Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002871 (anemia)
 52,094 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A gene therapy strategy involving direct myocardial administration of an adenovirus (Ad) vector encoding the vascular endothelial growth factor 121 cDNA (Ad(GV)VEGF121.10) has been shown to be capable of "biological revascularization" of ischemic myocardium in an established porcine model [Mack, C.A. (1998). J. Thorac. Cardiovasc. Surg. 115, 168-177]. The present study evaluates the local and systemic safety of this therapy in this porcine ischemia model and in normal mice. Myocardial ischemia was induced in Yorkshire swine with an ameroid constrictor 21 days prior to vector administration. Ad(GV)VEGF121.10 (10(9) or 10(10) PFU), Ad5 wild type (10(9) PFU), AdNull (control vector with no transgene; 10(9) PFU), saline, or no injection (naive) was administered in 10 sites in the ischemic, circumflex distribution of the myocardium. Toxicity was assessed by survival, serial echocardiography, blood analyses, and myocardial and liver histology at 3 and 28 days after vector administration. All pigs survived to sacrifice, except for one animal in the Ad(GV)VEGF121.10 (10(10) PFU) group, which died as a result of oversedation. Echocardiograms of Ad(GV)VEGF121.10-treated pigs demonstrated no differences in pericardial effusion, mitral valve regurgitation, or regional wall motion compared with control pigs. Intramyocardial administration of Ad(GV)VEGF121.10 included only minimal myocardial inflammation and necrosis, and no hepatic inflammation or necrosis. Only a mild elevation of the white blood cell count was encountered on day 3, which was transient and self-limited in the Ad(GV)VEGF121.10 group as compared with the saline-treated animals. As a measure of inadvertent intravascular administration of vector, normal C57/BL6 mice received intravenous Ad(GV)VEGF121.10 (10(4), 10(6), 5 x 10(7), or 10(9) PFU), AdNull (5 x 10(7) or 10(9) PFU), or saline. Toxicity was assessed by survival, blood analyses, and organ histology at 3 and 7 days after vector administration. A separate group of C57/BL6 mice received intravenous AdmVEGF164 (Ad vector encoding the murine VEGF164 cDNA), Ad(GV)VEGF121.10, AdNull (10(8) PFU each group), or saline to assess duration of expression and safety of a homologous transgene. All mice survived to sacrifice except for 40% of the mice in the highest (10(9) PFU; a dose more than 10(3)-fold higher by body weight than the efficacious dose in pigs) Ad(GV)VEGF121.10 dose group, which died on days 5-6 after vector administration. The only differences seen in the blood analyses between treated and control mice were in the very high Ad(GV)VEGF121.10 dose group (10(9) PFU), which demonstrated an anemia as well as an increase in alkaline phosphatase when compared with all other treatment groups. Hepatic VEGF levels by ELISA in AdmVEGF164-treated mice did not persist beyond 14 days after vector administration, suggesting that persistent expression of a homologous VEGF gene transferred with an Ad vector is not a significant safety risk. Although this is not a chronic toxicity study, these data demonstrate the safety of direct myocardial administration of Ad(GV)VEGF121.10, and support the potential use of this strategy to treat human myocardial ischemia.
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PMID:Safety of direct myocardial administration of an adenovirus vector encoding vascular endothelial growth factor 121. 1036 64

In discordant xenotransplantation, the recipientOs blood initiates hyperacute xenorejection (HXR). We hypothesized that HXR-related lung edema may be reduced if a new xenograft is perfused by blood which previously has perfused another xenograft. In a syngeneic control group (n = 6), a rat lung (lung XR) was perfused by rat blood (blood AR), following which the blood was collected (blood BR). After another rat lung (lung YR) was perfused by blood BR, the blood was collected (blood CR). In a xenogeneic experimental group (n = 6), a guinea pig lung (lung XG) was perfused by rat blood (blood AG), and the blood was collected (blood BG). Then, another guinea pig lung (lung YG) was perfused by blood BG, and once more the blood was collected (blood CG). White blood cells (WBC), polymorphonuclear leukocytes (PMN), red blood cells (RBC), hemoglobin, hematocrit, and complement (CH50) in the blood were measured pre- and post-perfusion. The wet/dry weight ratio (W/D) of the lung was calculated after the perfusion. WBC and PMN were higher in blood CR/BR than in blood BR/AR. CH50 was higher in blood CG/BG than in blood BG/AG. RBC, hemoglobin, and hematocrit were not different among the blood AR, BR, CR, AG, BG, and CG. The W/D was not different between lung XR and lung YR. The W/D of lung YG was lower than lung XG. In conclusion, the lung edema associated with HXR is reduced when blood which has perfused another xenograft is used to perfuse the new xenograft without anemia, and complement plays a critical role in reducing lung edema.
Ann Thorac Cardiovasc Surg 2000 Jun
PMID:Hyperacute xenorejection of guinea pig-to-rat lung transplantation can be attenuated by blood which has perfused another xenograft. 1089 82

