Impact of mediastinal lymph node dissection on octogenarians with non-small cell lung cancer

Objective: Impacts of mediastinal lymph node dissection on a patient’s course after pulmonary resection is unclear in octogenarians with non-small cell lung cancer. Methods: Retrospectively identified subjects included 39 octogenarians and 1 nonagenarian, with grades according to the Charlson Comorbidity Index ranging from only 0 to 2. We performed mediastinal lymph node dissection in 19 patients (D group), and just lymph node sampling biopsy in the other 21 (S group). We compared clinicopathologic features and outcome after surgery between both groups. Results: Deterioration of performance status at the time of discharge, evident in 17 patients overall, was significantly more frequent in the D group. Postoperative complications occurred in 27 patients overall and there was no significant difference between the two groups. Survival rates in younger patients at 1, 3, and 5 years were 86, 59, and 49%, respectively; in octogenarians these were 83, 58, and 42% (no significant difference). Nor did survival differ significantly by surgical management of mediastinal lymph nodes; 1-, 3-, and 5-year survival rates were 94, 63, and 40%, respectively in the D group and 78, 66, and 43%, respectively in the S group. Conclusion: Octogenarians with non-small cell lung cancer should be treated by urgent pulmonary resection whenever possible. Since mediastinal lymph node dissection has little effect on long-term survival or the carried risk of worsening performance status at discharge, pulmonary resection without complete mediastinal lymph node dissection should be considered.     

Role of Papillary Muscle Dysfunction in the Pathogenesis of Mitral Regurgitation in Myocardial Infarction:

To elucidate the pathogenesis of mitral regurgitation (MR) after myocardial infarction (MI), the incidence of papillary muscle dysfunction (PMD), mitral annular size, and the extent of wall-motion abnormalities were examined in 81 patients with previous MI by two-dimensional echocardiography and real-time two-dimensional Doppler flow imaging. The prevalence of pathological MR was lower in patients with anterior MI (36%) than in those with inferior (65%) or anterior and inferior MI (88%) (P < 0.01 vs anterior MI group). The incidence of PMD in patients with MR in the anterior MI group (15%) was lower than that in the inferior (50%, P < 0.01) or anterior and inferior MI group (43%, P < 0.05). The mitral annular dimension in patients with MR was significantly greater than in those without MR, but it was similar among the three groups. The extent of wall-motion abnormality correlated significantly with the area of MR jet in the anterior MI group (y = 3.1x + 15.5, r = 0.52, P < 0.01) and in the inferior MI group (y = 8.3x + 32.7, r = 0.57, P < 0.01). However, the slope of this relationship was significantly steeper in the inferior MI group than in the anterior MI group (P < 0.05). These results indicated that the degree of MR with inferior MI was greater than with anterior MI for a given MI area. PMD may play an important role in the higher prevalence and greater degree of MR in inferior MI.     

HMG-CoA reductase inhibitor cerivastatin prolonged rat cardiac allograft survival by blocking intercellular signals.

BACKGROUND: The development of atherosclerotic cardiovascular complications caused by hyperlipidemia is a common and serious problem for long-term survivors of organ transplantation. However, adhesion molecules such as intercellular adhesion molecule (ICAM)-1 and lymphocyte function-associated antigen (LFA)-1 are involved in allograft rejection, possibly by providing costimulatory signals. 3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor cerivastatin has been shown to suppress ICAM-1 expression in acute inflammatory responses. METHODS: In this study, we evaluated the immunosuppressive effects of cerivastatin in rat cardiac allografts. The hearts of Fischer rats were transplanted heterotopically into Lewis rats. Cerivastatin (2 mg/kg) was administrated intraperitoneally to recipients for 7 consecutive days from the day before transplantation. RESULTS: Graft survival in the cerivastatin-treated group (n = 8) was significantly longer than in controls (n = 10) (24.6 +/- 2.2 days vs 10.2 +/- 1.3 days, p < 0.05). Mixed lymphocyte reaction (MLR) showed that on Day 8 after grafting, the proliferative response of alloreactive T cells against F344 alloantigen in cerivastatin-treated rats was significantly more suppressed than in Lewis rats. The Interleukin-2 concentration of supernatant in MLR cultures in the cerivastatin-treated group was lower than in the control group. Immunohistochemical analysis showed that the percentage of CD4-positive cells to infiltrating mononuclear cells was less prominent in the cerivastatin-treated group (9.8% +/- 2.2%) than in the control group (20.9% +/- 3.2%). CONCLUSIONS: The HMG-CoA reductase inhibitor cerivastatin effectively suppressed acute graft rejection, possibly by blocking intercellular signals via ICAM/LFA-1, and cerivastatin may be a candidate for treating patients with hyperlipidemia who undergo organ transplantation.     

