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.

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.

Granulocytosis associated with malignant neoplasms: a clinicopathologic study and demonstration of colony-stimulating activity in tumor extracts.

We studied seven cases of malignant neoplasms, taken from various sites in the body, that were associated with marked granulocytosis. The seven cases were characterized clinically by marked granulocytosis with mature neutrophils, nonspecific inflammatory signs, and a rapid and progressive fatal course of the disease. The elevation of granulocyte count generally paralleled the increase in tumor size. Postmortem examination revealed no evidence of extensive bone marrow metastases or significant suppuration in any case. The bone marrows showed varying degrees of granulocytic hyperplasia with or without a shift to the left in the maturation series. Erythroid cell hyperplasia was observed in some cases, and in one instance there was an increase in immature eosinophils. The spleen showed various degrees of infiltration by neutrophils, from minimal to extremely marked; some spleens had foci of extramedullary hemopoiesis. Colony-stimulating activity was demonstrated in tumor extracts from three of these cases and from the serum in another case. Thus, it is suggested that marked granulocytosis in these patients was caused, at least in part, by colony-stimulating factor produced by the neoplastic cells.

Ascending aorta-supraceliac abdominal aorta bypass: successful removal of an infected graft in the descending thoracic aorta.

An infected graft and a mycotic pseudoaneurysm were successfully resected by employing an ascending aortasupraceliac abdominal aorta bypass graft in a 19-year-old man. He had formerly undergone graft replacement surgery for traumatic aneurysm of the descending thoracic aorta, with the aid of a temporary external bypass graft. After this first operation, the patient had suffered from septicemia due to Psudomonas aeruginosa, which resulted in formation of mycotic pseudoaneurysms at the distal anastomotic site of the prosthetic graft and at both stumps of the formerly employed external bypass graft.

Abdominal aortic aneurysm in a 3-year-old child: a case report and review of the Japanese-language literature.

A case of abdominal aortic aneurysm associated with renovascular hypertension in a 3-year-old boy is reported. The child was treated by resection of the aneurysm and replacement with a 12 mm polyester (Dacron) bifurcated graft. The cause of the aneurysm was not revealed by clinical and pathologic examination. In addition to the case report, the Japanese-language literature is reviewed. The most frequently reported etiologic factor was Kawasaki disease; we could not find any evidence of connective-tissue disorder as a cause for abdominal aortic aneurysms occurring in children.

Use of a new stapling instrument for permanent occlusion of the aorta in the surgical procedure for thromboexclusion.

Permanent aortic occlusion is required in the surgical procedures for the flow reversal and thromboexclusion technique and also for the permanent exclusion of aneurysms of the thoracic aorta. We have designed a stapling instrument for the permanent occlusion of the aorta and have used it in 5 patients with aortic dissections and 2 patients with aneurysms of the thoracic aorta. This report describes our newly designed surgical stapler for the closure of the aorta with 2 case reports.

Clinical results of cardiopulmonary bypass with selective cerebral perfusion for aneurysm of the ascending aorta and the aortic arch.

The purpose of this report is to describe our experience using cardiopulmonary bypass with selective cerebral perfusion in 10 patients whose aneurysms required cross-clamping the aorta and brachiocephalic vessels. Cerebral perfusion was carried out with individual roller pumps. Flow rate was 11.2 +/- 4.8 ml per kilogram of body weight per minute to the right axillary artery, 8.5 +/- 1.0 to the right common carotid artery, 7.0 +/- 2.0 to the left common carotid artery, and 3.9 to the left subclavian artery. All the patients came off bypass smoothly, and only 3 required small amounts of inotropic agents postoperatively. One patient with mycotic aneurysm died in the fourth postoperative week of massive bleeding due to disruption of the suture line. No cerebral complications were experienced. The operative results of this series suggest the usefulness of cardiopulmonary bypass with selective cerebral perfusion, and reasonably favorable outlook for patients with aneurysm involving the aortic arch and the ascending aorta.

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.

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.

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.

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.

[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.

[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.

[Extra-anatomic bypass grafting for vascular occlusive disease in the upper and lower extremities].

Twenty-four patients with poor risk factors underwent an extra-anatomic bypass operation for aortoiliac occlusive disease and subclavian steal syndrome. A femoro-femoral bypass was performed on 5 patients, an axillo-femoral bypass on 15, a subclavian-subclavian bypass on 2 and an ascending aorta-femoral bypass on 2. There was only one operative death and there were 2 late deaths (8.3%). The patients were 20 males and 4 females with a mean age of 69.3 years. Among risk factors, high age (70 year old) was present in half of the patients, ischemic heart disease in 9, and cerebral vascular disease in 8. Seventy-five percent of the patients were suffering from two or more dysfunctions. During the limited follow-up period from 8 to 94 months (mean 46.1 months) there was a 96% patency rate. We had good results using externally supported ring graft and by the administration of prostaglandin E1 and ticlopidine during the pre and postoperative period.