Congestive heart failure describes a syndrome with complex and variable symptoms and signs, including dyspnea, increased fatigability, tachypnea, tachycardia, pulmonary rales, and peripheral edema. Although this syndrome usually is associated with low cardiac output, it may occur in a number of so-called high output states, when the cardiac output is normal or greater than normal. A high output state may occur in chronic severe anemia, large arteriovenous fistula or multiple small arteriovenous shunts as in Paget's bone disease, some forms of severe hepatic or renal disorders, and acutely in septic shock. The syndrome of systemic congestion in a high output state is traditionally referred to as high output heart failure. However, the term is a misnomer because the heart in these conditions is normal, capable of generating very high cardiac output. The underlying problem in high output failure is a decrease in the systemic vascular resistance that threatens the arterial blood pressure and causes activation of neurohormones, resulting in an increase in salt and water retention by the kidney. Many of the high output states are curable conditions, and because they are associated with decreased peripheral vascular resistance, the use of vasodilator therapy for treatment of congestion may aggravate the problem. There are other clinically important issues in high output failure that have received little attention in the current medical literature. This article reviews the available data on high output cardiac failure with particular emphasis on the underlying mechanisms and treatment.
Curr Treat Options Cardiovasc Med 2001 Apr
PMID:High Output Cardiac Failure. 1124 61

A 32-year-old man underwent surgical excision of a malignant hemangioendothelioma of the heart and received multidisciplinary treatment. Thirty-three months later, he underwent a second surgical treatment for a recurrent tumor of the posterior chest wall of the right thorax. Five months after this surgery (thirty-eight months after the initial surgery), a second recurrent tumor in the right thorax developed. Although radiotherapy and recombinant interleukin-2 were administered, anemia of unknown origin (hemoglobin 6.7 g/dl) developed. The patient died of sudden shock due to a rupture of an omental metastatic tumor. The patient survived for 41 months after the first surgical resection. We present this case because it is the first reported case of sudden death due to bleeding from an omental metastatic tumor, and because our patient was the second-longest survivor after surgical treatment for cardiac angiosarcoma.
J Cardiovasc Surg (Torino) 2001 Aug
PMID:Sudden death due to rupture of an omental metastatic tumor arising from cardiac angiosarcoma. A case report. 1145 85

A 13-year-old girl presented with dyspnea and chest pain. Chest radiography showed a massive left pleural effusion. Computed tomography revealed a tumor of the fourth rib. A large bloody effusion was drained. Her anemia worsened (hemoglobin: 4.8 g/dl), and hemorrhagic shock ensued. An emergency thoracotomy was performed. Bleeding from the ruptured tumor was identified. The fourth rib, the tumor, and the adjacent tissues were resected. Histopathologic examination revealed a ruptured primary osteosarcoma of the rib with pleural dissemination.
Ann Thorac Cardiovasc Surg 2001 Aug
PMID:Hemorrhagic shock due to intrathoracic rupture of an osteosarcoma of the rib. 1157 64

The antiphospholipid syndrome (APS) has been associated with multiple cardiac abnormalities. The present report describes a case of right ventricle thrombus in a 51-year-old woman with a history of autoimmune haemolytic anemia and antiphospholipid antibodies. Transthoracic echocardiography demonstrated the presence of a right ventricle mass, mimicking a myxoma. She underwent open heart removal of the mass and was started on indefinitely anticoagulant therapy. At 2 years follow-up she was free of symptoms.
J Cardiovasc Surg (Torino) 2002 Aug
PMID:Antiphospholipid antibodies and intracardiac thrombosis. A case report. 1212 58

Recent studies suggest a possible link between recombinant human erythropoietin (rhEPO)-induced hypertension and endothelium-derived vasoconstrictor autocoids. The current study was designed to evaluate the role of eicosanoids such as thromboxane (TX) A and prostacyclin (PGI ) and of endothelin-1 (ET-1) and the relationship between these vasoactive substances in rhEPO-induced hypertension in uremic rats. Renal failure was induced by a two-stage 5/6 nephrectomy followed by a 6-week stabilization period. In protocol A, rats were divided into four groups: vehicle, rhEPO (100 u/kg, subcutaneously, three times per week), a selective ET receptor antagonist (ABT-627, 10 mg/kg/d), and rhEPO + ABT-627 for 5 weeks. In protocol B, uremic animals were divided into two groups: rhEPO and rhEPO + a TX receptor antagonist and synthesis inhibitor, ridogrel (25 mg/kg/d), for 5 weeks. At the end of the study, immunoreactive eicosanoid metabolites (TXB and 6-keto-PGF, stable metabolites of TXA and PGI ), and ET-1 were measured in either the thoracic aorta or in the mesenteric arterial bed. After 5/6 nephrectomy, the animals developed uremia, anemia, and hypertension. rhEPO corrected the anemia but aggravated the hypertension. Both drugs were effective in preventing the progression of hypertension in rhEPO-treated rats although ABT-627 was more potent than ridogrel. rhEPO increased the concentration of ET-1 and TXB in blood vessels and ABT-627 decreased tissue levels of both vasopressors. The concentration of 6-keto-PGF was not significantly changed. Ridogrel significantly decreased tissue TXB concentrations but had no effect on ET-1 levels. These results suggest that endothelium-derived vasoconstrictor autacoids (TXA and ET-1) are involved in the pathogenesis of rhEPO-induced hypertension in uremic rats. TXA probably serves as a mediator of the vascular effect of ET-1.
J Cardiovasc Pharmacol 2003 Mar
PMID:Relationship between eicosanoids and endothelin-1 in the pathogenesis of erythropoietin-induced hypertension in uremic rats. 1260 17

