FUS immunoreactivity of neuronal and glial intranuclear inclusions in intranuclear inclusion body disease.

AIMS: Recent studies have shown that fused-in-sarcoma (FUS) protein is a component of 'neuronal' intranuclear inclusion bodies (INIBs) in the brains of patients with intranuclear inclusion body disease (INIBD). However, the extent and frequency of FUS-immunoreactive structures in INIBD are uncertain. METHODS: We immunohistochemically examined the brain, spinal cord and peripheral ganglia from five patients with INIBD and five control subjects, using anti-FUS antibodies. RESULTS: In controls, the nuclei of both neurones and glial cells were intensely immunolabelled with anti-FUS and neuronal cytoplasm was weakly positive for FUS. In INIBD, neuronal and glial INIBs in the brain and spinal cord were positive for FUS. FUS-positive INIBs were also found in the peripheral ganglia. The proportion of FUS-positive neuronal INIBs relative to the total number of inclusion-bearing neurones ranged from 55.6% to 83.3% (average 73.2%) and that of FUS-positive glial INIBs ranged from 45.9% to 85.7% (average 62.7%). The nucleus and cytoplasm of inclusion-bearing neurones and glial cells showed no FUS immunoreactivity. CONCLUSIONS: These findings suggest that FUS is incorporated into INIBs in both neurones and glial cells and that loss of normal FUS immunoreactivity may result from reduced protein expression and/or sequestration within inclusions.

Linezolid versus vancomycin for the treatment of infections caused by methicillin-resistant Staphylococcus aureus in Japan.

OBJECTIVES: To compare the efficacy and safety of linezolid and vancomycin for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections in Japan. METHODS: Patients with nosocomial pneumonia, complicated skin and soft-tissue infections or sepsis caused by MRSA were randomized to receive linezolid (600 mg every 12 h) or vancomycin (1 g every 12 h). RESULTS: One hundred patients received linezolid and 51 received vancomycin with outcomes evaluated at the end of therapy (EOT) and at the follow-up (FU), 7-14 days later. At EOT, clinical success rates in the MRSA microbiologically evaluable population were 62.9% and 50.0% for the linezolid and vancomycin groups, respectively; and microbiological eradication rates were 79.0% and 30.0% in the two groups, respectively (P < 0.0001). At FU, the clinical success rates were 36.7% for both groups and the microbiological eradication rates were 46.8% and 36.7%, respectively. Reversible anaemia (13%) and thrombocytopenia (19%) were reported more frequently in linezolid patients; laboratory analysis showed mild decrease in platelet counts with full recovery by FU. The mean platelet count in linezolid patients with thrombocytopenia was 101,000/mm(3). Significantly low platelet counts (<50,000/mm(3)) were observed more frequently in patients receiving vancomycin than in linezolid patients (6% versus 3%). Mean changes in haemoglobin levels between the two groups were not different. CONCLUSIONS: Linezolid is as effective as vancomycin for the treatment of MRSA infections and may be more effective than vancomycin in achieving microbiological eradication. Haematological adverse events were reported more frequently in linezolid-treated patients; analysis of laboratory data showed a mild reversible trend towards lower platelet counts.

Comparative clinical study of cefcapene pivoxil and cefteram pivoxil in chronic respiratory tract infections by a double-blind method.

In a double-blind study, the efficacy and safety of the novel cephem antibiotic cefcapene pivoxil (CFPN-PI; 450 mg/day) was compared with cefteram pivoxil (CFTM-PI; 600 mg/day) in 171 patients with chronic respiratory tract infections. There was no significant difference between the clinical efficacy of the two drugs (80.2% for CFPN-PI versus 78.9% for CFTM-PI). There was no significant difference in the rate of elimination of the causative bacteria (60.5% for CFPN-PI versus 65.9% for CFTM-PI). Side-effects were observed in 6.0% of patients treated with CFPN-PI compared with 6.4% of patients treated with CFTM-PI. There were no significant differences in incidence of abnormal laboratory findings following treatment with the two drugs (13.9% for each), and none of the side-effects was severe. We conclude that CFPN-PI (450 mg/day) was as effective and as well tolerated as CFTM-PI (600 mg/day) in the treatment of chronic respiratory tract infections.

Hyperthyroidism causes mechanical insufficiency of myocardium with possibly increased SR Ca2+-ATPase activity.

