-
Daniel's Texas Medical Journal Jan 1889
PubMed: 36953778
DOI: No ID Found -
Gut and Liver Mar 2017Second-line chemotherapy in patients with advanced pancreatic ductal adenocarcinoma (PDAC) that progresses following gemcitabine-based treatment has not been...
BACKGROUND/AIMS
Second-line chemotherapy in patients with advanced pancreatic ductal adenocarcinoma (PDAC) that progresses following gemcitabine-based treatment has not been established. This study aimed to investigate the efficacy and safety of second-line combination chemotherapy with capecitabine and oxaliplatin (XELOX) in these patients.
METHODS
Between August 2011 and May 2014, all patients who received at least one cycle of XELOX (capecitabine, 1,000 mg/m twice daily for 14 days; oxaliplatin, 130 mg/m on day 1 of a 3-week cycle) combination chemotherapy for unresectable or recurrent PDAC were retrospectively recruited. The response was evaluated every 9 weeks, and the tumor response rate, progression-free survival and overall survival, and adverse events were assessed.
RESULTS
Sixty-two patients were included; seven patients (11.3%) had a partial tumor response, and 20 patients (32.3%) had stable disease. The median progression-free and overall survival were 88 days (range, 35.1 to 140.9 days) and 158 days (range, 118.1 to 197.9 days), respectively. Patients who remained stable longer with frontline therapy (≥120 days) exhibited significantly longer progression-free and overall survival. The most common grade 3 to 4 adverse events in patients were vomiting (8.1%) and anorexia (6.5%). There was one treatment-related mortality caused by severe neutropenia and typhlitis.
CONCLUSIONS
Second-line XELOX combination chemotherapy demonstrated an acceptable response and survival rate in patients with advanced PDAC who had failed gemcitabine-based chemotherapy.
Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Carcinoma, Pancreatic Ductal; Deoxycytidine; Disease-Free Survival; Drug Administration Schedule; Female; Fluorouracil; Humans; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Oxaloacetates; Pancreatic Neoplasms; Retrospective Studies; Survival Rate; Treatment Outcome; Gemcitabine
PubMed: 27965478
DOI: 10.5009/gnl16307 -
Bone Marrow Transplantation Jun 2000Mucositis is an inevitable side-effect of the conditioning regimens used for haematopoietic stem cell transplantation. The condition is better referred to as mucosal... (Review)
Review
Mucositis is an inevitable side-effect of the conditioning regimens used for haematopoietic stem cell transplantation. The condition is better referred to as mucosal barrier injury (MBI) since it is primarily the result of toxicity and is a complex and dynamic pathobiological process manifested not only in the mouth but also throughout the entire digestive tract. A model has been proposed for oral MBI and consists of four phases, namely inflammatory, epithelial, ulcerative and healing phases. A variety of factors are involved in causing and modulating MBI including the nature of the conditioning regimen, the elaboration of pro-inflammatory and other cytokines, translocation of the resident microflora and their products, for example, endotoxins across the mucosal barrier, exposure to antimicrobial agents and whether or not the haematopoietic stem cell graft is from a donor. Neutropenic typhlitis is the most severe gastrointestinal manifestation of MBI, but it also influences the occurrence of other major transplant-related complications including acute GVHD, veno-occlusive disease and systemic infections. The pathobiology, clinical counterparts and the means of measuring MBI are discussed together with potential approaches for prevention, amelioration and, perhaps, even cure. Bone Marrow Transplantation (2000) 25, 1269-1278.
Topics: Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Immunity, Mucosal; Mouth Mucosa; Stomatitis
PubMed: 10871732
DOI: 10.1038/sj.bmt.1702447 -
Memorias Do Instituto Oswaldo Cruz Dec 2003An investigation related to the frequency and pathology of Heterakis gallinarum and pathology of Heterakis isolonche in pheasants from Rio de Janeiro, Brazil was...
