Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01185 (vasopressin)
 23,126 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The congenital combined deficiency of Factor V and Factor VIII, a rare bleeding disorder, was identified in a 25-year-old woman. She was admitted to our hospital with a complaint of genital bleeding. Her prothrombin time and activated partial thromboplastin time were prolonged. She had low levels of Factor V coagulant activity (F. V:C) 14%, and Factor VIII coagulant activity (F. VIII:C), 12%, and normal levels of von Willebrand factor antigen (vWF:Ag), ristocetin cofactor (Rcof) and Protein C antigen. Her Protein C inhibitor level was slightly low. Her Rcof, vWF:Ag and F. VIII:C were elevated following administration of 1-deamino-8-D-arginine-vasopressin (DDAVP), but her F. V:C remained unchanged. Four years later, her F. VIII:C rose to 70% during the course of her pregnancy, but her F. V:C value remained low. It was expected that the vaginal delivery would be possible at the termination of pregnancy. Premature rupture of the membranes and an anomaly of rotation appeared in the course of delivery, however, and cesarean section was accomplished without excess bleeding under replacement therapy with Factor VIII concentrates. These findings suggested that DDAVP and Factor VIII concentrates were useful for management of her delivery. However the mechanisms of the rise of plasma F. VIII:C during pregnancy in a case with congenital combined deficiency of Factor V and Factor VIII are unclear.
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PMID:[Management of cesarean section under replacement therapy with factor VIII concentrates in a pregnant case with congenital combined deficiency of factor V and factor VIII]. 194 44

We describe two families with heterozygous plasminogen deficiency. In the first the patient was a 27 year-old female who suffered an acute episode of ischemic cerebrovascular disease affecting the left temporal lobe documented by arteriographic, gammagraphic and CAT studies. She had no family history of thrombotic conditions. In the other family the propositus was a 31 year-old man with spontaneous deep venous thrombosis in the left leg. His father was also symptomatic, with a history of recurrent thrombotic complications after predisposing factors, that included multiple venous thrombosis and a pulmonary embolism. Laboratory data showed normal hemostasis test results. Antigenic and functional levels of protein C, protein S and antithrombin III were within normal limits. The only abnormality found was decreased plasminogen activity in plasma; antigenic and functional levels were reduced to about half-normal levels. In both cases crossed immunoelectrophoresis revealed a normal migration pattern of plasminogen. Thus, we conclude that our patients were carriers of congenital hypoplasminogenemia or familial type I plasminogen deficiency, due to decreased synthesis. We also reported on fibrinolytic response to infusion of DDAVP, a synthetic analogue of the antidiuretic hormone. Fibrinolytic activity was normal in basal conditions as well as in response to DDAVP infusion.
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PMID:[Plasminogen deficiencies in 2 Spanish families. Response to the administration of DDAVP]. 236 94

Severe sepsis and septic shock are relatively common problems in intensive care. The mortality in septic shock is still high, and the main causes of death are multiple organ failure and refractory hypotension. Impaired tissue perfusion due to hypovolemia, disturbed vasoregulation and myocardial dysfunction contribute to the multiple organ dysfunction. Treatment of hemodynamics in septic shock consists of appropriate fluid therapy guided by invasive monitoring combined with vasoactive drugs aiming to correct hypotension and inappropriately low cardiac output. The drug of choice for low vascular resistance is norepinephrine, while insufficient myocardial contractility is commonly treated with dobutamine. The use of norepinephrine seems to be associated with better prognosis as compared to results from the use of dopamine or epinephrine. In septic shock, vasopressin levels are low, and therefore, vasopressin has been advocated as a vasopressor. Its effectiveness and safety have not yet been documented, and so far it is regarded as an experimental treatment Recent data support the use of corticosteroid, at least in some of the patients with septic shock. Also, activated protein C, a drug with anti-inflammatory and antithrombotic properties, decreases mortality in patients with septic shock.
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PMID:Treatment of impaired perfusion in septic shock. 1255 99

Despite advances in supportive care, septic shock remains a major cause of morbidity and mortality. With the identification of the systemic inflammatory response as a major component in the pathogenesis of the septic shock syndrome, much of the recent work has focused on modulating this response. This includes antiendotoxin therapies in patients with Gram-negative sepsis, and therapies to modulate the pro-inflammatory mediators produced in response to infection, such as TNF-alpha, platelet-activating factor and complement. High-flow haemofiltration has the potential advantage of clearing both endotoxin and pro-inflammatory mediators. Antithrombotic strategies have been investigated and have yielded the first major success in the treatment of sepsis with activated protein C. Nitric oxide produces the cardiovascular features of sepsis and investigators have looked at both reducing its production and mopping up the excess. Attempts to reduce apoptosis have been a new focus in the treatment of sepsis. There have also been recent developments in supportive care suggesting a role for vasopressin and replacement corticosteroid therapy.
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PMID:Recent developments in the treatment of sepsis. 1255 10

