An Unusual Case of an Acquired Aortopulmonary Fistula after Surgical Replacement of a Bicuspid Aortic Valve.

Aortopulmonary fistulas are extremely rare and often occur as a result of long-standing aortic aneurysms. They are most frequently due to the erosion of a false aneurysm of the ascending or descending thoracic aorta into the pulmonary artery. Patients generally present with symptoms of acute decompensated heart failure due to a sudden formation of a left-to-right shunt. Here, we present the case of a 63-year-old male who acquired an aortopulmonary fistula four months after undergoing successful bioprosthetic aortic valve replacement.

Impact of CD34+ cell dose in children who receive unrelated PBSCT with in vivo T-cell depletion for hematologic malignancies.

PBSCs are increasingly being chosen as the mode of donation among unrelated donors. Pediatric patients, in particular, may receive very high CD34(+) and CD3(+) doses during unrelated PBSCT. In this work, we analyzed survival and GVHD outcomes in a cohort of 81 children who received unrelated PBSCT with uniform antithymocyte globulin (ATG)-based in vivo T-cell depletion for treatment of hematologic malignancy, with emphasis on the impact of cell dose on transplant outcomes. EFS was 61.5±5.6%, with higher CD34(+) dose (>10.0 × 10(6)/kg) and lower patient risk status predicting improved survival in multivariate study. Cumulative incidence of relapse was 30.2±5.2%; a low CD34(+) dose was the only significant factor for relapse. Neither CD34(+) nor CD3(+) dose was a significant determinant of acute or chronic GVHD. Importance of CD34(+) dose was reaffirmed in a subcohort of younger patients who received greater median cell doses than the overall cohort. In summary, for children who received unrelated PBSCT with ATG-based T-cell depletion for treatment of hematologic malignancy, the CD34(+) dose was the most important factor for relapse and EFS, and neither the CD34(+) nor the CD3(+) dose influenced incidence of acute or chronic GVHD.

High CTLA-4 expression on Th17 cells results in increased sensitivity to CTLA-4 coinhibition and resistance to belatacept.

The CD28/cytotoxic T-lymphocyte antigen 4 (CTLA-4)blocker belatacept selectively inhibits alloreactive T cell responses but is associated with a high incidence of acute rejection following renal transplantation,which led us to investigate the etiology of belatacept­resistant graft rejection. T cells can differentiate into functionally distinct subsets of memory T cellsthat collectively enable protection against diverse classes of pathogens and can cross-react with allogeneicantigen and mediate graft rejection. T helper 17(Th17) cells are a pro-inflammatory CD4+ lineage that provides immunity to pathogens and are pathogenic in autoimmune disease. We found that T helper 1 (Th1)and Th17 memory compartments contained a similar frequency of divided cells following allogeneic stimulation.Compared to Th1 cells, Th17 memory cells expressed significantly higher levels of the coinhibitory molecule CTLA-4. Stimulation in the presence of belatacept inhibited Th1 responses but augmented Th17 cells due to greater sensitivity to coinhibition by CTLA-4. Th17 cells from renal transplant recipients were resistant to ex vivo CD28/CTLA-4 blockade with belatacept, and an elevated frequency of Th17 memory cells was associated with acute rejection during belatacept therapy. These data highlight important differences in costimulatory and coinhibitory requirements of CD4+ memory subsets, and demonstrate that the heterogeneity of pathogen-derived memory has implications for immunomodulation strategies.

Electro-optical properties of nano-thickness polymer film.

We report the electro-optical (E/O) characteristics of the Langmuir-Blodgett film of poly(vinylidene fluoride with trifluoroethylene) copolymers. The structural origin of E/O response of nano LB films was discussed with the result of temperature dependent E/O response at a temperature range from 20 to 100 degrees C. Thermal hysteresis of E/O response and the ferroelectric-paraelectric phase transition were observed at a 20 monomolecular layers Langmuir-Blodgett films.

Two children with differing outcomes after treatment for pulmonary tuberculosis diagnosed after allogeneic hematopoietic stem cell transplantation.

