Uniportal video-assisted thoracic surgery and perioperative pirfenidone for lung cancer and idiopathic pulmonary fibrosis: a case report

Patients with idiopathic pulmonary fibrosis (IPF) occasionally experience acute exacerbations after surgery for lung cancer. Several recent studies have revealed a prophylactic effect of perioperative pirfenidone treatment on postoperative acute exacerbations of IPF in patients with lung cancer. A 75-year-old woman consulted with her pulmonologist because of an IPF shadow detected by follow-up chest computed tomography 2 months after surgical treatment of biliary cancer. Another 7 months later, chest computed tomography showed a 23- × 14-mm nodule located in the right lower lobe with high accumulation of fluorodeoxyglucose detected by positron emission tomography, resulting in a radiological diagnosis of primary lung cancer with IPF. We administered perioperative pirfenidone treatment followed by right lower lobectomy using uniportal video-assisted thoracoscopic surgery after attaining a pathological diagnosis of adenocarcinoma. The patient developed no acute exacerbations of IPF during the postoperative period, and she had no recurrence of lung cancer for 15 months after surgery. We successfully used a combination of perioperative antifibrotic medication and minimally invasive surgery after lung cancer surgery in a patient with IPF.     

Single unit responses of human cutaneous mechanoreceptors to air-puff stimulation.

OBJECTIVE: To investigate responsiveness of human cutaneous mechanoreceptor to selective tactile stimuli produced by brief air-puff stimulation. METHODS: Using percutaneous microneurography, activities of single sensory units innervating glabrous skin of the hand were recorded, and air-puff stimuli with a short rise time (0.5 ms), generated by a high-speed air control system, were applied to the receptive field. Receptor activation time was estimated as the latency difference between electrically and air-puff evoked responses. RESULTS: Thirty units were analyzed: all 4 kinds of mechanoreceptors of human glabrous skin (fast adapting type 1 [FA I, n=7], fast adapting type 2 [FA II, n=4], slowly adapting 1 [SA I, n=5] and slowly adapting 2 [SA II, n=14]) were activated by air-puff stimulation. Estimated receptor activation times were 0.6-6.2 ms (mean 2.2 ms). FA II units occasionally responded twice or more to a single air-puff stimulus. CONCLUSIONS: Brief air-puffs can activate all 4 human cutaneous mechanoreceptors, and the receptor transduction time is estimated as approximately 2.0 ms. Properties of human mechanoreceptors can be studied using air-puff stimulation and microneurography.     

Mechanical properties of the femur filled with calcium phosphate cement under torsional loading: a model in rabbits

 We conducted an experimental study using rabbits to determine the effect of injection of calcium phosphate cement (CPC) through a small cortical window on the torsional strength of the long bone. A drill hole created in the femoral shaft and medullary curettage before CPC injection simulates the clinical procedure for managing benign bone tumors. Torsional loading always produced a spiral fracture through the drill hole. The CPC-treated femurs, but not the polymethylmethacrylate-treated femurs, tolerated greater torsional loads and had greater energy absorption to failure at 24 h and 2 weeks postoperatively compared with the con-tralateral sham-operated femurs. These two parameters, however, were only 54% and 26%, respectively, of those in normal femurs at 24 h, but they were 71% and 51% of those in normal femurs at 12 weeks. Histologic sections demonstrated progressive covering of the drill hole by new bone in the CPC-treated specimens and invagination by newly formed cortical bone into the medullary cavity following sham operation. CPC increases the torsional strength of the long bones immediately after injection, although not sufficiently to preclude the need for external fixation in clinical applications. Better management of the cortical defect is needed to further improve torsional strength. Received: February 21, 2002 / Accepted: May 8, 2002     

Expression and regulation of heme oxygenase isozymes in the developing mouse cortex

