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

Interleukin-2 (IL-2) and alpha-interferon have each shown antitumor activity in patients with disseminated malignant melanoma. Because animal studies suggest enhanced activity for the combination over each agent used alone, this trial using a relatively low-dose outpatient regimen was undertaken. IL-2 at a dose of 2 x 10(6) U/m2/day (Roche units) was given by continuous intravenous infusion for 4 days a week with interferon-alpha-2a at a dose of 6 x 10(6) U/m2/day given by s.c. or i.m. injection on days 1 and 4 of each treatment week. One cycle consisted of 4 consecutive weeks of treatment followed by a 2-week rest period. Fourteen patients were entered in this study. No complete or partial responses were seen. One patient required dose reduction because of grade 3 diarrhea and two patients had interruption of treatment because of central-line-related sepsis. Fatigue was common in all patients. This low-dose combination regimen of IL-2 and alpha-interferon does not appear to be better than the single agents used alone in optimal dosage.
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PMID:A phase II trial of concomitant human interleukin-2 and interferon-alpha-2a in patients with disseminated malignant melanoma. 831 96

Ventilatory pump failure can occur in the setting of severe infection. Recent in vivo studies have shown a significant decrease in diaphragm force production in rats with pneumococcal sepsis and sepsis secondary to Escherichia coli endotoxin. We hypothesized that diaphragm impairment during sepsis may be mediated by a direct effect of tumor necrosis factor-alpha (TNF) or endotoxin. To test this hypothesis we studied the mechanical characteristics of isolated rat diaphragm strips in tissue baths containing rTNF-alpha or endotoxin and compared the results with control strips. The strips were stimulated to contract isometrically in the tissue baths that were aerated with 95% O2-5% CO2. Baseline force-frequency determinations were made at 60 min. Following this, the strips were fatigued over a 4-min period (20 Hz, 0.33-s trains, 1 train/s) and force-frequency relationships determined 30 s, 10 min, and 60 min post-fatigue. There were no significant differences found between control and experimental strips in any aspect of contractile function tested, including force-frequency characteristics, fatiguability, and recovery from fatigue. Using an isolated cell line assay (L929), we found evidence of attenuated cytotoxicity of TNF at 26 degrees C compared with 37 degrees C. Therefore, we repeated the experiments studying the effects of TNF on in vitro muscle at 37 degrees C. We once again found no effect of TNF on contractile function. We conclude that the impairment of diaphragm function during sepsis is not mediated by a direct effect of TNF or endotoxin.
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PMID:Tumor necrosis factor and endotoxin do not directly affect in vitro diaphragm function. 834 89

Fat oxidation provides a fuel for many tissues and it provides an important signal to decrease glucose utilization and oxidation in muscle and so conserve glucose for essential organs such as the brain. The control of fatty acid oxidation is achieved in part through its plasma concentrations, which may be precisely controlled by the triacylglycerol-fatty acid substrate cycle, which can also, if oxidation is taken into account, be viewed as a branch point in this important pathway. Branch points may provide precision in regulation if one of the fluxes at the branch is low compared with the other flux. Both branch points and substrate cycles are energetically expensive and may account for some of the increases in energy expenditure in conditions of injury, burns, and sepsis and in the postexercise condition. Fatty acids, through effects on plasma free tryptophan concentrations and hence 5-hydroxytryptamine concentrations in the brain, may play a role in central fatigue. Polyunsaturated fatty acids are claimed to have immunosuppressive properties. Work has been done to provide a biochemical analysis of how they might influence some functions of cells of the immune system.
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PMID:The regulatory, informational, and immunomodulatory roles of fat fuels. 847 91

Some conditions that predispose to ventilatory failure increase the work of breathing (chronic obstructive pulmonary disease [COPD], obesity, kyphoscoliosis), whereas others cause severe respiratory muscle weakness. Specific reasons for muscle weakness include critical illness (electrolyte imbalance, acidemia, shock, sepsis), chronic illness (poor nutrition, cachexia), and neuromuscular diseases. Inspiratory muscle weakness from mechanical disadvantage to the diaphragm is characteristic of asthma and COPD. The increased work of breathing combined with muscle weakness increases the pressure needed to inspire a breath and decreases maximal inspiratory pressure. When this pressure exceeds 0.4, dyspnea and inspiratory muscle fatigue ensue. One way to lower this pressure and avert fatigue is to lower the tidal volume. Ventilatory drive is high, not low, in ventilatory failure. Concomitant shortening of inspiration and breath duration cause the small tidal volume and increased respiratory rate. Gas exchange is compromised by ventilation/perfusion imbalance, and the ratio of dead space to tidal volume is also increased by rapid, shallow breathing. Reduction in tidal volume minimizes dyspnea, but the small tidal volume is inadequate for gas exchange. Acute treatment of respiratory muscle failure involves respiratory muscle rest through mechanical ventilation and removal of noxious influences (infection, metabolic disarray), whereas chronic treatment involves rebuilding the contractile apparatus by nutritional repletion and training.
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PMID:Respiratory muscles and ventilatory failure: 1993 perspective. 850 1

