Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0243026 (sepsis)
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Macrophage inflammatory proteins 1 alpha and beta (MIP-1 alpha and beta) and macrophage inflammatory protein 2 (MIP-2) are approximately 6-8 kd, heparin binding proteins that exhibit a number of inflammatory and immunoregulatory activities. The MIP proteins are members of a superfamily of cytokines called chemokines, many of which have been shown to possess chemotactic activity for inflammatory and immune effector cells. While MIPs were originally identified as secretory products of endotoxin-stimulated mouse macrophages, these chemokines are produced by a variety of cell types including neutrophils, fibroblasts, and epithelial cells. In addition, proteins with a high degree of structural and functional homology to murine MIP-1 alpha and beta and MIP-2 have been identified in other species including humans. MIP-1 alpha and beta are chemotactic for monocytes and lymphocytes and MIP-2 is a potent chemotactic factor for neutrophils. MIPs likely also play a role in regulating hematopoiesis and stimulating production of other inflammatory mediators such as IL-1, TNF alpha, and histamine. Studies using animal models of lung injury and inflammation have implicated MIPs as important mediators of lung defense. Increased MIP expression has been observed in models of bacterial sepsis, silicosis, and oxidant-induced lung injury. Studies in humans indicate MIP-1 alpha contributes to the inflammatory cell response associated with sarcoidosis and idiopathic pulmonary fibrosis. Given the bioactivities of MIP-1 alpha and beta and MIP-2 and the recent studies demonstrating their association with lung inflammation, it is likely these chemokines play a significant role in respiratory tract defenses and may contribute to the pathogenesis of inflammatory lung disease.
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PMID:Macrophage inflammatory proteins: biology and role in pulmonary inflammation. 788 2

Extremely low birthweight infants are attracting increasing attention in the medical literature, mainly in audits from selected hospitals not representative of the entire population of a country. The Swiss Neonatology Group gathered selected data on mortality, morbidity and medical treatment of all liveborn infants weighing between 500 and 999 g at birth for the years 1979-81, 1983-85 and 1989-91. The results were compared and completed with information from the Swiss Office of Statistics. From 1979-81 to 1989-91 the incidence of extremely low birthweight infants increased from 1.3 to 2.2 per thousand livebirths. At the same time the survival rate increased from 23% to 53%, resulting in three times more infants being discharged from hospital in this weight group. The number of days of mechanical ventilation, which is an indicator of intensity of care, increased from 320 days to 1440 days per year. In contrast to mortality, morbidity scarcely decreased within this 12-year period and was still considerable in 1989-91. 57% of the survivors had chronic lung disease and 15% had sepsis. Intracranial hemorrhage was present in 35% of the survivors and 71% of the deaths. Retinopathy was noted in 38% of survivors. These facts, which are representative of the whole of Switzerland, show the increasing medical and economic significance of this patient group. Before the implications of this development can be fully assessed, extremely low birthweight infants must be followed up until adult life.
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PMID:[Improved chance of survival for very small premature infants in Switzerland]. 793 32

Lung transplantation nowadays has become a therapeutic modality in the treatment of patients with a variety of end-stage lung diseases. Between July 1991 and December 1992, twelve patients received an isolated lung transplant (eight single lungs and four double lungs) at the University Hospitals of Leuven. The indication for transplantation was emphysema in five patients, pulmonary fibrosis in three, cystic fibrosis in three and primary pulmonary hypertension in one. There were four early, in-hospital deaths (30%): two from sepsis and multi-organ failure, one from anoxia following a bronchial dehiscence and another patient exsanguinated following stent insertion for a partial bronchial dehiscence. Three more patients have died during follow-up: two from chronic respiratory failure secondary to the development of obliterative bronchiolitis (one at 8 months and one at 17 months), and one from a late bronchovascular fistula 4 months following transplantation. The overall actuarial one and two year-survival was 50.0% and 41.6% respectively. All patients discharged from hospital were oxygen free with an improved lung function and exercise capacity. We conclude that lung transplantation is a viable therapeutic option for selected patients with end-stage, irreversible lung disease. In our experience, the bronchial anastomosis remains an important keystone in the early success. Lung transplantation provides a good quality of life in patients free from infection and rejection. Nevertheless, chronic rejection resulting in obliterative bronchiolitis is a major problem in long-term survivors.
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PMID:Isolated lung transplantation; initial experience at the University Hospitals Leuven. Leuven Lung Transplant Group. 797 65