Tuberculosis (TB) is a rare infectious complication after hematopoietic stem cell transplantation (HSCT), but may be more significant in areas where the disease is endemic. Here, we present the clinical course of 2 children with acute lymphoblastic leukemia who were diagnosed with pulmonary TB after allogeneic HSCT. Both patients were treated for either probable or possible invasive fungal infection, as well as TB. One patient, diagnosed with TB 3 months after HSCT, showed remittent fever and symptoms that progressed to acute respiratory distress syndrome and death, despite 3 modifications to the anti-TB regimen. In contrast, another patient who was diagnosed with TB 8 months after transplantation, responded well to anti-TB medication and completed 1 year of treatment with resolution of lung lesions. Co-morbid opportunistic infections, profound host immunosuppression early after transplantation, and potential risk of multi-drug resistant-TB may act as major barriers to effective treatment of TB after HSCT despite appropriate anti-TB medication.

Hypothalamic AMP-activated protein kinase mediates counter-regulatory responses to hypoglycaemia in rats.

AIMS/HYPOTHESIS: Appropriate counter-regulatory hormonal responses are essential for recovery from hypoglycaemia. Although the hypothalamus is known to be involved in these responses, the molecular mechanisms have not been fully elucidated. AMP-activated protein kinase (AMPK) functions as a cellular energy sensor, being activated during energy depletion. As AMPK is expressed in the hypothalamus, an important site of neuroendocrine regulation, the present study was undertaken to determine whether hypothalamic AMPK mediates counter-regulatory responses to hypoglycaemia. MATERIALS AND METHODS: Hypoglycaemia was induced by i.p. injection of regular insulin (6 U/kg) in Sprague-Dawley rats. Hypothalamic AMPK phosphorylation and activities were determined 1 h after i.p. insulin injection. To investigate the role of hypothalamic AMPK activation in mediating counter-regulatory responses, an AMPK inhibitor, compound C, was pre-administered intracerebroventricularly (i.c.v.) or dominant-negative (DN)-AMPK was overexpressed in the hypothalamus before induction of hypoglycaemia. RESULTS: Insulin-induced hypoglycaemia increased hypothalamic AMPK phosphorylation and alpha2-AMPK activities in rats. The change was significant in the arcuate nucleus/ventromedial hypothalamus (ARC/VMH) and paraventricular nuclei (PVN). Prior i.c.v. administration of compound C attenuated hypoglycaemia-induced increases in plasma concentrations of corticosterone, glucagon and catecholamines, resulting in severe and prolonged hypoglycaemia. ARC/VMH DN-AMPK overexpression impaired early counter-regulation, as evidenced by reduced glucagon and catecholamine responses. In contrast, PVN DN-AMPK overexpression attenuated late counter-regulation and corticosterone responses. CONCLUSIONS/INTERPRETATION: Systemic hypoglycaemia causes hypothalamic AMPK activation, which is important for counter-regulatory hormonal responses. Our data indicate that hypothalamic AMPK acts as a fuel gauge, sensing the whole-body energy state and regulating not only energy homeostasis but also neuroendocrine functions.

Chronic central administration of ghrelin reverses the effects of leptin.

OBJECTIVE: To determine whether chronic central administration of ghrelin can block the effects of leptin on food intake, adiposity, and plasma concentrations of metabolic parameters and hormones. DESIGN: Intracerebroventricular (ICV) infusions of leptin (5 microg/day) for 7 days, with or without ghrelin (1.2 microg/day), in rats. Rats administered leptin plus ghrelin were divided into ad lib-fed and food-restricted groups. MEASUREMENT: Body weight and food intake were monitored daily. Following killing on day 8, epididymal fat weight and fasting plasma concentrations of glucose, insulin, leptin, ghrelin, IGF-1, and adiponectin were determined. RESULTS: ICV infusion of leptin decreased food intake by 39% and fat weight by 41%. Leptin decreased plasma concentrations of glucose, insulin, and leptin and increased plasma ghrelin levels. Central coadministration of ghrelin blocked the effects of leptin. Most of the effects of ghrelin were diminished by food restriction but ghrelin effect on adiposity and plasma insulin concentrations remained in food-restricted rats. CONCLUSION: Chronic central administration of ghrelin reversed the effects of leptin, primarily by altering food intake, but ghrelin may have regulatory effects on adiposity and plasma insulin levels independent of feeding effect.

Mutation analysis of Korean patients with citrullinemia.

