SEARCH · PubMed Health

Results for “Defining Death”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,009 records · Page 56Linked to original sources

PubMed1992

Energy metabolism and selective neuronal vulnerability following global cerebral ischemia.

A short period of global ischemia results in the death of selected subpopulations of neurons. Some advances have been made in understanding events which might contribute to the selectivity of this damage but the cellular changes which culminate in neuronal death remain poorly defined. This overview examines the metabolic state of tissue in the post-ischemic period and the relationship of changes to the development of damage in areas containing ischemia-susceptible neurons. During early recirculation there is substantial recovery of ATP, phosphocreatine and related metabolites in all brain regions. However, this recovery does not signal restitution of normal energy metabolism as reductions of the oxidative metabolism of glucose are seen in many areas and may persist for several days. Furthermore, decreases in pyruvate-supported respiration develop in mitochondria from at least one ischemia-susceptible region at times coincident with the earliest histological evidence of ischemia-induced degeneration. These mitochondrial changes could simply be an early marker of irreversible damage but the available evidence is equally consistent with these contributing to the degenerative process and offering a potential site for therapeutic intervention.

Animals↗

PubMed2006

Complications of brain death: frequency and impact on organ retrieval.

Brain death is associated with complex hemodynamic, endocrine, and metabolic dysfunction that can lead to major complications with the potential donor. Untreated, this can progress to cardiovascular collapse with loss of valuable organs for transplantation. We hypothesized that brain death-related complications would have no effect on the number of organs donated if an aggressive donor management protocol was in place. We identified all successful organ donations between January 2000 and December 2003 and evaluated them for brain death-associated complications (defined as vasopressor requirement, coagulopathy, diabetes insipidus, cardiac ischemia, lactic acidosis, renal failure, and acute respiratory distress syndrome) and donated organs per donor. Sixty-nine organ donors were identified. Complications identified were as follows: intravenous vasopressor requirement in 97.1 per cent, coagulopathy in 55.1 per cent, thrombocytopenia in 53.6 per cent, diabetes insipidus in 46.4 per cent, cardiac ischemia in 30.4 per cent, lactic acidosis in 24.6 per cent, renal failure in 20.3 per cent, and acute respiratory distress syndrome in 13 per cent. There was no significant effect of complications on the average number of organs harvested, with the exception of an increase in organs harvested in the presence of diabetes insipidus. With the implementation of an aggressive organ donor management protocol, these complications can be effectively managed with no impact on the number of organs harvested for transplant.

Adult↗

PubMed1998

A population-based prospective evaluation of risk of sudden cardiac death after operation for common congenital heart defects.

OBJECTIVES: This study sought to define 1) the risk of sudden death after operation for common congenital heart defects; and 2) factors associated with an increased risk of sudden death. BACKGROUND: Although the prognosis for patients with congenital heart defects is improved by surgical treatment, they remain at a well recognized but poorly defined risk of late sudden death. METHODS: This population-based study evaluated all patients < 19 years old undergoing surgical treatment of common forms of congenital heart disease in the state of Oregon between 1958 and 1996. Patients were identified retrospectively through 1958, with prospective biannual follow-up beginning in 1982. The incidence and cause of late sudden death were evaluated for 3,589 patients surviving operation for the following defects: atrial, ventricular and atrioventricular septal defects; patent ductus arteriosus; pulmonary stenosis; aortic stenosis; coarctation of the aorta; tetralogy of Fallot; and D-transposition of the great arteries. RESULTS: There were 41 unexpected late sudden deaths during 45,857 patient-years of follow-up, an overall event rate of 1/1,118 patient-years. Thirty-seven of the 41 late sudden deaths occurred in patients with aortic stenosis, coarctation, transposition of the great arteries or tetralogy of Fallot, an event rate of 1/454 patients-years. In contrast, only four sudden deaths occurred among the other defects, an event rate of 1/7,154 patient-years (p < 0.01). The risk of late sudden death increased incrementally 20 years after operation for tetralogy of Fallot, aortic stenosis and coarctation. However, risk was not dependent on patient age at operation or surgical era. The causes of sudden death were arrhythmia in 30 patients, circulatory (embolic or aneurysm rupture) in 7 and acute heart failure in 4. CONCLUSIONS: The risk of late sudden death for patients surviving operation for common congenital heart defects is 25 to 100 times greater than an age-matched control population. This increased risk is primarily represented by patients with cyanotic or left heart obstructive lesions. The risk of sudden death appears to be time dependent, increasing primarily after the second postoperative decade.

