Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Clinical and manometric results of Delorme's operation and sphincteroplasty were assessed retrospectively in patients undergoing this procedure for fecal incontinence and rectal prolapse. A series of 33 patients (11 males, 22 females; aged 18-83 years, mean 59) with external rectal prolapse were treated by Delorme's operation between 1989 and 1996. Mean follow-up was 39 months (range 7-84). Sphincteroplasty was associated in 12 cases with severe fecal incontinence due to striated muscle defects. Good results were achieved in 27 patients (79%); prolapse recurrence was observed in 6 (21%), the mean recurrence time being 9 months (range 1-24 months). There were no postoperative deaths. Minor complications occurred in 15 patients. Changes in preoperative and postoperative manometric patterns were as follows (mean +/- SEM): voluntary contraction from 59 +/- 6.9 to 66 +/- 7.1 mmHg (P = 0.05), resting tone from 33 +/- 5 to 32 +/- 4.3 mmHg, rectal sensation from 59 +/- 5 to 61 +/- 5.2 ml of air (n.s.). A solitary rectal ulcer syndrome was detected in five patients. The histological pattern demonstrated pathological changes in 40% of cases. Fecal incontinence was resolved in 6 of 20 cases (30%) and chronic constipation in 4 of 9 (44%). Failure (n = 3) was related primarily to postoperative sepsis. The incontinence score showed a mean improvement of 35% decreasing, from 4.5 +/- 0.39 to 2.9 +/- 0.44 after surgery (P < 0.01). In conclusion, Delorme's procedure did not lead to constipation and improved anal continence when associated with sphincteroplasty.
 ...
PMID:Delorme's operation and sphincteroplasty for rectal prolapse and fecal incontinence. 987 Jan 65

Acute tubular injury in sepsis is associated with proximal tubular epithelial cell (PTEC) detachment into the lumen leading to back-leakage of glomerular ultrafiltrate and tubule obstruction. Inflammatory cytokines, such as IL-1alpha, IFNgamma and TNFalpha, are important mediators in sepsis-induced acute renal failure, although their precise role is unclear. We used primary cultures of human PTEC to investigate the hypothesis that inflammatory cytokines exert cytotoxic effects and cause detachment of cells from adherent monolayers, possibly through the intermediate nitric oxide (NO). At 5 days post-confluence, PTEC monolayers were stimulated for 24 hours with IL-1alpha (10 ng/ml), IFNgamma (200 u/ml) and TNFalpha (10 ng/ml). Monolayer viability was assessed by a live/dead dual fluorescence labeling technique. Apoptosis within monolayers was determined by morphological examination and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL). PTEC in supernatants were counted and then analyzed by flow cytometry, using propidium iodide to assess cell viability and annexin V labeling to determine apoptosis. Results (mean +/- SEM; monolayers, n = 4; cell counts, n = 3; flow cytometry, n = 2) are shown below (at test, p < 0.05). Monolayers Supernatants Viable necrotic% of cells apoptotic countsx104/ml viable necrotic% of cells apoptotic Unstimulated 99.0+/-0.5 1.0+/-0.5 0 8.0+/-0.6a 64.6+/-2.5a 26.7+/-1.9a 6.2+/-0.6a Stimulated 92.4+/-3.2 7.6+/-3.2 0 14.7+/-0.6a 37.9+/-0.05a 48.0+/-0.3a 14.1+/-0.35a Following cytokine stimulation, there were significantly increased numbers of shed cells in supernatants. This cell population demonstrated significant loss of viability with increased numbers of both necrotic and apoptotic cells, as compared to unstimulated PTEC supernatants. Cytokine-stimulated monolayers maintained viability with no significant cell necrosis and no evidence of apoptosis. Preliminary experiments with the NO synthase inhibitor L-NMMA show that it reduces the number of cytokine-induced shed cells to the levels found in unstimulated cells (8.0 +/- 1.0 x 104/ml), although the percentages of necrotic and apoptotic cells are unchanged from cytokine-stimulated PTEC (44% and 15%, respectively). In conclusion, inflammatory cytokines induce necrotic and apoptotic cell shedding from PTEC monolayers with maintenance of monolayer viability. Preliminary data suggest that NO plays a cytotoxic role in this process.
 ...
PMID:Inflammatory cytokines induce apoptotic and necrotic cell shedding from human proximal tubular epithelial cell monolayers 1035 8

