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)

Diagnosis of acute cholecystitis in critically ill patients is often difficult; clinical signs are subtle, and radiologic tests are nonspecific and have a high incidence of false-positive results. This study reviews our experience with intravenous morphine sulfate as an adjunct to promote gallbladder filling in 18 critically ill patients who demonstrated nonvisualization of the gallbladder during cholescintigraphy performed as part of a diagnostic workup for occult sepsis. Findings suggestive of a biliary source included fever, leukocytosis, abdominal tenderness, abnormal liver function test results, fasting, and total parenteral nutrition. Morphine was administered to all 18 patients after nonvisualization of the gallbladder; in 17 cases prompt visualization was noted, thus excluding cystic duct obstruction. The remaining patient underwent operation for acalculous cholecystitis. None of the 17 patients whose gallbladders were visualized had a subsequent clinical course consistent with untreated biliary sepsis. Radionuclide cholescintigraphy with morphine appears to be useful in the evaluation of critically ill patients with suspected biliary sepsis. It is particularly helpful in confirming or excluding the diagnosis of acute acalculous cholecystitis in patients who are fasting or receiving total parenteral nutrition and initially demonstrate nonvisualization of the gallbladder and in patients who have previously documented gallstones.
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PMID:Use of cholescintigraphy with morphine in critically ill patients with suspected cholecystitis. 279 41

Morphine-augmented radionuclide cholescintigraphy (MC) is a useful adjunctive diagnostic tool for the identification of acute cholecystitis (AC) in patients who are hospitalized and critically ill with occult sepsis. The results of previous studies have demonstrated a reduction in false-positive rates, that is, nonvisualization, from 40 percent with standard radionuclide cholescintigraphy to 5 percent with MC in these high-risk patient groups, with an overall accuracy of 92 percent. This study was performed to determine the significance of a positive test result from MC in patients with occult sepsis. We reviewed the records of all 20 patients at high risk in whom MC was positive during the 35-month period ending 31 May 1992. AC was confirmed by laparotomy in all 16 patients who underwent surgical treatment. There were two patients who recovered with antibiotic therapy alone (considered false-positives) and two additional patients who died without operation or a confirmed diagnosis of AC (excluded from analysis). Thus, in this series, MC was associated with a positive predictive value of 0.89, confirming that it is a valuable adjunct in establishing the diagnosis of AC in patients who are seriously ill and hospitalized with occult sepsis.
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PMID:The significance of a positive test of morphine cholescintigraphy in hospitalized patients. 835 94

Fentanyl citrate analgesia attenuates the excess nitrogen excretion in the urine and glucose production induced by trauma. On the other hand, intracerebroventricular injection of morphine stimulates excretion of stress hormones, such as catecholamines and corticosterone. Furthermore, morphine levels in the brain are increased during fasting and sepsis. The aims of this study were to determine whether intracerebroventricular injection of tumor necrosis factor-alpha (TNF-alpha) elevates morphine levels in the rat brain and whether prophylactic administration of fentanyl blocks metabolic responses induced by intracerebroventricular injection of TNF-alpha because of a reduction of morphine levels in the brain. Morphine levels in the brain were increased from 648 to 1,134 fmol/g at 30 min after intracerebroventricular injection of TNF-alpha (P < 0.05 vs. control). This increase was associated with an increase in stress hormones (corticosterone: 416.1 +/- 69.1 ng/ml, P < 0.05 vs. control; epinephrine: 3,778.3 +/- 681.3 pg/ml, P < 0.01 vs. control) and an enhancement of proteolysis (254.2 +/- 45.7 micromol Leu . kg-1 . h-1, P < 0.01 vs. control) and glucose production (7.5 +/- 0. 7 mg . kg-1 . min-1, P < 0.05 vs. control). Fentanyl reduced morphine levels in the brain to 624 fmol/g (not significant vs. control), resulting in a reduction of stress hormone levels in the plasma and blunted metabolic responses. In conclusion, prophylactic administration of fentanyl prevented an increase in morphine levels in the brain induced by intracerebroventricular injection of TNF-alpha, leading to a reduction in stress hormone levels and subsequent metabolic responses.
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PMID:Effect of fentanyl on morphine levels in the brain in rats receiving intracerebroventricular injection of TNF-alpha. 975 82

