Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Twenty-four patients with histologically proven metastatic malignant melanoma were included in a phase II trial of recombinant IL-2 (rIL-2, RU 49637). Twenty million international units (IU)/m2/day were given by continuous intravenous infusion on days 1 to 5, 15 to 18, and 29 to 31, and then monthly for 5 days until disease progression or major intolerance developed. All patients were evaluable for response and toxicity. Toxicity was consistent with one case of myocardial ischemia, 13 cases of grade III and IV hypotension, and 15 cases of proven sepsis. There were 8 objective responses: 4 of them were of short duration as they were observed on day 31 only. An activation of the immune system was detected in all patients. It was demonstrated by an increase in lymphocyte populations, especially in activated NK cells. A tendency for higher numbers of cytotoxic cells was found in patients with objective tumor responses. These results indicate a role for rIL-2 RU 49637 in treating patients with metastatic malignant melanoma. However, further trials are required to determine its optimal dosage and schedule of administration.
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PMID:IL-2 phase II trial in metastatic melanoma: analysis of clinical and immunological parameters. 130 93

Cytokines, interleukin-1 (IL-1) and tumor necrosis factor (TNF) are known to mediate host cell response to sepsis, trauma, and myocardial ischemia. We have previously found increased levels of IL-1 in the venous effluent during the reperfusion phase of skeletal muscle ischemia in a canine model. This study was done to evaluate whether TNF also played a role in skeletal muscle ischemia-reperfusion injury since IL-1 and TNF have inter-related functions. In twelve adult mongrel dogs (28-32 kg) one gracilis muscle was subjected to six hours of normothermic ischemia followed by normothermic reperfusion. The contralateral side served as a control and remained normally perfused throughout the experiment. Gracilis venous samples were collected at pre-ischemia and one hour of reperfusion. Systemic (arterial) blood samples were taken simultaneously with the venous samples at one hour of reperfusion. At the end of the experiment the muscles were harvested and amount of necrosis quantitated by serial transections, nitroblue tetrazolium staining and computerized planimetry. Muscle necrosis on the experimental side was found to be 48.86 +/- 5.37%. Sera were analyzed for TNF activity using a bioassay. TNF levels in the gracilis venous effluent at one hour of reperfusion were not significantly different from the simultaneous systemic (arterial) levels (27.15 +/- 5.05 pg/ml vs 18.23 +/- 4.27 pg/ml). Pre-ischemic levels of TNF were 96.50 +/- 20.12 pg/ml, which was significantly higher than either venous or arterial levels obtained after one hour of reperfusion (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Do cytokines play a role in skeletal muscle ischemia and reperfusion? 144 79

Septic shock, a distributive form of shock, is a common and lethal disease characterized by tachycardia, hypotension, normal or elevated cardiac index, and decreased systemic vascular resistance (SVR). For 2 to 4 days after onset of shock, the left ventricular ejection fraction (LVEF) is depressed; with adequate volume replacement, the left ventricle dilates and cardiac output (CO) is maintained or increased. In survivors, these abnormalities reverse to normal within 7 to 10 days. The myocardial depression found in patients with septic shock is not associated with global myocardial ischemia. In our animal model of sepsis, myocardial depression is not associated with impaired myocardial high-energy stores, or abnormal myocardial oxygen utilization. However, septic animals have histopathologic evidence of coronary nonocclusive microvascular damage and myocyte injury. The majority of human deaths caused by septic shock are related to the peripheral vascular dysfunction and multiorgan system failure that occurs over time. The pathophysiology of this disease is complex. Clinical and experimental evidence support the notion that myocardial depression, peripheral vascular abnormalities, and multiorgan dysfunction result from the combined effect of exogenous and endogenous mediators (eg, endotoxin, cytokines, and nitric oxide) released during septic shock. Although conventional therapy with fluids, vasopressors, and antibiotics is effective, the disease still has a high mortality rate. Studies investigating the effects of bacterial toxins and potentially harmful host mediators offer the greatest hope in finding new ways to eradicate this highly lethal disease.
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PMID:Systemic hemodynamic abnormalities and vasopressor therapy in sepsis and septic shock. 151 2