Hyperthyroidism is known to affect multiple organ functions, and thyroid hormone has been known to improve myocardial function in a failing heart. The purpose of this study is to elucidate the functional and metabolic effects of thyroid hormone on myocardium in a rat model exposed to long-term excess thyroid hormone, particularly focusing on the SR Ca(2+)-ATPase (SERCA2) function. 3,5,3'-Triiodo-L-thyronine (T3), or the vehicle, was subcutaneously given for 4 weeks (T3 and control [C] group). Bolus I.V. Thapsigargin (TG) was used to test the SERCA2 function (C-TG and T3-TG) in Langendorff perfused heart. Myocardial functions such as LV-developed pressure (LVDP; mmHg), +/- dP/dt (mmHg/s), tau (ms), and oxygen consumption (MVO(2); ml/min/g wt) were measured. SERCA2 and GLUT4 protein level were also evaluated by Western immunoblotting. Left ventricle to body weight (LV/BW) ratio was significantly higher in the T3 group. Both negative dP/dt and tau were significantly decreased by TG. It is interesting that the decrement of negative dP/dt and tau attained by TG was significantly larger in the hyperthyroid group (T3-TG) than in a normal heart (C-TG). SERCA2 and GLUT4 protein levels were not significantly different between control and the T3 group. We conclude that prolonged exposure to thyroid hormone causes hypertrophy of the myocardium and an augmentation of the SR Ca(2+) ATPase activity. Care must be taken in hyperthyroid heart during the ischemia-reperfusion process where the SRECA2 function is inhibited.

Cigarette smoking depletes cells spontaneously secreting Th(1) cytokines in the human airway.

Cigarette smoking may modify the immune balance in the airway since it alters the course of diseases in which immune system has an important role. This study examined whether cigarette smoking could affect the distribution of cells secreting Th(1) or Th(2) cytokines in the human airway. We utilized cytokine ELISPOT assay to detect and quantitate the frequencies of cells spontaneously secreting cytokines in bronchoalveolar lavage fluid (BALF). BALF was collected from six non-smokers and four heavy cigarette smokers without clinical airway symptoms. Cytokine ELISPOT assay was performed to quantitate cells secreting interleukin (IL-)2, IL-4 and interferon (IFN-)gamma with or without phorbor 12-myristate 13-acetate (PMA) stimulation. There were no cells spontaneously secreting IL-2 detected in all samples from smokers whereas most of non-smokers had detectable IL-2-secreting cells. The number of IFN-gamma-secreting cells was also extremely decreased in smokers. Mitogen-stimulated Th(1) cytokine-secreting cells were again significantly decreased in smokers' airways. The frequency of IL-2-secreting cells and CD4/CD8 ratio in BALF had a weak positive correlation. IL-4-secreting cells were not detected in any samples from both groups. These results show that cigarette smoking depletes Th(1) cytokine-secreting cells in the human airway. It may explain the susceptibility of smokers to certain airway disease conditions such as viral or mycobacterial infections and allergic diseases.

Fatal aspiration of sardine fry in a patient with lung cancer.

We report a fatal case of death due to unusual aspiration of sardine fry in an elderly Japanese man with lung cancer. The cause of death was sudden respiratory arrest while eating. Autopsy revealed peculiar materials with cell nests and pigmented particles, together with striated muscle and skin, in the ectatic bronchioles of the left lower lobe. Serial histologic sections suggested that the structures observed were the eyeballs of small animals that appeared to have been inhaled. The patient had habitually eaten sardine fry and rice gruel, which were also detected in the gastric contents. Therefore, the eyes were considered to be those of the fry, which is a popular food item in Japan. This was confirmed by histologic examination of fry that were obtained commercially.

Detection of pulmonary metastasis of low-grade endometrial stromal sarcoma 25 years after hysterectomy.

Endometrial stromal sarcoma (ESS) is a rare uterine sarcoma. Low-grade ESS occasionally recurs or metastasizes after long disease-free periods, a fact that may complicate the diagnosis. Here we report a case of multiple lung metastases in a 68-year-old woman who had been disease-free for 25 years after hysterectomy for a uterine tumor. Biopsy revealed that the tumor was composed of oval cells with slight nuclear atypism but without mitotic figures, suggesting a low-grade neoplasm. Immunostaining for intermediate filaments revealed strong positivity for vimentin and weak positivity for alpha-smooth muscle actin. In addition, immunostaining for estrogen and progesterone receptors, performed under suspicion of low-grade ESS, was positive. The uterine tumor resected many years before had shown a similar morphology. Thus, it was demonstrated that the lung neoplasm was a metastatic low-grade ESS that had appeared after many disease-free years. A review of the literature revealed that this case had the longest recorded interval between the occurrence of the initial ESS and the development of distant metastases. When low-grade sarcoma appears in the lungs of female patients, it is important to consider the possibility of low-grade ESS. Detailed information on the past clinical history, together with immunostaining for estrogen and progesterone receptors, are important diagnostic keys.

