Background: Tracheobronchial stent-related biofi lm formation encountered in interventional pulmonology that can result in pneumonia and in tissue granulation. Breath analysis by means of ion mobility spectrometry (IMS) has been reported for detection of volatile organic compounds (VOCs) indicative of bacteria biofi lm. We hypothesized that IMS can detect specifi c VOCs in patients with bacterial biofi lm formation resulting from tracheobronchial stent placement, and we tested our hypothesis in a prospective study conducted between October 2011 and October 2012. Methods: During the study period, stent placement, removal, or replacement was performed in 21 patients with tracheobronchial stenosis. A silicone stent was used in 11 of these patients. In 11 cases, 5 cases were placement procedures and 6 cases were replacement or removal procedures. Breath samples were obtained from these 6 patients before and after stent removal or replacement, and the samples were analyzed by IMS. Peaks were characterized with the use of Visual Now 2.2 software (BS P23, limonene (p < 0.05); P24: 2,2,4,6,6-pentaheptylmethane (p < 0.05); P31, 1-octanol (p < 0.05); and P35: phenylacetaldehyde (p < 0.05). Conclusions: Using IMS, we were able to assess the degree of Pseudomonas aeruginosa biofi lm formation resulting from stent placement. IMS breath analysis in conjunction with clinical symptoms will provide for non-invasive assessment of the need for stent replacement or removal.
T-kininogen degradation and kinin release were observed in rat macrophages cultured under acidic conditions. Bradykinin and Met-T-kinin-Leu (a kinin precursor) stimulated PGE2 production by macrophages and fibroblasts but had no effect on O2- production. PGE2 production by macrophages stimulated with 10 microM bradykinin increased by approximately 148% compared to non-stimulated macrophages (0.47 +/- 0.13 vs 0.31 +/- 0.16 ng 10(6) cells-1 30 min-1), and increased by 161% in stimulated as opposed to non-stimulated fibroblasts (0.50 +/- 0.07 vs 0.31 +/- 0.05 ng 10(5) cells-1 30 min-1). No O2- production was detectable in fibroblasts despite stimulation with PMA, A23187, bradykinin, and Met-T-kinin-Leu. O2- production by macrophages was 4.2 +/- 0.3 and 3.0 +/- 0.2 nmol 10(6) cells-1 min-1 after stimulation with PMA and A23187, respectively, but no O2- production was observed after stimulation with bradykinin or Met-T-kinin-Leu. These data suggest that bradykinin and the kinin precursor are implicated in granulomatous tissue formation and wound healing through arachidonic acid and its metabolites but not through O2-.
The effects of physical therapy on immunological parameters were evaluated in 12 patients (8 males and 4 females, 69.2 +/- 9.0 years) with cerebrovascular diseases in a stable situation two to three months after the onset of stroke who entered in our hospital between 1994 and 1997. After a two-month physical therapy program, the proportions of helper-inducer T (Thi) cells and suppressor-inducer T (Tsi) cells were increased significantly and that of cytotoxic T (Tc) cells was decreased, although those of HLA-DR+, suppressor T (Ts) and activated T (Tac) cells were not changed. The antibody dependent cellular cytotoxicity (ADCC) was significantly increased, although natural killer (NK) cell activity was not changed. The serum levels of interleukin-2 receptor was significantly increased but those of interleukin-2, interleukin-6 and interleukin-12 were not changed. The serum levels of interleukin-10, interleukin-12 and tumor necrosis factor-alpha were not detectable, while interleukin-1beta was decreased in 2 patients and interleukin-10 was increased in 2 patients. These findings suggest that daily physical exercise may activate the immune system possibly through the cytokine network in patients with cerebrovascular diseases (CVD).
Background: Long-term proteasome inhibitor (PI)-based therapy improves outcomes in multiple myeloma (MM). However, physical, social, and geographic access to health services and treatment toxicity may interfere with long-term PI therapy in clinical practice. Aims: To evaluate the efficacy and safety of treatment with the oral PI, ixazomib (IXA), lenalidomide (LEN) + dexamethasone (DEX) [IRd] in patients with relapsed/refractory MM (RRMM) initially treated with an injectable PI-based therapy. Methods: Nationwide, multicenter, open-label, single-arm study in Japan. Patients aged ≥20 years with RRMM (including those not refractory to bortezomib (BOR), carfilzomib (CFZ), or LEN who provided written informed consent were enrolled. Patients received BOR, LEN + DEX (VRd), or CFZ, LEN + DEX (KRd) for 3 cycles. Patients with at least a minor response to VRd or KRd transitioned to IRd. After transition, patients received 4 mg IXA on days 1, 8, and 15, 25 mg LEN on days 1 through 21, + 40 mg DEX on days 1, 8, 15, and 22 in 28-day cycles until progressive disease (PD) or unacceptable toxicity. The primary endpoint was the 12-month progression-free survival (PFS) rate from the start of injectable PI-based therapy, with dropouts, missing response data, PD, and death at 12-month included as events. Secondary endpoints included PFS with dropouts treated as censoring (Kaplan-Meier [KM] method), overall survival (OS), overall response rate (ORR), percentage of patients with very good partial response (VGPR) or