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1/28. Multiple organ dysfunction syndrome induced by whole-body hyperthermia and polychemotherapy in a patient with disseminated leiomyosarcoma of the uterus.

    OBJECTIVE: Whole-body hyperthermia (WBH) in combination with chemotherapy is a relatively new promising treatment modality for patients with cancer. The objective of this report is to present the development of an acute systemic inflammatory response syndrome (SIRS) with multiple organ dysfunction syndrome (MODS) following WBH in combination with chemotherapy. Although WBH can also induce cytokine production, MODS has not been described before in association with WBH. DESIGN: Case report. The patient was treated with WBH (core temperature 41.8 degrees C using a radiant heat device (Aquatherm) ) in combination with polychemotherapy (ifosfamide, carboplatin and etoposide (ice) ) in the context of a clinical trial for metastatic sarcomas. SETTING: Department of medical oncology and intensive care unit of a university hospital. PATIENT: A 58-year-old Caucasian woman treated for disseminated leiomyosarcoma of the uterus, who developed SIRS with brain dysfunction, hypotension, respiratory failure and renal dysfunction following WBH/ice. INTERVENTIONS: She was successfully treated in the intensive care unit by mechanical ventilation, inotropics and antibiotics. MEASUREMENTS AND RESULTS: There was a remarkable recovery within 2 days: she regained full conciousness, could be extubated, inotropic support was stopped and creatinine levels returned to pre-treatment levels. All cultures remained sterile. After almost complete recovery, 5 days later a second episode of fever during neutropenia occurred and, despite antibiotic treatment, she died of bacteroides distasonis sepsis. CONCLUSION: WBH should be added as a new cause to the already known list of physical-chemical insults which can result in MODS.
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2/28. systemic inflammatory response syndrome and acute renal failure associated with Hemophilus influenzae septic meningitis.

    sepsis is often associated with a downward spiral through a spectrum of systemic inflammatory response syndrome (SIRS) culminating in organ failure and death. Here we present a 3-year-old girl with Hemophilus influenzae septic meningitis who developed SIRS and acute renal failure. In the initial stage, the patient showed uremia, cytopenia, disseminated intravascular coagulation, elevation of tissue enzyme and ferritin values, hemophagocytosis and overproduction of nitric oxide. The serum cytokine profile revealed increased levels of soluble interleukin (IL)-2 receptor, IL-6, IL-10 and tumor necrosis factor alpha. The patient responded positively to early and intensive interventions including antibiotics, repeated exchange transfusions, dexamethasone and high-dose gamma-globulin. The above laboratory abnormalities almost normalized with clinical improvement. We consider that SIRS was probably responsible for the sequence of events resulting in renal failure in this case, and suggest that renal failure should be included among the serious complications of SIRS associated with Hemophilus influenzae septic meningitis.
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3/28. Bacteria in blood smears: overwhelming sepsis or trivial contamination.

    It is unusual to find microorganisms in peripheral blood smears, and their presence is frequently associated with overwhelming sepsis and consequently a poor prognosis. In this report, we demonstrate 4 cases with bacteria in blood smears. Two of them had a fatal outcome, but the other 2 were caused by a contamination either via the central venous catheter or in vitro, both without dramatic outcome. The finding of bacteria in blood smears has to be interpreted carefully, and thorough examination of peripheral blood smears may be of great importance in the early diagnosis of bacteremia; however, in vitro contamination must be excluded.
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4/28. A patient with severe acute pancreatitis successfully treated with a new critical care procedure.

    It has been accepted widely that excessive humoral mediators play important roles in the pathogenesis of organ failure in patients with severe acute pancreatitis (SAP) and that infection of the pancreas due to bacterial translocation (BT) is the most frequent cause of death in SAP. On the other hand, it has been reported that continuous hemodiafiltration (CHDF) removes humoral mediators on hypercytokinemic patients such as those with systemic inflammatory response syndrome. Furthermore, several clinical studies have demonstrated that selective digestive decontamination (SDD) effectively eliminates aerobic gram-negative bacteria from the intestinal tract and reduces the incidence of septic complications in SAP. Herein we report a case of SAP who was treated successfully with intensive care including CHDF and SDD. Thus, this case report suggests that CHDF aimed at removing causative humoral mediators and SDD for the prevention of BT are useful new tools for the management of SAP.
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5/28. methylene blue administration in severe systemic inflammatory response syndrome (SIRS) after thoracic surgery.

    A 66-year-old male patient developed significant pleural effusion on the right side six years after coronary bypass grafting and mitral valve replacement. After pleurocentesis, hemo-pneumothorax developed and finally resulted in complete atelectasis of the right lung. Three weeks later, the patient was transferred to our department, and underwent a right lateral thoracotomy. The hematoma was removed and a complete decortication was performed. Four hours postoperatively the patient developed severe SIRS with beginning multiorgan failure. Even extremely high doses of norepinephrine could not raise the systemic vascular resistance. Single intravenous administration of methylene blue lead to significant and permanent improvement of the hemodynamic status.
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6/28. Intravascular lymphomatosis presenting as systemic inflammatory response syndrome.

    Intravascular lymphomatosis is an unusual form of non-Hodgkin lymphoma characterized by intravascular proliferation of atypical lymphoid cells in multiple organs. It can cause systemic inflammatory response syndrome due to primary release of cytokines by the tumor cells or secondary release of cytokines after vascular occlusion by the tumor cells. It is a potentially fatal condition, because multiorgan failure can ensue due to thrombotic vascular occlusion. This is a very rare condition and most cases are diagnosed post mortem. We present a case of systemic inflammatory response syndrome and subsequent death from multiorgan failure in a patient with intravascular lymphoma.
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7/28. New thoughts on sepsis: the unifier of critical care.

