PNEUMOMEDIASTINUM,SUBCUTANEOUS EMPHYSEMA,AND PULMONARY FIBROSIS IN A PATIENT WITH IDIOPATHIC PNEUMONIA SYNDROME AFTER BONE MARROW TRANSPLANTATION

An adolescent female underwent bone marrow transplantation for relapsed leukemia and developed acute and chronic graft-versus-host disease and idiopathic pneumonia syndrome. Her lung disease responded to large doses of methylprednisolone but evolved to pulmonary fibrosis and pneumomediastinum and subcutaneous emphysema in the convalescent period. Pulmonary function tests revealed a restrictive pattern. Pneumomediastinum and subcutaneous emphysema are complications not only of obstructive but also of restrictive lung disease and vary with respect to time of onset.     

Intervenção Coronariana Percutânea em Lesões não Protegidas de Tronco

BackgroundThe advent of drug-eluting stents allowed the percutaneous coronary intervention to present safe results in lesions in the left main coronary artery.ObjectivesTo analyze the results of the percutaneous treatment of unprotected left main coronary artery lesion with the use of intravascular ultrasound.MethodsStudy of consecutive case series carried out from January 2010 to December 2018. Clinical data were collected from patients as well as prognostic scores and data on coronary lesion. Low-grade residual lesion (less than 50%) on angiography and minimum luminal area greater than 6 mm²on intravascular ultrasound were considered successful. The adopted significance level was 5%.Results107 cases were analyzed. The multivessel lesion was predominant, with most (39.25%) of the lesions being found in three vessels in addition to the left main coronary artery. The SYNTAX score had a mean of 46.80 (SD: 22.95), and 70 (65.42%) patients had a SYNTAX score above 32 points. Angiographic success of percutaneous intervention was considered in 106 (99.06%) patients. The overall rate of major cardiac and cerebrovascular events in the hospital outcome was 6.54%, being similar in patients with SYNTAX score ≤ 32 (8.10%) and ≥ 33 (5.71%; p = 0.68).ConclusionsPercutaneous intervention in cases of unprotected left main coronary artery lesion was safely performed and presented excellent results. Considerable angiographic success of treatment guided by intravascular ultrasound was achieved. The rate of major cardiac and cerebrovascular events was similar between patients at low and high risks.     

Recombinant AAV-transduced iris pigment epithelial cell transplantation may transfer vector to native RPE but suppress systemic dissemination

PURPOSE: To determine whether adenoassociated virus (AAV) vectors transduced into iris pigment epithelial (IPE) cells and transplanted into the subretinal space of rats will transfer the AAV genome to the host cells and whether the vectors are disseminated systemically. METHODS: Recombinant (r)AAV was transduced into rat IPE cells and transplanted into the subretinal space of rats. For the control, rAAVs alone were injected subretinally. The transplanted IPE cells were detected by LacZ staining. Immunohistochemistry, electron microscopy, electroretinography, and fluorescein-dextran angiography were performed. DNA was extracted from various organs and blood and examined for the AAV genome by polymerase chain reaction. RESULTS: No toxicity from rAAV transduction was observed in vitro. LacZ was expressed in the transplanted cells 1 and 2 weeks after transplantation. At 4 and 12 weeks, fewer transplanted cells were detected than at 1 week, and LacZ expression was occasionally detected at the level of host retinal pigment epithelial (RPE) cells. Expression was also detected in ciliary body epithelial cells. The electroretinograms and fluorescein-dextran angiography were only mildly altered. Significantly lower levels of AAV genome were detected in the organs and blood of rats receiving rAAV-IPE cell transplants than with direct intravenous injection of AAV vectors. CONCLUSIONS: AAV-mediated LacZ was expressed in the transplanted cells after subretinal transplantation, and the transplanted IPE cells may transfer the rAAV to host tissues, such as RPE cells, long after the transplantation. This method of gene delivery did not lead to systemic dissemination of the vectors.     