An investigation related to the frequency and pathology of Heterakis gallinarum and pathology of Heterakis isolonche in pheasants from Rio de Janeiro, Brazil was conducted by means of clinical examinations, necropsies, and histopathological analysis in 50 ring-necked pheasants from backyard flocks of 11 localities; also, histological sections of caeca of golden pheasants deposited in the Helminthological Collection of the Oswaldo Cruz Institute (CHIOC) have been considered in the present study. During necropsies, only specimens of H. gallinarum were recovered with a prevalence of 90%, mean intensity of 81.9 and range of infection of 1-413. Gross lesions were characterized by congestion, thickening, petechial haemorrhages of the mucosa, intussusception, and nodules in the cecal wall. Under microscopy, chronic diffuse typhlitis, haemosiderosis, granulomas with necrotic center in the submucosa and leiomyomas in the submucosa, muscular and serosa associated with immature H. gallinarum worms were observed. The examination of histological sections previously deposited in the CHIOC, revealed more severe alterations associated with concomitant infections with H. gallinarum and H. isolonche in golden pheasants, and were characterized by several necrotic areas with cholesterol clefts in the submucosa, giant cell granulomas in the submucosa, and serosa centralized by necrosis and worm sections and neoplastic nodules in the muscular and submucosa.
Topics: Animals; Bird Diseases; Birds; Brazil; Cecal Diseases; Cecal Neoplasms; Female; Male; Nematode Infections
PubMed: 15049081
DOI: 10.1590/s0074-02762003000800005 -
BMC Neuroscience Jul 2019Emerging data suggests that volatile anesthetic agents may have organ protection properties in the setting of critical illness. The purpose of this study was to better...
BACKGROUND
Emerging data suggests that volatile anesthetic agents may have organ protection properties in the setting of critical illness. The purpose of this study was to better understand the effect of inflammation on cerebral subcellular energetics in animals exposed to two different anesthetic agents-a GABA agonist (propofol) and a volatile agent (isoflurane).
RESULTS
Forty-eight Sprague-Dawley rats were anesthetized with isoflurane or propofol. In each group, rats were randomized to celiotomy and closure (sham) or cecal ligation and puncture (inflammation [sepsis model]) for 8 h. Brain tissue oxygen saturation and the oxidation state of cytochrome aa were measured. Brain tissue was extracted using the freeze-blow technique. All rats experienced progressive increases in tissue oxygenation and cytochrome aa reduction over time. Inflammation had no impact on cytochrome aa, but isoflurane caused significant cytochrome aa reduction. During isoflurane (not propofol) anesthesia, inflammation led to an increase in lactate (+ 0.64 vs. - 0.80 mEq/L, p = 0.0061). There were no differences in ADP:ATP ratios between groups. In the isoflurane (not propofol) group, inflammation increased the expression of hypoxia-inducible factor-1α (62%, p = 0.0012), heme oxygenase-1 (67%, p = 0.0011), and inducible nitric oxide synthase (31%, p = 0.023) in the brain. Animals exposed to inflammation and isoflurane (but not propofol) exhibited increased expression of protein carbonyls (9.2 vs. 7.0 nM/mg protein, p = 0.0050) and S-nitrosylation (49%, p = 0.045) in the brain. RNA sequencing identified an increase in heat shock protein 90 and NF-κβ inhibitor mRNA in the inflammation/isoflurane group.
CONCLUSIONS
In the setting of inflammation, rats exposed to isoflurane show increased hypoxia-inducible factor-1α expression despite a lack of hypoxia, increased oxidative stress in the brain, and increased serum lactate, all of which suggest a relative increase in anaerobic metabolism compared to propofol. Differences in oxidative stress as well as heat shock protein 90 and NF-κβ inhibitor may account for the differential expression of cerebral hypoxia-inducible factor-1α during inflammation.
Topics: Adenosine Diphosphate; Adenosine Triphosphate; Anesthetics, Inhalation; Animals; Brain; Electron Transport Complex IV; HSP90 Heat-Shock Proteins; Heme Oxygenase (Decyclizing); Hypoxia-Inducible Factor 1, alpha Subunit; Inflammation; Isoflurane; Lactic Acid; Male; NF-kappa B; Nitric Oxide Synthase Type II; Oxidation-Reduction; Oxygen; Propofol; Protein Carbonylation; Rats; Typhlitis
PubMed: 31307382
DOI: 10.1186/s12868-019-0514-8 -
Annals of Intensive Care Dec 2016Neutropenia is defined by either an absolute or functional defect (acute myeloid leukemia or myelodysplastic syndrome) of polymorphonuclear neutrophils and is associated... (Review)
Review
Management of neutropenic patients in the intensive care unit (NEWBORNS EXCLUDED) recommendations from an expert panel from the French Intensive Care Society (SRLF) with the French Group for Pediatric Intensive Care Emergencies (GFRUP), the French Society of Anesthesia and Intensive Care (SFAR),...