Interleukin-1 and thromboxane are known to mediate the host response to sepsis, trauma, and myocardial ischemia. A well-established model of canine isolated gracilis muscle was used to evaluate whether cytokine (interleukin-1) played a role in skeletal muscle ischemia-reperfusion injury. Six adult mongrel dogs (25-30 kg) were subjected to six hours of muscle ischemia followed by reperfusion. Gracilis venous samples were collected pre-ischemia and at one hour of reperfusion. Systemic (arterial) blood samples were taken at one hour of reperfusion. Sera were analyzed for interleukin-1 by bioassay and thromboxane (B2) by radio-immunoassay. The gracilis muscle of the operated limb was harvested in all the animals for assessment of the percentage of muscle necrosis. This was found to be 56.2 +/- 14.8% by serial transections, nitroblue tetrazolium staining, and computerized planimetry. Interleukin-1 levels in the gracilis venous effluent increased from 21.88 +/- 7.13 units/ml during pre-ischemic baseline to 50.42 +/- 9.12 units/ml after six hours of ischemia followed by one hour of reperfusion (p less than 0.04). Thromboxane B2 levels were 2983 +/- 1083 pg/ml and 9483 +/- 2218 pg/ml at pre-ischemia and at one hour of reperfusion respectively (p less than 0.04). Systemic levels of both interleukin-1 and thromboxane B2 at one hour of reperfusion were 0 units/ml and 1584 +/- 520 pg/ml respectively, which were significantly lower than the one hour reperfusion gracilis venous effluent levels (p less than 0.04). This is the first report in which cytokines have been implicated in skeletal muscle ischemia-reperfusion injury.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Interleukin-1 and thromboxane release after skeletal muscle ischemia and reperfusion. 154 81

Patients with infrequent recurrent syncope undiagnosed after extensive noninvasive and invasive testing pose a diagnostic and therapeutic dilemma. The purpose of this pilot study was to assess the feasibility of using an implanted, long-term monitor as an aid to diagnosis in these patients. This was done using commercially available pacemakers with monitoring functions. Sixteen patients (eight males and eight females), aged 59.7 +/- 17 years who had unexplained syncope despite a 12-lead electrocardiogram, repeated Holter monitoring, exercise testing, echocardiography, an electrophysiological study, and a tilt test (n = 6), were entered into the study. Patients had experienced a mean of 3.1 +/- 1 episodes of syncope in the 12 months prior to the study. All provided a history suggestive of Stokes-Adams attacks and were referred for consideration of pacemaker implantation. Two patients had ischemic heart disease and one patient had a long QT interval. Patients had an Intermedics Nova II or Medtronic Quintech DPG pulse generator capable of recording sensed and paced events implanted with a single right ventricular lead. Syncope or presyncope occurred in ten patients (62%) 4.9 +/- 4.2 months after pacemaker implantation. Bradycardia was detected in six patients and four patients had no arrhythmia. In addition to bradycardia, one patient also had tachycardia detected. Pacing therapy resulted in symptom relief in all six patients with syncope or presyncope due to bradycardia. Complications of pacemaker implantation (lead insulation failure) occurred in two patients. One of these patients subsequently had an infection of the generator pocket with associated systemic sepsis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Feasibility of long-term electrocardiographic monitoring with an implanted device for syncope diagnosis. 171 65

The aim of the study was to evaluate survival rates and causes of death of a large group of male patients with systemic lupus erythematosus (SLE). The group consisted of 120 patients with evident SLE that were observed at the Institute of Reanimatology from 1976 to 1989; the mean age was 31.3 years; the mean age for the disease onset was 29.6 years; the mean follow-up duration was 9.1 years. The survival pattern was obtained with the method of the life table analysis. Maximum lethality was observed during the first years of the disease: in 1-4 years 11 patients died, in 5-6 years--6 patients, and in 8-12 years--7 patients; 27 patients died during the follow-up period, 17--died of lupus nephritis, 4--of neurological involvement, one patient--of heart insufficiency, one--of lung tuberculosis, one--of ischemic heart disease, one--of amyloidosis, one--of sepsis and one patient died of chronic lung insufficiency.
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PMID:[An analysis of the survival of 120 male patients with systemic lupus erythematosus]. 207 48