We measured the plasma levels of adrenomedullin (AM), a novel vasodilating peptide, in 89 patients with various forms of systemic inflammatory response syndrome (SIRS) and 13 healthy volunteers serving as controls. Plasma levels of AM in SIRS (burns: 20.5 +/- 3. 2 fmol/ml [mean +/- SEM]; pancreatitis: 13.8 +/- 3.8 fmol/ml; trauma: 14.9 +/- 2.5 fmol/ml; traumatic shock: 41.1 +/- 7.8 fmol/ml; severe sepsis: 59.9 +/- 11.2 fmol/ml; septic shock: 193.5 +/- 30.1 fmol/ml) were significantly increased over those of controls (5.1 +/- 0.2 fmol/ml). The patients with traumatic shock or septic shock especially had higher levels of plasma AM than those with trauma or severe sepsis, respectively. These data showed that in patients with SIRS, plasma AM levels increased in proportion to the severity of illness. Subsequently, we measured the plasma levels of mediators such as tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-8, plasminogen activator inhibitor (PAI)-1, and thrombomodulin (TM) in patients with traumatic shock and septic shock. A significant correlation was observed between plasma AM and TNF-alpha levels in patients with septic shock, suggesting an important role for AM as well as of TNF-alpha in the pathophysiology of inflammation. Plasma AM and IL-8 levels correlated positively with Acute Physiology and Chronic Health Evaluation (APACHE) II score, peak multiple organ failure (MOF) score during the first month and prognosis in patients with septic shock, as did plasma IL-6 levels in patients with traumatic shock. The plasma AM level might serve as a useful marker for evaluating the severity of disease and as an early predictor of subsequent organ failure and outcome in septic shock.
 ...
PMID:Increased plasma levels of adrenomedullin in patients with systemic inflammatory response syndrome. 1039 Mar 90

This study aims to determine the prevalence of and risk factors associated with retinopathy of prematurity (ROP) in very low birth weight (VLBW) infants. All premature VLBW infants, admitted into the neonatal intensive care unit of the University Hospital Kuala Lumpur, were screened from 4 weeks of life. Perinatal and neonatal data were retrieved from the infants' medical notes. Between August 1994 and July 1996, 100 infants had their eyes examined serially. Of the 15 (15%) infants with ROP, all were less than 31 weeks gestation, and only 1 infant had birth weight above 1250 g. Five (5%) infants had severe ROP; 4 infants underwent cryotherapy for stage 3 threshold disease. Infants with ROP, as compared to infants without ROP, had lower birth weight [mean (SEM) 993 (50) g versus 1205 (22) g, P < 0.001], lower gestational age [mean (SEM) 28.0 (0.4) weeks versus 30.1 (0.2) weeks, P < 0.001], higher rates of patent ductus arteriosus and chronic lung disease, greater number of radiographic examinations and episodes of late-onset suspected/confirmed sepsis, and required longer duration of supplemental oxygen, ventilation, xanthine, antibiotics and intralipid use, but were slower to establish full enteral feeds. On multivariate logistic regression analysis, birth weight < or = 1000 g [OR 2.38, 95% CI 1.25, 4.55, P = 0.009] and gestational age < or = 28 weeks [OR 2.86, 95% CI 1.47, 5.56, P = 0.002] were significant predictors of increased risk of this disease. In conclusion, ROP is strongly associated with smaller, more immature and sicker neonates. Prevention of prematurity would help reduce the incidence of this disease.
 ...
PMID:Retinopathy of prematurity in very low birth weight infants. 1049 65

Critically ill patients admitted to the intensive care unit with severe sepsis or major blunt injury undergo massive changes in body composition. We compared these changes in 12 patients with generalized peritonitis, and in 18 patients with major blunt injury over a 21-day period soon after their admission. Body composition was measured as soon as the patients were hemodynamically stable, and again 5, 10, and 21 days later. In both groups, losses in total body protein (TBP) were greatest over the first 10 days. TBP lost over the study period averaged 13.1 +/- 1.3 (SEM)% for the sepsis group, and 14.6 +/- 1.3% for the trauma group. Total body water (TBW) lost postresuscitation averaged 11.1 +/- 1.3 L and 6.7 +/- 1.1 L for the two groups, respectively, these changes largely being accounted for by changes in extracellular water (ECW). Our results demonstrate a striking similarity in the changes in total body protein for these two groups of critically ill patients. The sepsis patients retained approximately twice the volume of fluid of those with major trauma.
 ...
PMID:Similarity of changes in body composition in intensive care patients following severe sepsis or major blunt injury. 1086 10