Insufficient effectiveness of 5-hydroxytryptamine-3 receptor antagonists due to oral morphine administration in patients with cisplatin-induced emesis.

PURPOSE: To compare the effect of 5-hydroxytryptamine-3 (5HT(3)) receptor antagonists in cancer patients receiving chemotherapy including cisplatin (CDDP), with or without sustained-release oral morphine (MS Contin; Shionogi Co, Osaka, Japan). PATIENTS AND METHODS: We retrospectively studied 58 lung cancer patients given chemotherapy including at least 50 mg/m(2) CDDP with 5-HT(3) receptor antagonists between January 1996 and December 1997. Number of vomiting episodes, average proportions of hospital-supplied meals consumed (0 to 100%, as an index of appetite), and nausea severity scores (0 to 2 points, subjective patient judgment) were compared between oral morphine-administered (+) and morphine-free (-) groups. RESULTS: Sixteen morphine(+) and 42 morphine(-) cases were used. In cases of acute emesis (within 24 hours after CDDP injection), morphine(+) and morphine(-) groups were significantly different in number of vomiting episodes (1.25 and 0.14, respectively; P <.0001), appetite (58.13% and 90.24%; P <.0001), and nausea severity scores (1.63 and 0.62; P <.0001). In delayed-emesis cases (24 to 120 hours after CDDP), these groups differed significantly in number of vomiting episodes (1.94 and 0.43, respectively; P =.0001), appetite (23.13% and 52.08%; P <.0001), and nausea severity (1.38 and 0.91; P =.009). There were no significant differences in sex, age, anticancer drugs concurrent with CDDP, CDDP dose, corticosteroid administration, clinical stage, or type of 5-HT(3) antagonist. CONCLUSIONS: These data suggest that morphine can markedly reduce the effectiveness of 5-HT(3) receptor antagonists in patients receiving chemotherapy that includes CDDP. These results require confirmation by reinvestigation of clinical data on the efficacy of 5-HT(3) receptor antagonists and by extensive prospective analyses.

[Usefulness of bronchoscopy for the diagnosis of atypical pulmonary mycobacteriosis].

In 14 subjects whose chest radiographs showed abnormal shadows during the two years from January 1995 until December 1996, no definite diagnosis could be obtained because sputum, smears and cultures all gave negative results for mycobacteria. Bronchoscopy was therefore performed, revealing atypical mycobacteria in cultures of the bronchial washing fluid for mycobacteria, and the significance of bronchoscopic examinations in cases diagnosed an atypical pulmonary mycobacteriosis was investigated. Most of the subjects (9) were women. Nine subjects had been informed that they had abnormal chest shadows; five had subjective symptoms; bloody sputum, 3 and cough, 2. The characteristics of the shadows were as follows: in the plain radiographs, the main shadows had a mottled or granular appearance in the majority of the patients (9) and there were infiltrative shadows in 3 patients and nodular shadows in another 3. In computed tomograms, the shadows in the vicinity of the pleura appeared as micronodular conglomerates in 12 patients, in 11 of whom bronchiectasis was also present near the shadows. Alveolar infiltrative shadows were present in four cases, and a cavity was seen in only one. Smears of the bronchial washing fluid for mycobacteria were positive in 7 patients, and cultures of this fluid yielded at least 100 colonies in 8 of the 14 subjects for whom the results were positive. By culture, Mycobacterium avium complex (MAC) was identified in 13 patients, but eleven of these in whom the bronchial washing fluid was concurrently tested for MAC by the polymerase chain reaction, only four were MAC-positive. Transbronchial lung biopsies were performed in 11 cases, in which the histological findings of mycobacterial infections showed granuloma in four, and caseation in three. Bronchoscopy is making possible initial-stage diagnosis, which are normally difficult, among the recently growing number of cases of the bronchial form of atypical pulmonary mycobacteriosis and is also useful for reaching definite diagnosis in the early stage.