14 newborn infants were ventilated with oscillation because of severe respiratory distress syndrome (n = 3), pulmonary air leaks (n = 4), pulmonary hypoplasia (n = 4) or sepsis and pneumonia (n = 3). All but four of the infants were more easily stabilized by oscillation than by conventional ventilation. Four infants survived after 1-5 (mean three) days of oscillation, and none developed severe chronic lung disease. New commercial ventilators make this mode of ventilation of newborn infants relatively simple. Small premature babies who require high pressures with conventional ventilation, babies with pulmonary air leaks and babies with hypoplastic lungs may benefit from oscillation.
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PMID:[High-frequency oscillation in newborn infants. A promising therapeutic principle when respirator therapy is hazardous]. 807 16

1. We investigated the relationship between circulating tumour necrosis factor-alpha concentrations, resting energy expenditure, cachexia and altered intermediary metabolism in patients with cystic fibrosis and chronic pulmonary infection. 2. Twenty adult patients with cystic fibrosis and chronic bronchial sepsis covering a spectrum of severity of lung disease (forced expiratory volume in 1 s 30-100% of predicted) were compared with 10 age matched, healthy, non-cystic fibrosis subjects. 3. Circulating tumour necrosis factor-alpha, C-reactive protein and neutrophil elastase-alpha 1-antiproteinase complex concentrations were determined simultaneously with glycerol, non-esterified fatty acids, catecholamines, anthropometric indices and resting energy expenditure (ventilated hood method). 4. Weight, body mass index and arm muscle mass were reduced in patients with cystic fibrosis compared with healthy control subjects (P < 0.01), whereas mean resting energy expenditure was increased [121 versus 101% predicted, mean difference 19.2% (95% confidence interval 11.0-27.4%), P < 0.001]. Circulating concentrations of glycerol (P < 0.01), non-esterified fatty acids (P < 0.01), adrenaline (P < 0.05), tumour necrosis factor-alpha, C-reactive protein and neutrophil elastase-alpha 1-antiproteinase complex (P < 0.01) were increased in patients compared with control subjects [tumour necrosis factor-alpha 96.9 versus 24.7 pg/ml, mean difference 72.2 pg/ml [95% confidence interval 27.7-116.7 pg/ml), P < 0.001]. Resting energy expenditure was significantly related to tumour necrosis factor-alpha levels and forced expiratory volume in 1 s. 5. In patients with cystic fibrosis and chronic pulmonary sepsis changes in resting energy expenditure, body composition and intermediary metabolism are consistent with the systemic effects of the host inflammatory response, which may be responsible for cachexia in adult patients. In particular these changes are consistent with the action of tumour necrosis factor-alpha, which was detected in the circulation during a period of apparent clinical stability.
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PMID:Tumour necrosis factor-alpha, resting energy expenditure and cachexia in cystic fibrosis. 828 44

The role of genital mycoplasmas in the pathogenesis of neonatal infection is incompletely understood. We performed nasopharyngeal, blood and cerebrospinal fluid (CSF) cultures for Mycoplasma hominis and Ureaplasma urealyticum in 69 neonates who underwent a diagnostic workup for suspected sepsis. The mean gestational age was 35.9 weeks (range, 25 to 42 weeks) with a mean birth weight of 2386 g (range, 652 to 4420 g). Twenty-seven infants (39.1%) had positive nasopharyngeal cultures; 6 were positive for M. hominis, 10 for U. urealyticum and 11 for both organisms. Seven (26%) of these 27 patients developed chronic lung disease compared with 2 (4.7%) infants in the non-colonized group. Nine infants had positive CSF cultures for M. hominis and one infant had a positive CSF culture for U. urealyticum. All blood cultures were sterile. One of the infants with a positive CSF culture for M. hominis had clinical evidence of systemic infection. All of the infants were treated with antibiotic agents that were not active against mycoplasmas. These data indicate that genital mycoplasmas can be found commonly in the CSF and nasopharynx of infants with suspected sepsis. Their etiologic role in the causation of infection and chronic lung disease, however, remains unclear.
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PMID:Mycoplasma hominis and Ureaplasma urealyticum in neonates with suspected infection. 834 98

