Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0243026 (sepsis)
 52,417 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neutrophil specific chemokines are potent chemoattractants for neutrophils. IL-8/CXCL8 is the most extensively studied member of this group, and its concentrations increase during inflammatory conditions of the newborn infant including sepsis and chronic lung disease. A significant amount of information exists on the effects of IL-8/CXCL8 on neutrophil chemotaxis of neonates, but little is known about the other neutrophil specific chemokines. The aim of this study was to determine the relative potency of the neutrophil specific chemokines on chemotaxis of neonatal neutrophils and to compare this effect with the effect on adult neutrophils. Neutrophils were isolated from cord blood or healthy adult donors and incubated in a Neuroprobe chemotaxis chamber. Chemokine concentrations ranging from 1-1000 ng/mL were used. Differences in chemotactic potency existed among the seven neutrophil specific chemokines. Specifically, at 100 ng/mL, the order was IL-8/CXCL8>GRO-alpha/CXCL1>GCP-2/CXCL6>NAP-2/CXCL7>ENA-78/CXCL5>GRO-gamma/CXCL2>GRO-beta/CXCL3. This pattern was observed for adult and neonatal neutrophils. We conclude that (1) neutrophils from cord blood exhibit the same pattern of potency for each ELR chemokine as neutrophils from adults, and (2) migration of neonatal neutrophils is significantly less than that of adults at every concentration examined except the lowest (1 ng/mL).
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PMID:The effects and comparative differences of neutrophil specific chemokines on neutrophil chemotaxis of the neonate. 1561 81

Close collaboration between obstetricians and neonatologists is essential for proper care of the growth-restricted fetus. A joint decision on the appropriate timing of delivery is made, based on the risk of fetal compromise compared with that of neonatal morbidity. A neonatal resuscitative team should be available at delivery. Gestational assessment, anthropological measurements and physical examination are necessary to confirm the diagnosis of intra-uterine growth retardation and establish the symmetric, asymmetric, combined or dysmorphic classification. Neonatal management requires special attention to a number of significant morbidities that growth-restricted infants are more prone to develop compared with normally grown infants, including asphyxia, meconium aspiration syndrome, respiratory distress syndrome, massive pulmonary haemorrhage, chronic lung disease, hypothermia, hypoglycaemia, hypocalcaemia, polycythaemia-hyperviscosity, intraventricular haemorrhage, sepsis, necrotizing enterocolitis, coagulation abnormalities, and congenital anatomical and genetic abnormalities. Intra-uterine growth retardation is associated with a higher stillbirth rate and infant mortality rate in preterm, term and post-term infants.
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PMID:Neonatal management of the growth-restricted infant. 1569 76

Ureaplasma urealyticum and Mycoplasma hominis colonized 20-40% of newborns and are more frequent in premature. They are responsible for localized infections such as pleural effusion, pneumopathy, adenopathy, abscess or systemic sepsis. An important hyperleukocytosis is often associated with pulmonary infections. Their responsibility, as pathogen agents, is questionable in some non bacterial meningitis. There is large controversy for their role as cofactor, in chronic lung disease (bronchopulmonary dysplasia) and periventricular leukomalacia, because of a too low number of newborns in prospective trials. Genital mycoplamas are resistant to beta lactamines. Macrolides have a good sensitivity, particularly josamycine, but Mycoplasma hominis is resistant to erythromycin. For systemic sepsis, fluoroquinolones such as ciprofloxacine have less deleterious effects than IV erythromycin.
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PMID:[Ureaplasma urealyticum and Mycoplasma hominis infections in newborns: personal data and review of the literature]. 1589 30

PTXF appears to be a promising adjunct to antibiotic therapy in neonatal sepsis. No adverse effects were noted in either study reported in the literature. However, there is a need for large randomized clinical trials to confirm or refute the role of PTXF in the treatment of sepsis in neonates. Clinically important comorbidities such as chronic lung disease, periventicular leukomalacia, duration of assisted ventilation, and NEC should be evaluated as a part of these studies. Comparison of PTXF with immunomodulatory agents such as colony-stimulating factors and intravenous immunoglobulins is suggested. Part II of this five-part series on immunomodulation will explore the use of colony-stimulating factors in neonates. Other topics will include the amino acid glutamine, intravenous immunoglobulins, and probiotics.
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PMID:Immunomodulation, part I: pentoxifylline. 1611 44

