The effects of pacing-induced left bundle branch block on left ventricular systolic and diastolic performances

To assess the effects of pacing-induced left bundle branch block on left ventricular (LV) systolic and diastolic performance, we performed digital subtraction ventriculography while simultaneously measuring LV pressure with a catheter tip micromanometer. The subjects included 10 patients with a sinus rhythm, a normal QRS duration and PR interval within 0.22 sec. LV performance was assessed during both right atrial pacing (AP) and atrioventricular sequential pacing (AVP) at the same pacing rate. The atrioventricular pacing interval during AVP was adjusted to be the maximal interval that showed the QRS configuration seen during complete right ventricular pacing. LV end-diastolic pressure and volume during AVP did not differ from those during AP. Peak positive and negative dp/dt during AVP were significantly lower than those during AP. Time constants were also significantly longer during AVP. The QRS duration during AVP significantly correlated with end-systolic volume and time constants, and inversely correlated with ejection fraction and +dp/dt. These observations indicated that conduction disturbance per se, induced by AVP, could not only impair LV systolic performance but also diastolic performance, possibly due to asynchronous contraction and relaxation of the left ventricle.     

Perforin gene mutations in adult-onset hemophagocytic lymphohistiocytosis

Perforin gene (PRF1) mutations cause the primary form of hemophagocytic lymphohistiocytosis (HLH). We report a genetic defect of PRF1 in a 62-year-old Japanese man with recurrent episodes of HLH. Sequencing of PRF1 from both peripheral blood mononuclear cells and nail clippings showed compound heterozygous mutation, including deletion of two base pairs at codons 1090 and 1091 (1090-1091delCT) and guanine-to-adenine conversion at nucleotide position 916 (916GAEA). Although primary HLH has been detected in infants and children, genetic mutation of PRF1 or other genes should be considered a differential diagnosis of HLH even in the elderly.     

A case of mucinous adenocarcinoma of descending colon with abscess formation and solitary metastasis at right side of the abdomen

A 59-year-old man realized a left lower abdominal pain and palpable mass about a month ago. He was admitted to our hospital because of the pain and high fever. Blood examinations revealed high levels of white blood cell count and CRP. Ultrasonography showed a wall thickness of the descending colon and 7 cm cystic mass with air around. Moreover, a 6 cm cystic mass was found an outside of the ascending colon. We first treated with antibiotics under the diagnosis of abscesses because of perforation of diverticulum. Colonoscopy revealed an obstructing tumor in descending colon and biopsy specimens of the tumor showed adenocarcinoma. The preoperative diagnosis of the right side tumor was unclear. We performed a partial resection of the descending colon, and the tumor outside of the ascending colon was resected. The pathological diagnosis of the tumors was both mucinous carcinoma of the colon. Mucinous carcinoma tends to be more found in the right side of the colon than in the left side. The rate of lymph node metastasis and dissemination is higher than that in differentiated adenocarcinoma. We report a rare case of mucinous carcinoma originated from the left side of the colon with a solitary dissemination in opposite side of the abdomen.     

Downregulation of a newly identified laminin, laminin-3B11, in vascular basement membranes of invasive human breast cancers

Laminins present in the basement membranes (BM) of blood vessels are involved in angiogenesis and other vascular functions that are critical for tumor growth and metastasis. Two major vascular laminins, the α4 (laminin-411/421) and α5 (laminin-511/521) types, have been well characterized. We recently found a third type of vascular laminin, laminin-3B11, consisting of the α3B, β1 and γ1 chains, and revealed its biological activity. Laminin-3B11 potently stimulates vascular endothelial cells to extend lamellipodial protrusions. To understand the roles of laminin-3B11 in blood vessel functions and tumor growth, we examined localization of the laminin α3B chain in normal mammary glands and breast cancers, in comparison with the α4 and α5 laminins. In the immunohistochemical analysis, the α3B laminin was co-localized with the α4 and α5 laminins in the BM of venules and capillaries of normal breast tissues, but α3B was scarcely detected in vessels near invasive breast carcinoma cells. In contrast, the α4 laminin was overexpressed in capillaries of invasive carcinomas, where a large number of macrophages were found. The α5 laminin appeared to be weakly downregulated in cancer tissues, especially in capillary vessels. Furthermore, our in vitro analysis indicated that TNF-α significantly suppressed the laminin α3B expression in vascular endothelial cells, while it, as well as IL-1β and TGF-α, upregulated the α4 expression. These results suggest that Lm3B11/3B21 may be required for normal mature vessels and interfere with tumor angiogenesis.     