Ultrastructural Assessment of Mineral Crystallization and Collagen Mineralization in Bone

Mineralization of bone matrix starts with the formation of matrix vesicles secreted by osteoblasts, which subsequently grow into mineralized nodules. These nodules are globular structures formed by mineral crystals assembled in a radial fashion, and appear to be the final inducers of collagen mineralization. Despite its apparent simplicity, the course of bone mineralization is tightly controlled by many factors in the microenvironment. In this review, we will present our recent experiments on the general processes of bone mineralization. First, we will discuss the ultrastructural alteration of mineral crystals in the context of magnesium (Mg) insufficiency, which causes an elevation of calcium (Ca) concentrations in bone and of the pure form of hydroxyapatite. Such elevated Ca concentrations also induced premature collagen mineralization without the mediation of mineralized nodules. This could mean that the availability of elements, such as Mg, in the bone microenvironment is important for the in vivo generation of the pure form of hydroxyapatite. Next, we will examine collagen mineralization in the context of ascorbic acid insufficiency. Ascorbic acid is essential for collagen formation and, when it is not available, the typical, stout collagen microfibrils with striations cannot be identified. In their place, filamentous fibrils of collagen without striations, i. e., immature collagen microfibrils, are observed. In the osteoid, however, many mineralized nodules feature some sort of “mineral extensions” towards the immature microfibrils. It seems that collagen microfibrils, even if immature, serve as a scaffold for the mineralization of collagen fibrils. These findings reaffirm that a sophisticated set of regulatory steps is necessary for proper mineralization in bone.     

Successful Collection of Peripheral Blood Stem Cells from an Infant with Acute Lymphoblastic Leukemia using the Haemonetics V50.

Peripheral blood stem cells (PBSC) were collected using the Haemonetics V50 from an 8 month old infant weighing 7.8 kg suffering from acute lymphoblastic leukemia in the first complete remission. Leukapheresis was performed according to an exchange transfusion procedure by the two arm method using only a single lumen Broviac catheter. No problem occurred in the patient during this procedure except for a reduction (by half) of the initial platelet count. This method enables one to collect PBSC very safely, even from infants, in a manner that is painless for patients.     

Triaxial accelerometry to evaluate walking efficiency in older subjects

PURPOSE: We tested the suitability of triaxial accelerometry to evaluate walking efficiency in older subjects. METHODS: First, we verified the accuracy to estimate the oxygen consumption rate (.VO2, mL.min-1) from the total impulse (Itotal, N.min-1), the square root of summed accelerations of each direction, during graded walking on a flat ground in 13 male and 27 female older subjects (61 +/- 6 yr, mean +/- SD). Second, to examine the effects of endurance/resistance training on walking efficiency, we assessed the relations of maximal isometric knee extension force (Fmax, N.m), maximal walking velocity (Vmax, m.min-1), and three-dimensional impulses (Ix, anterior-posterior; Iy, mediolateral; Iz, vertical) in 13 male and 40 female older subjects (62 +/- 7 yr) before and after 6 and 9 months of training. RESULTS: The following analyses were performed in all the data from the male and female groups. First, .VO2 was highly correlated with Itotal (r = 0.958, P < 0.0001) over the range of 250-2200 mL.min-1. Second, Fmax and Vmax increased by 48 +/- 7% (P < 0.001) and 21 +/- 2% (P < 0.001), respectively, after 9 months of training. Ix/Itotal and Iy/Itotal increased by 18 +/- 2% (P < 0.001) and 10 +/- 2%, respectively, after 9 months of training (P < 0.001), whereas Iz/Itotal decreased by 14 +/- 2% (P < 0.001). Vmax was negatively correlated with Iz/Itotal (r = -0.522, P < 0.0001) while positively correlated with Ix/Itotal (r = 0.561, P < 0.0001) and Iy/Itotal in the pooled data from before, after 6 and 9 months of training. Similarly, the product of Vmax and body weight was positively correlated with Fmax (r = 0.633, P < 0.0001). CONCLUSIONS: These results suggest that increased Fmax improved walking efficiency by increasing energy utilization in the anterior-posterior/mediolateral directions while decreasing energy loss in the vertical direction.     