The vascular endothelium has a central role in the control of microvascular tone, and it has been proposed that vascular endothelial damage occurs in septic shock, producing multiorgan failure. We have developed a method of detecting circulating endothelial cells (EC) that provides direct evidence of EC shedding in human sepsis. Human umbilical vein endothelial cells (HUVEC) were seeded in whole blood and recovered by isopycnic centrifugation to validate the technique. Blood samples were subsequently taken from 11 healthy volunteers, nine ventilated intensive care unit (ICU) control patients without sepsis, eight patients with sepsis but without shock, and 15 patients with septic shock. EC were identified by indirect immunofluorescence, using antibodies to von Willebrand factor (vWf) and the vascular endothelial growth factor receptor KDR. Mean HUVEC recovery was 86% for 20 to 100 seeded cells/ml of blood. vWf-positive EC counts per milliliter were significantly higher (analysis of variance [ANOVA], p < 0.0001) in patients with sepsis (16.1 +/- 2.7 [mean +/- SEM]) and septic shock (30.1 +/- 3.3) than in healthy (1.9 +/- 0.5) or ICU controls (2.6 +/- 0.6). KDR-positive EC counts per milliliter were also significantly higher (ANOVA, p < 0.0001) in patients with sepsis (4.2 +/- 1.1/ml) and septic shock (10.4 +/- 1.2/ml) than in healthy (0.7 +/- 0.3/ml) or ICU controls (0.5 +/- 0.2/ml). Cell counts made with anti-vWf antibody were consistently higher than those made with anti KDR antibody, but correlation between the two counts was high (r(2) = 0.93). The number of circulating KDR-positive EC was significantly higher in patients who died of septic shock than in survivors (12.0 +/- 1.6/ml versus 7.1 +/- 1.2/ml, p = 0.026). An increase in circulating EC can be identified during sepsis and septic shock. This supports the hypothesis that endothelial damage occurs in human sepsis.
 ...
PMID:Circulating endothelial cells in patients with septic shock. 1120 46

Pulmonary renal syndrome (PRS), defined as a combination of diffuse pulmonary hemorrhage and glomerulonephritis (GN), represents a severe syndrome for which minimal outcome data are available in the literature. We present a retrospective study of 14 consecutive patients from 1996 to 2000. Mean patient age was 65 +/- 2.1 (SEM) years, and 7 patients were women. At presentation, Po(2) on air was 6.0 +/- 0.5 kPa, and creatinine level was 554 +/- 70 micromol/L. Thirteen patients had systemic vasculitis, and 1 patient had systemic lupus erythematosus (SLE). Five patients were cytoplasmic antineutrophil cytoplasmic autoantibody (C-ANCA) positive, and 7 patients were perinuclear ANCA (P-ANCA) positive; 2 of the latter patients also were positive for anti-glomerular basement membrane antibodies. Renal biopsy was performed in 10 patients. Histological examination showed membranous GN in the patient with SLE and segmental necrotizing crescentic GN in the other 9 patients examined. Twelve of 14 patients were initially dialysis dependent, and 8 of 14 patients required ventilatory support. All patients were treated with corticosteroids, 8 of 14 patients were administered intravenous methylprednisolone, 13 of 14 patients were administered daily cyclophosphamide, and 12 of 14 patients underwent plasma exchange. Patients were followed up for 22 +/- 9 months. Early reduction in cyclophosphamide dosage was required in 9 patients for neutropenia. Seven patients were alive at the end of follow-up, but 5 patients (36%) died in the first month. Of the survivors, 85% and 67% were alive after 1 and 2 years of completed follow-up: 83% and 75% of these survivors were dialysis independent, respectively. Five relapses were seen in 4 patients. One patient died of progressive pulmonary fibrosis. Sepsis was a major factor in 6 of 7 deaths. This patient group was older than those previously reported. Findings confirm previous suggestions that PRS requiring intensive care treatment has high mortality, and early survivors have good 1- and 2-year outcomes. Cyclophosphamide-associated neutropenia and infection were frequent contributors to death, and less toxic alternatives may improve outcome in PRS.
 ...
PMID:Pulmonary renal syndrome: a 4-year, single-center experience. 1177

Critical illness outcome may be causally related to inflammatory response severity. Given that tissue angiotensin-converting-enzyme (ACE) regulates such responses and that the deletion (D) [rather than insertion (I)] variant of the ACE gene is associated with higher tissue ACE levels, DD genotype might be associated with a poorer outcome in a uniform infectious disease state. Illness severity (Pediatric RIsk of Mortality score, the Glasgow Meningococcal Septicaemia Prognostic Score [GMSPS], and clinical course) was recorded for consecutive white patients with meningococcal disease (n = 110, 34 DD genotype, 61 male, aged 49.4 +/- 5.4 months) referred to the Royal Liverpool Children's Hospital, UK. Compared with children with > or = I allele, DD genotype was associated with 14% higher predicted risk of mortality (p = 0.038), higher GMSPS (DD 9.4 +/- 0.5, ID/II 7.7+/- 0.4 [mean +/- SEM], p = 0.013), greater prevalence of inotropic support (76% versus 55%, p = 0.03) and ventilation (82% versus 63%, p = 0.04), and longer Pediatric Intensive Care Unit (PICU) stay (5.8 versus 3.9, p = 0.02). DD genotype frequency was 6% (1 case) for the 18 children who did not require PICU care, 33% for the 84 PICU survivors, and 45% for those who died (p = 0.01). ACE DD is associated with increased illness severity in meningococcal disease.
 ...
PMID:Severity of meningococcal disease in children and the angiotensin-converting enzyme insertion/deletion polymorphism. 1195 52