Skeletal Class III and open bite treated with bilateral sagittal split osteotomy and molar intrusion using titanium screws

Two-jaw surgery has been performed for the treatment of severe skeletal open bite cases to obtain stability of occlusion after treatment. If molar intrusion with titanium screws could be performed instead of surgical superior repositioning of the maxilla, the incidence of surgical invasion would be reduced. However, there have been few reports of such a therapy. This case report describes treatment for skeletal Class III and open bite with bilateral sagittal split osteotomy and intrusion of the molars using titanium screws. The patient had a concave profile, a long lower facial height, Class III malocclusion, and excessive anterior open bite following mandibular protrusion and a high mandibular plane angle. The mandible autorotated closed 3.5° following intrusion of the upper and lower molars using titanium screws during the presurgical orthodontic treatment phase. After the autorotation of the mandible, a mandibular setback with a bilateral sagittal split osteotomy was performed. The posttreatment records showed a good facial profile and occlusion. The mandible was stable 1 year after surgery. These results demonstrate that surgical orthodontic treatment combined with bilateral sagittal split osteotomy and intrusion of the molars using titanium screws can reduce the need for surgical invasion by avoidance of maxillary surgery and was effective for correcting the facial profile and occlusion in a skeletal Class III and open bite patient.     

Reproducibility of the abdominal and chest wall position by voluntary breath-hold technique using a laser-based monitoring and visual feedback system

PURPOSE: The voluntary breath-hold (BH) technique is a simple method to control the respiration-related motion of a tumor during irradiation. However, the abdominal and chest wall position may not be accurately reproduced using the BH technique. The purpose of this study was to examine whether visual feedback can reduce the fluctuation in wall motion during BH using a new respiratory monitoring device. METHODS AND MATERIALS: We developed a laser-based BH monitoring and visual feedback system. For this study, five healthy volunteers were enrolled. The volunteers, practicing abdominal breathing, performed shallow end-expiration BH (SEBH), shallow end-inspiration BH (SIBH), and deep end-inspiration BH (DIBH) with or without visual feedback. The abdominal and chest wall positions were measured at 80-ms intervals during BHs. RESULTS: The fluctuation in the chest wall position was smaller than that of the abdominal wall position. The reproducibility of the wall position was improved by visual feedback. With a monitoring device, visual feedback reduced the mean deviation of the abdominal wall from 2.1 +/- 1.3 mm to 1.5 +/- 0.5 mm, 2.5 +/- 1.9 mm to 1.1 +/- 0.4 mm, and 6.6 +/- 2.4 mm to 2.6 +/- 1.4 mm in SEBH, SIBH, and DIBH, respectively. CONCLUSIONS: Volunteers can perform the BH maneuver in a highly reproducible fashion when informed about the position of the wall, although in the case of DIBH, the deviation in the wall position remained substantial.     

YM-58483, a selective CRAC channel inhibitor, prevents antigen-induced airway eosinophilia and late phase asthmatic responses via Th2 cytokine inhibition in animal models

T cells play a regulatory role in the pathogenesis of various immune and allergic diseases, including human asthma. Recently, it was reported that a pyrazole derivative, YM-58483 (BTP2), potently inhibits Ca²⁺ release-activated Ca²⁺ (CRAC) channels and interleukin (IL)-2 production in T cells. We investigated the effects of YM-58483 on T helper type 2 (Th2) cytokine production in vitro and antigen-induced airway asthmatic responses in vivo. YM-58483 inhibited IL-4 and IL-5 production in a conalbumine-stimulated murine Th2 T cell clone (D10.G4.1), and IL-5 production in phytohemagglutinin-stimulated human whole blood cells with IC₅₀ values comparable to those reported for its CRAC channel inhibition (around 100 nM). YM-58483 inhibited antigen-induced eosinophil infiltration into airways, and decreased IL-4 and cysteinyl-leukotrienes content in inflammatory airways induced in actively sensitized Brown Norway rats. Furthermore, orally administered YM-58483 prevented antigen-induced late phase asthmatic broncoconstriction and eosinophil infiltration in actively sensitized guinea pigs. These data suggest that the inhibition of Ca²⁺ influx through CRAC channel leads to the prevention of antigen-induced airway inflammation, probably via the inhibition of Th2 cytokine production and inflammatory mediators release. YM-58483 may therefore be useful for treating airway inflammation in bronchial asthma.     

Histamine response in developing chick oesophagus. A pharmacological analysis of the response to histamine in the oesophagus of developing chick

Developmental changes in response to histamine were investigated in the oesophagus isolated from the chick between 15 days of incubation and 15 days after hatching. The contraction could be already caused by histamine (20 microM) in the chick oesophagus from 15 days of incubation. The pD2 values for histamine and acetylcholine did not change during the period between 17 days of incubation and 5 days after hatching. The response to histamine (20 microM) was extremely resistant to tetrodotoxin (0.78 microM), procaine (0.2 mM) and atropine (1 microM) during the period between 17 days of incubation and 20 days of incubation. The tetrodotoxin-resistant response was replaced by a tetrodotoxin-sensitive response after hatching. On the other hand, the neuronal response induced by transmural electrical stimulation (20 Hz) or dimethylphenylpiperazinium (20 microM) was uniformly sensitive to tetrodotoxin throughout the periods. Mepyramine (2 microM), but not metiamide (20 microM), inhibited the histamine-induced responses in every age tested. These results suggest that the myogenic receptivity of histamine transiently increases during the terminal period of embryonic development and declines after hatching.