Studies on the mechanisms underlying beta-adrenoceptor-mediated relaxation of rat abdominal aorta.

Mechanisms underlying beta-adrenoceptor (beta-AR)-mediated vascular relaxation were studied in the isolated rat abdominal aorta. In the endothelium-denuded helical preparations, a non-selective beta-AR agonist isoprenaline elicited a concentration-dependent relaxation. In the absence of beta-AR antagonists, isoprenaline-induced relaxation was not practically affected by an adenylyl cyclase inhibitor SQ 22,536 (300 microM), but was strongly diminished by high-KCl (80 mM). Isoprenaline-induced relaxation in the presence of SQ 22,536 was significantly diminished by iberiotoxin (IbTx, 0.1 microM), but was not affected by 4-aminopyridine (4-AP, 3 mM). Isoprenaline-induced relaxation was not also affected by SQ 22,536 (300 microM) even in the presence of CGP20712A (a beta(1)-selective antagonist) and ICI-118,551 (a beta(2)-selective antagonist) (0.1 microM for each), but was strongly diminished by high-KCl. By contrast, SQ 22,536-resistant, isoprenaline-induced relaxation in the presence of CGP20712A plus ICI-118,551 was not affected by IbTx (0.1 microM), but was inhibited significantly by 4-AP (3 mM). These results suggest that in rat abdominal aortic smooth muscle: 1) both beta(1)-/beta(2)-AR- and beta(3)-AR-mediated relaxations substantially involve cAMP-independent mechanisms; 2) beta(1)-/beta(2)-AR-mediated, cAMP-independent relaxant mechanisms are partly attributed to the large-conductance, Ca (2+)-sensitive K(+) (MaxiK, BK) channel whereas beta(3)-AR-mediated relaxant mechanisms are attributed to K(v) channel.     

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.     

Evidence for a defect in urinary concentrating ability in primary aldosteronism and its reversal by adrenal surgery

Of 15 patients with primary aldosteronism, 7 had idiopathic adrenal hyperplasia (IHA) and 8 had aldosterone-producing adenoma (APA). In order to determine any renal problems involved in the treatment, the renal clearance of these patients was analyzed and the results compared with those obtained from 12 patients with essential hypertension. With water diuresis or under antidiuresis status, levels of urine volume, Cosm and CH2O in patients with APA were greater (p less than 0.05-p less than 0.001) than those of patients with essential hypertension, while the fractional tubular sodium delivery of the former patients was lower than that of the latter patients (p less than 0.001 or less than 0.05). A similar tendency was observed in clearance studies in patients with IHA, although to a lesser extent. Adrenal surgery for patients with APA normalized these values, but administration of trilostane (3 beta-hydrosteroid dehydrogenase inhibitor) to patients with IHA failed to improve these values. These results indicate that impaired urinary concentrating ability as well as reduced urinary diluting capability is a common feature of primary aldosteronism. Such impaired renal function was improved only in patients with APA after adrenal surgery.     

Self-expandable metallic stent for unresectable malignant strictures in the esophagus and cardia

Objective Self-expandable metallic stent (EMS) placement has been the first choice for dysphagia because of the certainty over its safety, low invasiveness, and immediate efficacy. However, there still remain some problems in relation to the EMS placement site and anticancer therapies before and after EMS placement. Methods: Consecutive 78 patients in whom EMS was placed due to the unresectable malignant stricture in the esophagus or cardia from July 1995 to August 2003 in our department were studied. Results: Gastroesophageal reflux was found in 5 of 8 patients after placement of conventional EMS for the stricture in the gastroesophageal junction. Meanwhile, acid and bile reflux into the esophagus were not detected by pH and bilirubin monitoring, respectively, in 6 patients after placement of the EMS with an anti-reflux mechanism for the stricture in the gastroesophageal junction. The median survival period of all patients after EMS placement was 123 days. The median survival period of 7 patients with radiotherapy only after EMS placement was 138 days and that of 17 patients with radiotherapy before EMS placement was 60 days, which was shorter than that of the former (p<0.05). On the other hand, the median survival period after hospital admission due to dysphagia of these 7 patients was longer than that of 17 patients with radiotherapy only before EMS placement, although, the difference was not significant. Conclusion: EMS with an antireflux mechanism is not commercially available in Japan and approval is urgently required. The indication of radiotherapy associated with EMS placement is to be studied further.     