Endovascular repair of abdominal aortic aneurysms (EVAR) has been introduced as an alternative to open surgery with the purpose of reducing operative risk and improving survival. Since cardiac co-morbidity is a major risk factor for both the operative procedure and long-term survival, it seems worthwhile to compare the cardiac implication of the 2 procedures. If EVAR would indeed afford a cardioprotective effect, this could have clinical consequences. Preoperative cardiology work-up could be reduced and more high-risk patients could be treated. A review of the literature has been made focusing on studies that examined cardiology work-up and cardiac risk profile of EVAR and open surgery. Most literature data suggest that cardiac risk is indeed reduced with EVAR, since hemodynamic alterations are less severe, episodes of anaemia are less frequent, plasma catecholamine levels are lower and general anaesthesia can be avoided. There is no level I or II evidence that immediate or late cardiac complications are indeed reduced with EVAR. At present, there are not enough literature data on the cardiac implications of EVAR to justify a reduced preoperative cardiology work-up. Even if conclusive evidence was available that EVAR reduces operative cardiac risk, the value of preoperative cardiac screening and myocardial revascularisation would remain unchanged: the purpose of cardiology work-up is not only to reduce operative risk but also to improve long-term survival.
J Cardiovasc Surg (Torino) 2003 Jun
PMID:Does endovascular aortic aneurysm repair justify a reduced cardiology work-up? 1283 98

Erythropoietin is a hypoxia-induced hormone that is essential for normal erythropoiesis. The production of recombinant human erythropoietin (rHuEpo) has revolutionized the treatment of anemia associated with chronic renal failure and chemotherapy, and has been used as prophylaxis to prevent anemia after surgery. The erythropoietin receptor is widely distributed in the cardiovascular system, including endothelial cells, smooth muscle cells and cardiomyocytes. Epo has potentially beneficial effects on the endothelium including anti-apoptotic, mitogenic and angiogenic activities. On the other hand, some reports suggest that rHuEpo may have pro-thrombotic or platelet-activating effects. Hypertension develops in 20-30% of renal patients treated with rHuEpo. Many patients with heart failure have anemia. Despite some potential adverse effects, early studies in heart failure patients with anemia suggest that rHuEpo therapy is safe and effective in reducing left ventricular hypertrophy, enhancing exercise performance and increasing ejection fraction. Further studies are warranted to define the role of rHuEpo in chronic heart failure and other cardiovascular settings.
Cardiovasc Res 2003 Sep 01
PMID:The cardiovascular effects of erythropoietin. 1449 55

Enoxaparin (enoxaparin sodium) is a low-molecular-weight heparin that binds to and increases the activity of antithrombin III. The resulting complex inhibits prothrombinase-mediated thrombin generation and direct thrombin generation by binding to factor Xa and thrombin factor IIa. Enoxaparin, used as prophylaxis in medically ill patients at increased risk for thromboembolism, has shown significantly increased efficacy compared with placebo in reducing the incidence of deep vein thrombosis and pulmonary embolism. Indeed, 291 patients receiving subcutaneous enoxaparin 40 mg/day had a frequency of venous thromboembolism of 5.5% during 14 days of treatment, whereas 14.9% of the 288 placebo recipients experienced thromboemboli (p < 0.001). There was no reduction in the incidence of thromboembolism in the 287 recipients of enoxaparin 20 mg/day (15%). In other studies, prophylactic treatment for 7 days with subcutaneous enoxaparin 40 mg/day was at least as effective as unfractionated heparin in reducing the frequency of venous thromboembolism in 959 nonsurgical patients at increased risk for deep vein thrombosis and pulmonary embolism (total incidence = 0.2 and 1.4%, respectively). Moreover, enoxaparin recipients experienced fewer adverse events than did heparin recipients. The most frequent adverse events reported in medically ill and surgical patients receiving enoxaparin 40 mg/day were hemorrhage (17.4 vs 14.3% for placebo), hematoma at injection site, anemia, fever, peripheral edema, nausea, ecchymosis and edema (unspecified site).
Am J Cardiovasc Drugs 2001
PMID:Enoxaparin: in the prevention of venous thromboembolism in medical patients. 1472 9


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