Severe burn results in immunosuppression, with increased lymphocyte apoptosis in both the central and peripheral immune system. As atrophy of the small intestine has been described in mouse models and intestinal lymphocytes have been implicated in the burn inflammatory response, we examined the effects of burn and tumor necrosis factor (TNF)-alpha on lymphocytes in intestinal Peyer's patches. Anesthetized C57BL6 mice received a 30% full-thickness scald burn on the upper back. Sham-burned animals served as controls. Anti-TNF or control immunoglobulin (Ig) G antibody (200 microg) was given immediately after the burn. The animals were initially resuscitated with 2 mL of normal saline, and were then sacrificed 12 h postburn. Terminal deoxyuridine nick-end labeling (TUNEL) and proliferative cell nuclear antigen (PCNA) staining was performed. Apoptosis was quantified as apoptotic lymphocytes/high-powered field (hpf). Results, expressed as mean +/- SEM, were compared using analysis of variance (ANOVA) and the Student-Newman-Keuls test. All mice survived the burn. An initial time-course experiment demonstrated maximal Peyer's patch apoptosis 12 h after the burn. Sham mice had 25 +/- 7 TUNEL-stained cells/hpf in Peyer's patches, whereas burned mice had 93 +/- 18 cells/hpf (P < 0.05). In contrast, burned mice receiving anti-TNF antibody had 28 +/- 8 TUNEL-stained cells/hpf (P < 0.05 vs. burn), whereas sham mice receiving anti-TNF antibody had 20 +/- 4 cells/hpf. There were no significant differences in PCNA staining between the groups. Scald burn results in lymphocyte apoptosis in Peyer's patches. This apoptosis can be abrogated by the addition of anti-TNF antibody. Apoptotic changes may lead to the failure of the intestinal immunological barrier and increased risk of sepsis.
 ...
PMID:Decreased lymphocyte apoptosis by anti-tumor necrosis factor antibody in Peyer's patches after severe burn. 1281 72

Sepsis and its sequela remain a major source of morbidity and mortality in neonates despite advances in antimicrobials and aggressive supportive care. Many models of neonatal sepsis have been developed for investigating the pathophysiology of this disease and application of therapy, and a model with an infectious focus is closer to clinical reality. To establish an animal model that mimics the clinical characteristics of neonatal sepsis, the cecal devascularization and perforation procedure was implemented on 15 mixed-strain newborn piglets, which produced an infectious focus that acted as a continuous source of microorganisms to the peritoneal cavity. The mean survival time in animals with sepsis was 10.4 h (range 5.5-17.9 h), whereas all of the sham-operated control animals survived more than 24 h. Animals with sepsis showed a gradual significant decrease in the mean systemic blood pressure (mSBP; 71 +/- 3 mmHg in sepsis vs. 64 +/- 3 mmHg in control at 3 h, 38 +/- 7 mmHg in sepsis vs. 59 +/- 4 mmHg in control at 6 h, mean +/- SEM). They also showed an increase of serum levels of endotoxin (5.6 x 10 +/- 4.5 x 10 pg/mL in sepsis vs. 6.0 x 10 +/- 3.8 x 10 pg/mL in control at 6 h). Serum levels of TNF-alpha in the animals with sepsis became significantly higher than the control animals at 0 h (96 +/- 31 pg/mL in sepsis vs. 12 +/- 1 pg/mL in control) and remained significantly higher than all through the experiment. Serum levels of IL-6 in animals with sepsis showed a gradual increase (484 +/- 231 pg/mL in sepsis in its peak at 6 h vs. 24 +/- 5 pg/mL in control), however, there were no significant differences in serum IL-10 levels between the groups. Microorganisms detected in the blood of animals with sepsis were gram-negative enteric and anaerobic organisms. These results suggested that this model mimics the clinical state of neonatal sepsis and hence may have significant implications for the treatment of sepsis, including its use as a model in further investigations.
 ...
PMID:Development and characterization of a novel porcine model of neonatal sepsis. 1517 33


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>