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)

Aggressive adult T-cell leukemia-lymphoma (ATL) generally has a very poor prognosis. Deoxycoformycin (DCF, pentostatin), an inhibitor of adenosine deaminase, has shown promising therapeutic efficacy for ATL. To develop a new effective therapy against aggressive ATL, we carried out a multicenter phase II study of DCF-containing combination chemotherapy. Sixty-two previously untreated patients with ATL (34, 21, and 7 patients with diseases of the acute, lymphoma, and unfavorable chronic types, respectively) were enrolled, but 2 were ineligible because they were judged to be favorable chronic types. A regimen of 1 mg/m2 vincristine intravenously on days 1 and 8, 40 mg/m2 doxorubicin intravenously on day 1, 100 mg/m2 etoposide intravenously on days 1 through 3, 40 mg/m2 prednisolone orally on days 1 and 2, and 5 mg/m2 DCF intravenously on days 8, 15, and 22 was administered every 28 days for 10 cycles unless disease progression or toxic complications occurred. Fifty-two percent of 60 eligible patients responded (95% confidence interval [CI], 38%-65%), with 17 patients (28%) achieving a complete response (CR) (95% CI, 17%-41%) and 14 achieving a partial response. The CR rate was inferior to those of both the previous Japan Clinical Oncology Group (JCOG) study (JCOG8701, 43%), a 9-drug combination chemotherapy of the second generation, and the subsequent JCOG9303 study (35%), a granulocyte colony-stimulating factor-supported, dose-intensified, 9-drug regimen. The median survival time of the 60 eligible patients in JCOG9109 was 7.4 months, and the estimated 2-year survival rate was 15.5%; these results were identical with those of JCOG8701 but inferior to those of JCOG9303. Grade 4 neutropenia and infection of grade 3 or greater were frequent (67% and 22%, respectively), and treatment-related death was observed in 4 patients (7%), septicemia in 2, and cytomegalovirus pneumonia in 2. We conclude that DCF-containing combination chemotherapy is not a promising regimen against aggressive ATL.
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PMID:Deoxycoformycin-containing combination chemotherapy for adult T-cell leukemia-lymphoma: Japan Clinical Oncology Group Study (JCOG9109). 1262 52

Shock is a syndrome arising from any of several initiating causes, resulting in inadequate tissue perfusion. Untreated shock due to any cause can lead to irreversible cellular damage. Early diagnosis and intervention are, therefore, key to improved outcomes. In children, hypotension is not a sensitive marker for diagnosing peripheral circulatory failure. A detailed evaluation to assess perfusion particularly estimating capillary refill time and end organ perfusion is required. Septic shock is a complex condition with varying contribution of hypovolemia, cardiac dysfunction and distributive shock. Aggressive fluid therapy in the early stages is essential to recovery. Understanding the pathophysiology will help in judicious use of vasoactive drugs. Newer modalities of treatment for severe sepsis and septic shock still need evaluation in children.
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PMID:Peripheral circulatory failure. 1266 13

Liver injury is a frequent, serious complication of allogeneic hematopoietic cell transplantation (HCT) following myeloablative preparative regimens. We sought to determine the frequency and severity of hepatic injury after nonmyeloablative conditioning and its relationship to outcomes. One hundred ninety-three consecutive patients who received 2 Gy total body irradiation with or without fludarabine were evaluated for end points related to liver injury. Patients with diseases treatable by HCT who were ineligible for conventional myeloablative allogeneic HCT because of advanced age and/or comorbid conditions were included. Fifty-one patients (26%) developed hyperbilirubinemia of 68.4 microM (4 mg/dL) or greater, most commonly resulting from cholestasis due to graft-versus-host disease (GVHD) or sepsis. Pretransplantation factors associated with liver dysfunction were a diagnosis of aggressive malignancy (hazard ratio [HR] 1.9; P =.04) and the inclusion of fludarabine in the conditioning regimen (HR 1.8; P =.07). Overall survival at 1 year was superior for patients who had maximal serum bilirubin levels in the normal (78%) or minimally elevated (22.23-66.69 microM [1.3-3.9 mg/dL]) ranges (69%) compared with those in the 68.4 to 117.99 microM (4-6.9 mg/dL; 20%), 119.7 to 169.29 microM (7.0-9.9 mg/dL; 17%), and 171.0 microM (10 mg/dL; 19%) or greater groups. In summary, significant jaundice occurred in 26% of patients and was predominantly due to cholestasis resulting from GVHD and/or sepsis. Aggressive malignancies (mainly advanced disease) and later development of jaundice after transplantation predicted inferior survival.
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PMID:Hepatic injury after nonmyeloablative conditioning followed by allogeneic hematopoietic cell transplantation: a study of 193 patients. 1296 80