The heme-containing enzyme myeloperoxidase (MPO) is both present and active in inflammatory conditions. This enzyme is potentiated by its formation of multiple inflammatory mediators. The two most common mediators are the modified tyrosines: nitrotyrosine and 3-chlorotyrosine. Along with other modified tyrosines, these molecules have been found to be elevated in atherosclerosis, lung disease, sepsis, vasculitis, and other inflammatory diseases. By treating some of these diseases, the levels of modified tyrosines have been shown to decrease. There have been a wide range of animal models designed to study the in vivo effects of these tyrosine molecules. In addition, there are also several reports in the literature of the in vitro actions of modified tyrosine molecules demonstrated by various cell-culture models. The purpose of this review is to evaluate the clinical significance and biological functions of these modified tyrosine molecules in atherosclerosis as well as a variety of other inflammatory conditions. It is timely information because of their association with diseases as well as lack of overview of their molecular actions. This review will focus on the formation, clinical significance, and animal and cell-culture models of these important molecules.
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PMID:Nitrotyrosine and chlorotyrosine: clinical significance and biological functions in the vascular system. 1636 Jan 72

Acute lung injury (ALI) is a devastating illness, occurring in the setting of sepsis, with genetic variations contributing to ALI susceptibility and severity. We utilized the "candidate gene approach" with extensive expression profiling in animal and human ALI models to identify novel candidate genes. We noted significant expression of pre-B-cell colony enhancing factor (PBEF), a gene not previously associated with lung pathophysiology. This finding was validated by molecular, biochemical and immunohistochemical approaches with increased levels of PBEF also detected in human BAL and serum. DNA sequencing identified two single nucleotide polymorphisms (SNPs) in the PBEF promoter (T-1001G, C-1543T), which were genotyped in a Caucasian cohort of sepsis-associated ALI patients. Carriers of the GC haplotype exhibited a 5.7-fold relative ALI risk compared to controls associated with increased PBEF promoter activity. These studies demonstrate the successful application of genomic technologies in the identification of novel candidate genes in complex lung disease.
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PMID:Searching for candidate genes in acute lung injury: SNPs, Chips and PBEF. 1655 15

This paper is concerned with how those who prescribe antimicrobials should consider the wider repercussions of their actions. It is accepted that in an ecological system, pressure will cause evolution; this is also the case with antimicrobials, the result being the development of resistance and the therapeutic failure of drugs. To an extent, this can be ameliorated through advances by the pharmaceutical industry, but that should not stop us from critically appraising our use and modifying our behavior to slow this process down. Up to 50% of prescribing in human medicine and 80% in veterinary medicine and farming has been considered questionable. The Alliance for the Prudent Use of Antimicrobials (APUA) was approached by the WHO to review the situation. Their recommendations include decreasing the prescribing of antibacterials for nonbacterial infections. In the UK, there has been an initiative called "the path of least resistance". This encourages general practitioners to avoid prescribing or reduce the duration of prescriptions for conditions such as upper respiratory tract infections and uncomplicated urinary tract infections; this approach has been successful. Another recommendation is to reduce the prescribing of broad-spectrum antibacterials. In UK hospitals, the problems identified with the inappropriate use of antibacterials are insufficient training in infectious disease, difficulty in selecting empirical antibacterial therapy, poor use of available microbiological information, the fear of litigation and the fact that the majority of antibacterials are prescribed by the least experienced doctors. With close liaison between the laboratories and clinicians, and the development of local protocols, this can be addressed. Another recommendation is to tighten the use of antibacterial prophylaxis and to improve patient compliance. Through a combination of improved education for doctors and patients, and improved communication skills, these problems can be addressed. A further recommendation is to encourage teaching methods that modify prescribing habits. It has been shown that workshops have led to a significant reduction in the prescribing of broad-spectrum antibacterials in the community. Auditing the prescribing of antibacterials has also been recommended. Surveillance systems around the world monitor trends in resistance: the European Antimicrobial Resistance Surveillance Progamme (EARSS) monitors antibacterial resistance; the WHO and the International Union Against Tuberculosis and Lung Disease collaborate to monitor tuberculosis; the WHO and the International AIDS Society monitor HIV. In the third world, a bigger problem than resistance is whether drugs are even effective, as they are often spoiled by climactic conditions, and poor quality generics and counterfeit drugs are common. Also, patients may not be able to complete a course for financial reasons. Facts about Antimicrobial Resistance in Animals (and Agriculture) and Impact on Resistance (FAAIR) was commissioned by APUA. They conclude that the nonhuman use of antibacterials can lead to the development of antibacterial resistance in human pathogens. The European commission banned the use of antibacterials as growth promoters in 1999. In the Western world, we should improve our diagnosis of sepsis, access local guidelines and consider withholding treatment pending investigations, decide if treatment can be stopped earlier and treat the patient not the result. Many developing countries need improved access to more antimicrobials, preferably in the controlled environment of appropriate medical advice.
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PMID:Antimicrobial agents are societal drugs: how should this influence prescribing? 1674 4

