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Query: UMLS:C0243026 (sepsis)
 52,417 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of this study was to evaluate contemporary patterns of presentation and trends in the management and outcome of newborn infants with jejuno-ileal atresia at a regional paediatric surgical centre in the United Kingdom. The hospital neonatal surgical registry was used to identify patients with jejuno-ileal atresia (n = 83) admitted between 1976 - 1998, excluding those associated with gastroschisis. The clinical records were reviewed and antenatal information, patient demographics, associated anomalies, operative treatment, post-operative management and outcomes were analysed in three time periods to identify trends in management and survival: Group 1 1976 - 1982 (n = 32), Group 2 1983 - 1990 (n = 21), and Group 3 1991 - 1998 (n = 30). Overall survival was 90 %. The number of patients with associated anomalies were Group 1, 10 (31 %); Group 2, 7 (33 %); and Group 3, 11 (37 %). Cystic fibrosis was encountered in 4 (13 %), 1 (5 %) and 4 (13 %) patients, respectively. Resection with primary anastomosis was the definitive management in most of patients: Group 1, 25 (78 %); Group 2, 17 (81 %); and Group 3, 27 (90 %). Initial stoma followed by delayed primary anastomosis was performed in 14 infants; eight patients had divided stomas while 6 had Bishop-Koop stoma. Tapering was used in 10 patients (12 %) with proximal jejuno-ileal atresia. Parenteral nutrition was increasingly utilised over the three time periods studied. There were no deaths in Group 3 compared to 6 deaths in Group 1 and 2 in Group 2 (P = 0.02). Most of the deaths were due to overwhelming sepsis. Mortality did not correlate significantly with the TYPE of atresia, presence of associated anomalies or the need for long-term total parenteral nutrition. The overall complication rate in survivors was 18 %. In the infants undergoing Bishop-Koop operation the complication rate was 50 %. This study has shown a significant reduction in mortality from jejuno-ileal atresia, which may be attributed primarily to advances in perioperative management, including parenteral nutrition. Generous resection of the atretic segment with primary anastomosis is more frequently employed in preference to initial stoma formation. Cystic fibrosis remains an important co-morbid condition that must be excluded promptly in all newborns.
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PMID:Trends in the management and outcome of jejuno-ileal atresia. 1210 97

Cystic fibrosis (CF), an epithelial cell transport disorder caused by mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene, is not generally associated with malformations of the central nervous system (CNS). This report describes two African-American children who died at less than 2 years of age with known Chiari I malformations and were found, unexpectedly at autopsy, to have the classic pancreatic and respiratory changes of CF. Both patients had suffered from failure to thrive that had been attributed to their CNS malformations. One child also had recurrent pneumonia and died with Pseudomonas sepsis. Mutational analysis for > 70 common CFTR mutations identified a single delta F508 mutation in one patient and a single 3120+1G to A mutation in the other. Their second CFTR mutations were not identified. The association of CF with Chiari I malformation is not likely to be purely coincidental, as the probability of such an occurrence in African-Americans is greater than one in 7,500,000 patients. It is possible that the CFTR gene may play a previously unrecognized role in CNS development. Alternatively, this CNS abnormality may be acquired due to the metabolic and electrolyte imbalances that characteristically occur in CF.
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PMID:Cystic fibrosis and Chiari type I malformation: autopsy study of two infants with a rare association. 1241 81

