiting excessive postoperative blood transfusion after cardiac procedures. A review. 758 Mar 59

Bleeding remains a complication of certain complex surgical procedures, particularly those cardiac operations associated with long bypass times and profound hypothermia. Clinical and novel experimental strategies to reduce bleeding and the need for blood and blood-product transfusions are the focus of this review. Preoperative assessment of the patient will identify drug-induced, acquired, or inherited coagulation defects that may contribute to this problem. The main attention is directed to the perioperative period, and broad areas discussed include the preoperative use of erythropoietin to increase red blood cell mass, autologous donation either preoperatively or before bypass, autotransfusion/hemofiltration, and acceptance of relative anemia both during the operation and into the postoperative period. A further, often overlooked, management strategy in treating major coagulopathies is the consideration of the cost and half-lives of the coagulation factors in individual blood components. Prevention of bleeding has become possible both by manipulation of the control of coagulation and inflammatory processes and by the introduction of pharmacologic agents such as aprotinin. Aprotinin is widely used and has proven efficacy in the management of excess bleeding. It is a serine protease inhibitor and has several possible mechanisms of action, including inhibition of the plasma enzyme systems activated by contact with the foreign surface of the bypass circuit and preservation of platelet function. Safety issues include the possibility of hypersensitivity and anaphylactic reaction on a second exposure. Concerns that aprotinin may induce a prothrombotic or coagulant state have no basis in theory or any good evidence in the current literature. A recent study specifically sought to identify the presence of disseminated microvascular platelet-fibrin thrombi present at autopsy in patients who had received aprotinin therapy. The study concluded that diffuse platelet-fibrin thrombi were not a direct complication of aprotinin therapy. Finally, modern molecular biology has led to the recent development of an inhibitor for factor IXa that competitively replaced IXa in the intrinsic complex and blocked the conversion of factor X to factor Xa. This compound is under investigation in animal studies. These have so far shown efficacy in reducing blood loss after bypass in comparison with standard heparin anticoagulation.
 ...
PMID:Management of bleeding complications in redo cardiac operations. 956 96

A 20-year-old Jehovah's witness patient experienced a femur fracture, with a section of the femoral artery and vein. On admission, haemoglobin concentration was 5.6 g.dL-1 and haematocrit 17%. Because of aponevrotomy, blood losses persisted. As the patient refused blood transfusion, recombinant human erythropoietin and parenteral iron were administered, associated with mild hypothermia, sedation and mechanical ventilation. After 21 days, the haemoglobin concentration increased to 10.9 g.dL-1 and haematocrit to 33% Recombinant human erythropoietin and parenteral iron may provide an alternative safe and effective therapy in life-threatening anaemia when blood transfusions are not accepted by the patient.
 ...
PMID:[Treatment of post-traumatic acute anemia by recombinant human erythropoietin in Jehovah's Witnesses]. 963 94

Currently, intravenous recombinant tissue plasminogen activator is the only US Food and Drug Administration-approved therapy for acute ischemic stroke. Although efficacious, its usefulness is limited, mainly because of the very limited time window for its administration. Neuroprotective treatments are therapies that block the cellular, biochemical, and metabolic elaboration of injury during or after exposure to ischemia, and have a potential role in ameliorating brain injury in patients with acute ischemic stroke. More than 50 neuroprotective agents have reached randomized human clinical trials in focal ischemic stroke, but none has been unequivocally proven efficacious, despite successful preceding animal studies. The failed neuroprotective trials of the past have greatly increased understanding of the fundamental biology of ischemic brain injury and have laid a strong foundation for future advance. Moreover, the recent favorable results of human clinical trials of hypothermia in human cardiac arrest and global brain ischemia have validated the general concept of neuroprotection for ischemic brain injury. Recent innovations in strategies of preclinical drug development and clinical trial design that rectify past defects hold great promise for neuroprotective investigation, including novel approaches to accelerating time to initiation of experimental treatment, use of outcome measures sensitive to treatment effects, and trial testing of combination therapies rather than single agents alone. Although no neuroprotective agent is of proven benefit for focal ischemic stroke, several currently available interventions have shown promising results in preliminary trials and may be considered for cautious, off-label use in acute stroke, including hypothermia, magnesium sulfate, citicoline, albumin, and erythropoietin. Overall, the prospects for safe and effective neuroprotective therapies to improve stroke outcome remain promising.
 ...
PMID:Potential Role of Neuroprotective Agents in the Treatment of Patients with Acute Ischemic Stroke. 1289 99