Adolescent↗

PubMed1998

"Apoptotic" myocytes in infarct area in rabbit hearts may be oncotic myocytes with DNA fragmentation: analysis by immunogold electron microscopy combined with In situ nick end-labeling.

BACKGROUND: Modes of cell death have been defined morphologically as apoptosis and oncosis. Infarcted myocytes have been reported to show apoptosis, as revealed by DNA fragmentation by DNA ladder and by in situ terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) at the light microscopic level. We investigated whether TUNEL-positive infarcted myocytes have apoptotic or oncotic ultrastructures by using electron microscopic TUNEL, which can simultaneously observe the ultrastructure and DNA fragmentation of the same myocytes. METHODS AND RESULTS: Thirty rabbits were divided into 5 groups (n=6 each) that were subjected to a sham operation or to 30-minute ischemia followed by 0-minute, 30-minute, 2-hour, or 4-hour reperfusion of a coronary artery. In the 2- and 4-hour reperfusion groups only, DNA electrophoresis showed a ladder pattern, and the light microscopic TUNEL finding was positive in the nuclei of myocytes localized in the infarcted area (6+/-2% and 11+/-3%, respectively). Electron microscopic TUNEL showed that nuclei with a significant accumulation of immunogold particles (indicating an electronic microscopic TUNEL-positive result) were observed only in the infarcted myocytes with irreversibly oncotic ultrastructures that were found in the hearts of the 2- and 4-hour reperfusion groups (41+/-3% and 83+/-4%, respectively). Irreversibly oncotic myocytes (indicated by swelling, inhomogeneously clumped chromatin in nuclei, dense bodies in mitochondria, and/or ruptured plasma membranes) were also seen in the 0- and 30-minute reperfusion groups, which did not exhibit TUNEL-positive myocytes. There was no evidence of apoptotic ultrastructures in the myocytes. CONCLUSIONS: DNA fragmentation occurs in the myocytes that had already shown irreversibly oncotic, but not apoptotic, ultrastructures with ischemia and/or reperfusion. Therefore, DNA fragmentation itself does not always mean apoptosis, and so-called apoptotic infarcted myocytes may belong to a category of cell death other than apoptosis.

Animals↗

PubMed2006

Functional repression of cAMP response element in 6-hydroxydopamine-treated neuronal cells.

Impaired survival signaling may represent a central mechanism in neurodegeneration. 6-Hydroxydopamine (6-OHDA) is an oxidative neurotoxin used to injure catecholaminergic cells of the central and peripheral nervous systems. Although 6-OHDA elicits phosphorylation of several kinases, downstream transcriptional effects that influence neuronal cell death are less defined. The cAMP response element (CRE) is present in the promoter sequences of several important neuronal survival factors. Treatment of catecholaminergic neuronal cell lines (B65 and SH-SY5Y) with 6-OHDA resulted in repression of basal CRE transactivation. Message levels of CRE-driven genes such as brain-derived neurotrophic factor and the survival factor Bcl-2 were decreased in 6-OHDA-treated cells, but message levels of genes lacking CRE sequences were not affected. Repression of CRE could be reversed by delayed treatment with cAMP several hours after initiation of 6-OHDA injury. Furthermore, restoration of CRE-driven transcription was associated with significant neuroprotection. In contrast to observations in other model systems, the mechanism of CRE repression did not involve decreased phosphorylation of its binding protein CREB. Instead, total CREB and phospho-CREB (pCREB) were increased in the cytoplasm and decreased in the nucleus of 6-OHDA-treated cells. 6-OHDA also decreased nuclear pCREB in dopaminergic neurons of primary mouse midbrain cultures. Co-treatment with cAMP promoted/restored nuclear localization of pCREB in both immortalized and primary culture systems. Increased cytoplasmic pCREB was observed in degenerating human Parkinson/Lewy body disease substantia nigra neurons but not in age-matched controls. Notably, cytoplasmic accumulation of activated upstream CREB kinases has been observed previously in both 6-OHDA-treated cells and degenerating human neurons, supporting a potential role for impaired nuclear import of phosphorylated signaling proteins.

