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971.
972.
973.
Rob JM Strack van Schijndel Peter JM Weijs Rixt H Koopmans Hans P Sauerwein Albertus Beishuizen Armand RJ Girbes 《Critical care (London, England)》2009,13(4):1-11
Introduction
Infusing arginine vasopressin (AVP) in vasodilatory shock usually decreases cardiac output and thus systemic oxygen transport. It is still a matter of debate whether this vasoconstriction impedes visceral organ blood flow and thereby causes organ dysfunction and injury. Therefore, we tested the hypothesis whether low-dose AVP is safe with respect to liver, kidney, and heart function and organ injury during resuscitated septic shock.Methods
After intraperitoneal inoculation of autologous feces, 24 anesthetized, mechanically ventilated, and instrumented pigs were randomly assigned to noradrenaline alone (increments of 0.05 μg/kg/min until maximal heart rate of 160 beats/min; n = 12) or AVP (1 to 5 ng/kg/min; supplemented by noradrenaline if the maximal AVP dosage failed to maintain mean blood pressure; n = 12) to treat sepsis-associated hypotension. Parameters of systemic and regional hemodynamics (ultrasound flow probes on the portal vein and hepatic artery), oxygen transport, metabolism (endogenous glucose production and whole body glucose oxidation derived from blood glucose isotope and expiratory13CO2/12CO2 enrichment during 1,2,3,4,5,6-13C6-glucose infusion), visceral organ function (blood transaminase activities, bilirubin and creatinine concentrations, creatinine clearance, fractional Na+ excretion), nitric oxide (exhaled NO and blood nitrate + nitrite levels) and cytokine production (interleukin-6 and tumor necrosis factor-α blood levels), and myocardial function (left ventricular dp/dtmax and dp/dtmin) and injury (troponin I blood levels) were measured before and 12, 18, and 24 hours after peritonitis induction. Immediate post mortem liver and kidney biopsies were analysed for histomorphology (hematoxylin eosin staining) and apoptosis (TUNEL staining).Results
AVP decreased heart rate and cardiac output without otherwise affecting heart function and significantly decreased troponin I blood levels. AVP increased the rate of direct, aerobic glucose oxidation and reduced hyperlactatemia, which coincided with less severe kidney dysfunction and liver injury, attenuated systemic inflammation, and decreased kidney tubular apoptosis.Conclusions
During well-resuscitated septic shock low-dose AVP appears to be safe with respect to myocardial function and heart injury and reduces kidney and liver damage. It remains to be elucidated whether this is due to the treatment per se and/or to the decreased exogenous catecholamine requirements. 相似文献974.
Vladan Vukcevic Branko Beleslin Miodrag Ostojic Sinisa Stojkovic Goran Stankovic Milan Nedeljkovic Dejan Orlic Ana Djordjevic-Dikic Jelena Stepanovic Vojislav Giga Aleksandra Arandjelovic Miodrag Dikic Jelena Kostic Ivana Nedeljkovic Biljana Nedeljkovic-Beleslin Jovica Saponjski 《The international journal of cardiovascular imaging》2009,25(4):353-361
Evaluation of coronary pressures during angioplasty may functionally quantify collateral circulation. The aim of the study
was to evaluate the relation between the amount of collateral circulation and development of myocardial ischemia during balloon
occlusion, anatomic degree of collaterals, and functional improvement of myocardium. Study population consisted of 31 pts
(mean age 53 ± 7 years; 25 male) with previous myocardial infarction and significant one-vessel stenosis undergoing angioplasty.
Collateral circulation was calculated as the ratio between distal coronary pressure during balloon occlusion (P
w) and aortic pressure (P
a). Angiographic appearance of collaterals was evaluated by Rentrop classification. Patients were evaluated by echo for functional
improvement of myocardium in the follow-up period. Mean P
w/P
a was 0.24 ± 0.10 (range of 0.07–0.51). Rentrop grade 0 of collaterals was present in 16 patients (52%), grade 1 in11 patients
(35%), and grade 2 in 4 patients (13%). A mild correlation between angio and hemodynamic evaluation of collaterals was observed
(r = 0.38, P = 0.035). In patients without ECG changes during angioplasty (21 pts, 68%), P
w/P
a was significantly higher in comparison to patients with ECG changes (0.28 ± 0.09 vs. 0.15 ± 0.06, P < 0.001; area under the curve 0.93). In patients with myocardial functional improvement during follow-up (21 pts, 68%), P
w/P
a was significantly higher than in the patients without echo improvement (0.26 ± 0.10 vs. 0.18 ± 0.08, P = 0.035). The amount of recruitable collaterals is not negligible even in the patients with no angio visible collaterals.
Low values of P
w/P
a are associated with ECG changes during balloon occlusion. Higher P
w/P
a was associated with better functional improvement of myocardium. 相似文献
975.
