Novel Magnetic Resonance Imaging for Assessment of Bronchial Stenosis in Lung Transplant Recipients.

Bronchial stenosis in lung transplant recipients is a common disorder that adversely affects clinical outcomes. It is evaluated by spirometry, CT scanning, and bronchoscopy with significant limitations. We hypothesize that MRI using both ultrashort echo time (UTE) scans and hyperpolarized (HP) 129 Xe gas can offer structural and functional assessment of bronchial stenosis seen after lung transplantation. Six patients with lung transplantation-related bronchial stenosis underwent HP 129 Xe MRI and UTE MRI in the same session. Three patients subsequently underwent airway stent placement and had repeated MRI at 4-week follow-up. HP 129 Xe MRI depicted decreased ventilation distal to the stenotic airway. After airway stent placement, MRI showed that low-ventilation regions had decreased (35% vs. 27.6%, p = 0.006) and normal-ventilation regions had increased (17.9% vs. 27.6%, p = 0.04) in the stented lung. Improved gas transfer was also seen on 129 Xe MRI. There was a good correlation between UTE MRI and independent bronchoscopic airway diameter assessment (Pearson correlation coefficient = 0.92). This pilot study shows that UTE and HP 129 Xe MRI are feasible in patients with bronchial stenosis related to lung transplantation and may provide structural and functional airway assessment to guide treatment. These conclusions need to be confirmed with larger studies.

Significance of and risk factors for the development of central airway stenosis after lung transplantation.

Central airways stenosis (CAS) after lung transplant is a poorly understood complication. Objectives of this study were to determine if CAS was associated with chronic rejection or worse survival after transplant as well as to identify factors associated with CAS in a large cohort of lung transplant recipients. Lung transplant recipients transplanted at a single center were retrospectively reviewed for the development of CAS requiring airway dilation. A total of 467 subjects met inclusion criteria with 60 (13%) of these developing CAS requiring intervention. Of these 60 recipients, 22 (37%) had resolution of CAS with bronchoplasty alone, while 32 (53%) ultimately required stent placement. CAS that required intervention was not a risk factor for the development of bronchiolitis obliterans syndrome or worse overall survival. Significant risk factors for the subsequent development of CAS in a time-dependant multivariable model were pulmonary fungal infections and the need for postoperative tracheostomy. While CAS was not associated with BOS or worse survival, it remains an important complication after lung transplant with potentially preventable risk factors.

Successful treatment of Ochroconis gallopavum infection in an immunocompetent host.

Ochroconis gallopavum, a dematiaceous fungus, is a rare cause disease in immunocompromised patients and epidemic encephalitis in poultry. We report the first case of active O. gallopavum pulmonary infection in an immunocompetent host with rapid and complete response to oral antifungal therapy.

NK-1 antagonist reduces colonic inflammation and oxidative stress in dextran sulfate-induced colitis in rats.

Although substance P (SP) has been implicated as a mediator of neurogenic inflammation in the small intestine, little information is available regarding the role of SP in the pathogenesis of chronic ulcerative colitis. In this study, our aim was to investigate whether the intraperitoneal administration of a nonpeptide neurokinin-1 (NK-1) antagonist, CP-96345, which antagonizes the binding of SP to its NK-1 receptor, results in the attenuation of colonic inflammation induced in rats by 5% dextran sodium sulfate (DSS) in drinking water for 10 days compared with an inactive enantiomer, CP-96344. Disease activity was assessed daily for 10 days, after which colonic tissue damage was scored and myeloperoxidase activity and colon and urinary 8-isoprostanes were measured. Animals receiving DSS exhibited marked physical signs of colitis by day 5 compared with controls. Chronic administration of the NK-1 antagonist significantly reduced the disease activity index, mucosal myeloperoxidase activity, colonic tissue damage score, and mucosal and urinary levels of 8-isoprostanes compared with inactive enantiomer- or vehicle-injected (saline) animals receiving DSS alone. These data indicate that the administration of an NK-1 antagonist can attenuate colonic inflammation and oxidative stress and suggest a novel therapeutic approach in the treatment of chronic ulcerative colitis.

Seroprevalence of Babesia equi among horses in Israel using competitive inhibition ELISA and IFA assays.

Sera from 361 horses were tested by indirect immunofluorescence antibody test (IFA) and by competitive inhibition ELISA (cELISA), to detect antibodies to Babesia equi. The concordance between the assays was 95.7%. Application of a cutoff based on a calculated percent inhibition of < 20% gave a total of 22 discrepant results, while only 8 sera negative by the cELISA were found positive by the IFA when a cutoff of > 20% inhibition was used. Approximately one-third of all the horses tested were found serologically positive to B. equi, with more horses testing positive from northern Israel. Among horses raised with access to pasture there was a significant difference in the percentage of seropositive reactors (76.6% in the north and 20.1% in the central region), compared with horses without access to pasture (14.3 and 10.3%, respectively). Nineteen percent of stallions were found to be positive, which was significantly less than the proportions of seropositive mares and geldings: 38 and 42%, respectively. No significant association was found between the mean age of horses and seroreactivity to B. equi.

Effects of hypoxia and toxicant exposure on adenylate energy charge and cytosolic ADP concentrations in abalone.

Many studies have used adenylate energy charge (AEC) as an index of an organism's metabolic state under conditions of imposed stress, either through natural or xenobiotic stressors. AEC is a linear measure of the ratio of ATP concentration to total adenylate concentration, which ranges in value from 1 in the fully charged state to 0. Paradoxically, high values of AEC are often associated with high toxicant exposures, and low AEC values with low exposures. These discrepancies may be caused by the inability of AEC measurements to adequately evaluate cytosolic adenylate concentrations, which are the critical parameters in enzymatic regulation. Consequently, the goal of this study was to compare AEC values, as measured by high performance liquid chromatography (HPLC), to free adenosine diphosphate (ADPfree) concentrations, as measured using the arginine kinase equilibrium reaction and in vivo 31P-NMR, in red abalone (Haliotis rufescens) in response to either hypoxia or toxicant (pentachlorophenol, or sodium azide) exposure. AEC values remain essentially constant when compared with control animals during periods of stress exposure and recovery. In contrast, calculated ADPfree concentrations are approximately a third of those determined by HPLC and nearly double in response to stress exposure. The physiologic importance of this response is demonstrated by increases in ATP formation via arginine kinase. These results are discussed in light of the pertinent mammalian literature.