Heme oxygenase (HO), the rate-limiting enzyme in heme degradation, plays a role in neonatal jaundice. Understanding the regulation of the developmental expression patterns of the two HO isozymes, HO-1 and HO-2, is essential for targeting HO to control pathologic jaundice, and uncovering the fundamental role that they play in mammalian development. Here we characterized the ontogeny of HO-1 and HO-2 expression in the developing mouse cortex by in vivo bioluminescence imaging, quantitative RT-PCR, and Western blot. HO-2, the predominant isoform in the adult cortex, was relatively stable throughout all ages. HO-1 was observed to be progressively down-regulated in an age-related manner. HO-1 expression in the adult cortex was also the lowest among the eight adult tissues analyzed. Because there is a 283-bp CpG island region in the HO-1 promoter, we hypothesized that methylation of the island is responsible for the age-related HO-1 down-regulation in the cortex. Methylation status was assessed using regular and quantitative methylation-specific PCR and the CpG island was found to be hypomethylated at all ages. Therefore, we conclude that HO-1 gene expression in the cortex is developmentally-regulated and that methylation of the HO-1 CpG island is not associated with the down-regulation of the gene.     

铁杉灵芝多糖FⅢ-2对人组织瘤细胞和人外周血白细胞产生炎症性细胞因子的影响(英文)

用放射免疫分析法及逆转录聚合酶链反应法 ,比较研究水不溶性铁杉灵芝多糖 (FⅢ 2 )及其吡啶 氯磺酸修饰产物 (FⅢ 2 S)对人炎症性细胞因子蛋白质及其mRNA产生的影响 .结果表明 ,FⅢ 2 (4 ,4 0或 4 0 0mg·L- 1)显著提高低剂量脂多糖 (LPS) 10mg·L- 1协同佛波醇 14烷酰乙酸盐 (PMA) 2 0 0nmo1·L- 1诱导的人组织瘤THP 1细胞产生肿瘤坏死因子α(TNFα) ,然而明显地抑制高剂量LPSl0 0mg·L- 1协同PMA诱导的THP 1细胞产生TNFα .FⅢ 2 S(4或4 0mg·L- 1)提高无刺激剂细胞产生TNFα ,高浓度FⅢ 2 S(4 0 0mg·L- 1)抑制TNFα产生 .FⅢ 2与FⅢ 2 S提高白介素 8的产生 ,降低刺激剂引起的白介素 1α的产生 .FⅢ 2的抗肿瘤作用可能是与TNFα产生有关 .FⅢ 2对人外周血单核细胞产生各种细胞因子和对THP 1细胞产生细胞因子的机理基本上相同 .结果提示 ,松杉灵芝菌丝体水不溶性多糖在不同的刺激条件下具有双向免疫调节作用 .化学修饰的多糖可改变原多糖对细胞因子产生的调节方向 .     

Universal Screening for Familial Hypercholesterolemia in Children in Kagawa,Japan

Aim: Familial hypercholesterolemia (FH) is an underdiagnosed autosomal dominant genetic disorder characterized by high levels of plasma low-density lipoprotein cholesterol (LDL-C) from birth. This study aimed to assess the genetic identification of FH in children with high LDL-C levels who are identified in a universal pediatric FH screening in Kagawa, Japan. Method: In 2018 and 2019, 15,665 children aged 9 or 10 years underwent the universal lipid screening as part of the annual health checkups for the prevention of lifestyle-related diseases in the Kagawa prefecture. After excluding secondary hyper-LDL cholesterolemia at the local medical institutions, 67 children with LDL-C levels of ≥ 140 mg/dL underwent genetic testing to detect FH causative mutations at four designated hospitals. Results: The LDL-C levels of 140 and 180 mg/dL in 15,665 children corresponded to the 96.3 and 99.7 percentile values, respectively. Among 67 children who underwent genetic testing, 41 had FH causative mutations (36 in the LDL-receptor, 4 in proprotein convertase subtilisin/kexin type 9, and 1 in apolipoprotein B). The area under the curve of receiver operating characteristic curve predicting the presence of FH causative mutation by LDL-C level was 0.705, and FH causative mutations were found in all children with LDL-C levels of ≥ 250 mg/dL. Conclusion: FH causative mutations were confirmed in almost 60% of the referred children, who were identified through the combination of the lipid universal screening as a part of the health checkup system and the exclusion of secondary hyper-LDL cholesterolemia at the local medical institutions.     