Granulocyte transfusions may be beneficial in neutropenic patients with progressive infections despite appropriate antibiotics. In order to evaluate both the feasibility of granulocyte collection in normal donors receiving granulocyte colony-stimulating factor (G-CSF) and the efficacy of infusing these cells into neutropenic patients with progressive sepsis, four donors received between 5-10 micrograms/kg G-CSF per day and underwent leucapheresis within a day of the first dose. Different red cell sedimenting agents and interface settings were evaluated to determine the optimal method of granulocyte collection. The number of granulocytes collected, the peripheral blood granulocyte level in the recipient at various time points after infusion, and the clinical response were evaluated. Results showed that G-CSF and the leucaphereses caused mild to moderate fatigue in two donors and profound fatigue and a brief episode of hypoxia in one donor. Efficient granulocyte collections were only obtained using dextran 40 or dextran 70 as the sedimenting agent and a deep interface setting which extended sampling into the upper red cell layer. Infusion of granulocytes obtained with this technique resulted in a sustained increase in circulating granulocyte numbers in three recipients, one of whom gained significant clinical benefit. In conclusion, granulocyte transfusions from donors given G-CSF are feasible and may be clinically beneficial, particularly if given early in the course of infection in neutropenic patients.
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PMID:G-CSF stimulated donor granulocyte collections for neutropenic sepsis. 853 1

Thirty-four patients with advanced malignant melanoma were treated with recombinant alpha-interferon (IFN) and chemotherapy consisting of carboplatin, vinblastine, and bleomycin (CVB). CVB was given for four cycles and IFN for 1 year or until progression. Of the 34 analyzed patients, 17 (50%) achieved an objective response, including two complete (6%) and 15 partial responses (44%). Responses were noted in cutaneous, lymph node, and pulmonary sites, with a median time to disease progression of 5 months (range, 3-20 months). The median survival from onset of therapy was 8 months (range, 1-22 months) for the 34 patients. Ninety-four percent of the patients experienced flu-like symptoms and 82% fatigue or weakness. Leukopenia grade 3-4 was observed in four patients (12%). There were two toxicity-related deaths (6%); one from bleomycin-induced pneumonitis and one from neutropenic sepsis. It is concluded that the addition of IFN to CVB regimen, in this study, showed no apparent advantage on response rates, disease-free interval, or survival. The observed treatment-related mortality was unacceptably high. IFN administered as maintenance therapy following CVB conferred no survival benefit.
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PMID:Recombinant interferon ALFA-2A in combination with carboplatin, vinblastine, and bleomycin in the treatment of advanced malignant melanoma. 863 45

Thirty-six patients with advanced epithelial ovarian cancer received epirubicin as second-line therapy after primary treatment with carboplatin and cyclophosphamide. Thirty-four patients were evaluatable for response, 36 for toxicity. There were 9 responses (response rate 26.4%, 95% CI = 12.9-44.4), 2 complete and 7 partial. Median duration of response was 149 days (range 42-183); 4 patients with partial remission are still on study. Toxicity consisted of fatal cardiac failure and paravenous injection (1 patient), fatal leukopenia and sepsis (1 patient), and severe loss of appetite, nausea and vomiting, fatigue, and general malaise in 3 patients. Platelet nadir grade 4 (WHO) was observed in 2 patients while leukocyte nadir grade 4 was seen in 3 patients. The present study showed a high response rate from standard-dose epirubicin. Toxicity was acceptable in most patients, but 2 patients died from treatment complications which gives a treatment-related mortality rate of 6%. Response was primarily seen in patients with minor tumor load and in good general condition.
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PMID:A phase 2 study with epirubicin as second-line treatment of patients with advanced epithelial ovarian cancer. 891 Jun 29

A case of septicemia due to Aeromonas hydrophila (A. hydrophila) in a 54-year-old male suffering from progressive severe jaundice and fatigue is reported. The patient developed multiple organ failure despite aggressive therapy including plasma exchange and glucose-insulin therapy. Upon admission to our hospital, therapy was started with ampicillin (ABPC) 4 g/day, gentamicin (GM) 120 mg/day, hemodialysis, continuous hemofiltration, catecholamines and a respirator, but he expired on the 2nd hospital day. Blood culture and histology revealed A. hydrophila. Postmortem examination showed alcoholic liver fibrosis which was most likely liver cirrhosis. In the literature, patients with septicemia due to Aeromonas had underlying hepatic cirrhosis more often than did those with septicemia due to other gram-negative bacilli. Therefore, it is important-to consider the possibility of liver cirrhosis in patients with A. hydrophila septicemia.
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PMID:[A case of severe acute hepatorenal failure due to Aeromoas hydrophila septicemia]. 895 74