Animals↗

PubMed1999

Analgesia and sedation in preterm neonates who require ventilatory support: results from the NOPAIN trial. Neonatal Outcome and Prolonged Analgesia in Neonates.

BACKGROUND: Preterm neonates are exposed to multiple painful procedures after birth and exhibit acute physiological responses to pain. Occurrence of early intraventricular hemorrhage within 24 to 72 hours after birth suggests a role of pain and stress in the multifactorial causation of severe intraventricular hemorrhage and periventricular leukomalacia. We proposed that such neurologic outcomes in preterm neonates who require ventilatory support may be reduced by morphine analgesia or midazolam sedation compared with a placebo. OBJECTIVES: To define the incidence of clinical outcomes in the target study population, to estimate the effect size and adverse effects associated with analgesia and sedation, and to calculate the sample size for a definitive test of this hypothesis. METHODS: Sixty-seven preterm neonates were randomized in a pilot clinical trial from 9 centers. Neonates of 24 to 32 weeks gestation were eligible if they had been intubated and required ventilatory support for less than 8 hours and if they were enrolled within 72 hours after birth. Exclusion criteria included major congenital anomalies, severe intrapartum asphyxia, and participation in other research studies. Severity of illness was assessed by the Clinical Risk Index for Babies, and neonates were randomized to receive continuous infusions of morphine sulfate, midazolam hydrochloride, or 10% dextrose (placebo). Masked study medications were continued as long as clinically necessary, then weaned and stopped according to predefined criteria. Levels of sedation (COMFORT scores) and responses to pain (Premature Infant Pain Profile scores) were measured before, during, and 12 hours after discontinuation of drug infusion. Cranial ultrasound examinations were performed as part of routine practice, and poor neurologic outcomes were defined as neonatal death, severe intraventricular hemorrhage (grade III or IV), or periventricular leukomalacia. RESULTS: No significant differences occurred in the demographic, clinical, and socioeconomic variables related to mothers and neonates in the 3 groups or in the severity of illness at birth as measured by Clinical Risk Index for Babies scores. Two neonates in the placebo group and 1 neonate in the midazolam group died; no deaths occurred in the morphine group. Poor neurologic outcomes occurred in 24% of neonates in the placebo group, 32% in the midazolam group, and 4% in the morphine group (likelihood ratio chi2 = 7.04, P = .03). Secondary clinical outcomes and neurobehavioral outcomes at 36 weeks' postconceptional age were similar in the 3 groups. Responses elicited by endotracheal tube suction (Premature Infant Pain Profile scores) were significantly reduced during the morphine (P<.001) and midazolam (P = .002) infusions compared with the placebo group. CONCLUSIONS: This pilot trial suggests that preemptive analgesia given by continuous low-dose morphine infusion may reduce the incidence of poor neurologic outcomes in preterm neonates who require ventilatory support. Limitations in the sample size of this pilot study suggest that these results should be confirmed in a large multicenter randomized trial.

Analgesia↗

PubMed1994

Second renal transplantations. Ethical issues clarified by outcome; outcome enhanced by a reliable crossmatch.