Relationship of Daily Coffee Intake with Vascular Function in Patients with Hypertension

We evaluated the relationship of daily coffee intake with endothelial function assessed by flow-mediated vasodilation and vascular smooth muscle function assessed by nitroglycerine-induced vasodilation in patients with hypertension. A total of 462 patients with hypertension were enrolled in this cross-sectional study. First, we divided the subjects into two groups based on information on daily coffee intake: no coffee group and coffee group. The median coffee intake was two cups per day in the coffee group. There were significant differences in both flow-mediated vasodilation (2.6 ± 2.8% in the no coffee group vs. 3.3 ± 2.9% in the coffee group, p = 0.04) and nitroglycerine-induced vasodilation (9.6 ± 5.5% in the no coffee group vs. 11.3 ± 5.4% in the coffee group, p = 0.02) between the two groups. After adjustment for confounding factors, the odds ratio for endothelial dysfunction (OR: 0.55, 95% CI: 0.32–0.95) and the odds ratio for vascular smooth muscle dysfunction (OR: 0.50, 95% CI: 0.28–0.89) were significantly lower in the coffee group than in the no coffee group. Next, we assessed the relationship of the amount of daily coffee intake with vascular function. Cubic spline curves revealed that patients with hypertension who drank half a cup to 2.5 cups of coffee per day had lower odds ratios for endothelial dysfunction assessed by flow-mediated vasodilation and vascular smooth muscle dysfunction assessed by nitroglycerine-induced vasodilation. Appropriate daily coffee intake might have beneficial effects on endothelial function and vascular smooth muscle function in patients with hypertension.     

Ischemic electrocardiographic change induced by exercise in a patient with chronic autonomic failure

Abstract We report a patient with chronic autonomic failure, who had exercise-induced ischemic electrocardiographic changes without coronary artery abnormalities. Orthostatic hypotension and exercise-induced release of humoral vasoconstrictors may have caused the myocardial ischemia.     

A case of vacuolated meningioma

A rare case of falx meningioma with extensive vacuolization was reported. A 57-year-old woman was admitted to Okayama University Hospital because of numbness in her left lower limb. A plain CT scan showed a hypodense mass in the right frontal region with marked enhancement after contrast medium injection. MRI on T1 weighted images showed low intense mass with the so-called "peritumoral band" of low intensity at the periphery of the mass. Angiogram showed a mass effect and a tumor stain fed by the right pericallosal artery and left middle meningeal artery. The mass was excised en bloc. Microscopic examination demonstrated tumor cells with varied sized vacuoles, which were mostly fat-negative, except for small islands with typical meningothelial cells in the periphery of the tumor. Ultrastructurally, there were two kinds of vacuole in the tumor cells. The smaller, round vacuoles were in the cytoplasm, while the larger ones were in the extracellular space. The cell processes had developed junctional complex, and numerous cytoplasmic filaments were evident. With these findings, this mass was diagnosed as vacuolated meningioma. It is important especially in frozen section not to misdiagnose the tumor as liposarcoma, chordoma, metastatic brain tumor and so on.     

Complexity in the treatment of pulmonary large cell neuroendocrine carcinoma

Purpose According to the World Health Organization (WHO) classification of pulmonary large cell neuroendocrine carcinoma (LCNEC), one of the neuroendocrine tumors of the lung, is considered as a variant of non-small cell lung carcinoma. The objective of this study was to investigate the treatment strategy for LCNEC.Methods We retrospectively reviewed the clinical information of 12 patients with LCNEC.Results Three patients with stage I disease underwent curative resection but all relapsed within 20 months. One with stage IIA disease underwent non-curative resection received adjuvant chemoradiotherapy (cisplatin plus etoposide) and is well with no evidence of recurrence. Two with stage IIIB disease received concurrent chemoradiotherapy. Both achieved partial response (PR) but relapsed within 2 months. One elderly patient with stage IIIA disease received vinorelbine alone and did not respond. Of five patients with stage IV disease, three received platinum-based chemotherapy but no patient achieved PR. Of five patients with gefitinib as salvage therapy, one achieved PR.Conclusions The prognosis of LCNEC is poor. To improve the outcome, we must evaluate the effectiveness of adjuvant or neoadjuvant therapy in patients with resectable disease. In addition, the evaluation of systemic and multimodality treatment strategies similar as in small cell lung cancer is worthy of consideration.