The most common hepatic complications of cystic fibrosis (CF) are steatosis, fibrosis, biliary cirrhosis, atretic gallbladder, cholelithiasis, and sclerosing cholangitis. Cholestatic liver disease is a slow progressive disorder, but will stabilize for many patients. CF patients may suffer from the consequences of their liver disease and without liver transplantation, variceal hemorrhage, malnutrition, or end-stage liver disease can lead to death. Prospective data were collected and reviewed on 311 liver transplants performed in 283 patients at the Children's Medical Center of Dallas between October 1984 and November 2000. Ten children received an orthotopic liver transplant (OTLX) for end-stage liver disease associated with cystic fibrosis. Pulmonary function tests were obtained preoperatively in all cases. There were nine boys and one girl. Six are currently alive, and four are dead. Both patient and graft survival was 5.75 yr. Among those currently alive, mean patient and graft survival is 7.71 yr (range 0.10-12.62 yr). Mean patient and graft survival of those who died was 2.35 yr (range 0.78-5.33 yr). No survivor required re-transplantation and currently, all have normal serum aminotransferase values. Chronic sinusitis was not a significant pre- or post-transplant morbidity, although systematic radiographic evaluation of the sinuses did not occur. Pulmonary deaths occurred in three patients from pulmonary hemorrhage, pulmonary infection with Aspergillus and Candida glabrata, and acute bronchopneumonia associated with polymicrobial sepsis because of Pseudomonas, Klebsiella, and Candida albicans 1.44, 0.78, and 1.83 yr, respectively, after transplantation. The fourth death was associated with chronic rejection, and occurred 5.33 yr after transplantation. All non-survivors were below the 5th percentile for height and weight at the time of liver transplantation. Mean age at transplantation was 9.72 yr (range 1.23-19.09, median 9.61). Survivors were transplanted at a younger age than non-survivors (mean of 9.21 yr vs. 10.66 yr), and had shorter waiting times from diagnosis of end-stage liver disease to transplantation (6.87 months vs. 13.83 months). Eighty percentage (n = 8) of patients had pretransplant variceal bleeds (83% of survivors, 75% of non-survivors). While all non-survivors had a history of meconium ileus and preoperative need of pancreatic enzymes, only 67% of those alive experienced these complications. Preoperative forced vital capacity FVC was 103% for survivors and 95% for non-survivors. The corresponding numbers for forced expiratory flow (FEF) 25-75 were 74-84% respectively. Preoperative Aspergillus was identified in 30% of patients (n = 3). Two of these patients are alive. Cystic fibrosis constitutes an indication for 3.5% of pediatric liver transplants. Evaluation and transplantation for end-stage liver disease associated with cystic fibrosis should be undertaken at an early age. Most deaths were associated with pulmonary/septic events, and occurred less than 2 yr after OLTX. Those children who did not survive had poor growth and nutrition, prolonged waiting times prior to transplantation, were transplanted at an older age, and had a higher incidence of pancreatic insufficiency and meconium ileus. The presence of Aspergillus in the sputum does not constitute a contraindication for OLTX.
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PMID:Liver transplantation for cholestasis associated with cystic fibrosis in the pediatric population. 1265 48

Tuberculosis and aspergillosis are two of the most common chronic lung infections that occur in children. They both present in a variety of ways, acutely or insidiously. Tuberculosis is increasing in incidence due to increased immigration and the HIV pandemic. Symptoms can range from subclinical to acute sepsis with respiratory distress requiring intensive care support. Aspergillus is an important pathogen, particularly in patients who are immunocompromised either due to organ impairment such as cystic fibrosis or due to primary or secondary suppression of the immune system. Aspergillosis can also present with mild to fulminant symptomatology. Imaging is often the cornerstone of diagnosis. This article concentrates on the wide range of radiological features that these two organisms can cause.
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PMID:Chronic lung infection in children. 1288 Jul 57

Bronchiectasis is primarily the result of airway injury and remodeling attributable to recurrent or chronic inflammation and infection. The underlying etiologies include autoimmune diseases, severe infections, genetic abnormalities, and acquired disorders. Recurrent airway inflammation and infection may also be the result of allergic or immunodeficiency states such as allergic bronchopulmonary mycoses or HIV/AIDS. Bronchiectasis should be included in the differentiation diagnosis of any patient with chronic respiratory complaints such as cough and sputum production. Early clinical manifestations may be subtle. Hallmarks of severe bronchiectasis include fetid breath, chronic cough, and sputum production. The associated chronic respiratory infections and airway sepsis are punctuated by episodes of acute exacerbation. Prompt recognition and treatment of bronchiectasis may allow for prevention of disease progression and irreversible loss of lung function. This review of severe non-cystic fibrosis bronchiectasis describes the current pathophysiology, clinical presentations, and management of bronchiectasis. We review how impaired airway clearance and the inability to resolve infection and inflammation creates a vicious cycle of recurrent injury. The common clinical features of bronchiectasis and findings are presented and illustrated by radiographic images. The common species and significance of various organisms often recovered from the distal airways including: tuberculous and environmental mycobacteria, aspergillus, and bacteria such as Pseudomonas aeruginosa will be covered. Management strategies including sputum surveillance, sputum clearance, antimicrobial therapy including antifungal and antimyobacterial agents as well as the evidence for the use of inhalational and anti-inflammatory therapies such as corticosteroids are also discussed. Recommendations for the work-up and therapy of complications including hemoptysis and respiratory failure are presented.
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PMID:Severe bronchiectasis. 1471 69