Currently, intravenous recombinant tissue plasminogen activator is the only US Food and Drug Administration-approved therapy for acute ischemic stroke. Although efficacious, its usefulness is limited, mainly because of the very limited time window for its administration. Neuroprotective treatments are therapies that block the cellular, biochemical, and metabolic elaboration of injury during or after exposure to ischemia, and have a potential role in ameliorating brain injury in patients with acute ischemic stroke. More than 50 neuroprotective agents have reached randomized human clinical trials in focal ischemic stroke, but none have been unequivocally proven efficacious, despite successful preceding animal studies. The failed neuroprotective trials of the past have greatly increased understanding of the fundamental biology of ischemic brain injury and have laid a strong foundation for future advance. Moreover, the recent favorable results of human clinical trials of hypothermia in human cardiac arrest and global brain ischemia have validated the general concept of neuroprotection for ischemic brain injury. Recent innovations in strategies of preclinical drug development and clinical trial design that rectify past defects hold great promise for neuroprotective investigation, including novel approaches to accelerating time to initiation of experimental treatment, use of outcome measures sensitive to treatment effects, and trial testing of combination therapies rather than single agents alone. Although no neuroprotective agent is of proven benefit for focal ischemic stroke, several currently available interventions have shown promising results in preliminary trials and may be considered for cautious, off-label use in acute stroke, including hypothermia, magnesium sulfate, citicoline, albumin, and erythropoietin. Overall, the prospects for safe and effective neuroprotective therapies to improve stroke outcome remain promising.
 ...
PMID:Potential Role of Neuroprotective Agents in the Treatment of Patients with Acute Ischemic Stroke. 1457 21

Dietary dehydroepiandrosterone (DHEA) inhibits the proliferation of syngeneic bone marrow cells (BMC) infused into lethally irradiated mice. Potential mechanisms for suppression of hematopoiesis were evaluated and the findings were as follows: (i) depletion of NK, T, B or macrophage cells failed to reverse suppression by DHEA; (ii) stem cell stimulation by erythropoietin, growth hormone, interleukin-2, Friend leukemia virus, or cyclophosphamide failed to reverse suppression; (iii) supplementation of fatty acids, mevalonate, or deoxyribonucleotides, which are dependent upon glucose-6-phosphate dehydrogenase function, did not enhance BMC growth in mice fed DHEA; (iv) DHEA downstream metabolites 4-androstenedione and 17beta-estradiol, as well as the synthetic steroid, 16alpha-chloroepiandrosterone (but not testosterone or 5-androstene-3beta,17beta-diol), also inhibited BMC growth. Tamoxifen antagonized the effects of 17beta-estradiol but not DHEA; (v) dietary DHEA causes hypothermia, but housing of DHEA-fed mice at 34 degrees C to maintain normal body temperature did not reverse suppression; (vi) DHEA leads to a decrease in food intake in rodents. Pair-feeding control diet to mice fed DHEA mimicked the effects of dietary DHEA; (vii) adrenalectomy and orchiectomy decrease the levels of stress and sex hormones, respectively. Neither procedure affected the ability of food restriction or DHEA feeding to inhibit hematopoiesis; (viii) growth of GR-3 NM pre-B leukemia cells in unirradiated mice was also suppressed by DHEA or food restriction. We conclude that DHEA, by reducing food intake in mice, inhibits bone marrow and leukemia cell growth. The precise mechanism(s) by which reduced food intake per se inhibits hematopoiesis is not known, but may involve an increased rate of cellular apoptosis.
 ...
PMID:Dietary dehydroepiandrosterone inhibits bone marrow and leukemia cell transplants: role of food restriction. 1468 46

Neuroprotection for patients with intracranial aneurysms encompasses the preservation of brain cells endangered by a limited blood and oxygen supply due to aneurysm rupture, clipping or coiling, as well as vasospasm. A large variety of prophylactic and therapeutic neuroprotective strategies have been proposed, but success in human disease is quite limited. Topics of this chapter are the pathophysiology and treatment options of aneurysms, as well as promising neuroprotective strategies in further developmental stages: both physiologically based (hyperoxygenation, hypothermia, avoidance of hyperthermia and hyperglycaemia, hypertension, haemodilution and hypervolaemia) and pharmacologically based (antifibrinolytic drugs, calcium antagonists, anaesthetics, magnesium, erythropoietin and others). New concepts are ischaemic preconditioning, growth factors, and gene therapy. Each strategy is rated on underlying evidence, and research agendas are mentioned.
 ...
PMID:Strategies of neuroprotection for intracranial aneurysms. 1546 May 48