OBJECTIVE: To determine whether the appropriate use of scarce donor resources has been accomplished by renal retransplantation by reviewing the initial and long-term outcomes of second-renal transplant recipients at the Massachusetts General Hospital, Boston. PATIENTS AND RESULTS: With a mean follow-up of nearly 5 years following transplantation, 54 (68%) of 80 second-transplant recipients had functioning allografts (allograft failure was defined by patient death or a return to dialysis). Rejection was the most common cause of failure (14 [54%] of 26 patients). The 1-, 3-, and 5-year actuarial allograft survival rates were 86%, 78%, and 69%, respectively, which were not significantly different from the survival rates of primary allografts at this center. These results support the continued approach of providing both cadaver-donor and living-donor renal allografts for recipients whose primary renal allograft has failed. The antiglobulin crossmatch may have contributed to the successful outcome by accurately determining compatibility and by averting early rejection failures. CONCLUSIONS: Health care policy reviewers should clearly distinguish the prospects for successful second renal transplants from the outcomes of extrarenal retransplantation. Moreover, because excellent second-renal allograft survival is attainable and comparable to primary-renal allograft survival and because the costs are comparable, restricting suitable patients to subsequent lifelong dialysis becomes unethical.

Adult↗

PubMed2002

Fluvastatin for prevention of cardiac events following successful first percutaneous coronary intervention: a randomized controlled trial.

CONTEXT: Percutaneous coronary intervention (PCI) is associated with excellent short-term improvements in ischemic symptoms, yet only three fifths of PCI patients at 5 years and one third of patients at 10 years remain free of major adverse cardiac events (MACE). OBJECTIVE: To determine whether treatment with fluvastatin reduces MACE in patients who have undergone PCI. DESIGN AND SETTING: Randomized, double-blind, placebo-controlled trial conducted at 77 referral centers in Europe, Canada, and Brazil. PATIENTS: A total of 1677 patients (aged 18-80 years) recruited between April 1996 and October 1998 with stable or unstable angina or silent ischemia following successful completion of their first PCI who had baseline total cholesterol levels between 135 and 270 mg/dL (3.5-7.0 mmol/L), with fasting triglyceride levels of less than 400 mg/dL (4.5 mmol/L). INTERVENTIONS: Patients were randomly assigned to receive treatment with fluvastatin, 80 mg/d (n = 844), or matching placebo (n = 833) at hospital discharge for 3 to 4 years. MAIN OUTCOME MEASURE: Survival time free of MACE, defined as cardiac death, nonfatal myocardial infarction, or reintervention procedure, compared between the treatment and placebo groups. RESULTS: Median time between PCI and first dose of study medication was 2.0 days, and median follow-up was 3.9 years. MACE-free survival time was significantly longer in the fluvastatin group (P =.01). One hundred eighty-one (21.4%) of 844 patients in the fluvastatin group and 222 (26.7%) of 833 patients in the placebo group had at least 1 MACE (relative risk [RR], 0.78; 95% confidence interval [CI], 0.64-0.95; P =.01). This result was independent of baseline total cholesterol levels (above [RR, 0.76; 95% CI, 0.56-1.04] vs below [RR, 0.77; 95% CI, 0.57-1.02] the median). In subgroup analysis, the risk of MACE was reduced in patients with diabetes (n = 202; RR, 0.53; 95% CI, 0.29-0.97; P =.04) and in those with multivessel disease (n = 614; RR, 0.66; 95% CI, 0.48-0.91; P =.01) who received fluvastatin compared with those who received placebo. There were no instances of creatine phosphokinase elevations 10 or more times the upper limit of normal or rhabdomyolysis in the fluvastatin group. CONCLUSION: Fluvastatin treatment in patients with average cholesterol levels undergoing their first successful PCI significantly reduces the risk of major adverse cardiac events.

Adult↗

PubMed2005

High-dose atorvastatin vs usual-dose simvastatin for secondary prevention after myocardial infarction: the IDEAL study: a randomized controlled trial.