    In the united states, more than $16 billion annually is spent managing patients with severe sepsis and its sequelae. Insight into the inflammatory response, endothelial tissue, and the coagulation cascade suggest promising new treatment regimens that limit morbidity and mortality due to sepsis and multisystem organ failure. This article will discuss new information regarding the pathophysiology of the inflammatory response and sepsis. Current thoughts on clinical management and a promising new agent, Activated protein c, will be presented.
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8/28. Eradication of invasive mucormycosis--effectiveness of the Echinocandin FK463.

    BACKGROUND: Invasive rhinocerebral mucormycosis is a rare and often fatal opportunistic fungal infection. It is encountered in immunocompromised hosts exemplified by those with diabetes, human immunodeficiency viruses and particularly haematologic malignancies typically after high-dose chemotherapy and stem cell transplantation. In contrast to the more usual outcome with rapid progression and death. We now describe a successful eradication attributable to the use of a newly available antifungal agent. SETTING: Haematology department and bone marrow transplantation unit. MATERIAL AND METHOD: Two patients are contrasted. The first with acute leukaemia developed rapidly progressive facial swelling with mucormycosis proven on biopsy. Treatment over 2 months with maximally tolerated doses of amphotericin failed to halt intracranial extension and death resulted. The second, presented with acute lymphoblastic leukaemia in August 1997, underwent successful autologous bone marrow transplantation in February 1998. Relapse followed in March 1999 and after reinduction and consolidation receive a matched unrelated volunteer allograft in September 1999. A second recurrence was documented in April 2000 and in spite of achieving remission he developed a fever that was managed empirically with intravenous amphotericin and, on discharge, oral itraconazole. Left-sided facial swelling expanded rapidly and biopsy showed extensive invasion of the maxillary sinus with mucormycosis. FK463 was added on 5 June 2000 with gradual reduction in facial pain and within 1 month all clinical signs and resolved. Serial biopsies that included histopathologic investigation and microbiologic cultures confirmed eradication of the invasive mucor. In view of the potential danger of recrudescence this treatment regimen was continued through further chemotherapy and, once again disease-free, a second matched unrelated volunteer allograft took place in August 2000. Full reassessment at the time failed to demonstration any residual fungus. Engraftment was confirmed but neutropenic sepsis resulted in severe inflammatory response syndrome with progression to multiple organ dysfunction to which he succumbed without any evidence of leukaemic or systemic mycosis. CONCLUSION: Echinocandin FK463 is of documented value in managing invasive candidiasis and aspergillosis. This is believed to be the first case of successful outcome with one of the angiotrophic zygomycetes.
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9/28. Immunoparalysis as a cause for invasive aspergillosis?

    aspergillus infections are among the most feared opportunistic infections in humans. These organisms are ubiquitous in nature; protection against infection is usually provided by anatomical barriers and by the immune system. Tissue invasion by aspergillus is uncommon, occurring primarily in the setting of immunosuppression. The prognosis of invasive aspergillosis is very poor. Although it is widely recognised that critically ill patients in the intensive care Unit (ICU) are at risk for nosocomial infections, it is not generally appreciated that such patients may also be at risk for opportunistic infections usually seen only in immunocompromised patients. This might be explained by a biphasic immunological pattern during sepsis: an early hyperinflammatory phase followed by an anti-inflammatory response, leading to a hypo-inflammatory state, the so-called compensatory anti-inflammatory response syndrome (CARS or immunoparalysis). We describe four patients admitted to our ICU for various reasons, without a history of abnormal immune function, who developed invasive pulmonary aspergillosis. We hypothesise that the occurrence of these opportunistic infections in our patients may have been due to immunoparalysis, and that perhaps all ICU patients with sepsis and multiple organ dysfunction syndrome (MODS) may be at risk for opportunistic infections such as aspergillosis as a result of this syndrome. physicians treating critically ill patients in the ICU should be aware of the CARS/immunoparalysis syndrome and its potential to cause opportunistic infections, even in patients with normal immune function prior to ICU admission.
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10/28. Continuous cardiac output and hemodynamic monitoring: high temporal correlation between plasma TNF-alpha and hemodynamic changes during a sepsis-like state in cancer immunotherapy.

    Through continuous cardiac output monitoring, we investigated the temporal relationship between hemodynamic changes and plasma cytokines in a cancer patient who developed collateral sepsis to immunotherapy. A 52-year-old male with metastatic renal cell carcinoma received interleukin-2 (IL-2) infusion completing 72 h of administration. The patient developed 3 sepsis-like states including systemic inflammatory response syndrome (SIRS), shock, and multiple organ dysfunction syndrome (MODS). Hemodynamic parameters including systemic vascular resistance index (SVRI), left ventricular stroke work index (LVSWI) and cardiac index (CI) were measured over 60 h. Peripheral blood was drawn when SVRI dropped 20% in the patient and plasma cytokines including TNF-alpha, IL-6 and IL-1beta were measured using ELISA. After 60 h of immunotherapy, the patient showed a 63.4% decrease in SVRI, 54.5% decrease in LVSWI and 65.4% increase in CI. The evaluation of systemic cytokines revealed different kinetic patterns: (i) a sustained increase in TNF-alpha levels through all 3 sepsis-like states; (ii) IL-6 increased preferentially during SIRS and shock, while up/down-responses were found during MODS; (iii) IL-1beta was undetectable during the entire study period. A high temporal relationship between hemodynamic changes and plasma TNF-alpha, but not IL-6, was found. Although there are factors other than cytokines that can alter vascular resistance, this finding could represent an approach to evaluate the course of hemodynamia and probably the systemic cytokine expression after IL-2 administration in renal cancer.
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