Citrullinemia is an autosomal recessive disease due to the mutations in the argininosuccinate synthetase (ASS) gene. Mutation analysis was performed on three Korean patients with citrullinemia. All of the three patients had the splicing mutation previously reported as IVS6-2A>G mutation. Two had Gly324Ser mutation and the other patient had a 67-bp insertion mutation in exon 15. The IVS6-2A>G mutation was reported to be found frequently in Japanese patients with citrullinemia, but Caucasian patients showed the extreme mutational heterogeneity. Although a limited number of Korean patients were studied, the IVS6-2A>G mutation appears to be one of the most frequent mutant alleles in Korean patients with citrullinemia. The Gly324Ser mutation identified in two patients also suggests the possible high frequency of this mutation in Korean patients as well.

Effects of synthesized voice warning parameters on perceived urgency.

The effects of synthesized voice warning parameters on perceived urgency were examined in order to build a detailed and usable description of the relation between the parameters of synthesized voice warnings and perceived urgency. Ten native and 10 non-native English speakers participated in 4 experiments to evaluate and quantify the effects of the voice parameters. The results showed that speech rate, average fundamental frequency [F(0)], voice type, and fundamental frequency contour have clear effects on the perceived urgency of synthesized voice warnings. The effects of quantitative parameters on perceived urgency were scaled using an application of Stevens's power law (1957). In addition, the results showed significant differences in the perceived urgency of average F(0) and F(0) contour types between native and non-native English speakers. Implications of the results for the design and improvement of synthesized voice warnings are discussed.

Effect of t-butylhydroperoxide on chloride secretion in rat tracheal epithelia.

Oxidative stress has been known to play important roles in various inflammatory diseases of lung such as allergic bronchitis, dust particle-induced inflammatory diseases, or chronic bronchitis. However, the effects of oxidants on Cl- secretion in tracheal epithelia have not been determined. To examine the effects of oxidants on Cl- secretion of the airway epithelia rat tracheal epithelial cells were cultured on porous filters and short circuit current (Isc) was measured in an Ussing chamber system. t-Butylhydroperoxide, which was widely used as a model substance to study the mechanism of cell injury resulted from oxidative stress, induced a transient increase in Isc by dose-dependent manner. The response was not observed in Cl(-)-free medium, and inhibited by 100 microM bumetanide. N(-Diphenyl-1,4-phenylene-diamine (DPPD, 5 microM), an inhibitor of lipid peroxidation, blocked the t-butylhydroperoxide response. When t-butylhydroperoxide was added after the administration of forskolin or H-89, a protein kinase A inhibitor, the t-butylhydroperoxide-induce Isc increase was abolished. Pretreatment of indomethacin (10 microM) completely inhibited the t-butylhydroperoxide response, but pretreatment of thapsigargin (1 microM) did not, t-Butylhydroperoxide induced gradual increases in cytosolic Ca2+ level, and increased [3H]arachidonic acid release in the presence of thapsigargin. These results indicate that t-butylhydroperoxide stimulates Cl-secretion via activation of phospholipase A2 and subsequent production of cyclooxygenase metabolities by Ca(2+)-dependent and -independent mechanisms.

Amniotic fluid composition changes during urine drainage and tracheoesophageal occlusion in fetal sheep.

OBJECTIVE: Recently an intramembranous pathway was reported in the ovine fetus as a route for the rapid exchange of water, ions, and molecules between the amniotic fluid and the fetal blood that perfuses the fetal surface of the placenta and the fetal membranes. Our study was designed to test the hypothesis that the amniotic fluid composition would gradually equilibrate with fetal plasma when the major flows to and from the amniotic compartment were eliminated. STUDY DESIGN: Eleven near-term fetal sheep underwent ligation of the urachus to eliminate the allantoic fluid. An inflatable cuff was placed around the esophagus and trachea, and catheters were placed in the fetal urinary bladder, fetal circulation, and maternal circulation. At > or = 5 days after surgery the animals were subjected to either a control experiment or a continuous urine drainage plus tracheoesophageal occlusion for 8 hours. RESULTS: During the urine drainage plus occlusion study, amniotic fluid osmolality (p < 0.0001), Na+ (p < 0.0001), K+ (p < 0.01) Cl- (p < 0.001), and lactate (p < 0.001) increased compared with the control experiment. These corresponded to 50% reductions in the gradients for osmolality and Na+ between fetal plasma and amniotic fluid; the K+ gradient increased, and the Cl- gradient reversed. The percentage increases in amniotic Na+, K+, Cl-, and lactate were all 10% at 8 hours. CONCLUSION: These observations suggest that water is absorbed from the amniotic fluid through the intramembranous pathway into the fetal circulation at a rate of 1.25% of the total amniotic volume per hour or approximately 240 ml/day.