misoprostol and Pneumonia

This study compared prophylactic administration of either intragastric misoprostol (200 micrograms four times a day), a prostaglandin E1 analog, or bolus intravenous cimetidine (300 mg every 6 hours) in preventing stress lesions and stress bleeding in 127 adult postoperative patients who required mechanical ventilation and also had developed hypotension or sepsis. Both drug treatments were equally effective in preventing the development of diffuse gastritis (greater than 10 gastric hemorrhagic lesions) and in preventing upper gastrointestinal hemorrhage (UGIH). The combined data from both groups showed that for the 44 (35%) patients who died, death was significantly associated with the presence at study entry of renal failure (64% of 25 patients with renal failure died), hepatic failure (57% of 23 patients) or coagulopathy (62% of 29 patients) (p less than 0.02 for each), and with the number of organ system failures at study entry (48% of 69 patients with multiple organ system failures died, p less than 0.001). Death was also significantly associated with the presence of adult respiratory distress syndrome (ARDS) at study entry or the development of ARDS (63% of 24 patients with ARDS died, p less than 0.001), and the development of UGIH (5% of 93 patients with known bleeding outcome died, p less than 0.05). The number of stress lesions that developed was significantly associated with subsequent UGIH (p less than 0.001). Additional organ system failure developed during the study in 31% of the 127 patients, as did diffuse gastritis in 20% of 111 patients who had a follow-up endoscopy. These results demonstrate that postoperative patients who require mechanical ventilation and have hypotension or sepsis are at significant risk for the development of stress gastric lesions and multiple organ system failure even when prophylaxis for stress ulcers is provided. Furthermore, the presence of ARDS, renal failure, hepatic failure, coagulopathy, and UGIH are significantly associated with death.

Topics: Cause of Death; Cimetidine; Critical Care; Double-Blind Method; Female; Follow-Up Studies; Gastroscopy; Humans; Male; Middle Aged; Misoprostol; Multiple Organ Failure; Peptic Ulcer; Peptic Ulcer Hemorrhage; Placebos; Pneumonia; Postoperative Complications; Prospective Studies; Respiratory Distress Syndrome; Stress, Physiological; Surgical Procedures, Operative; Survival Rate; Treatment Outcome; Wound Healing

Endogenous prostanoids have been suggested to modulate sensitization during experimental allergic asthma, but the specific role of prostaglandin (PG) E₂ or of specific E prostanoid (EP) receptors is not known.. Here we tested the role of EP2 signaling in allergic asthma.. Wild-type (WT) and EP2(-/-) mice were subjected to ovalbumin sensitization and acute airway challenge. The PGE2 analog misoprostol was administered during sensitization in both genotypes. In vitro culture of splenocytes and flow-sorted dendritic cells and T cells defined the mechanism by which EP2 exerted its protective effect. Adoptive transfer of WT and EP2(-/-) CD4 T cells was used to validate the importance of EP2 expression on T cells.. Compared with WT mice, EP2(-/-) mice had exaggerated airway inflammation in this model. Splenocytes and lung lymph node cells from sensitized EP2(-/-) mice produced more IL-13 than did WT cells, suggesting increased sensitization. In WT but not EP2(-/-) mice, subcutaneous administration of misoprostol during sensitization inhibited allergic inflammation. PGE₂ decreased cytokine production and inhibited signal transducer and activator of transcription 6 phosphorylation by CD3/CD28-stimulated CD4(+) T cells. Coculture of flow cytometry-sorted splenic CD4(+) T cells and CD11c(+) dendritic cells from WT or EP2(-/-) mice suggested that the increased IL-13 production in EP2(-/-) mice was due to the lack of EP2 specifically on T cells. Adoptive transfer of CD4(+) EP2(-/-) T cells caused greater cytokine production in the lungs of WT mice than did transfer of WT CD4(+) T cells.. We conclude that the PGE2-EP2 axis is an important endogenous brake on allergic airway inflammation and primarily targets T cells and that its agonism represents a potential novel therapeutic approach to asthma.

Topics: Adoptive Transfer; Allergens; Animals; Asthma; Bronchoalveolar Lavage Fluid; CD4-Positive T-Lymphocytes; Cells, Cultured; Cytokines; Dendritic Cells; Dinoprostone; Lymph Nodes; Male; Mice; Mice, Knockout; Misoprostol; Ovalbumin; Pneumonia; Receptors, Prostaglandin E, EP2 Subtype; Spleen

Topics: Adolescent; Adult; Female; Gestational Age; Humans; Misoprostol; Oxytocin; Pneumonia; Postpartum Hemorrhage; Pre-Eclampsia; Pregnancy; Uterine Diseases