Papillary carcinoma of the thyroid with exuberant nodular fasciitis-like stroma

 We describe a rare case of papillary carcinoma with extensive proliferation of stromal cells. The stromal cells were immunocytochemically positive for vimentin, α-smooth muscle actin and desmin, but negative for cytokeratin, epithelial membrane antigen, S-100, thyroglobulin and CD34. These results and the ultrastructure of the stromal cells, which exhibited the characteristics of both fibroblasts and smooth muscle cells, indicated an origin from myofibroblasts. We conclude that myofibroblastic proliferation may contribute to the stromal response in the slow growth of the papillary carcinoma. Received: 29 August 1996 / 26 May 1997     

Pulmonary lesions of acquired immunodeficiency syndrome--analysis of 24 Japanese autopsy cases with AIDS]

The pulmonary lesions were studied in 24 autopsy cases of Japanese patients with AIDS. The major pathological findings were opportunistic infections, which were the major clinical symptoms in some patients. The pathogens identified were as follows; Pneumocystis carinii (PC) in 10, cytomegalovirus (CMV) in 14, atypical mycobacterium in 5, cryptococcus in 2, candida in 2, and nocardia in 1. PC pneumonia was prominent in 8 cases and was the cause of death. In such patients, the lung were heavy and appeared parenchymatous. Histological examination revealed numerous protozoa in the foamy material in the alveolar spaces, associated with swelling of the alveolar lining cells and edematous thickening of the alveolar septa. In some cases, only hyaline membrane formation was prominent without foamy material in the alveolar spaces. Immunostaining with anti-PC monoclonal antibody or in-situ hybridization with oligopeptide demonstrated pathogens in the hyaline membranes. Many cases with PC pneumonia had concomitant opportunistic infections such as CMV, Herpes simplex virus, and atypical mycobacterium. Extrapulmonary infection of PC was seen in only one case. CMV infection was found in 14 cases; 7 had innumerable inclusion bodies, and in some cases the lesions were most prominent around the bronchioles. Of the 5 cases of atypical mycobacterial infection, 2 were caused by M. kansaii (MK) and 3 by M. avium intracellulare (MAI). Both lesions of MK infection showed necrosis and cavitation. One of three cases of MAI infection showed cavitation. Around the cavitary lesions, numerous cytomegalic inclusion bodies were identified in the mesenchymal cells, which may have been the cause of necrosis and cavitation of the lesions. MAI infection was systemic and pronounced in the lymph nodes, spleen, and intestinal mucosa. Neoplastic lesions comprised 2 cases of Kaposi's sarcoma and 4 of extranodal non-Hodgkin lymphoma in other organs. Lung involvement was seen in only one case of Kaposi's sarcoma although very small in size. The lesion was situated along the pulmonary vein and appeared hemorrhagic macroscopically. Pulmonary lesions in AIDS are complicated, and many of opportunistic pathogens were identified in single patients.     

Measurements of active and passive force of horizontal muscles in strabismus

A precision device was developed for quantitative measurement of the active and passive forces of the horizontal muscles in several different types of strabismus. The device consists of a tension gauge for measuring isometric muscle tension (active force) and passive length-tension (passive force), and a circular-motion guide mechanism. In normal subjects, the active force showed nearly linear changes with the eye position, as was reported in past studies. A similar relationship between the active force and the eye position was observed also in strabismus patients in our study. Normal subjects showed a stronger force in the medial than the lateral rectus muscle. Among strabismus patients, those with normal retinal correspondence (NRC)-intermittent exotropia showed a force closest to that of the normal controls. However, the force of the lateral rectus muscle was significantly greater in those with constant exotropia than in the normal controls. The active force of the medial rectus muscle was significantly smaller in those with dual retinal correspondence (DRC)-intermittent exotropia and constant exotropia. Conversely, the active force of the medial rectus muscle was significantly greater in those with esotropia, compared with the normal group. As for the passive force, there was no significant difference between the temporal passive force and the nasal passive force in the normal and esotropic groups, but the temporal passive force was significantly greater in the esotropic group. The magnitude of the force was greater in both directions when traction was applied against the muscle having the stronger active force. These results suggest that the lateral rectus muscle force is relatively stronger in patients with DRC-intermittent exotropia due to a weakness of the medial rectus muscle force, and that the absolute strength of the lateral rectus muscle force is increased in patients with constant exotropia, but in NRC-intermittent exotropia the muscle forces are almost normal. Those with esotropia are considered to have an absolute increase in the medial rectus muscle force.     

Movement-related cortical potential in patients with cerebellar dentate degeneration]

We reported movement-related cortical potentials (MRCPs) in 11 patients with lesion of the dentate nucleus (Machado-Joseph disease (MJD) 7 cases, dentato-rubro-pallido-luysian atrophy (DRPLA)1, myoclonus epilepsy associated with ragged-red fibers (MERRF)1, dyssynergia cerebellaris myoclonica (DCM) 2), and compared with those of 7 cases of multiple system atrophy (MSA) who were postulated to have mild dentate lesions (striato-nigral degeneration 2 cases, Shy-Drager syndrome 2, sporadic olivo-ponto-cerebellar atrophy 3), and 7 control subjects without any neurological findings. Further we classified the diseases into the following two groups based on the lesion of the dentate nucleus. One was MJD group that had normal or slightly abnormal electroencephalogram (EEG), and the other was DN group (DRPLA, MERRF, DCM) that had markedly abnormal EEG. One of the main findings from this study was smaller slope of the Ns' in the MJD and DN group and normal slope of BP. There was no significant difference in the slope of Ns' between MJD patients and DN patients. This result shows EEG abnormalities have no influence on MRCP recordings. These results suggest that Ns' component may reflect the function in the cerebellar dentate nucleus, and that MRCP is a useful diagnostic method in patients with cerebellar ataxia.