BACKGROUND: Zonisamide is licensed in the EU and USA for the adjunctive treatment of partial-onset seizures in adults but there are few data about its use in children. AIMS: To assess the long-term safety and efficacy of zonisamide in children and adolescents. METHODS: Zonisamide-na?ve patients (n=109, aged 3-15 years, weight >or=12.5 kg) with a clinical diagnosis of epilepsy (>or=4 seizures/month, receiving 1-2 antiepileptic drugs [AEDs] daily) received zonisamide once or twice daily in an open-label trial. The starting dose was 1mg/kg/day, increased by 2 mg/kg/day every 1-2 weeks at the investigator's discretion to an initial maximum of 12 mg/kg/day. The occurrence of adverse events (AEs) was the primary safety measure. Efficacy was measured via the reductions in seizure frequency and via investigator- and carer-rated global assessment ratings. RESULTS: The mean dose received was 8.5 mg/kg/day. Of the 109 children, 52 (48%) completed 15 months' treatment. Treatment-related AEs, mostly mild-to-moderate in severity, were reported by 58 patients. Seven patients discontinued due to treatment-related AEs. Serious AEs (pancreatitis, decreased sweating, and vertigo) were reported by three patients. A significant (p=0.033) median reduction in 'all seizure' frequency of 2.60 seizures per week was observed. Additionally, a significant (p=0.029) median reduction of 1.80 seizures/week in 'complex partial' seizures was reported. Improvements in investigator- and carer-rated global assessments were noted. CONCLUSIONS: Zonisamide treatment was generally well tolerated and was associated with significant reductions in seizure frequency in this pediatric population with a variety of both partial and generalized medically refractory epilepsy syndromes. 相似文献
976.
The purpose of this study was to examine relationships between aerobic fitness and birthweight in adolescents. A representative cohort of 1015 males and females aged 12 and 15 y was studied, at baseline, with 89% of the 12-y-olds being re-examined 3 y later.The main outcome measures were an index of aerobic fitness, measured in laps completed at voluntary exhaustion by a twenty-metre shuttle run test, and recorded birthweight. Multiple linear regression, with and without adjustment for known and potential confounding variables, was performed to examine associations between fitness and birthweight.Birthweight and aerobic fitness were positively related so that for each kg decrease in birthweight, there was a mean (95% confidence interval) decrease in fitness score of 4.84 (0.35 to 9.33) laps and 3.21 (0.32 to 6.10) laps, in 12-y-old boys and girls respectively. This relationship is of a similar order to the strength of association between birthweight and adult blood pressure previously reported. Associations between birthweight and physical fitness at the age of 15 were weaker and were not significant.Our findings suggest that aerobic fitness may be involved in mediating the association between birthweight and cardiovascular disease risk later in life. The weakening of the association between birthweight and fitness between the ages of 12 and 15 y is similar to the weaker associations between birthweight and blood pressure seen among adolescents compared to younger children. We are currently re-examining this cohort to see if, as with blood pressure, the association with fitness re-emerges at an older age. 相似文献
977.
Rett syndrome results from mutations in the X-linked methyl-CpG-binding protein 2 (MECP2) gene, which are nearly always lethal in males and lead to regression and reduced life expectancy in females. Herein we report one propositus with five tandem deletions and a second propositus with three tandem deletions within MECP2 exon 4 that encode truncated protein products resulting in classic Rett syndrome. These deletion breakpoints and single deletions in 3 other patients were all found within a 185-bp region along with 64 of 69 other reported deletion breakpoints in the MECP2 gene. Illegitimate recombination resulting in deletion at a substantial proportion of the shared MECP2 sites is enhanced by repeated guanosine (G) DNA sequences in the antisense direction, consistent with reports at other gene loci that polypurine (multiple guanosine or adenosine (A)) basepairs enhance sequence deletion. Multiple deletions at the same poly G recombination sites confirm the existence of deletion hotspots in this gene region with numerous repeated antisense sites that are enriched 26- to 161-fold. Deletion by illegitimate recombination within a single allele can occur during mitotic or meiotic cell cycles. Although prone to disease-causing deletion, this region is unique in humans and highly conserved among mammals for the last 75 000 000 years to maintain the MECP2 gene's critical function. 相似文献
978.
979.
Iris D Nagtegaal Corrie AM Marijnen Elma Klein Kranenbarg Adri Mulder-Stapel Jo Hermans Cornelis JH van de Velde J Han JM van Krieken 《BMC cancer》2001,1(1):7-11
Background
Invasion and metastasis is a complex process governed by the interaction of genetically altered tumor cells and the immunological and inflammatory host reponse. Specific T-cells directed against tumor cells and the nonspecific inflammatory reaction due to tissue damage, cooperate against invasive tumor cells in order to prevent recurrences. Data concerning involvement of individual cell types are readily available but little is known about the coordinate interactions between both forms of immune response. 相似文献980.