Many advances have improved the care of critically ill patients, but only a few have been through the use of pharmaceutical agents. Recently, the US Food and Drug Administration (FDA) approved drotrecogin alfa (activated), or recombinant human activated protein C, for the treatment of patients with a high risk of death from severe sepsis. Drotrecogin alfa (activated) has antiinflammatory, antithrombotic and fibrinolytic properties. When given as a continuous intravenous infusion, recombinant human activated protein C decreases absolute mortality of severely septic patients by 6.1%, resulting in a 19.4% relative reduction in mortality. The absolute reduction in mortality increases to 13% if the population treated is restricted to patients with an APACHE II score greater than 24, as suggested by the FDA. The most frequent and serious side effect is bleeding. Severe bleeds increased from 2% in patients given placebo to 3.5% in patients receiving drotrecogin alfa (activated). The risk of bleeding was only increased during the actual infusion time of the drug, and the bleeding risk returned to placebo levels 24 hours after the infusion was discontinued. Patients treated in the intensive care unit frequently develop anemia, usually severe enough to require at least one transfusion of red blood cells. With the recent discovery of the harmful effects of allogeneic red blood cell transfusions and the increasing shortage of available red blood cell products, emphasis has been placed on minimizing transfusions. Patients who receive exogenous recombinant human erythropoietin maintain higher hemoglobin levels, in spite of requiring fewer transfusions during their stay in the intensive care unit. Recombinant human erythropoietin appears to be effective whether it is given as 300 units/kg of body weight subcutaneously every other day or as 40,000 units subcutaneously every week. Differences in hemoglobin values were not apparent until at least one week of therapy, but they continued to diverge after that initial week. Furthermore, the incidence of adverse events was similar to that of patients receiving placebo and there was no difference in mortality, suggesting that avoidance of blood transfusions did not translate into increased survival. Thus, recombinant human erythropoietin appears to be both safe and effective in treating the anemia found in critically ill patients, but it is less clear that such treatment is cost effective, especially in the higher dose regimens. Hypotension in patients with septic shock is often difficult to correct. Despite enormous dosages of catecholamines, many of these patients continue to have inadequate blood pressures. Inadequate levels of vasopressin have been identified in patients with septic shock, as well as in other patients with hypotension secondary to refractory vasodilatation. Vasopressin is a peptide hormone secreted from the posterior pituitary in response to hyperosmolality, hypovolemia or hypotension. Levels of vasopressin initially rise in patients with septic shock, but as hypotension persists, vasopressin levels fall below normal. Administration of exogenous vasopressin in physiologic dosages significantly increases blood pressure in patients with shock associated with sepsis and other vasodilatory states. This rise in blood pressure is often significant enough that endogenous catecholamines can be decreased and frequently discontinued entirely. Early withdrawal of the vasopressin replacement infusion results in recurrent hypotension. Unfortunately, randomized, blinded, placebo-controlled trials showing improvement in long-term outcomes such as mortality and length of stay are still lacking.
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PMID:New additions to the intensive care armamentarium. 1504 37

This article will review for bedside clinicians how to manage septic ALI.ARDS and shock to use the principles of EBM to evaluate the various therapeutic approaches for them. Low tidal volume ventilation (6 mg/dl/kg) is recommended for ALI.ARDS, but application of a minimum amount of PEEP, recruitment maneuvers with high PEEP and prone position are needed to confirm any benefit. NO inahalation, ECMO/ECCR, and glucocorticoid therapies don' t recommended for ALI.ARDS. Sivelestat Na, is available for ALI.ARDS in Japan, is needed further prospective randomized studies. Aggressive infusion of crystalloid and colloid is recommended for septic shock, but blood transfusion and bicarbonate administration are not recommended. Vasopressors are recommended for septic shock: preference for norepinephrine and cautious use of vasopressin. Stress-dose of steroid and activated protein C for severe sepsis are useful if shock don't recover by aggressive fluid infusion and vasopressors' administration.
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PMID:[Respiratory and cadiovascular management of septic ALI-ARDS and shock]. 1559