The purpose of the present study was to review the results obtained in patients with a ventricular assist devices (VAD) in our hospital, and to discuss various problems concerning a VAD use, such as indications, right ventricular failure, and evaluation of cardiac function. Fourteen VADs were applied to 11 patients for left ventricular assist, including two for right ventricular assist and for one as biventricular assist with a VAD in the left and a biopump in the right. The clinical diagnoses of the patients were as follows: 10 ischemic heart disease, two valvular disease, one acute aortic dissection, and one corrected transposition of the great arteries. VADs were indicated in 11 patients because of difficulty in weaning from cardiopulmonary bypass (CPB), and in three patients because of cardiogenic shock after discontinuing CPB. Among the 14 patients, 11 had an effective VAD, six were successfully weaned from a VAD, and two survived. The VAD was ineffective due to uncontrollable bleeding and improper indications for the device, as in applying a one-sided heart assist when a biventricular assist was necessary. In spite of an effective VAD, five patients could not be weaned from VAD because of brain damage, sepsis, and hypoxia. After removing a VAD, four patients died; one due to mediastinitis, two due to respiratory failure, and one due to low output syndrome. All the four patients had renal failure followed by multi-organ failure finally, because of prolonged CPB time. The CPB time was shorter among the long survivors than in others. Cardiac function during assist and the weaning probability from a VAD were evaluated not only by the so-called on-off test, but also by transesophageal Doppler echocardiography. Ventricular wall motion and pulmonary venous flow pattern were analyzed by transesophageal Doppler echocardiography. The pattern of monophasic forward flow in the pulmonary vein was associated with reduced wall motion during deteriorated cardiac function, while the flow pattern became biphasic as cardiac function recovered. From these results, we concluded as follows: 1. Early decisions as to whether VAD is indicated are important. 2. A right VAD should be considered in cases with biventricular failure, during left ventricular assist, if right atrial pressures elevated more than 18 mmHg constantly. 3. The evaluation of cardiac function by transesophageal Doppler echocardiography is useful for making decisions as to wean patients from a VAD.
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PMID:[Problems in patients with use of a ventricular assist device]. 210 21

The hearts of eight patients aged 22 to 67 years (mean, 41 years) who died during or within 4 days of interleukin-2 (IL-2) based immunotherapy for treatment of renal cell carcinoma or melanoma were studied at necropsy. Death resulted from combined cardiorespiratory failure in two patients, sepsis in four patients, acute myocardial infarction in one patient, and myocarditis in one patient. Transmural left ventricular necrosis was present in one of the two patients with significant atherosclerotic coronary artery narrowing. Noninfectious myocarditis was present in five patients: the inflammatory infiltrate was lymphocytic in four and composed of a mixture of eosinophils and lymphocytes in one. Although treatment-related deaths associated with high-dose IL-2 therapy are uncommon (1.5% in 652 consecutive patients), the potential for significant myocardial ischemia or myocarditis exists, and careful monitoring for arrhythmias or myocardial failure is warranted.
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PMID:Myocarditis or acute myocardial infarction associated with interleukin-2 therapy for cancer. 220 2

The cardiac mechanisms responsible for endotoxin-mediated disruptions in left ventricular (LV) contraction-relaxation dynamics have been controversial. Recently, a combination of clinical cardiodynamic studies in patients along with experimental cardiodynamic studies in endotoxemic/septic animals and isolated heart tissue has yielded corroborating evidence for a consistent deleterious alteration(s) of intrinsic LV contractility during shock syndromes. Cardiac dysfunction in shock patients and intact animals was characterized by reduced LV ejection fraction in the presence of unchanging LV stroke volume, or by reduced LV end-systolic pressure-volume ratio. In hearts isolated from experimental shock subjects, LV contractile abnormality was characterized by reduced isovolumetric intraventricular pressure development and stroke volume, even in the presence of maximally effective increments in end-diastolic volume or preload. Cardiodynamic changes developed early in experimental septicemic shock syndromes (less than 4 hr) and were not irreversible. Furthermore, and this is a key element, both clinical and experimental study indicated that coronary perfusion inadequacy was not an obligatory etiologic factor in the shock-associated loss of cardiac contractile function. Thus, clinical and experimental data are now available to assemble a consensus that 1) intrinsic LV contractile reserves are diminished early during endotoxemia and sepsis and 2) this diminution is not simply a consequence of global myocardial ischemia.
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PMID:Intrinsic myocardial dysfunction during endotoxemia: dependent or independent of myocardial ischemia? 240 37

The production and deployment of polymorphonuclear neutrophils (PMNs) are under close regulation. PMNs interact through cytokines with a number of cell types, including macrophages, lymphocytes, and endothelial cells. PMNs are guided by bacterial products and cytokines to target sites, where microbes are recognized and killed. Killing occurs through oxygen-dependent and oxygen-independent mechanisms. The frequent and severe infections seen in patients with defects (either congenital or acquired) in PMN function demonstrate the importance of PMNs in host defense against infection. PMNs are potent inflammatory cells and can exacerbate disease states such as myocardial ischemia, gram-negative bacterial sepsis, and the adult respiratory distress syndrome.
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PMID:Polymorphonuclear neutrophils: an effective antimicrobial force. 255 63


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