Although relatively rare, pulmonary hypertension can be devastating for those individuals who are affected and has significant societal implications. The 2003 WHO classification separates PAH (idiopathic, specific disease linked) from pulmonary hypertension related to lung disease, thromboembolic disease, and pulmonary venous hypertension. Another form of pulmonary hypertension, persistent pulmonary hypertension (PPHN), occurs in the newborn. In general, PPHN is thought to be responsible for approximately 10% of admissions to neonatal intensive care units and can be a complicating factor in 5 of 1000 live births. Acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS) are complex disorders that pose a significant threat to critically ill patients. They are usually related to direct lung injury or indirect injury from sepsis, trauma, and other disorders. Although these pulmonary disorders reflect distinct pathophysiologic mechanisms, current evidence strongly suggests that a common denominator underlying many of the established molecular and cellular elements is endothelial cell activation and dysfunction. This summary statement briefly summarizes the state of the science and suggests future avenues of public health research.
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PMID:Vascular endothelium summary statement V: Pulmonary hypertension and acute lung injury: public health implications. 1719 49

Preterm infants are at risk of developing sepsis, necrotizing enterocolitis (NEC), chronic lung disease (CLD), and retinopathy of prematurity (ROP). We used high-throughput mass spectrometry to investigate whether cord blood proteins can be used to predict development of these morbidities. Cord blood plasma from 44 infants with a birth weight of <1500 g was analyzed by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF). Six infants developed ROP >or=stage II, 10 CLD, three sepsis, and one NEC. We detected 814 protein signals representing 330 distinct protein species. Nineteen biomarkers were associated with development of >or=stage II ROP [false-discovery rate (FDR) <5%] and none with CLD. Several proteins with molecular weight (Mr) 15-16 kD and pI 4-5 were detected with increased abundance in infants with ROP, while similar Mr proteins with pI 7-9 were less abundant in these patients. Sodium dodecylsulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and sequence analysis identified these proteins as alpha-, beta-, and gamma-globin chains. Partial deamidation of Asn139 in beta-globin chains was observed only in the pI 4-5 proteins. We conclude that there are several promising biomarkers for the risk of ROP. Deamidation of globin chains is especially promising and may indicate underlying prenatal pathologic mechanisms in ROP. Validation studies will be undertaken to determine their clinical utility.
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PMID:A potential biomarker in the cord blood of preterm infants who develop retinopathy of prematurity. 1723 25

Intravenous indomethacin and intravenous ibuprofen are widely used for the treatment of patent ductus arteriosus (PDA) in premature infants. Intravenous indomethacin may lead to renal impairment, enterocolitis, and intraventricular hemorrhage. Intravenous ibuprofen was shown to be as effective and to cause fewer side effects. If ibuprofen is effective intravenously, it will probably be effective orally, too. This study was conducted to test oral ibuprofen in early curative closure of PDA in very premature infants hoping for a better tolerance and the same efficacy as intravenous ibuprofen. Forty very premature infants (mean gestational age: 29.4 +/- 1 to 2 weeks [range: 26 to 31.5 weeks]; mean weight: 1237.2 +/- 198 g [range: 650-1770 g]) with PDA and respiratory distress were studied prospectively. They received, while between 48 and 96 hours old, oral ibuprofen at a dose of 10 mg/kg, followed, if needed, at 24-hour intervals by one or two additional doses of 5 mg/kg each. Color Doppler echography of the heart, brain, and abdomen were performed before treatment and after each dose administration. Ductal closure, early outcome (1 week after treatment), and late outcome were recorded. Thirty-eight patients (95%) achieved pharmacological closure. Two patients did not respond to the treatment: One required surgical ligation of the ductus, and the other patient received and well tolerated ductal shunting. Twenty-four patients were treated with one dose of oral ibuprofen, 10 were treated with two doses, and 6 were treated with three doses. Early outcome showed no case of renal impairment, no significant differences in serum creatinine levels, nine cases (22.5%) of intraventricular hemorrhage, three cases (7.5%) of necrotizing enterocolitis, and two cases (5%) of gastrointestinal bleeding. Late outcome showed 15 cases (37.5%) of nosocomial sepsis, 3 cases (7.5%) of chronic lung disease, 2 cases (5%) of periventricular leukomalacia, and 17 cases of death. In this study, oral ibuprofen was effective and well tolerated for early curative closure of PDA in very premature infants. Nevertheless, larger randomized comparative studies with pharmacokinetics measures are warranted.
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PMID:Oral ibuprofen in early curative closure of patent ductus arteriosus in very premature infants. 1756 58


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