The immune response against a bacterial aggression involves the monocytes-macrophages and polymorphonuclear neutrophils (PMN) in the first line of defense. This natural or innate immunity controls the proliferation of micro-organisms while waiting for the development of aspecific immunity related to lymphocytes. Establishing a link between innate and specific immunity, interleukin-12 (IL-12) is an essential cytokine of the inflammatory response. In a first in vitro study, we showed that IL-12 potentiates the effect of LPS on the production of IL-8 by stimulated PMN, the main chemotactic and activating cytokine of neutrophils. IL-12 would thus support the local recruitment of PMN via an autocrine loop of amplification. In a second in vivo study in septic patients, we noted a defect in the pulmonary and systemic production of IL-12, suggesting a dysregulation of innate immunity during the course of sepsis.
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PMID:[A new role for neutrophils during sepsis: target and source of interleukin-12]. 1507 2

Calciphylaxis is a confusing disease process that affects people with end-stage renal disease. The prognosis of this increasingly common condition is poor and mortality rates range from 60% to 80% related to wound infection, sepsis, and organ failure. Its presenting sign is skin necrosis related to calcification of the arteriole microvasculature. The disease is painful and debilitating, particularly due to the necrotic wounds. Aggressive wound care to prevent infection is vital when eschar does not protect the wound and drainage is present, but debridement is contraindicated for wounds covered with dry, noninfected eschars. The decision to debride is based on the patient's total clinical picture. Patients with calciphylaxis have poor healing potential due to ischemia and comorbidity factors such as diabetes mellitus, peripheral vascular disease, and obesity. The goal of care is prevention of infection and pain management. Some of the sensitizers and challengers responsible for the chemical imbalance leading to the arteriole calcification, as well as risk factors and clinical manifestations of calciphylaxis, are reviewed. A discussion of treatment focuses on wound care of stable necrotic ulcers and a case report illustrating the progression of calciphylaxis is presented.
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PMID:Mysterious calciphylaxis: wounds with eschar--to debride or not to debride? 1525 2

Pancreatic surgery has advanced considerably during the past decades. Recent studies report reduced morbidity rates and virtually no mortality after resection. However, postoperative complications are still a formidable menace. In this chapter we discuss the management of postoperative bleeding and leakages which are considered the most feared complications, and discuss the advent of minimal invasive methods for management of these complications. Patients who develop postoperative bleeding almost always present with septic complications and a sentinel bleed before onset of bleeding. These patients should undergo early diagnostic angiography followed by embolisation. If this does control the bleeding an emergency laparotomy should be performed as last resort. Patients who develop pancreatic leakage are generally managed conservatively by means of percutaneous drainage. Aggressive surgery should be performed at the first sign of severe sepsis. The condition of the pancreatic remant found during reoperation dictates the type of surgical intervention best performed.
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PMID:Management of bleeding and leakage after pancreatic surgery. 1549 82