The nuclear factor kappa B (NF-kappaB) transcription factor plays a key role in the induction of pro-inflammatory gene expression, leading to the synthesis of cytokines, adhesion molecules, chemokines, growth factors and enzymes. Results of studies in in vitro and in vivo models of inflammation and malignancy have also suggested central roles for NF-kappaB in programmed cell death, or apoptosis. NF-kappaB plays a central role in a variety of acute and chronic inflammatory diseases. In the common lung diseases associated with a significant inflammatory component such as severe sepsis, acute lung injury, acute respiratory distress syndrome, cystic fibrosis and asthma, the pathogenic roles of NF-kappaB have been extensively investigated. In COPD, activation of NF-kappaB has been implicated in disease pathogenesis but its exact role is less clearly demonstrable in this heterogeneous patient population. However, the principal risk factor for COPD, cigarette smoking, is strongly associated with NF-kappaB activation. Activation of NF-kappaB has been demonstrated in mineral dust diseases and probably plays a role in the pathogenesis of these chronic illnesses. NF-kB also plays a variety of roles in lung cancer including resistance to chemotherapy, inhibition of tumorigenesis and inducing expression of antiapoptotic genes. The complex NF-kappaB pathway offers a variety of potential molecular targets for chemotherapeutic intervention. A variety of agents aimed at modulating NF-kappaB activity are in various stages of investigation.
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PMID:The role of nuclear factor kappa B in the pathogenesis of pulmonary diseases: implications for therapy. 1472 3

Organisms from the Burkholderia cepacia complex are important pathogens in cystic fibrosis and are associated with increased rates of sepsis and death. These organisms comprise nine closely related species known as genomovars. B. cenocepacia (genomovar III) is the most prevalent and appears the most virulent. We investigated the biological activity of a reference panel of strains using whole-cell lysates to induce septic-shock related cytokines from differentiated human monocytic cells. We found varying biological activity within and between genomovars, with B. cenocepacia strains possessing the greatest cytokine induction activity. This activity was CD-14 dependent, suggesting that LPS was responsible for the cytokine induction. Cytokine induction was not simply related to the expression of rough or smooth LPS. We purified LPS from two strains, B. cenocepacia LMG 12614 and B. multivorans LMG 14273, each possessing rough LPS. Divergence in biological activity of the two genomovars was preserved when human monocytic cells were stimulated with purified LPS. Lipid A purified from LMG 14273 and LMG 12614 were analyzed by matrix-assisted laser desorption ionization/time of flight mass spectrometry. Lipid A from the less effective cytokine inducer LMG 14273 was found to be missing a beta-hydroxymyristate (3-OH C14:0) relative to the lipid A of B. cenocepacia LMG 12614.
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PMID:Burkholderia cenocepacia lipopolysaccharide, lipid A, and proinflammatory activity. 1522 Jan 20

Pseudomonas aeruginosa is a serious human pathogen in a variety of patient groups including those with burns, hospitalized in intensive care, cystic fibrosis and neutropenia. Since there is no vaccine available, passive antibody prophylaxis against protective epitopes is an alternative strategy to prevent P. aeruginosa infection. However, immunoglobulin derived from multiple donors has variable anti-pseudomonas antibody titers, and human Mab are difficult to make from patient samples. We previously reported the use of XenoMouse mice, Ig-inactivated transgenic mice reconstituted with human immunoglobulin loci, to generate human Mab against a single serotype of P. aeruginosa lipopolysaccharide O-specific side chain (PS). We now report the creation of a panel of anti-PS human IgG2 Mab against nine additional O-specific side chain P. aeruginosa serotypes. The majority of the Mab were highly opsonic for uptake and killing of homologous P. aeruginosa by human PMN in the presence of human complement, and all the Mab protected cyclophosphamide-induced neutropenic mice from fatal P. aeruginosa sepsis with homologous serotypes. DNA sequence analysis showed that the Mab used V(H)3, V(H)4, V(H)5 and V(H)6 and Vkappa2, 3 and 4 variable region genes consistent with the heterogeneity of P. aeruginosa LPS O-side chain structure. We conclude that human Mab made in these transgenic mice against common pathogenic serotypes of P. aeruginosa are opsonic and highly protective, and that a high titer, multi-valent human Mab preparation against the majority of circulating O-side chain serotypes of P. aeruginosa could be used as prophylaxis against invasive infections in selected patient groups.
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PMID:Multi-valent human monoclonal antibody preparation against Pseudomonas aeruginosa derived from transgenic mice containing human immunoglobulin loci is protective against fatal pseudomonas sepsis caused by multiple serotypes. 1583 31

