Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: UMLS:C0038454 (stroke)
147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

For patients with acute respiratory distress syndrome (ARDS) the most important objective of mechanical ventilation is opening and keeping open the alveoli to achieve adequate oxygenation, without further damaging the lungs or negatively affecting the circulation. Alveolar recruitment is achieved by making use of positive end-expiratory pressure (PEEP). The best PEEP level is that with which the largest improvement in oxygen transport and lung compliance is achieved, without a decrease in the stroke volume of the left ventricle. In addition to the usual volume-controlled ventilation with PEEP, pressure-limited ventilation is also possible. In this a preselected pressure is never exceeded, whereas a maximum inspiratory airflow at the start of inspiration provides more opportunity for gaseous exchange. The oxygenation can possibly be further improved by increasing the inspiration-expiration ratio. As a result of the reduced expiratory period the alveoli which tend to collapse at the end of a normal expiration are kept open. Mechanical ventilation with a lower tidal volume decreases mortality. Ventilation in a prone position increases the end-expiratory lung volume and reduces the intrapulmonary shunt and the regional differences in the degree of ventilation. These factors possibly contribute to preventing ventilation-induced lung damage. Administration of natural surfactant during the ventilation of patients with ARDS seems to be a highly promising strategy; the clinical effectiveness still needs to be demonstrated.
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PMID:[Mechanical ventilation in acute respiratory distress syndrome (ARDS): lung protecting strategies for improved alveolar recruitment]. 1275 82

The sulfonamides constitute an important class of drugs, with several types of pharmacological agents possessing antibacterial, anticarbonic anhydrase, diuretic, hypoglycemic, and antithyroid activity among others. A large number of structurally novel sulfonamide derivatives have ultimately been reported to show substantial protease inhibitory properties. Of particular interest are some metalloprotease inhibitors belonging to this class, which by inhibiting several matrix metalloproteases (MMPs) show interesting antitumor properties. Some of these compounds are currently being evaluated in clinical trials. The large number of sulfonamide MMP inhibitors ultimately reported also lead to the design of effective tumor necrosis factor-alpha converting enzyme (TACE) inhibitors, potentially useful in the treatment of inflammatory states of various types. Since both MMPs and TACE contribute synergistically to the pathophysiology of many diseases, such as arthritis, bacterial meningitis, tumor invasion; the dual inhibition of these enzymes emerged as an interesting target for the drug design of anticancer/antiinflammatory drugs, and many such sulfonamide derivatives were recently reported. Human neutrophyl elastase (HNE) inhibitors of the sulfonamide type may also be useful in the treatment of inflammatory conditions, such as emphysema, cystic fibrosis, chronic bronchitis, ischemia reperfusion injury, and acute respiratory distress syndrome. Inhibition of some cysteine proteases, such as several caspase and cathepsin isozymes, may lead to the development of pharmacological agents effective for the management of several diseases, such as rheumatoid arthritis, inflammatory bowel disease, brain damage, and stroke. Another research line that progressed much in the last time regards different sulfonamides with remarkable antiviral activity. Some clinically used HIV protease inhibitors (such as amprenavir) possess sulfonamide moieties in their molecules, which are critical for the potency of these drugs, as shown by means of X-ray crystallography, whereas a very large number of other derivatives are constantly being synthesized and evaluated in order to obtain compounds with lower toxicity or augmented activity against viruses resistant to the such first generation drugs. Other viral proteases, such as those isolated from several types of herpes viruses may be inhibited by sulfonamide derivatives, leading thus to more effective classes of antiviral drugs.
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PMID:Protease inhibitors of the sulfonamide type: anticancer, antiinflammatory, and antiviral agents. 1278 86

