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)

The case of a 59-year-old woman who presented with signs and symptoms of biliary obstruction and cholangitis is reported. The patient's clinical course was punctuated by recurring sepsis and acute hemorrhagic pancreatitis. Computed tomography revealed extrinsic compression of the common hepatic duct, which was nonfilling on cholangiography, thus raising the suspicion of a solid tumor; the common hepatic duct diverticulum was not revealed until autopsy. Diverticula in this region of the biliary tract are extremely rare and may, as in this case, present a diagnostic challenge and result in a fatal outcome.
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PMID:A rare common hepatic duct diverticulum causing fatal biliary obstruction and sepsis. 949 68

Few studies have addressed the influence of profound myelosuppressive therapy in contemporary protocols on infectious morbidity in pediatric oncology patients. This study evaluates the types of infections and the methods used to diagnose infection in patients enrolled in current Children's Cancer Group (CCG) protocols. Data were collected on patients enrolled in CCG protocols from January 1, 1992, through December 31, 1995. Of the 155 protocol patients, 102 were completely evaluated and had data collected through August 1, 1996. Patients were divided into two diagnosis groups: leukemia/lymphoma (N = 51) and solid tumor (N = 51). Eighty-five (83%) patients had documented infections and 17 (17%) did not. Overall, 96 (94%) patients had in-dwelling central venous catheters. Twelve categories of infection were identified. Data were analyzed for age, gender, diagnosis, neutropenia, organism, and disease state (primary active, recurrent active, primary remission, and secondary remission). Statistical comparisons were made only on rates, whereas descriptive comparisons were given for numbers of infections and organisms. The infection rates for patients with active disease were 1.01 and 1.15 per 100 patient days (primary versus recurrent) and 0.59 and 0.38 per 100 patient days for patients with disease in remission (primary versus secondary). Diagnosis-group infection rates were 0.66 and 0.68 per 100 patient days for patients with solid tumors and leukemia/lymphoma, respectively. Three hundred thirty infections, including 19 polymicrobial infections, were recorded. The three most common types of infection were otitis media, septicemia, and urinary tract infection. More infections were associated with an age at diagnosis of less than 3 years, a leukemia/lymphoma diagnosis in remission, and an absolute neutrophil count >500 cells/microL. One hundred ninety-four organisms were isolated from 330 infections. Gram-positive organisms (n = 74) such as coagulase-negative Staphylococci (n = 38) predominated over gram-negative organisms (n = 63) for all infectious categories. Specifically, gram-positive organisms (n = 39) were isolated more often from blood cultures than were gram-negative organisms (n = 27). The overall mortality for patients was 36%. Seven of the 37 (19%) patient deaths were attributed to infection. These patients predominantly were girls with neutropenia and leukemia/ lymphoma in active disease who died of gram-negative sepsis. Infections with gram-positive organisms continue to be major causes of morbidity in pediatric oncology patients receiving contemporary CCG protocols. However, infection-related mortality, especially with gram-negative organisms, occurs less frequently than does malignancy-related mortality. Common childhood infections (such as otitis media) seem equally as prevalent as bacteremia in pediatric oncology patients. Thus, a comprehensive physical examination is as imperative as the microbiologic evaluation in diagnosing infection in this patient population.
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PMID:Infections in children with cancer: a continued need for the comprehensive physical examination. 1059 61

FTY720, a potent immunosuppressive agent, is phosphorylated in vivo into FTY720-P, a high affinity agonist for sphingosine 1-phosphate (S1P) receptors. The effects of FTY720 on vascular cells, a major target of S1P action, have not been addressed. We now report the metabolic activation of FTY720 by sphingosine kinase-2 and potent activation of vascular endothelial cell functions in vitro and in vivo by phosphorylated FTY720 (FTY720-P). Incubation of endothelial cells with FTY720 resulted in phosphorylation by sphingosine kinase activity and formation of FTY720-P. Sphingosine kinase-2 effectively phosphorylated FTY720 in the human embryonic kidney 293T heterologous expression system. FTY720-P treatment of endothelial cells stimulated extracellular signal-activated kinase and Akt phosphorylation and adherens junction assembly and promoted cell survival. The effects of FTY720-P were inhibited by pertussis toxin, suggesting the requirement for Gi-coupled S1P receptors. Indeed, transmonolayer permeability induced by vascular endothelial cell growth factor was potently reversed by FTY720-P. Furthermore, oral FTY720 administration in mice potently blocked VEGF-induced vascular permeability in vivo. These findings suggest that FTY720 or its analogs may find utility in the therapeutic regulation of vascular permeability, an important process in angiogenesis, inflammation, and pathological conditions such as sepsis, hypoxia, and solid tumor growth.
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PMID:Phosphorylation and action of the immunomodulator FTY720 inhibits vascular endothelial cell growth factor-induced vascular permeability. 1295 48