Early success in clinical lung transplantation was believed due in part to the technique of bronchial anastomosis, routine bronchial omentopexy, and avoidance of early postoperative corticosteroid therapy. A recent 16-month consecutive experience at the University of Toronto and Washington University with single or bilateral lung transplantation was compared to study the current short-term effect of these perioperative strategies. At the University of Toronto, of 37 patients undergoing lung transplantation, 30 (group I) had telescoped bronchial anastomoses, coverage of the bronchus with local tissue only (no omentopexy), and routine perioperative corticosteroid administration. At Washington University, of 50 patients having lung transplantation, 44 (group II) had end-to-end bronchial anastomoses wrapped in omentum and received no routine perioperative corticosteroid. In group I, septic lung disease was the most frequent indication (14 of 29 patients), whereas in group II obstructive lung disease was the most frequently encountered condition (24 of 44 patients). Sepsis accounted for three of five early deaths in group I (all due to resistant Pseudomonas cepacia infection in recipients who had cystic fibrosis) and for two of four perioperative deaths in group II (one Pseudomonas, and Candida). In group I, cytomegalovirus prophylaxis was administered to all patients except recipients negative for cytomegalovirus receiving grafts from donors also negative for cytomegalovirus. Cytomegalovirus infection requiring treatment was encountered in 5 of 30 patients in group I in comparison with 23 of 44 recipients in group II where only D+ and R- mismatches received prophylaxis. Routine omentopexy is not essential for successful lung transplantation. Early postoperative corticosteroids do not impair airway healing, but neither do these agents appear to protect against acute rejection episodes. While routine corticosteroids do not predispose the recipient to cytomegalovirus infection, their use may increase the likelihood of postoperative bacterial sepsis.
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PMID:An evaluation of the role of omentopexy and of early perioperative corticosteroid administration in clinical lung transplantation. The University of Toronto and Washington University Lung Transplant Programs. 838 97

This report describes the Vermont-Oxford Trials Network, a voluntary collaborative research network, and summarizes the outcomes and medical interventions for very low birth weight infants at participating centers in 1990. The Vermont-Oxford Trials Network included 36 centers in 1990 (11% university hospitals, 44% university affiliates, 44% nonaffiliated) with a total of 2961 infants weighing 501 to 1500 g (median 73 infants, range 5 to 172). Eighty percent of the infants were inborn and 65% were white. The overall network frequencies for selected interventions and outcomes were as follows: prenatal care, 90%; a complete course of antenatal corticosteroids, 12%; cesarean section, 56%; surfactant therapy, 49%; postnatal steroids for chronic lung disease, 16%; high-frequency ventilation, 4%; patent ductus arteriosus, 31%; necrotizing enterocolitis, 6%; bacterial sepsis, 16%; and intraventricular hemorrhage, 26%. By 28 days, 15% of the infants had died and 8% had been transferred, whereas by discharge 18% had died and 18% had been transferred. There were marked variations among the centers in the frequencies of different medical interventions and in the frequencies of various clinical outcomes. The Vermont-Oxford Trials Network is a unique collaborative research group composed of a broad range of neonatal intensive care units. During 1990 there were considerable differences among the centers in the interventions used and patient outcomes observed. The investigators plan to devote the resources of the Network to a research program of randomized trials and outcome studies so that effective interventions can be identified and the quality of neonatal intensive care can be continuously improved.
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PMID:The Vermont-Oxford Trials Network: very low birth weight outcomes for 1990. Investigators of the Vermont-Oxford Trials Network Database Project. 844 56

It is common to assign an upper age limit for potential lung transplant recipients. The influence of age on LTX outcome is, however not, documented. A review of our first 103 LTXs, 51 single LTXs and 52 double LTXs, includes 31 recipients aged 50-63 years (mean 55.3 +/- 3.9); 19 received single LTX, and 12 received double LTX. Indications for LTX in those aged greater than 50 included proportionately more patients with emphysema and interstitial lung disease. Actuarial survivals in those aged less than 50 at 12, 36, and 60 months were 68%, 60%, and 55%, and in those aged greater than 50 was 70%, 61%, and 61%, respectively. The causes of death reflect a tendency of younger patients to die from graft rejection and older patients to die from sepsis. Acute rejection more than 6 weeks posttransplant and chronic rejection were less frequent in older patients (P < 0.05). The 6-minute walk and modified Bruce protocol tests, the incidence of CMV pneumonitis, and the late post-LTX renal function were not related to age. In conclusion, in carefully selected candidates in their sixth and seventh decades, LTX is an acceptable operation for end-stage lung disease. The tendency of older patients to a lower incidence of late allograft rejection (acute or chronic) may reflect decreased immunological responsiveness with age.
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PMID:Lung transplantation in patients over the age of 50. 845 77

The first clinically successful lung transplantation was performed in 1983. Since that time, more than 2700 transplants have been recorded by the International Lung Transplant Registry [1]. Lung transplantation is currently limited to patients with endstage lung disease and a life expectancy of less than 18 months [1]. Unilateral lung transplantation is the most commonly performed procedure. Bilateral transplantation generally is reserved for patients with pulmonary sepsis. One-year survival after transplantation is currently 80-90%, and 5-year survival is estimated at 50% [1]. Early detection and treatment of the complications of lung transplantation are critical to decrease patient morbidity and mortality [2-4]. This article reviews the radiologic findings of the most common complications of lung transplantation, using our experience with 85 patients.
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PMID:Complications of lung transplantation: radiologic findings. 863 54


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