Inducible nitric oxide synthase (iNOS) is implicated in the pathogenesis of acute respiratory distress syndrome (ARDS). ARDS treatment is frequently complicated by significant extrapulmonary comorbidity. This study was designed to clarify the role of iNOS in mediating extrapulmonary comorbidity in sheep after combined burn and smoke inhalation injuries using a potent and highly selective iNOS dimerization inhibitor, BBS-2. Twenty-two female sheep were operatively prepared. After 5 days of recovery, tracheostomy was performed under ketamine-halothane anesthesia. Sheep were given a 40% total body surface third-degree burns and insufflated with cotton smoke (48 breaths, <40 degrees C). Sheep were divided into four groups: noninjured and nontreated (sham group; n = 6), noninjured but treated with BBS-2 (sham/BBS-2 group; n = 4), injured but nontreated (control group, n = 6), and injured but treated with 100 microg.kg-1.h-1 BBS-2 (BBS-2 group; n = 6). Evaluation was in a laboratory intensive care unit setting for 48 h. The sham group had stable cardiopulmonary and systemic hemodynamics. Control animals showed multiple signs of morbidity. Decreased left ventricular stroke work index and stroke volume index with elevated left atrial pressure indicated myocardial depression. Systemic vascular leak was evidenced by robust hemoconcentration, decreased plasma oncotic pressure, and increased transvascular fluid flux into the lymphatic system. Finally, severely impaired renal function (urinary output) was associated with adverse net fluid balance. Treatment with BBS-2 prevented all these morbidities without adversely effecting cardiovascular hemodynamics such as cardiac index and mean arterial pressure. The results identify a major role for iNOS in mediating extrapulmonary comorbidity in a clinically relevant and severe trauma model and support the use of highly selective iNOS inhibitors as novel treatments in critical care medicine.
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PMID:Inducible nitric oxide synthase dimerization inhibitor prevents cardiovascular and renal morbidity in sheep with combined burn and smoke inhalation injury. 1291 29

Until recently, national coding and analysis of routine mortality statistics in most countries included only underlying cause of death. There were changes in the rules for selection and coding of underlying cause in England in 1984 and 1993. We report on trends in mortality rates in an English region from 1979 to 1998, comparing multiple-cause and underlying-cause coded rates, for individual diseases that were affected by coding changes. Among many others, these include pneumonia, venous thromboembolism, heart failure, respiratory distress syndrome, tuberculosis, diabetes, dementia, alcohol and drug abuse, epilepsy, multiple sclerosis, stroke, asthma, peptic ulcer, appendicitis, and cancers of the breast, colon and prostate. Comparisons over time of mortality rates based on underlying cause alone will be misleading when the time-period crosses years in which rules changed for selecting underlying cause.
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PMID:Trends in mortality rates comparing underlying-cause and multiple-cause coding in an English population 1979-1998. 1457 3

The risk of venous thromboembolism (VTE) in medical patients has been substantially underestimated and prophylaxis is used far less than it is in surgical patients, reflecting the scarcity of evidence supporting antithrombotic therapy in nonsurgical settings. Reports of the frequency of deep venous thrombosis (DVT) in general medical patients in the absence of prophylaxis vary from 10 to 26%, depending on the methods used for diagnosis of DVT and the patient population studied. The risk in specific groups may be higher and may exceed that reported in low- or moderate-risk surgical patients. Data from several studies show that DVT developed in approximately 55% of patients with stroke, 24% of patients with myocardial infarction, and, in general medical populations, congestive heart failure, respiratory distress and/or underlying chest infections appeared to increase the risk of VTE. The frequency of VTE in patients with congestive heart failure has been reported to be as high as 40%. In a study among patients in a medical intensive care unit, it was found that 33% had VTE, of which 48% were proximal leg thromboses. Many other medical conditions increase the risk of thromboembolic events. These include malignant disease, which is commonly associated with a hypercoagulable state; inflammatory conditions such as systemic lupus erythematosus and inflammatory bowel disease; coma; and nephrotic syndrome. Accurate risk assessment and prompt implementation of appropriate prophylaxis, selected on the basis of evidence from well-designed, controlled clinical trials, may reduce future morbidity and mortality due to VTE in medical patients.
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PMID:Venous thromboembolism in medical patients--the scope of the problem. 1473 Apr 74

Heat stroke (HS) is a serious and potentially life-threatening condition defined as a core body temperature >40.6 degrees C. Two forms of HS are recognized, classic heat stroke, usually occurring in very young or elderly persons, and exertional heat stroke, more common in physically active individuals. An elevated body temperature and neurologic dysfunction are necessary but not sufficient to diagnose HS. Associated clinical manifestations such as extreme fatigue; hot dry skin or heavy perspiration; nausea; vomiting; diarrhea; disorientation to person, place, or time; dizziness; uncoordinated movements; and reddened face are frequently observed. Potential complications related to severe HS are acute renal failure, disseminated intravascular coagulation, rhabdomyolysis, acute respiratory distress syndrome, acid-base disorders, and electrolyte disturbances. Long-term neurologic sequelae (varying degrees of irreversible brain injury) occur in approximately 20% of patients. The prognosis is optimal when HS is diagnosed early and management with cooling measures and fluid resuscitation and electrolyte replacement begins promptly. The prognosis is poorest when treatment is delayed >2 hours.
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PMID:Heat stroke: a comprehensive review. 1546 Oct 44