Aneurysms of the anterior communicating artery and subclavian artery in association with congenital absence of unilateral internal carotid artery]

We encountered a rare case of unilateral internal carotid arterial defect complicated with anterior communicating aneurysm and subclavian artery aneurysm. The patient was a 56-year-old man in whom cerebral angiography and 3D-CTA revealed defects in the right internal carotid artery and the right carotid canal, and an unruptured aneurysm in the anterior communicating artery. In addition, the patient was also found to have an unruptured aneurysm in the right subclavian artery. As both the aneurysms were considered to have a high risk of rupture and such subclavian aneurysms were likely to cause an embolism, radical surgery was performed for each aneurysm. The postoperative course was uneventful, and the patient was discharged without ambulatory limitations. Although the defect in the internal carotid artery is a relatively rare vascular deformity, the incidence of cerebral aneurysm is about 30% in such cases due to the marked hemodynamic stress involved. On the other hand, there have been only two previous case reports of internal carotid arterial defect complicated with a subclavian aneurysm. Moreover, there have been no previous reports of internal carotid arterial defect complicated with both an intracranial aneurysm and a subclavian aneurysm, as observed in the present case. Thus, this case was very rare and is reported here.     

Late massive hemoptysis after transbronchial biopsy of hamartoma: an involvement of pulmonary artery and vein.

Pulmonary hamartoma is a common benign neoplasm that is usually asymptomatic and that arises in the periphery of the lung. However, when the tumor is growing without showing characteristic findings of hamartoma, such as involving calcification, fat density, and chondromatous contents in chest X-rays or computed tomography, the diagnosis is sometimes that problematic and definitive histological diagnosis should be established. We herein report a case with a massive hemoptysis 10 days after a successful transbronchial biopsy. A 69-year-old man who underwent mitral valve plasty 6 years earlier presented a left lung shadow during a routine chest X-ray. The shadow was seen to be growing by a series of chest X-rays. A week after warfarin had been stopped, a bronchoscopic biopsy was performed. No bronchial hemorrhage was observed during the procedure, and warfarin was not restarted. The patient began noticing bloody sputa once or twice a day, and 10 days after the biopsy, 400 mL of hemoptysis was suddenly disgorged. An emergency left upper lobectomy of the lung was performed, and the hemoptysis soon disappeared postoperatively. The patient is well without respiratory symptoms 36 months after the surgery.     

Idiopathic mediastinal fibrosis: Report of a case

(Received for publication on Nov. 14, 1996; accepted on May 12, 1997)     

Fetal anaesthesia for intrauterine treatment

Fetal anaesthesia was performed 5 times in 1 patient to treat pleural effusions, obtain fetal blood sampling, provide albumin infusion, and establish and replace a pleuro-amniotic indwelling shunt catheter under ultrasound guidance. A maternal epidural catheter was placed and used for epidural anaesthesia for the first 4 anaesthetics. Fetal administration of pancuronium 0.15 mg·kg^?1 via the umbilical vein or 0.25 mg·kg^?1 intramuscularly was enough to produce immobilization without maternal effect. However, maternal pretreatment with intravenous diazepam and fentanyl was required for fetal sedation and analgesia, which was necessary for accurate and safe injection, and for suppression of fetal stress.     