Impaired pulmonary gas exchange can result from lung parenchymal failure inducing oxygenation deficiency and fatigue of the respiratory muscles, which is characterized by hypercapnia or a combination of both mechanisms. Contractility of and coordination between the diaphragm and the thoracoabdominal respiratory muscles predominantly determine the efficiency of spontaneous breathing. Sepsis, cardiac failure, malnutrition or acute changes of the load conditions may induce fatigue of the respiratory muscles. Augmentation of spontaneous breathing is not only achieved by the application of different technical principles or devices; it also has to improve perfusion, metabolism, load conditions and contractility of the respiratory muscles. Intermittent mandatory ventilation (IMV) allows spontaneous breathing of the patient and augments alveolar ventilation by periodically applying positive airway pressure tidal volumes, which are generated by the respirator. Potential advantages include lower mean airway pressure (PAW), as compared with controlled mechanical ventilation, and improved haemodynamics. Suboptimal IMV systems may impose increased work and oxygen cost of breathing, fatigue of the respiratory muscles and CO2 retention. During pressure support ventilation (PSV), inspiratory alterations of PAW or gas flow (trigger) are detected by the respirator, which delivers a gas flow to maintain PAW at a fixed value (usually 5-20 cm H2O) during inspiration. PSV may be combined with other modalities of respiratory therapy such as IMV or CPAP. Claimed advantages of PSV include decreased effort of breathing, reduced systemic and respiratory muscle consumption of oxygen, prophylaxis of diaphragmatic fatigue and an improved extubation rate after prolonged periods of mechanical ventilation. Minimum alveolar ventilation is not guaranteed during PSV; thus, close observation of the patient is mandatory to avoid serious respiratory complications. Continuous positive airway pressure breathing (CPAP) maintains PAW above atmospheric pressure throughout the respiratory cycle, which may increase functional residual capacity and decrease the effort of breathing. CPAP has been conceptually designed for the augmentation of spontaneous breathing and requires the intact central and peripheral regulation of the respiratory system. Airway pressure release ventilation (APRV) improves alveolar ventilation by intermittent release of PAW, which is kept above atmospheric pressure by means of a high-flow CPAP system. The opening of an expiratory valve for 1-2 s induces a decreased PAW and lung volume, which increases rapidly to pre-exhalation values after closure of the valve due to the high gas flow within the circuit (90-100 1/min). APRV may improve haemodynamics and VA/Q distribution as compared with conventional mechanical ventilation. Biphasic positive airway pressure (BIPAP) is characterized by the combination of spontaneous breathing and time-regulated, pressure-controlled mechanical ventilation. During the respiratory cycle the ventilator generates two alternating CPAP levels, which can be modified with regard to time and pressure. As with APRV, alveolar ventilation is maintained even if the spontaneous breathing efforts of the patient cease, which improves the safety of both modes of respiratory therapy. The contribution of spontaneous breathing to total minute ventilation may be important, since a decreased shunt and improved VA/Q relationship have been observed in experimental non-cardiogenic lung oedema. These data give support to the concept that spontaneous breathing should be maintained and augmented in the setting of acute respiratory failure.
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PMID:[Augmented spontaneous breathing]. 896 3

The combination of abnormally low plasma cystine and glutamine levels, low natural killer (NK) cell activity, skeletal muscle wasting or muscle fatigue, and increased rates of urea production defines a complex of abnormalities that is tentatively called "low CG syndrome." These symptoms are found in patients with HIV infection, cancer, major injuries, sepsis, Crohn's disease, ulcerative colitis, chronic fatigue syndrome, and to some extent in overtrained athletes. The coincidence of these symptoms in diseases of different etiological origin suggests a causal relationship. The low NK cell activity in most cases is not life-threatening, but may be disastrous in HIV infection because it may compromise the initially stable balance between the immune system and virus, and trigger disease progression. This hypothesis is supported by the coincidence observed between the decrease of CD4+ T cells and a decrease in the plasma cystine level. In addition, recent studies revealed important clues about the role of cysteine and glutathione in the development of skeletal muscle wasting. Evidence suggests that 1) the cystine level is regulated primarily by the normal postabsorptive skeletal muscle protein catabolism, 2) the cystine level itself is a physiological regulator of nitrogen balance and body cell mass, 3) the cyst(e)ine-mediated regulatory circuit is compromised in various catabolic conditions, including old age, and 4) cysteine supplementation may be a useful therapy if combined with disease-specific treatments such as antiviral therapy in HIV infection.
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PMID:Role of cysteine and glutathione in HIV infection and other diseases associated with muscle wasting and immunological dysfunction. 936 43


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