Cerebral paradoxical embolism has not until now been described as a cause of cryptogenic stroke in newborn infants. A male infant was born at 27 weeks 2 days' gestational age by emergency Caesarean section in a twin pregnancy because of intrauterine growth retardation and absence of diastolic flow in the twin. His birthweight was 950g (50th centile). Apgar scores were 7 and 8 at 1 and 5 minutes respectively. At 17 days of life he showed sudden respiratory distress and signs of encephalopathy. Presence of deep venous thrombosis, patent foramen ovale (PFO), and clinical progression suggested paradoxical embolism which were confirmed by neuroradiological findings. The high incidence of PFO and central venous catheter-related deep venous thrombosis in newborn infants suggest that paradoxical embolism is probably a more common complication than has been thought.
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PMID:Paradoxical embolism in a preterm infant. 1547 78

The Kunitz-type proteinase inhibitor, tissue factor pathway inhibitor (TFPI), is the only endogenous inhibitor of the tissue factor (TF)-mediated coagulation pathway that plays a dominant role in normal haemostasis. TFPI exerts its action by binding to factor Xa (FXa) forming a TFPI-FXa complex that then, in a second step, binds and effectively inhibits the TF-factor VIIa (FVIIa) complex. Both full-length TFPI and chemically modified forms (e.g., truncated, glycosylated or phosphorylated TFPI variants) exert various pharmacological effects. The anticoagulant and antiplatelet actions of TFPI, its potency in inhibiting thrombin and FXa generation, as well as its favourable antithrombotic effectiveness seen in different animal models of venous and arterial thrombosis make this inhibitor a promising agent that could be potentially useful in several clinical indications. The inhibitory action of TFPI is accelerated by heparin. Heparin, as well as low molecular weight heparin (LMWH) derivatives, release TFPI from the vascular endothelium, an effect which seems to contribute mainly to the antithrombotic effectiveness of these drugs. The clinical relevance of TFPI is still undefined. Based on the beneficial actions in animal studies, as well as on the results obtained in first clinical investigations, TFPI is expected to be effective in the treatment of various diseases, such as disseminated intravascular coagulation, sepsis, coronary syndromes, stroke and acute respiratory distress syndrome (ARD). Further clinical trials should clarify the role of TFPI and more importantly define its potential usefulness as a prophylactic and/or therapeutic agent.
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PMID:Recombinant TFPI and variants: potential implications in the treatment of cardiovascular disorders. 1599 20

Here, we review the biochemical and molecular properties of thymosin beta(4) (Tbeta(4)), the major actin-sequestering molecule in eukaryotic cells, and its key role in dermal- and corneal-wound healing. Tbeta(4) has several, novel, potential clinical applications in the repair and remodeling of ulcerated tissues and solid organs following hypoxic injuries, such as myocardial infarction and stroke. It might also have important repair functions in the pathophysiologic sequelae that are associated with actin toxicity and with septic shock, such as respiratory distress syndrome, multi-organ failure and severe tissue trauma.
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PMID:Thymosin beta4: actin-sequestering protein moonlights to repair injured tissues. 1609 19

CytRx is developing Flocor, an amphipathic copolymer, as a potential treatment for acute sickle cell crisis and acute respiratory distress syndrome (ARDS)/acute lung injury 1. It is currently undergoing phase III clinical trials for the treatment of sickle cell crisis. Flocor has rheologic, cytoprotective, anti-adhesive and antithrombotic effects and has potential in the treatment of acute ischemic vascular disorders such as stroke and myocardial infarction (MI). A US NDA is planned for filing in late 1999 or 2000. Flocor is a highly purified form of the nonionic surfactant poloxamer 188, composed of a central block of hydrophobic poly(oxypropylene) units flanked by chains of hydrophilic poly(oxyethylene) units. It has superseded RheothRx (commercial grade poloxamer 188) because of its more favorable therapeutic index. The FDA has informed CytRx that data generated with RheothRx can be used to support an NDA for Flocor.
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PMID:Flocor (CytRx Corp). 1615 56


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