This article will review for bedside clinicians how to manage septic ALI.ARDS and shock to use the principles of EBM to evaluate the various therapeutic approaches for them. Low tidal volume ventilation (6 mg/dl/kg) is recommended for ALI.ARDS, but application of a minimum amount of PEEP, recruitment maneuvers with high PEEP and prone position are needed to confirm any benefit. NO inahalation, ECMO/ECCR, and glucocorticoid therapies don' t recommended for ALI.ARDS. Sivelestat Na, is available for ALI.ARDS in Japan, is needed further prospective randomized studies. Aggressive infusion of crystalloid and colloid is recommended for septic shock, but blood transfusion and bicarbonate administration are not recommended. Vasopressors are recommended for septic shock: preference for norepinephrine and cautious use of vasopressin. Stress-dose of steroid and activated protein C for severe sepsis are useful if shock don't recover by aggressive fluid infusion and vasopressors' administration.
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PMID:[Respiratory and cadiovascular management of septic ALI-ARDS and shock]. 1559

Necrotizing fasciitis is a soft-tissue infection characterized by extensive necrosis of subcutaneous fat, neurovascular structures, and fascia. In general, fascial necrosis precedes muscle and skin involvement, hence its namesake. Initially, this uncommon and rapidly progressive disease process can present as a form of cellulitis or superficial abscess. However, the high morbidity and mortality rates associated with necrotizing fasciitis suggest a more serious, ominous condition. A delay in diagnosis can result in progressive advancement highlighted by widespread infection, multiple-organ involvement, and, ultimately, death. We present a case of limb salvage in a 52-year-old patient with type 2 diabetes mellitus and progressive fascial necrosis. A detailed review of the literature is presented, and current treatment modalities are described. Aggressive surgical debridement, comprehensive medical management of the sepsis and comorbidities, and timely closure of the resultant wound or wounds are essential for a successful outcome.
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PMID:Necrotizing fasciitis in a patient with type 2 diabetes mellitus. 1641 86

Neuromuscular impairments occurring in the critically ill patient have been attributed to factors such as sepsis, release of inflammatory mediators, or the use of drugs unfavorably affecting neuromuscular function. The role of metabolic and nutritional factors in the development of this condition has received little attention. Currently, the use of protocols of intensive glycemia monitoring might be of great interest in preventing neuromuscular impairments in critically ill patients. The precise mechanisms of hyperglycemia involvement in this condition are still unknown, although evidence from research data is important. Cachectic myopathy (muscle atrophy) usually is the result of the obliged changes of metabolic response to stress. The effect of nutrients intake on muscle mass gaining is very limited, so that other actions aimed at more rapidly recovering lost muscle mass should be studied. Aggressive renutrition schedules should be avoided in order to prevent re-nutrition syndrome and further deterioration of muscle function. Intake of specific substrates, such as glutamine, might have a beneficial effect on recovering neuromuscular impairments in the critically ill patient. However, there are still no data to justify its use if the only purpose is to recover neuromuscular function.
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PMID:[Contribution of nutritional support to treatment neuromuscular impairmets of critically ill patients]. 1676 39

Enteral nutrition is a technique that even though it was used in times immemorial, in the last 25 years has suffered a considerable development, from being considered a secondary therapeutic weapon destined only to feed the patient, to occupying an important status that goes beyond the single act of nourishing. The quantitative composition but overall the qualitative one, is object of an interesting argument in which a profile allowing the modulation of certain aspects of the organism response through the supplementation with different nutrients is searched. That includes from the keeping of the intestinal trophism and of the anti-bacteria intestinal barrier, so important to avoid the frightening multiple organ dysfunction, up to the lessening of the Systemic Response Inflammatory Syndrome (SRIS), going through the immuno-modulative feeding concepts, specific-feeding, pharmaco-nutrient or eco-nutrition. In this new dynamic not only certain nutrients such as glutamine, arginine, nucleotides, omega-3 fatty acids and many antioxidants have acquired importance, but also the manipulation of other molecules of a non- nutritional nature, such as hormones, cytokines and blockers. These aspects that imply passionate ways of investigation for the future are born from the better knowledge that is being acquired from such a severe pathophysiology processes such as sepsis and the organism response before fast and severe aggression; therefore, the modulation of that response through changes in the quantitative and qualitative formulas composition is being attempted.
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PMID:Perspectives in the design and development of new products for enteral nutrition. 1677 Oct 77


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