Gram-negative sepsis and subsequent endotoxic shock after surgery remain problematic in the United States and throughout the world. While morphine is widely prescribed for postoperative trauma pain management, there are reports that morphine may compromise the immune system and contribute to postoperative sepsis. The current study tested the hypothesis that morphine attenuates leukocyte rolling and sticking in both arterioles and venules via nitric oxide production. Nude mice implanted with slow-release morphine pellets were used in this study. The dorsal skinfold chamber model for intravital fluorescence microscopy on awake mice was used. Leukocyte/endothelial interactions were evaluated after bolus injection of oxidized low density lipoprotein. Morphine was found to significantly attenuate leukocyte rolling and sticking in both the arterial and venular side of the microcirculation. This attenuation was reversed by simultaneous implantation of naloxone pellets. The mechanisms of this attenuation were further investigated by administration of the nitric oxide synthase inhibitors NG-nitro-l-arginine (NOLA) and aminoguanidine (AG) in drinking water. NOLA was found to significantly reverse this morphine-induced attenuation of leukocyte rolling and sticking in both arterioles and venules. However, AG did not have the same effect. The results indicate that morphine interferes with leukocyte/endothelial cell interactions via stimulation of nitric oxide production.
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PMID:Morphine attenuates leukocyte/endothelial interactions. 1096 86

In this study we investigated the capacity of morphine to modulate expression of cytokines in peritoneal macrophages. Mice were implanted subcutaneously with a 75-mg morphine slow-release pellet, and 48 h later resident peritoneal macrophages were harvested. Control groups received placebo pellets, naltrexone pellets, or morphine plus naltrexone pellets. Adherent cells were stimulated with lipopolysaccharide (LPS: 10 microg/mL) plus interferon-gamma (IFN-gamma: 100 units/mL) to induce cytokine production. After 24 h RNA was extracted for analysis of cytokine mRNA levels by reverse transcriptase-polymerase chain reaction, or supernatants were collected after 48 h for determination of cytokine production by enzyme-linked immunosorbent assay (ELISA). Morphine enhanced mRNA expression of interleukin (IL)-12 p40 and tumor necrosis factor alpha (TNF-alpha) compared with controls, whereas IL-10 levels were unchanged by drug treatment. ELISA data showed that both IL-12 p40 and p70 were increased by morphine. The enhancement of IL-12 at both the mRNA and protein levels was antagonized by naltrexone, indicating that the modulation of this cytokine by morphine is via a classic opioid receptor. These results are particularly interesting in light of our previous observation that 48 h after morphine pellet implantation, the peritoneal cavity is colonized with gram-negative and other enteric bacteria. The enhancement of IL-12 by morphine might be related to morphine-induced sepsis.
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PMID:Morphine enhances interleukin-12 and the production of other pro-inflammatory cytokines in mouse peritoneal macrophages. 1107 13

Endothelial cell (EC) barrier dysfunction (i.e., increased vascular permeability) is observed in inflammatory states, tumor angiogenesis, atherosclerosis, and both sepsis and acute lung injury. Therefore, agents that preserve vascular integrity have important clinical therapeutic implications. We examined the effects of methylnaltrexone (MNTX), a mu opioid receptor (mOP-R) antagonist, on human pulmonary EC barrier disruption produced by edemagenic agents including morphine, the endogenous mOP-R agonist DAMGO, thrombin, and LPS. Pretreatment of EC with MNTX (0.1 muM, 1 h) or the uncharged mOP-R antagonist naloxone attenuated morphine- and DAMGO-induced barrier disruption in vitro. However, MNTX, but not naloxone, pretreatment of EC inhibited thrombin- and LPS-induced barrier disruption, indicating potential mOP-R-independent effects of MNTX. In addition, intravenously delivered MNTX attenuated LPS-induced vascular hyperpermeability in the murine lung. We next examined the mechanistic basis for this MNTX barrier protection and observed that silencing of mOP-R attenuated the morphine- and DAMGO-induced EC barrier disruption, but not the permeability response to either thrombin or LPS. Because activation of the sphingosine 1-phosphate receptor, S1P(3), is key to a number of barrier-disruptive responses, we examined the role of this receptor in the permeability response to mOP-R ligation. Morphine, DAMGO, thrombin, and LPS induced RhoA/ROCK-mediated threonine phosphorylation of S1P(3), which was blocked by MNTX, suggesting S1P(3) transactivation. In addition, silencing of S1P(3) receptor expression (siRNA) abolished the permeability response to each edemagenic agonist. These results indicate that MNTX provides barrier protection against edemagenic agonists via inhibition of S1P(3) receptor activation and represents a potentially useful therapeutic agent for syndromes of increased vascular permeability.
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PMID:Attenuation of vascular permeability by methylnaltrexone: role of mOP-R and S1P3 transactivation. 1739 91