[Peripheral blood dendritic cell dysfunction in patients with Sjögren's syndrome].

The function of dendritic cell (DC), that has the strongest antigen-presenting ability, was investigated for the purpose of clarifying immune abnormalities in Sjögren's syndrome (SS) from the point of view of antigen-presenting cells. DCs were separated from peripheral blood of SS patients, and mixed lymphocyte reaction (MLR) with DCs was observed to examine the function of DC. Autologous MLR (AMLR), which was induced by mixed culture of DCs with autologous T cells, significantly decreased in SS patients (p < 0.01). Allogeneic MLR (alloMLR), which was induced by mixed culture of DCs with allogeneic T cells, also decreased in SS patients, suggesting the presence of DC dysfunction. Cell surface expression rates of HLA-DR, CD 80, and CD 83, which are a first signal of cell surface antigen presentation, a second signal, and a specific antigen of DC, respectively, were then examined. Among HLA-DR-positive cells, CD 80-positive cells and CD 83-positive cells increased in SS patients, compared with normal subjects (p < 0.0003 and p < 0.00009, respectively). From these results, it was inferred that SS patients have not only DC dysfunction, but abnormalities in cell surface antigens as well.

[Reoperative coronary artery bypass grafting without cardiopulmonary bypass].

Between October 1995 and February 1997, 2 men and 4 women aged 53 to 75 years (mean, 66.3) underwent reoperative coronary artery bypass grafting without cardiopulmonary bypass. Isolated reoperative circumflex or intermediate artery bypass was performed through a left thoracotomy (n = 2), reoperative bypass to the left anterior descending coronary artery was performed through a median sternotomy (n = 3), and bypass to the right coronary artery was performed through an upper median laparotomy (n = 1). Single coronary bypass grafting utilizing arterial grafts (left internal thoracic artery: 3, right gastroepiploic artery: 3) was performed in all cases. There were no operative deaths. All cases required neither cathecolamine nor intraaortic balloon pumping). Peri/post operative blood transfusion was necessary in only one case. Postoperative coronary angiography revealed that the 6 arterial grafts were patent. Reoperative coronary artery bypass grafting without cardiopulmonary bypass can be performed with low perioperative morbidity and mortality, easy postoperative management, satisfactory graft patency, and good symptomatic improvement.

[Coronary artery bypass grafting without cardiopulmonary bypass].

From October 1995 until April 1996. CABG (coronary artery bypass grafting) was performed under the beating heart without CPB (cardiopulmonary bypass) in nine cases. They consisted of 7 males and 2 females ranging in age from 31 to 79 years old (mean 64.7 years). Single bypass grafting was performed in 6 cases, and double bypass grafting was done in 3 cases, involving 2 re-do cases. With regard to the major associated diseases, two patients had required chronic hemodialysis three time a week, four patients were administered with insulin for diabetes mellitus. There were other three patients with renal dysfunction not requiring hemodialysis, two patients had pulmonary problems, and one patient had Parkinson's disease. Further more two patients were older than 75th years in age. Graft anastomosis to the coronary artery was performed with 7-0 polypropylene. In one case, left thoracotomy was done to approach the heart for the anastomosis to intermediate artery, and in the other eight cases, median sternotomy was done. The grafts used in the nine cases were 4 right internal thoracic arteries, 6 left internal thoracic arteries, one gastroepiploic artery and one saphenous vein, 12 grafts in total. Subtotal gastrectomy for gastric cancer and cholecystectomy for cholecystitis was done in one patient for each. Heterologous blood transfusion was required two cases (22.2%). The postoperative course was very good in all cases. Eleven grafts in postoperative angiographed 8 cases were all patent, although presenting the string sign in one case, and angina pectoris disappeared in all cases. CABG under the beating heart without CPB was considered to be useful for the patients with considerable other diseases from the point of view of safety and ease of postoperative managements. We think that this procedure should be considered particularly for patients on chronic hemodialysis who required CABG.

[Bilateral internal thoracic artery-left descending artery anastomosis in pediatric for the Bland-White-Garland syndrome].

BWG syndrome, a rare congenital heart disease, is a prognostically unsatisfactory disease that causes many patients to die of the myocardial ischemia within one year. Recently in pediatric BWG patients, a two coronary-system established has been the accepted treatment. We experimented positive results with a patient who was convalescing after direct closure of the left coronary arterie's orfice in the pulmonary artery and the establishment of the two-coronary-system by bilateral internal thoracic artery-left descending artery anastomosis. We report this case as a possible effective method of surgical treatment for BWG syndrome in pediatric.