This manuscript gives a review about important studies addressing problems in intensive care medicine that have been published in journals focussing on critical care medicine and surgery in 2004. Only clinical studies are included in this review, mostly metaanalyses, randomized controlled trials and a few important or interesting observational studies. In addition to describing major results a critical appraisal of each study is undertaken, which, however, is neither comprehensive nor complete. It is merely intentioned to address some important aspects for the reader that should be accounted for while interpreting the results. It is important to note that among the large number of excellent studies there is a substantial proportion of trials with negative results that significantly add to our knowledge. Some of the topics addressed in this manuscript include vasopressin as an alternative to epinephrine during cardiopulmonary resuscitation, a specification concerning the use of activated protein C in patients with sepsis, the role of steroids in the treatment of sepsis and traumatic brain injury, the epidemiology of ALI and ARDS, the role of sedation protocols, weaning protocols and the timing of tracheostomy for the duration of mechanical ventilation, the potential benefit of catheters with antimicrobial coating to reduce catheter-related sepsis, and the benefit of enteral nutrition as compared to the parenteral application.
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PMID:[Intensive care medicine -- update 2004]. 1596 70

Sepsis causes microvascular dysfunction. Increased heterogeneity of capillary blood flow results in local tissue hypoxia, which can cause local tissue inflammation, impaired oxygen extraction, and, ultimately, organ dysfunction. Microvascular dysfunction is clinically relevant because it is a marker for mortality: it improves rapidly in survivors of sepsis but fails to improve in nonsurvivors. This, along with the fact that resuscitation of mean arterial pressure and cardiac output alone fails to improve microvascular function, means that microvascular resuscitation is therefore a therapeutic goal. In animal studies of sepsis, volume resuscitation improves microvascular permeability and tissue oxygenation, and leads to improved organ function, including a reduction in myocardial dysfunction. Microvascular resuscitation strategies include hemodynamic resuscitation using the linked combination of volume resuscitation, judicious vasopressor use, and inotropes and vasodilators. Alternative vasoactive agents, such as vasopressin, may improve microcirculatory function to a greater degree than conventional vasopressors. Successful modulation of inflammation has a positive impact on endothelial function. Finally, targeted treatment of the endothelium, using activated protein C, also improves microvascular function and ultimately increases survival. Thus, attention must be paid to the microcirculation in patients with sepsis, and therapeutic strategies should be employed to resuscitate the microcirculation in order to avoid organ dysfunction and to reduce mortality.
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PMID:Microvascular resuscitation as a therapeutic goal in severe sepsis. 1616 71

The severe impairment of the microcirculation plays a substantial role in the pathogenesis of severe sepsis and septic shock, and leads to multiple organ failure and death. Therapeutic strategies to resuscitate the microcirculatory blood flow and to improve the functional capillar density are therefore essential to surmount the microcirculatory pathology and to avoid tissue hypoxia. Based on reasonable scientific evidence, early fluid resuscitation directed by defined haemodynamic and metabolic goals (EGDT) as well as the application of activated protein C (rhAPC) according to the guidelines could be recommended. Dobutamine is the first choice to improve cardiac output and to overcome myocardial depression in septic shock whereas phosphodiesterase-III-inhibitors and levosimendane are still experimental options. Furthermore selective inhibitors of iNOS, nitroglycerol, as well as vasopressin have to be investigated relating to their specific effects on the microcirculation and their influence on survival in seevere sepsis and septic shock.
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PMID:[Therapeutic options to improve the microcirculation in sepsis and septic shock]. 1727 78

Severely septic patients continue to experience excessive morbidity and mortality despite recent advances in critical care. Although significant resources have been invested in new treatments, almost all have failed to improve outcomes. An improved understanding of sepsis pathophysiology, including the complex interactions between inflammatory, coagulation, and fibrinolytic systems, has accelerated the development of novel treatments. Recombinant human activated protein C (rhAPC), or drotrecogin alfa (activated) (DAA), is currently the only US Food and Drug Administration (FDA)-approved medicine for the treatment of severe sepsis, and only in patients with a high risk of death. This review will discuss the treatment of severe sepsis, focusing on recent discoveries and unresolved questions about DAA's optimal use. Increasing pharmacological experience has generated enthusiasm for investigating medicines already approved for other indications as treatments for severe sepsis. Replacement doses of hydrocortisone and vasopressin may reduce mortality and improve hypotension, respectively, in a subgroup of patients with catecholamine-refractory septic shock. In addition to discussing these new indications, this review will detail the provocative preliminary data from four promising treatments, including two novel modalities: antagonizing high mobility group box protein and inhibiting tissue factor (TF). Observational data from the uncontrolled administration of heparin or statins in septic patients will also be reviewed.
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PMID:Treatment of severe sepsis: where next? Current and future treatment approaches after the introduction of drotrecogin alfa. 1731 65


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