A 38-year-old woman who had familial adenomatous polyposis was admitted to the intensive care unit with an episode of severe sepsis 5 days after undergoing a pancreas-preserving duodenectomy. Laparotomy with removal of an intra-abdominal abscess, followed by closed postoperative continuous lavage for 10 days, was performed. During two courses of planned tracheal extubation, the patient developed an acute lung injury, making a reintubation necessary. In both events, the patient received small doses of continuous morphine before the extubation. Morphine may induce the development of an acute lung injury in patients, whereas the exact pathophysiologic and pharmacologic mechanisms remain unclear.
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PMID:Morphine-induced acute lung injury. 1861 31

Patients prescribed morphine for the management of chronic pain, and chronic heroin abusers, often present with complications such as increased susceptibility to opportunistic infections and inadequate healing of wounds. We investigated the effect of morphine on wound-healing events in the presence of an infection in an in vivo murine model that mimics the clinical manifestations seen in opioid user and abuser populations. We show for the first time that in the presence of an inflammatory inducer, lipopolysaccharide, chronic morphine treatment results in a marked decrease in wound closure, compromised wound integrity, and increased bacterial sepsis. Morphine treatment resulted in a significant delay and reduction in both neutrophil and macrophage recruitment to the wound site. The delay and reduction in neutrophil reduction was attributed to altered early expression of keratinocyte derived cytokine and was independent of macrophage inflammatory protein 2 expression, whereas suppression of macrophage infiltration was attributed to suppressed levels of the potent macrophage chemoattractant monocyte chemotactic protein-1. When the effects of chronic morphine on later wound healing events were investigated, a significant suppression in angiogenesis and myofibroblast recruitment were observed in animals that received chronic morphine administration. Taken together, our findings indicate that morphine treatment results in a delay in the recruitment of cellular events following wounding, resulting in a lack of bacterial clearance and delayed wound closure.
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PMID:Chronic morphine administration delays wound healing by inhibiting immune cell recruitment to the wound site. 2004 74

The incidence of end-stage renal disease (ESRD) is rising and represents an important group of patients admitted to intensive care units (ICU). ESRD patients have significant co-morbidities and specific medical requirements. Renal replacement therapy (RRT), cardiovascular disease, disorders of electrolytes, drug metabolism, and sepsis are discussed. This review provides a practical approach to problems specific to the ESRD patient and common problems on ICU that require special consideration in ESRD patients. ESRD patients are at risk of hyperkalaemia. I.V. insulin and nebulized salbutamol lower serum potassium until definitive treatment with RRT is instituted. ESRD patients are prone to hypocalcaemia, which requires i.v. replacement if associated with complications. Midazolam has delayed metabolism and elimination in renal impairment and should be avoided. Morphine and its derivatives accumulate in renal failure and shorter-acting opiates are preferable. The use of diuretics is limited to patients with residual urine output. When required, therapeutic systemic anticoagulation should be achieved with unfractionated heparin as it is reversible and its metabolism and clearance are independent of renal function. The risk of sepsis is higher among ESRD patients when compared with patients with normal renal function. Empiric treatment should include both Gram-positive and Gram-negative cover, and methicillin-resistant Staphylococcus aureus cover if the patient has a dialysis catheter. Cardiovascular events account for the majority of deaths among ESRD patients. Troponin-I and CK-MB in combination should be used as markers of acute myocardial damage in the appropriate context, whereas B-type natriuretic peptide and troponin-T values are of less value.
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PMID:Management of the dialysis patient in general intensive care. 2221 52

Morphine derived from Papaver somniferum is commonly used as an analgesic compound for pain relief. It is now accepted that endogenous morphine, structurally identical to vegetal morphine-alkaloid, is synthesized by mammalian cells from dopamine. Morphine binds mu opioid receptor and induces antinociceptive effects. However, the exact role of these compounds is a matter of debate although different links with infection, sepsis, inflammation, as well as major neurological pathologies (Parkinson's disease, schizophrenia) have been proposed. The present review describes endogenous morphine and morphine derivative discovery, synthesis, localization and potential implications in physiological and pathological processes.
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PMID:Endogenous morphine and its metabolites in mammals: history, synthesis, localization and perspectives. 2326 49


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