CONTEXT: Evidence suggests that more intensive lowering of low-density lipoprotein cholesterol (LDL-C) than is commonly applied clinically will provide further benefit in stable coronary artery disease. OBJECTIVE: To compare the effects of 2 strategies of lipid lowering on the risk of cardiovascular disease among patients with a previous myocardial infarction (MI). DESIGN, SETTING, AND PARTICIPANTS: The IDEAL study, a prospective, randomized, open-label, blinded end-point evaluation trial conducted at 190 ambulatory cardiology care and specialist practices in northern Europe between March 1999 and March 2005 with a median follow-up of 4.8 years, which enrolled 8888 patients aged 80 years or younger with a history of acute MI. INTERVENTIONS: Patients were randomly assigned to receive a high dose of atorvastatin (80 mg/d; n = 4439), or usual-dose simvastatin (20 mg/d; n = 4449). MAIN OUTCOME MEASURE: Occurrence of a major coronary event, defined as coronary death, confirmed nonfatal acute MI, or cardiac arrest with resuscitation. RESULTS: During treatment, mean LDL-C levels were 104 (SE, 0.3) mg/dL in the simvastatin group and 81 (SE, 0.3) mg/dL in the atorvastatin group. A major coronary event occurred in 463 simvastatin patients (10.4%) and in 411 atorvastatin patients (9.3%) (hazard ratio [HR], 0.89; 95% CI, 0.78-1.01; P = .07). Nonfatal acute MI occurred in 321 (7.2%) and 267 (6.0%) in the 2 groups (HR, 0.83; 95% CI, 0.71-0.98; P = .02), but no differences were seen in the 2 other components of the primary end point. Major cardiovascular events occurred in 608 and 533 in the 2 groups, respectively (HR, 0.87; 95% CI, 0.77-0.98; P = .02). Occurrence of any coronary event was reported in 1059 simvastatin and 898 atorvastatin patients (HR, 0.84; 95% CI, 0.76-0.91; P<.001). Noncardiovascular death occurred in 156 (3.5%) and 143 (3.2%) in the 2 groups (HR, 0.92; 95% CI, 0.73-1.15; P = .47). Death from any cause occurred in 374 (8.4%) in the simvastatin group and 366 (8.2%) in the atorvastatin group (HR, 0.98; 95% CI, 0.85-1.13; P = .81). Patients in the atorvastatin group had higher rates of drug discontinuation due to nonserious adverse events; transaminase elevation resulted in 43 (1.0%) vs 5 (0.1%) withdrawals (P<.001). Serious myopathy and rhabdomyolysis were rare in both groups. CONCLUSIONS: In this study of patients with previous MI, intensive lowering of LDL-C did not result in a significant reduction in the primary outcome of major coronary events, but did reduce the risk of other composite secondary end points and nonfatal acute MI. There were no differences in cardiovascular or all-cause mortality. Patients with MI may benefit from intensive lowering of LDL-C without an increase in noncardiovascular mortality or other serious adverse reactions.Trial Registration ClinicalTrials.gov Identifier: NCT00159835.

Aged↗

PubMed1997

Larynx-associated lymphoid tissue (LALT) in young children.

BACKGROUND: Mucosa-associated lymphoid tissue (MALT) plays a central role in mucosal immunity. Whereas the characteristics and function of MALT in the intestine are well established, almost nothing is known about MALT in the larynx. METHODS: In this study we examined the morphology and the lymphocyte subset composition of MALT in the larynges of children who had died of sudden infant death or various defined traumatic or nontraumatic causes. RESULTS: Organized lymphoid tissue was found in the supraglottic parts of the larynx in nearly 80% of the children in both groups. This lymphoid tissue showed all morphological signs of MALT, such as typical lymphoid follicles with germinal centers, infiltration of the overlying epithelium by lymphocytes, and high endothelial venules (HEV). Thus we will use the term LALT (larynx-associated lymphoid tissue) to refer to this tissue. The lymphoid follicles of LALT contained mainly B lymphocytes with some CD4+ lymphocytes in the germinal centers. Remarkably, T lymphocytes of both subset types and B lymphocytes were observed in comparable numbers in the parafollicular area. CONCLUSIONS: We assume that LALT is a physiological structure of the larynx in young children. The morphology and the distribution of lymphocyte subsets are similar to those of MALT in the human gut. LALT may be a regular part of the mucosal immune system in young children with the role of respiratory inductive site for mucosal immunity.