WSX-1 is required for resistance to Trypanosoma cruzi infection by regulation of proinflammatory cytokine production

WSX-1 is a class I cytokine receptor with homology to the IL-12 receptors and is essential for resistance to Leishmania major infection. In the present study, we demonstrated that WSX-1 was also required for resistance to Trypanosoma cruzi. WSX-1-/- mice exhibited prolonged parasitemia, severe liver injury, and increased mortality over wild-type mice. WSX-1-/- splenocytes produced enhanced levels of Th2 cytokines, which were responsible for the prolonged parasitemia. Massive necroinflammatory lesions were observed in the liver of infected WSX-1-/- mice, and IFN-gamma that was overproduced in WSX-1-/- mice compared with wild-type mice was responsible for the lesions. In addition, vast amounts of various proinflammatory cytokines, including IL-6 and TNF-alpha, were produced by liver mononuclear cells in WSX-1-/- mice. Thus, during T. cruzi infection, WSX-1 suppresses liver injury by regulating production of proinflammatory cytokines, while controlling parasitemia by suppression of Th2 responses, demonstrating its novel role as an inhibitory regulator of cytokine production.     

ATP regulation of ciliary beat frequency in rat tracheal and distal airway epithelium

Ciliary beat frequency (CBF) was measured by video-optical microscopy in rat tracheal and distal airway ciliary cells using a slice preparation. In tracheal ciliary cells (tracheal slice), ATP or 2-methylthio ATP (MeSATP) increased CBF, which was inhibited by suramin (100 microm, an inhibitor of purinergic receptor). Ionomycin (5 microm) or thapsigargin (2 microm) increased CBF similarly. Ca2+-free solution or addition of Ni2+ (1 mm) decreased CBF gradually by approximately 25% and subsequent stimulation with ATP (10 microm) increased CBF transiently. The purinergic agonist experiments demonstrated that ATP increases CBF in tracheal ciliary cells via both P2X and P2Y receptors. ATP increased the intracellular calcium concentration ([Ca2+]i) in tracheal ciliary cells. However, in distal airway ciliary cells (lung slice), ATP did not increase CBF and [Ca2+]i, although a Ca2+-free solution decreased CBF, and ionomycin (5 microm) or thapsigargin (2 microm) increased it. Moreover, acetylcholine (100 microm) did not increase CBF in distal airway ciliary cells, although it increased CBF in tracheal ciliary cells. Terbutaline (10 microm), a selective beta2-adrenergic agonist, increased CBF in both tracheal and distal airway ciliary cells. These observations suggest that the Ca2+-mobilization mechanisms via purinergic or muscarinic receptors of the distal airway ciliary cell may be different from those of the tracheal ciliary cell. In conclusion, the CBF increase is differently regulated in the tracheal and distal airway epithelia of the rat.     

Abeta-degrading endopeptidase,neprilysin, in mouse brain: synaptic and axonal localization inversely correlating with Abeta pathology

Metabolism of amyloid-beta peptide (Abeta) is closely associated with the pathology and etiology of Alzheimer's disease (AD). Since neprilysin is the only rate-limiting catabolic peptidase proven by reverse genetics to participate in Abeta metabolism in vivo, we performed detailed immunohistochemical analysis of neprilysin in mouse brain using neprilysin-deficient mice as a negative control. The aim was to assess, at both the cellular and subcellular levels, where Abeta undergoes neprilysin-dependent degradation in the brain and how neprilysin localization relates to Abeta pathology in amyloid precursor protein (APP)-transgenic mice. In hippocampus, neprilysin was present in the stratum pyramidale and stratum lacunosum-moleculare of the CA1-3 fields and the molecular layer of the dentate gyrus. Confocal double immunofluorescence analyses revealed the subcellular localization of neprilysin along axons and at synapses. This observation suggests that after synthesis in the soma, neprilysin, a type II membrane-associated protein, is axonally transported to the terminals, where Abeta degradation is likely to take place. Among various cell types, GABAergic and metabotropic glutamate 2/3 receptor-positive neurons but not catecholaminergic or cholinergic neurons, expressed neprilysin in hippocampus and neocortex, implying the presence of a cell type-specific mechanism that regulates neprilysin gene expression. As expected, Abeta deposition correlated inversely with neprilysin expression in TgCRND8 APP-transgenic mice. These observations not only support the notion that neprilysin functions as a major Abeta-degrading enzyme in the brain but also suggest that down-regulation of neprilysin activity, which may be caused by aging, is likely to elevate local concentrations of Abeta at and around neuronal synapses.