Antiallergic effects of mequitazine. 1. In vitro experiments

The antiallergic effects of 10-(3-quinuclidinylmethyl)phenothiazine (mequitazine) were investigated in vitro. The results obtained were as follows: 1) In the isolated trachea and lung parenchyma of guinea pigs, mequitazine showed a fairly potent antagonistic action against contractions induced by both histamine (Hi) and acetylcholine (ACh). Mequitazine was much less potent in antihistaminic action and slightly more potent in anticholinergic action than ketotifen. The contractions of the preparation by leukotriene (LT) D4 were antagonized by mequitazine, although the potency was moderate, showing an IC50 value of 2.3 x 10(-5) g/ml in the trachea and 5.1 x 10(-5)g/ml in the lung parenchyma. Mequitazine had no effect on the contraction of the trachea by PGF2 alpha, but inhibited that of the lung parenchyma with pA2 = 7.0. 2) Mequitazine (10(-6) g/ml) slightly inhibited the Schultz-Dale reaction of the isolated guinea pig trachea, while ketotifen at the same concentration did not show any effect. 3) The contraction of the isolated guinea pig trachea by Ca2+ influx was slightly inhibited by mequitazine (10(-5) g/ml). 4) Mequitazine competitively inhibited the cyclic AMP-dependent phosphodiesterase activity from the rat lung with a potency of 10 times and 5 times more than those of ketotifen and theophylline, respectively. 5) Mequitazine (10(-6) to 10(-5) M) suppressed both the anaphylactic and phospholipase A2-induced histamine release from the peritoneal cells of rats. 6) Mequitazine (10(-5) g/ml) also inhibited the anaphylactic and Ca ionophore-induced histamine release from the leukocytes of the atopic patients and normal subjects. 7) The anaphylactic releases of histamine, LTB4 and peptide LT from the human lung fragments were dose-dependently inhibited by mequitazine (10(-7) approximately 10(-5) g/ml).     

Secondary anti-D immunization by Del red blood cells

BACKGROUND: Recent molecular studies of the RHD gene have revealed that D(el) individuals retain a grossly intact RHD gene or have a portion of RHD in their genomes. No D(el) phenotype has yet been shown to induce a primary or secondary alloanti-D immunization, however. CASE REPORT: A 67-year-old D- Japanese woman with a history of allosensitization from transfusion of D+ red blood cells (RBCs) was negative for anti-D at admission. After she received RBCs from 19 apparently D- donors, she developed anti-D with an 8-fold titer. The titer of anti-D increased further to 128-fold after transfusions of cross-match-compatible D- negative RBCs from 40 donors over the next 2 years. Two of 59 donors were found to be RHD gene-positive and antigen D- with a D(el) phenotype, that is, RHD(K409K). CONCLUSION: This is the first case in which RBCs having the D(el) phenotype induced a secondary alloanti-D immunization. A D- donor with the RHD(K409K) allele was associated with the development of anti-D. Adverse episodes or evidence of hemolysis was not observed after the transfusion of RHD(K409K) RBCs. Further clinical evidence is needed to reveal whether the D(el) phenotype has a clinically relevant potential for anti-D immunization.     

Sevoflurane enhances nitroglycerin tolerance in rat aorta: implications for the desensitization of soluble guanylate cyclase possibly through the additive generation of superoxide anions and/or hydroxyl radicals within vascular smooth muscle

Nitroglycerin (TNG) tolerance, defined as an impaired vasodilation response to TNG, has been recently demonstrated to be associated with increased production of reactive species. We designed this study to investigate the mechanisms that mediate TNG tolerance and to compare the effects of sevoflurane and isoflurane on the development of TNG tolerance. Tension changes in rat aortic rings without endothelium were recorded. The cumulative relaxant responses to TNG (10(-8)-10(-5) M) were assessed in phenylephrine-contracted rings. To induce TNG tolerance, the rings were then incubated in the bathing solution containing TNG (10(-5) M) for 30 min in the presence or absence of each anesthetic (1 to 3 MAC). After washout of TNG and anesthetic, the second response to TNG was obtained. Some rings were pretreated with oxygen radical scavengers or sulfhydryl supplements. The first and the second responses to TNG were compared. Sevoflurane at 3 MAC, but not sevoflurane at smaller concentrations or isoflurane, enhanced TNG tolerance when administered in combination with TNG. Sevoflurane alone had no effect on TNG tolerance. The enhancement of TNG tolerance in the case of a combined sevoflurane and TNG treatment was inhibited in the presence of oxygen radical scavengers or at a smaller oxygen concentration (25%). Sevoflurane at a concentration of 3 MAC in hyperoxic condition enhances the development of TNG tolerance, possibly by additive generation of superoxide anions or hydroxyl radicals within vascular smooth muscle. IMPLICATIONS: The effects of sevoflurane and isoflurane on the development of nitroglycerin (TNG) tolerance were investigated in isolated rat aorta. TNG tolerance was induced by incubation of the vascular tissue in the bathing media containing TNG (10-5 M) for 30 min. Sevoflurane, but not isoflurane, enhances TNG tolerance, possibly by additive generation of oxygen-derived free radicals.