Antigens, Differentiation, B-Lymphocyte↗

PubMed1997

Mortality and sudden death in anorexia nervosa.

OBJECTIVE: Mortality rates of anorexia nervosa (AN) are generally assumed to rise with increasingly protracted follow-up periods. Reports are highly variable, with rates ranging between 5 and 20%. A rate of 5.9% resulted from very recent meta-analyses. Causes of death of AN patients ranged from suicide to sudden death. METHOD: Findings so far published on clinical course, follow-up, outcome, prognosis, mortality, and sudden death in AN cases were systematically analyzed with the view to checking on divergent definitions of mortality rate, crude mortality rate, mortality death rate, and methodological problems of recording which may be causes of variability of data and evaluations. The same variability applied to descriptions of causes of death in AN. While suicide data usually are precise, most of all deaths resulted from inadequately defined complications of eating disorder, and in some cases the cause of death, including sudden death, is reported as unknown. RESULTS: The crude mortality rate due to all causes of death of AN patients was found to be 5.9% by means of linear regression in a meta-analysis. However, no absolute, precise data were given on causes of death, including sudden death in AN. Reference is made to the great variety of somatic alterations as well as to the role played by cardiac arrhythmia and acute circulatory failure in the context of sudden death. DISCUSSION: Any AN death should be fully reported for proper elucidation of the causes. Neuroanatomic, neuropathological, and neurohistological studies should be conducted, primarily into the right brain hemisphere for accurate determination of etiological relationships between cerebral function, brain alterations, and AN. An account is given in this paper of preliminary results obtained from a quantitative-neurohistological investigation of the brain of a female AN patient aged 13.5 years who died a sudden death.

Adolescent↗

PubMed1982

Coronary heart disease mortality after irradiation for Hodgkin's disease.

The authors conducted a study designed to evaluate the hypothesis that irradiation to the heart in the treatment for Hodgkin's disease (HD) is associated with increased coronary heart disease (CHD) mortality. This report describes 957 patients diagnosed with HD in 1942-75 and analyzes follow-up findings through December 1977. Twenty-five coronary heart disease deaths have been observed, and 4258.2 person-years of experience at risk have been accrued. The relative death rate (RDR), defined as the CHD mortality for heart-irradiated subjects divided by the mortality for nonirradiated subjects, was estimated. After adjustment for the effect of interval of observation, age, stage, and class, the RDR estimate is 1.5 but does not differ significantly from unit (95% confidence limits: 0.59, 3.7).

Adolescent↗

PubMed1988

Analysis of the possibility that transurethral resection promotes metastasis in prostate cancer.

The issue of transurethral resection (TURP) in patients with known prostatic adenocarcinoma is a current clinical controversy. Data have accumulated to associate this procedure with an adverse risk of distant spread and death for a defined subset of patients with moderate and poorly differentiated, T3 and T4 (Stage C) tumors. Review of available literature demonstrates that examination of this subset is incomplete in studies that do not find an adverse prognosis. The reason for the association of TURP and metastasis may be related directly to the resection via mechanical dissemination of tumor or indirectly through association with unknown adverse factors. Retrospective review may be unable to separate these two hypotheses, but hazard function analysis is presented and is consistent with surgical enhancement of metastases. Strategies for avoiding the adverse effect represent areas for possible further clinical research.

Adenocarcinoma↗

PubMed2006

Inhaled nitric oxide for respiratory failure in preterm infants.