[Systemic-to-pulmonary artery shunt using the internal thoracic artery].

Systemic-to-pulmonary artery shunts may be useful for palliation of cyanotic congenital heart disease. We report the two cases of a 2-year-girl and a 5-year-girl in whom the internal thoracic artery was used to create a systemic-to-pulmonary artery shunt. This technic may have distinct advantages in selected cases and should be considered as an alternative during investigation of the older child who requires a systemic-to-pulmonary shunt.

[A case of extended surgery in acute aortic dissection by perfusion into extra anatomic bypass].

Total aortic arch replacement creates various problems involving surgical techniques, myocardial protection and perfusion methods. The most important problem during this procedure is cerebral ischemia. We developed a technique to prevent this problem by bypass grafting through the right axillo-left external carotid-left axillary artery and perfusing the brain continuously through the side branch attached to this bypass graft. A 62-year-old man with acute aortic dissection underwent ascending aorta and total aortic arch replacement using this alterative perfusion method. No cerebral dysfunction was seen in this case. The advantages of this method are as follows: there is no time limit required even for total aortic arch replacement; adequate and reliable anastomosis is possible; the dissecting aortic branches are not touched directly; it is possible to prevent cerebral infarction caused by mural thrombus and pieces of atherosclerotic plaque by clamping the aorta and aortic arch branches; and it is possible to prevent air embolism.

Infected aneurysms--clinical study of 5 cases.

The infected aneurysm has been assumed to be a disease with a poor prognosis due to the occurrence of aneurysmal ruptures and sepsis, in contrast to the outcome of atherosclerotic aneurysms. In the present study, we conducted surgical treatment on five patients with infected aneurysms (infected abdominal aortic aneurysm in three cases and iliac artery aneurysm in two cases). In particular, two of the three patients suffering from infected abdominal aortic aneurysms underwent extra-anatomic bypass and the remaining one case underwent vascular graft replacement in situ. In the two patients who underwent an extra-anatomic bypass, an aneurysm was found at the site of aortic stump closure. In the patient who underwent in situ replacement, wrapping was carried out using the omentum after vascular graft replacement, and the postoperative course was uneventful. Accordingly, we consider that the optimum primary therapeutic intervention for infected aneurysms is in situ revascularization followed by wrapping with the omentum after removal of the aneurysm and debridement of the surrounding infected tissue to the maximum extent possible.

[CABG operation with sequential bypass using arterial grafts].

We evaluated 39 cases where sequential anastomoses had been performed using arterial graft (AG) in coronary artery bypass grafting (CABG). Fourty three AGs were used, and anastomosed to 87 coronary arterial branches. The details of these anastomoses were: 25 right gastroepiploic arteries (RGEA) to 51 branches; 10 left internal thoracic arteries (LITA) to 20 branches; 8 right internal thoracic arteries (RITA) to 16 branches. The interrupted suture was employed for all anastomoses. The proxymal site was initially anastomosed in the parallel way to a native coronary artery, and then, the distal anastomosis was done. In CABG using RGEA, the number of cases receiving anastomoses to RCA and LCX was the largest as in 13 cases, and the patent rate was favorable. There were also 8 cases of anastomoses to LAD and Dx and these GEA'S grafts were all patent. But, in the 2 cases of astomoses to RCA and LAD, the GEA's grafts between RCA and LAD were occluded. Therefore, this combination was thought to be inadequate for sequential hypass. On the other hand, in the 10 cases using LITA, these grafts were all anastomosed to LCA system, and were all patent. In the 8 cases using RITA, 4 in-situ grafts and 4 free grafts were employed. There were 3 anastomoses to LAD and D1 in the former, and 2 cases each of anastomoses to LAD and D1, and LCx (segment 12) in the latter. The patency was excellent, 100%. Although there were 1 case of post-operative early death (renal failure) and 1 case of remote death (cerebral infarction), they were found not due to arterial sequential bypass. In the 37 cases of post-operative angiography, patency was recognized in 40 AGs out of the 41 (97.6%) and 78 anastomosed branches out of the 83 (94.0%). These satisfactory findings indicate that it is possible and effective to perform sequential bypass in multivessel GABG using AG.