better, healthcare resource utilization, time to next treatment (TTNT), and safety. Results: Forty-five RRMM patients were enrolled, 36 of whom achieved minor response or better after 3 cycles of VRd (n=6) or KRd (n=30) and received IRd, and followed up for at least 12 months after the last patient startedinjectable PI-based therapy. Mean age was 70.7 (SD±9.2) years, the median (min, max) number of prior lines of therapy was 2 (1, 4), and 95.6% had an ECOG PS of 0−1. At a median follow-up of 20.8 (95% CI: 17.4-23.7) months, the 12-month PFS rate (primary endpoint) was 48.9% (22/45, 90% CI: 35.9−62.0) with 11 events of PD/death, 8 dropouts, and 4 missing response data, which exceeded the threshold of 36% but did not meet significance (p=0.0518). As secondary endpoints, the 12-month PFS rate (dropouts as censoring) by KM analysis was 74% (95% CI: 56−86). Median PFS and TTNT were 29.0 (95% CI: 21.3−NE) months and 32.3 (95% CI: 14.9−35.4) months, respectively; median OS was not estimable. The ORR was 73.3% (95% CI: 58.1−85.4) and 42.2% (95% CI: 27.7−57.8) of patients had a VGPR or better. The length of hospital stay, and outpatient visits during the initially 3 cycles of injectable PI-based treatment and following IRd treatment were 5.3 vs 1.0 days per person-month, and 4.2 vs 1.9 visits per person-month, respectively. The safety profile of IRd was similar and consistent to that previously reported. Frequent (≥10% incidence) Grade ≥3 treatment emergent adverse events were neutrophil count decreased (n=7 [15.6%]) and platelet count decreased (n=7 [15.6%]); the only SAE with a ≥10% incidence was pneumonia (n=5 [11.1%]). Two deaths occurred during the study, one during KRd treatment (pneumonia, bacterial, n=1 [2.2%]) and one during IRd treatment (pneumonia, n=1 [2.2%]), which was related to IRd. Summary/Conclusion: Long-term treatment with the oral PI, IXA, + LEN and DEX after an injectable PI-based treatment was tolerable and had favorable efficacy in patients with RRMM in the real-world setting.
<b><i>Background:</i></b> Relapsing polychondritis (RP) is a rare systemic disease of unknown origin, with cartilaginous involvement in multiple organs. Airway involvement is the most important prognostic factor in RP. <b><i>Objectives:</i></b> Spirometric measurements and minimum tracheal cross-sectional area (mtCSA) have been reported as useful to assess the degree of airway stenosis. Because the length and severity of tracheal involvement in RP can vary, mtCSA might not provide enough information to assess tracheal abnormalities. We introduced tracheal volume (TrV) as a new method to evaluate correlations between chest computed tomography (CT) measurements and pulmonary function tests, including impulse oscillometry (IOS). <b><i>Method:</i></b> We analyzed chest CT images, spirometry, and IOS collected at our institution from April 2004 to March 2019. We calculated correlations between chest CT measurements using software (TrV, TrV/tracheal length [TrV/TL], and mtCSA) and pulmonary function parameters. <b><i>Results:</i></b> Twenty-five of 73 clinically diagnosed patients with RP were included. Spirometric findings showed moderate airway obstruction. Peak flow (PEF) was strongly correlated with mtCSA, TrV, and TrV/TL (ρ = 0.74, <i>p</i> < 0.001). FEV1 was significantly correlated with mtCSA (ρ = 0.56, <i>p</i> = 0.004), TrV (ρ = 0.52, <i>p</i> = 0.007), and TrV/TL (ρ = 0.53, <i>p</i> = 0.006). Whereas respiratory resistance at 5 Hz (R5) and 20 Hz (R20) and resonant frequencies (RFs) were significantly correlated with TrV (ρ = −0.46, <i>p</i> = 0.021; ρ = −0.46, <i>p</i> = 0.046; and ρ = −0.42, <i>p</i> = 0.037, respectively), IOS parameters and mtCSA were not. <b><i>Conclusions:</i></b> In patients with RP, TrV and mtCSA were strongly correlated with spirometric measurements. Respiratory resistances assessed by IOS correlated only with TrV. This suggests TrV assessment reflects pulmonary function in patients with RP more appropriately than mtCSA.
It is experimentally know that vitamin E enhances both humoral immune response and protection against micro-organism infection, but the mechanism has not been clarified. On the other hand, T-kininogen, a kinin precursor, cysteine proteinase inhibitor, and acute phase protein, is suggested to be induced by activation of macrophages. In order to clarify the action of vitamin E on the immune response, we investigated the relationship between vitamin E and T-kininogen in rat. T-kininogen level in rat serum was determined by single radial im-munodiffusion using specific antiserum against T-kininogen. Vitamin E provides a potent stimulus in vivo for the production of T-kininogen, such as seen in lipopolysaccharide (LPS) administration. Namely, T-kininogen level in rat serum, that was given intraperitoneal injection of vitamin E for six days ranging from 1.5 mg to 25 mg per day, increased from 758±218 to 3, 220±263, μg protein/ml with an increase of vitamin E level in the serum (12.9±1.1 to 38.8±6.2μg/ml) . Whereas normal and vehicle (polyethylene 60-hydrogenated castor oil) -received rats were 452 ± 77 to 483 ± 82 μg/ml of T-kininogen and 7.4±0.7 to 7.2±0.9 μg/ml of vitamin E. In addition, vitamin E enhanced induction of T-kininogen by LPS administration. From these results, the pharmacological action of vitamin E on the immune response was discussed.