Lung transplantation is currently the most effective means of improving survival and quality of life in patients with end-stage cystic fibrosis. In reviewing our 6-year experience we sought to evaluate complications and survival after sequential bilateral lung transplantation. Between October 1996 and October 2002, 114 patients with cystic fibrosis were referred to us from 15 Italian regional centers and 2 support centers for cystic fibrosis as possible candidates for lung transplantation. Of these 114 patients, 99 were included in the waiting list and 15 were refused. The mean time spent on the waiting list was 6.8+/-5.2 months (range 1 day-21 months) for those patients receiving lung transplantation, and 5.4+/-4.5 months (range 10 days-18 months) for those 35 patients who died while on the waiting list. A total 55 patients (6 children and 49 adults), mean age 25.6+/-6.6 years (range 9-52 years), 29 males, underwent bilateral sequential lung transplantation. One patient had a second transplantation 14 months after the first. The most frequent medical non-infective complications after transplantation were chronic renal failure (n=27 patients), diabetes (n=31), osteoporosis (n=17), arterial hypertension (n=14), seizures (n=4), transient cerebral ischaemia (n=1), and transient bilateral blindness (n=1). Bacterial lower airways respiratory infections with the organisms that colonized patients' airways before lung transplantation developed in 42 patients; cytomegalovirus (CMV) infection in 41; and opportunistic infections of the lung with Pneumocystis carinii in 3 patients. Cultures of sputum or bronchoalveolar lavage fluid grew Aspergillus fumigatus in nine patients; aspergillosis of right bronchial anastomosis developed in one patient and a lung infection in another. Another patient had a pulmonary infection secondary to Aspergillus niger. An average of 1.3 episodes of acute rejection developed per patient in the first 6 months after lung transplantation. Freedom from bronchiolitis obliterans syndrome was 95% at 1 year, 82.5% at 2 years, 70% at 3 years, and 65% at 4, 5 and 6 years. Actuarial survival rates were 80% at 1 month, 79% at 1 year, 74% at 2 years, 70% at 3 years and 58% at 4, 5 and 6 years. Ten patients (17.8%) died in the early postoperative period (1-30 days) for the following reasons: primary graft failure (n=4), multiorgan failure (n=3), Burkholderia cepacia sepsis (n=1), myocardial infarction (n=1), and pulmonary embolism (n=1). Mortality was accounted for by 9 patients (16%) who died from 9 to 43 months after lung transplantation, for the following reasons: P. carinii infection (n=2), bronchiolitis obliterans syndrome (n=4), A. fumigatus pulmonary infection (n=1), unknown cause (n=1) and suicide (n=1). In conclusion, the leading causes of morbidity after lung transplantation for cystic fibrosis are pulmonary bacterial infection and opportunistic infections. Bronchiolitis obliterans develops in more than half of lung transplant recipients who survive for more than 3 years and is an important cause of death in the late post transplantation period.
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PMID:Lung transplantation for cystic fibrosis: 6-year follow-up. 1591 93

Cystic fibrosis (CF) is a genetic disease where abnormalities in ion transport lead to poor clearance of viscoelastic secretions and a susceptibility to bacterial colonisation. Once established the infection/inflammatory cascade appears to be self-perpetuating. Treatment is therefore based on a number of strategies. Recently, advances have been concentrated at correcting the gene defect. Other strategies include correction of the ion transport defect. These may be crucial in patients if started before there is significant pulmonary disease. Developments aimed at improving the rheological properties of secretions, controlling airway infection and inflammation are essential once bronchopulmonary sepsis is established. This report looks at some of the clinical trials that are ongoing or planned in the treatment of pulmonary disease in CF.
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PMID:Ongoing planned clinical trials investigating the pulmonary management of cystic fibrosis. 1599 22


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