BACKGROUND: Inhaled nitric oxide has been proven effective in term infants with hypoxic respiratory failure. The pathophysiology of respiratory failure, and the potential risks, differ substantially in preterm infants. Analysis of the efficacy and toxicities of inhaled nitric oxide in infants born before 35 weeks is therefore necessary. OBJECTIVES: To determine whether, in preterm newborn infants (< 35 weeks gestation) who have hypoxic respiratory failure, treatment with inhaled nitric oxide improves oxygenation within 2 hours and reduces the rates of death, bronchopulmonary dysplasia, intraventricular haemorrhage, or neurodevelopmental disability SEARCH STRATEGY: Standard methods of the Cochrane Neonatal Review Group were used. We searched MEDLINE, EMBASE, Healthstar and the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library), using the following keywords: nitric oxide, clinical trial, newborn, and covering years from 1985 to 2005. In addition, we searched the abstracts of the Pediatric Academic Societies. SELECTION CRITERIA: Randomised and quasi randomised studies in preterm infants with hypoxic respiratory failure. Administration of inhaled nitric oxide compared to control with or without placebo. Clinically relevant outcomes that were analysed included death, bronchopulmonary dysplasia (defined as oxygen dependence at 36 weeks postconceptional age), intraventricular haemorrhage, long term neurodevelopmental outcome and short term effects on oxygenation. DATA COLLECTION AND ANALYSIS: Standard methods of the Cochrane Neonatal Review Group were used. Two investigators extracted, assessed and coded separately all data for each study. Any disagreement was resolved by discussion. MAIN RESULTS: Seven randomised controlled trials of inhaled nitric oxide therapy in preterm infants were found. One study consisted of infants determined to have a high risk of developing bronchopulmonary dysplasia (Subhedar 1997). One study studied routine use of inhaled NO in all ventilated preterm infants (Schreiber 2003). The remaining studies consisted of infants with high predicted mortality based on poor oxygenation (Kinsella 1999; Hascoet 2005; INNOVO 2005; Van Meurs 2005; Mercier 1999). No significant effect of inhaled nitric oxide on mortality or bronchopulmonary dysplasia was demonstrated. There was no evidence of effect on the risk of intraventricular haemorrhage. There may be short term improvements in oxygenation. Two studies (Schreiber 2003; INNOVO 2005) have so far presented data on long term neurodevelopmental outcome, one of which demonstrated improved outcome at two years corrected age. AUTHORS' CONCLUSIONS: The currently published evidence from randomised trials does not support the use of inhaled nitric oxide in preterm infants with hypoxic respiratory failure. Further studies may need to be performed to evaluate the potential benefit of routine use of this therapy in infants with milder forms of respiratory failure, and these trials will need to be designed to evaluate not only neonatal survival, and the occurrence of neonatal morbidities, but should be powered to evaluate neurodevelopmental outcome at a minimum of two years of age.

Administration, Inhalation↗

PubMed2002

The membrane attack complex of complement induces caspase activation and apoptosis.

Activation of the terminal pathway of the complement system leads to insertion of terminal complement complexes (C5b-9) into the cell membrane, which may induce cytolysis. Recent data indicate that the terminal complement pathway can also result in apoptosis in vivo. To further define the cell death pathway induced by complement, we examined induction of apoptosis by complement in vitro. Rat mesangial cells opsonized with a complement-activating antibody and exposed to rat serum as a complement source underwent apoptotic cell death in a time- and dose-dependent fashion, as demonstrated by membrane exposure of phosphatidylserine and fragmentation of nuclei. No significant apoptosis was detected in either cultures treated with C6-deficient serum or in control cultures. The pan-caspase-inhibitor zVAD-fmk inhibited complement-induced apoptosis completely. In line with this observation, complement induced cleavage and activation of caspase 3. Importantly, cellular exposure to purified cytolytically inactive C5b-9, in the absence of antibody and early complement components, also resulted into caspase activation and apoptosis. Together, these results indicate that C5b-9 is involved in induction of apoptosis via a caspase-dependent pathway. Apoptosis as a consequence of complement-mediated cell damage may provide an explanation for the presence of apoptosis in inflammatory processes, for instance in hyperacute xenograft rejection.

Amino Acid Chloromethyl Ketones↗

PubMed2006

Fatal motor vehicle crashes among veterans of the 1991 Gulf War and exposure to munitions demolitions at Khamisiyah: a nested case-control study.