In the last decade, a remarkable increase in the incidence of nosocomial Gram-negative infections has been observed. These pathogens represent a substantial problem in clinical practice, due to the high resistance profile of most commonly used antibiotics. This phenomenon is surely a co-factor that exposes these susceptible patients to infections caused by selected pathogens like multiresistant Gram-negative rods. A typical example is represented by VAP (ventilator-associated pneumonia) sustained by Acinetobacter spp., Pseudomonas aeruginosa, Bulkolderia cepacia. The Authors describe a case of a central venous cather (CVC)-related Stenotrophomonas maltophilia sepsis in a patient affected by solid tumor, successfully treated with systemic antibiotic therapy associated with "lock therapy". This combination was able to cure the infection, allowing the patient to continue chemotherapy and saving the in situ CVC. The surveillance of CVCs, good adherence to the protocols and guidelines and "good practice" are the cornerstones for the prevention of nosocomial infections.
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PMID:Multiresistant Stenotrophomonas maltophilia tunneled CVC-related sepsis, treated with systemic and lock therapy. 1556 19

Primary effusion lymphoma (PEL) is an unusual form of non-Hodgkin's lymphoma, which is characterized by lymphomatous effusion in body cavities, but no associated mass lesions. It is usually associated with an immunodeficient state most often with the human immunodeficiency virus (HIV). We describe a 54-year-old man with HIV-negative PEL, with a history of hepatitis B virus-related liver cirrhosis. Both abdominal and pleural cavities were involved; no solid tumor masses were found and bone marrow investigations were normal. The ascites and pleural effusion contained numerous pleomorphic lymphoid cells. Immunophenotyping was positive for CD138. Chromosome study showed complex cytogenetics. The genomic human herpesvirus-8 was detected in the lymphoma cells. It is postulated that the immunosuppressed state in this patient may have been caused by cirrhosis. The patient received four cycles of chemotherapy of CHOP and Picibanil (OK-432) intraperitoneal administration. However, no durable remission was achieved. Adefovir failed to halt the progressive liver failure after the development of YMDD mutant related to lamivudine. He died of sepsis and hepatic failure.
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PMID:Primary effusion lymphoma involving both pleural and abdominal cavities in a patient with hepatitis B virus-related liver cirrhosis. 1758 46

Collection of PBSC by leukapheresis requires one venous access (VA) for inflow and one for outflow. The use of implantable venous access devices (IVAD) has never been reported in this setting. We retrospectively analyzed the use of IVAD for performing apheresis. The study was conducted between January 2000 and June 2005 on 64 patients (41 children) requiring intensification for treatment of a solid tumor. Mean body weight was 26 kg (range 8-91 kg) for a median age of 8.5 years (range 0.7-66 years). A total of 121 aphereses were performed (mean 1.89 apheresis/patient). The second VA was in a cubital vein in 84 procedures and was a temporary central VA in 31. Mean duration of apheresis was 3 h (range 30-274 min). Mean flow rate was 41.3 ml/min (range 12-85 ml/min). Mean collection rate was 59.2% for CD34+ cells and 70% for mononuclear cells. The total number of CD34+ cells collected was 2.5 x 10(6)/kg per apheresis, and 5.9 x 10(6)/kg per patient. Several complications occurred: one catheter-related sepsis (0.86%), four catheter occlusions (3.47%) and eight hemodynamic instabilities related to extracorporeal volume. Weight <10 kg is a risk factor for complication (P=0.0006). IVAD are effective and safe for PBSC collection. Placement of a second central VA (requiring general anesthesia for children) could be avoided.
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PMID:Use of totally implantable catheters for peripheral blood stem cell apheresis. 1760 15