Neutropenia is defined by either an absolute or functional defect (acute myeloid leukemia or myelodysplastic syndrome) of polymorphonuclear neutrophils and is associated with high risk of specific complications that may require intensive care unit (ICU) admission. Specificities in the management of critically ill neutropenic patients prompted the establishment of guidelines dedicated to intensivists. These recommendations were drawn up by a panel of experts brought together by the French Intensive Care Society in collaboration with the French Group for Pediatric Intensive Care Emergencies, the French Society of Anesthesia and Intensive Care, the French Society of Hematology, the French Society for Hospital Hygiene, and the French Infectious Diseases Society. Literature review and formulation of recommendations were performed using the Grading of Recommendations Assessment, Development and Evaluation system. Each recommendation was then evaluated and rated by each expert using a methodology derived from the RAND/UCLA Appropriateness Method. Six fields are covered by the provided recommendations: (1) ICU admission and prognosis, (2) protective isolation and prophylaxis, (3) management of acute respiratory failure, (4) organ failure and organ support, (5) antibiotic management and source control, and (6) hematological management. Most of the provided recommendations are obtained from low levels of evidence, however, suggesting a need for additional studies. Seven recommendations were, however, associated with high level of evidences and are related to protective isolation, diagnostic workup of acute respiratory failure, medical management, and timing surgery in patients with typhlitis.
PubMed: 27638133
DOI: 10.1186/s13613-016-0189-6 -
Helicobacter Apr 2015Helicobacter cinaedi, an enterohepatic helicobacter species (EHS), is an important human pathogen and is associated with a wide range of diseases, especially in...
BACKGROUND
Helicobacter cinaedi, an enterohepatic helicobacter species (EHS), is an important human pathogen and is associated with a wide range of diseases, especially in immunocompromised patients. It has been convincingly demonstrated that innate immune response to certain pathogenic enteric bacteria is sufficient to initiate colitis and colon carcinogenesis in recombinase-activating gene (Rag)-2-deficient mice model. To better understand the mechanisms of human IBD and its association with development of colon cancer, we investigated whether H. cinaedi could induce pathological changes noted with murine enterohepatic helicobacter infections in the Rag2(-/-) mouse model.
MATERIALS AND METHODS
Sixty 129SvEv Rag2(-/-) mice mouse were experimentally or sham infected orally with H. cinaedi strain CCUG 18818. Gastrointestinal pathology and immune responses in infected and control mice were analyzed at 3, 6 and 9 months postinfection (MPI). H. cinaedi colonized the cecum, colon, and stomach in infected mice.
RESULTS
H. cinaedi induced typhlocolitis in Rag2(-/-) mice by 3 MPI and intestinal lesions became more severe by 9 MPI. H. cinaedi was also associated with the elevation of proinflammatory cytokines, interferon-γ, tumor-necrosis factor-α, IL-1β, IL-10; iNOS mRNA levels were also upregulated in the cecum of infected mice. However, changes in IL-4, IL-6, Cox-2, and c-myc mRNA expressions were not detected.
CONCLUSIONS
Our results indicated that the Rag2(-/-) mouse model will be useful to continue investigating the pathogenicity of H. cinaedi, and to study the association of host immune responses in IBD caused by EHS.
Topics: Animals; Cecum; Colitis; Colon; Cytokines; DNA-Binding Proteins; Female; Gene Expression Profiling; Helicobacter; Male; Mice; Mice, Knockout; Nitric Oxide Synthase Type II; Typhlitis
PubMed: 25381744
DOI: 10.1111/hel.12179 -
Hematology, Transfusion and Cell Therapy Aug 2023High-dose cytarabine is considered standard of care as consolidation chemotherapy in adults with acute myeloid leukemia (AML) who are not eligible for allogeneic...
INTRODUCTION
High-dose cytarabine is considered standard of care as consolidation chemotherapy in adults with acute myeloid leukemia (AML) who are not eligible for allogeneic hematopoietic cell transplantation, but may be associated with significant toxicity. We evaluated the toxicity associated with high-dose cytarabine given as consolidation in AML patients treated at a Brazilian public hospital.
METHODS
We retrospectively reviewed the charts of all patients with AML treated between 2008 and 2020 who obtained complete remission (CR) after one cycle of induction chemotherapy and received consolidation with at least one cycle of high-dose cytarabine (defined as 3 g/m every 12 h days 1, 3 and 5).