Delayed cerebral ischemia as a result of cerebral vasospasm is the most common cause of death and disability after aneurysmal subarachnoid hemorrhage (SAH). It leads to death or permanent neurologic deficits in over 17-40% of SAH patients. The initial and main symptom of cerebral vasospasm is diffuse headache and may be accompanied with a slight increase in discomfort from neck stiffness and fever. The clinical diagnosis of cerebral vasospasm is made when the patient experiences an altered level of consciousness or a new focal neurologic deficit. There has been a great progress in identifying the patients at risk, putative mechanisms, and possible treatment options for cerebral vasospasm. However, the problem is by no means solved, mainly due to a limited understanding of the pathologic mechanisms of this complex disease. The iatrogenic factors that can increase the risk of cerebral vasospasm include prolongation of the subarachnoid clot by antifibrinolytic drugs, hypotension, inappropriate treatment of hyponatremia, hypovolemia, hyperthermia and increased intracranial pressure. Nimodipine has been shown to improve neurologic outcome and decrease the incidence of cerebral vasospasm. Triple H therapy is a treatment designed to augment cerebral blood flow for patient with cerebral vasospasm. Hypervolemic hypertension is induced with intravenous volume expansion with crystalloid or colloid to increase cardiac output and raise blood pressure. However, small randomized trials showed no clear benefit. Recently, balloon and chemical angioplasty with superselective intra-arterial injection of vasodilators has emerged as the primary intervention for treating medically refractory ischemia from cerebral vasospasm and in many centers is being used as a first-line treatment or even prophylactically. In addition, promising new treatments for cerebral vasospasm or its ischemic complications include magnesium sulfate, fasudil hydrochloride, tirilazad mesylate, erythropoietin, and induced hypothermia; however, all still need further clinical trials. Newly recognized mediators of cerebral vasospasm after SAH include endothelium-derived mediators, vascular smooth-muscle-derived mediators, proinflammatory mediators involved in blood-brain barrier disruption, cytokines and adhesion molecules, stress-induced gene activation, and platelet-derived growth factors. Moreover, observations in the laboratory have, in many circumstances, matched those of reported small series. Larger, prospective, randomized trials are needed to verify several hypotheses of molecular pathophysiology and clinical treatment regimens.
 ...
PMID:Treatment of cerebral vasospasm after subarachnoid hemorrhage--a review. 1567 31

Acute spinal cord injury (ASCI) occurs as a result of physical disruption of spinal cord axons through the epicenter of injury leading to deficits in motor, sensory, and autonomic function. This is a debilitating neurological disorder common in young adults that often requires life-long therapy and rehabilitative care, placing a significant burden on our healthcare system. While no cure exists, research has identified various pharmacological compounds that specifically antagonize primary and secondary mechanisms contributing to the etiology of ASCI. Several compounds including methylprednisolone (MPSS), GM-1 ganglio-side, thyrotropin releasing hormone (TRH), nimodipine, and gacyclidine have been tested in prospective randomized clinical trials of ASCI. MPSS and GM-1 ganglioside have shown evidence of modest benefits. Clearly trials of improved neuroprotective agents are required. Promising potential therapies for ASCI include riluzole, minocycline, erythropoietin, and the fusogen polyethylene glycol, as well as mild hypothermia.
 ...
PMID:Current status of clinical trials for acute spinal cord injury. 1599 12

Circulating erythropoietin (EPO) is mainly produced in the kidneys, depending on blood oxygen level. The present study investigated the postmortem serum EPO levels with regard to the cause of death and survival time. Serial medicolegal autopsy cases of postmortem time within 48 h (n = 536) were examined. Serum EPO levels were within the clinical reference range in most cases. Uremic patients with medical administration of an EPO agent (n = 11) showed a markedly high level (140-4,850 mU/ml; median, 1,798 mU/ml). Otherwise, an elevation in serum EPO level (>30 mU/ml) was mainly seen in protracted deaths due to blunt injury and fire fatality, depending on the survival time (r = 0.69, p < 0.0001, and r = 0.45, p < 0.0001, respectively), and in subacute deaths from gastrointestinal bleeding and infectious diseases. However, mildly to moderately elevated serum EPO levels were sporadically found in acute deaths due to mechanical asphyxiation, fire fatality, and acute ischemic heart disease, and in fatal hypothermia cases, especially for elderly subjects. Protracted deaths due to mechanical asphyxiation and ischemic heart disease did not show any survival time-dependent increase in serum EPO level (p > 0.05). EPO was immunohistochemically detected in the tubular epithelia and interstitial cells, showing no evident difference among the causes of death, independent of survival time or serum level. These findings suggest that serum EPO can be used as a marker for investigating anemia and/or hypoxia as a consequence of fatal insult in subacute or prolonged deaths, or a predisposition to traumatic deaths or fatal heart attacks in acute deaths.
 ...
PMID:Postmortem serum erythropoietin levels in establishing the cause of death and survival time at medicolegal autopsy. 1868 67


1 2 3 4 5 6 Next >>