BACKGROUND: A proposed explanation for the observed higher risk of fatal motor vehicle crashes (MVC) among 1991 Gulf War-deployed veterans is neurocognitive deficits resulting from nerve agent exposure at Khamisiyah, Iraq. Our objective was to assess any association between postwar fatal MVC and possible nerve agent exposure based on 2000 modeled plume data. METHODS: Cases were defined as MVC deaths with a record in the Department of Transportation Fatality Analysis Reporting System through 1995. Cases (n = 282) and controls (n = 3,131) were derived from a larger nested case-control study of Gulf War-era veterans and limited to Army, male, deployed personnel. Exposure and cumulative dose by case-control status were analyzed using multivariate techniques. RESULTS: Exposure status was not associated with fatal MVC (OR 0.96, 95% CI 0.72-1.26), nor were tertiles of cumulative dose. CONCLUSIONS: Findings do not support an association between possible exposures at Khamisiyah and postwar fatal MVC among Gulf War veterans.

Accidents, Traffic↗

PubMed2005

Preoperative plasma N-terminal pro-brain natriuretic peptide as a marker of cardiac risk in patients undergoing elective non-cardiac surgery.

BACKGROUND: Plasma N-terminal pro-brain natriuretic peptide (NTproBNP) is a sensitive marker for heart failure. This study tested whether the preoperative plasma level of NTproBNP could predict cardiac complications in patients undergoing non-cardiac surgery. METHODS: A total of 190 consecutive patients who underwent elective non-cardiac surgery that required general anaesthesia were studied. In addition to routine preoperative evaluation, a blood sample was taken for estimation of plasma NTproBNP concentration. Postoperative cardiac complications were defined as cardiac death, acute coronary syndrome, heart failure and haemodynamic compromise from cardiac arrhythmias. RESULTS: Fifteen of the 190 patients had a cardiac complication: four had acute coronary syndrome and 13 had congestive heart failure. NTproBNP concentration was significantly higher in patients with a cardiac complication; a level greater than 450 ng/l was predictive of cardiac complications with a sensitivity of 100 per cent and a specificity of 82.9 per cent. Other factors associated with cardiac complications were a higher American Society of Anesthesiologists grade, age and clinical cardiac impairment, but in a multivariate analysis NTproBNP level was the only independent factor. CONCLUSION: Preoperative plasma NTproBNP concentration may be an independent predictor of cardiac complications in patients undergoing non-cardiac surgery.

Atrial Natriuretic Factor↗

PubMed2002

Long-term prognostic value of an index of myocardial performance in patients with myocardial infarction.

BACKGROUND: The Tei index of myocardial performance (IMP), which combines parameters of both systolic and diastolic ventricular function, is a useful prognostic factor in many clinical settings. HYPOTHESIS: This study assessed the long-term prognostic value of IMP in patients discharged from hospital after acute myocardial infarction (AMI). METHODS: Doppler/echocardiographic studies were recorded in 90 consecutive patients on Day 14 +/- 2 following an AMI. The IMP was calculated from the Doppler recordings, as a sum of isovolumetric contraction time and isovolumetric relaxation time, divided by the ejection time. RESULTS: The patients were followed for an average (SD) of 57.8 (16.1) months. During this period there were 22 (24%) cardiac events, defined as cardiac deaths (10) or nonfatal recurrent myocardial infarctions (12). After multivariate Cox analysis, Tei index > 0.55 (relative risk [RR] 4.45; 95% confidence interval [CI] 1.28-15.45; p = 0.019), LV end-systolic volume > 65 ml (RR 3.23; 95% CI 1.34-7.79; p = 0.009), and mitral E wave deceleration time < or = 0.145 s (RR 2.94; 95% CI 1.24-6.92; p = 0.014) were the only independent predictors of cardiac events during the follow-up period. In a subgroup of patients with preserved LV systolic function (ejection fraction > 0.40), IMP was the only predictor of cardiac events (RR 6.37; 95% CI 1.32-30.77, p = 0.02). CONCLUSIONS: The Tei index of myocardial performance, which is simple and easy to calculate, is a useful tool for risk assessment in patients following myocardial infarction, and in a subgroup of patients with normal or only mildly impaired systolic function.

Aged↗