RESULTS
Among 61 patients who received induction remission, 32 obtained CR and 28 received at least one cycle of high-dose cytarabine, for a total of 67 cycles (median 2 cycles per patient, range 1 - 4). In 45 cycles (67.2%) the patient was discharged after the end of chemotherapy, with a median of 6 days at home (range 3 - 8). Readmission occurred in 31 of the 45 cycles (68.9%). The most frequent toxicities were febrile neutropenia (56.7%), nausea and vomiting (23.9%), oral mucositis (14.9%) and diarrhea (11.9%). Bacteremia was documented in 13 cycles (34.2%). There were three cases of typhlitis and two of invasive fungal disease (aspergillosis and candidemia). Four patients died (14.3%), with two deaths considered treatment-related (candidemia and typhlitis).
CONCLUSION
In the setting of a Brazilian public hospital, high-dose cytarabine as consolidation therapy is feasible, with manageable toxicity profile.
PubMed: 37684163
DOI: 10.1016/j.htct.2023.07.007 -
Gastrointestinal Endoscopy Clinics of... Oct 1998The colon is a frequent site of gastrointestinal complications in patients with HIV infection, and these colonic disorders increase in frequency as immunodeficiency... (Comparative Study)
Comparative Study Review
The colon is a frequent site of gastrointestinal complications in patients with HIV infection, and these colonic disorders increase in frequency as immunodeficiency worsens. The most common clinical manifestations of colonic disease in AIDS are diarrhea, lower gastrointestinal bleeding, and abdominal pain. Toxic megacolon, intussuseption, typhlitis, idiopathic colonic ulcer, and pneumatosis intestinalis also have been described. In the HIV-infected patient with preserved immunity, the most common cause of colitis is bacterial, but as the degree of immunodeficiency worsens, opportunistic pathogens (CMV, protozoa, mycobacteria, fungi) and neoplasms become more frequent. The frequent use of antibiotics, chemotherapeutic agents, and frequent hospitalization increase the susceptibility to cf2Clostridium difficule cf1colitis. Endoscopy plays an integral role in the management of many colonic disorders in AIDS.
Topics: AIDS-Related Opportunistic Infections; Acquired Immunodeficiency Syndrome; Adult; Anti-Infective Agents; Biopsy; Colectomy; Colon; Colonic Diseases; Colonoscopy; Diagnosis, Differential; Follow-Up Studies; Humans; Immunosuppressive Agents; Tomography, X-Ray Computed
PubMed: 9730938
DOI: 10.1016/S1052-5157(18)30238-1 -
Revista Brasileira de Parasitologia... Aug 2019Diseases related to the alimentary system are the main cause of death in horses. This retrospective study aimed to describe the pathological findings of fatal...
Diseases related to the alimentary system are the main cause of death in horses. This retrospective study aimed to describe the pathological findings of fatal parasite-induced enteritis and typhlocolitis caused by cyathostominae, Eimeria leuckarti, Balantidium coli, and Strongyloides westeri in horses. The records of parasite-induced intestinal lesions in horses necropsied in Southern Brazil between 2005 and 2017 were reviewed. Ten horses had fatal parasitic enteritis and/or typhlocolitis, and the main causes were: cyathostominae typhlocolitis (6/10), E. leuckarti enteritis (1/10), S. westeri enteritis (1/10), B. coli colitis related to cyathostominae (1/10), and infection by multiple agents (1/10). Cyathostominae typhlocolitis showed marked mucosal thickening, with multifocal elevated nodules containing tangled filiform parasites. Microscopic examination revealed that the mucosa and submucosa had encysted parasitic structures surrounded by eosinophilic and granulomatous inflammation. E. leuckarti enteritis was microscopically characterized by macrogamonts, microgamonts, and oocysts inside the host cells. S. westeri enteritis showed microscopic atrophy of the villi with numerous mucosal encysted parasitic structures. B. coli typhlocolitis showed severe diffuse mucosal reddening, with microscopic superficial mucosal necrosis associated with multiple protozoan trophozoites. Fatal parasite-induced enteritis and typhlocolitis are important causes of death in horses in Southern Brazil.
Topics: Animals; Balantidium; Colitis; Eimeria; Enteritis; Feces; Female; Horse Diseases; Horses; Male; Retrospective Studies; Seasons; Strongyloides; Typhlitis
PubMed: 31390438
DOI: 10.1590/S1984-29612019056