The metabolites of N-[(trimethylamineboryl)-carbonyl]-L-phenylalanine methyl ester 1 proved to be active in a number of pharmacological screens where the parent had previously demonstrated potent activity. The proposed metabolites demonstrated significant activity as cytotoxic, hypolipidemic, and anti-inflammatory agents. In cytotoxicity screens several of the proposed metabolites afforded better activity than the parent compound against the growth of suspended and solid tumor cell lines. Evaluation of in vivo hypolipidemic activity demonstrated that the proposed metabolites of 1 were only moderately active and were generally less effective than the parent compound. Interestingly, L-phenylalanine methyl ester hydrochloride 3, which contains no boron atom, demonstrated equivalent hypolipidemic activity as the parent at 8 mg/kg/day in CF(1) male mice. As anti-inflammatory agents the proposed metabolites demonstrated variable capacities to reduce foot pad inflammation. These compounds were similarly effective as the parent 1 at blocking local pain and were generally better than the parent at protecting CF(1) male mice from LPS induced sepsis.
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PMID:The pharmacological activities of the metabolites of N-[(trimethylamineboryl)-carbonyl]-L-phenylalanine methyl ester. 1847 97

One of the more insidious outcomes of patients who survive severe sepsis is profound immunosuppression. In this study, we addressed the hypothesis that post septic immune defects were due, in part, to the presence and/or expansion of regulatory T cells (Tregs). After recovery from severe sepsis, mice exhibited significantly higher numbers of Tregs, which exerted greater in vitro suppressive activity compared with controls. The expansion of Tregs was not limited to CD25(+) cells, because Foxp3 expression was also detected in CD25(-) cells from post septic mice. This latter group exhibited a significant increase of chromatin remodeling at the Foxp3 promoter, because a marked increase in acetylation at H3K9 was associated with an increase in Foxp3 transcription. Post septic splenic dendritic cells promoted Treg conversion in vitro. Using a solid tumor model to explore the function of Tregs in an in vivo setting, we found post septic mice showed an increase in tumor growth compared with sham-treated mice with a syngeneic tumor model. This observation could mechanistically be related to the ability of post septic Tregs to impair the antitumor response mediated by CD8(+) T cells. Together, these data show that the post septic immune system obstructs tumor immunosurveillance, in part, by augmented Treg expansion and function.
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PMID:The post sepsis-induced expansion and enhanced function of regulatory T cells create an environment to potentiate tumor growth. 2052 17

Combination antimicrobial therapy represents common practice in the treatment of febrile neutropenia aiming to broaden the antimicrobial spectrum against Gram-negative pathogens. We did a prospective, non-randomized, comparative study to evaluate ceftazidime plus either levofloxacin or once-daily amikacin as empirical regimens for febrile neutropenia in patients with solid tumor or hematopoietic neoplasm in a region of high baseline resistance prevalence. We included 285 febrile neutropenic episodes in 235 individual patients. One hundred forty-eight cases received levofloxacin and 137 received amikacin, both in combination with ceftazidime. More cases in the levofloxacin than the amikacin group had underlying hematological malignancy; most other characteristics of the two groups were well balanced. Nephrotoxicity requiring treatment discontinuation occurred in one case in the amikacin group. No difference in clinical success (79.7% vs. 80.3%, p>0.99) or all-cause mortality (12.8% vs. 11.7%, p=0.86) was noted between the levofloxacin and the amikacin groups, even after adjustment for the independent predictor variables for each endpoint. Sepsis at presentation, presence of localizing symptoms/signs of infection, and isolation of a non-susceptible Gram-negative pathogen independently predicted both clinical success and all-cause mortality. Additionally, underlying solid tumor independently predicted clinical success, while poor prognosis of the underlying neoplasia and skin/soft tissue infection independently predicted mortality. Ceftazidime plus levofloxacin had similar effectiveness to ceftazidime plus amikacin as empirical regimens for febrile neutropenia. Nephrotoxicity with once-daily amikacin was minimal. Inappropriate empirical therapy was associated with worse prognosis.
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PMID:Empirical therapy with ceftazidime combined with levofloxacin or once-daily amikacin for febrile neutropenia in patients with neoplasia: a prospective comparative study. 2203 22

Typhlitis is a necrotizing colitis that usually occurs in neutropenic patients and develops most often in patients with hematologic malignancies such as leukemia and lymphoma. Typhlitis may proceed to bowel perforation, peritonitis and sepsis, which requires immediate treatment. Irinotecan is a semisynthetic analogue of the natural alkaloid camptothecin which prevents DNA from unwinding by inhibition of topoisomerase I. It is mainly used in colon cancer and small cell lung carcinoma (SCLC), of which the most common adverse effects are gastrointestinal toxicities. To the best of our knowledge, no case of typhlitis after chemotherapy with a standard dose of irinotecan in a solid tumor has been reported in the literature. We, herein, report the first case of typhlitis developed after chemotherapy combining irinotecan and cisplatin in a patient with SCLC.
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PMID:A case of typhlitis developed after chemotherapy with irinotecan and Cisplatin in a patient with small cell lung carcinoma. 2323 22


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