[Hyperthermia in cancer therapy].

Hyperthermia is being re-evaluated and currently used in the treatment of malignant tumor. There have been numerous in vitro and in vivo experimental data presented which confirm the selective heat damage on malignant cells. This review will attempt to summarize the information on experimental and clinical reports concerning hyperthermia. The results of extracorporeally induced hyperthermia of our series are also mentioned.

[Effects of coenzyme Q10 on ischemic myocardium during coronary artery occlusion--evaluation of the time needed to change irreversible myocardium].

We studied the irreversible change of myocardium on coronary artery occlusion using mongrel dogs. These dogs were divided into 2 groups. One group was administered CoQ10 before and after coronary artery occlusion and the other received placebo. Results are summarized as follows. 1) In both groups the hemodynamic change showed no significant change. 2) In the biochemical studies there was no significant difference between both groups, but in the infarction group, serum GPT and pyruvic acid in a sampling of blood taken from the coronary sinus were significantly higher than in the non-infarction group (P less than 0.05, 0.025). 3) By the triphenyl tetrazolium chloride (TTC) technique for the myocardial infarction, infarction did not appear in the CoQ10 group until 90 minutes after coronary occlusion but in the placebo group infarction appeared as early as 60 minutes. 4) In the ultrastructural studies of myocardium the electron microscopy detected irreversible change of mitochondrias when the TTC technique identified infarction. In conclusion, the administration of CoQ10 has a protective effect for the irreversible change of ischemic myocardium.

[Clinical study of cefminox in respiratory tract infections].

A new cephem cefminox (CMNX, MT-141) was used in the treatment of 22 cases of respiratory tract infections without taking into account background factors of patients. The dosage was 2 to 4 g/day in 2 divided doses and the treatment was continued for a period 2 to 17 days. The breakdown of the diseases treated was; pneumonia in 7 cases, secondary lung abscess (rS3)+middle lobe syndrome in 1 case, chronic bronchitis in 3 cases, bronchiectasis in 10 cases and intrapulmonary lymphangitis carcinomatosa (suspected) in 1 case. The clinical results were rated as excellent in 7 cases, good in 11 cases, fair in 1 case and unknown in 3 cases, with an excellent rate of 36.8% and excellent+good rate of 94.7%. The causative organisms were identified in 10 cases and included H. influenzae for 8 cases, Klebsiella sp. for 1 case and S. aureus for 1 case. The analysis of bacteriological study revealed disappearance of all of these organisms. However, in 3 out of 8 cases where H. influenzae was isolated and in 1 case where Klebsiella sp. was isolated the changes of organisms to P. aeruginosa were observed. As the adverse reactions, rashes developed in 1 case and moreover laboratory test results revealed elevation in transaminase in 3 cases. All of these symptoms were mild in nature and none of our cases experienced serious adverse reactions attributable to CMNX. From these results, we believe that CMNX is one of the useful drugs for the treatment of respiratory tract infections.

[Clinical study of S 6472 granule preparation (sustained-release cefaclor) in chronic respiratory airway infections].

S 6472 granule preparation, a sustained-release preparation of cefaclor, was administered to 21 patients with chronic respiratory airway infections for its clinical study; a daily dosage between 750 and 1,500 mg was orally given in 2 divided doses after breakfast and dinner for a duration of 3 to 14 days. Clinical effects were good in 15 cases, fair in 1 case, poor in 4 cases and unknown in 1 case. No side effects were observed except for a case of impaired appetite. There appeared to be no abnormal laboratory test valued due to the drug.

[An evaluation study on arbekacin for MRSA-infectious diseases including pneumonia, septicemia and others].

Availability of arbekacin (ABK) was analyzed in the chemotherapy of 24 MRSA-infected patients with symptoms of pneumonia (12), sepsis (6) and others (6). Most patients had background diseases such as malignant tumors or cerebrovascular disorders. 47% (7/15) of them were immunologically abnormal. 17 of them had been previously treated with cephems, imipenem, minocycline or fosfomycin. The ABK therapy was performed with doses ranging 50-400 mg a day, divided into 1-3 times (mostly 100 mg x 2), and for 5-24 days. (18 patients were treated between 5 and 14 days). 14 patients (58%) received combined therapy with other antibiotics (mostly with beta-lactams, 12). The clinical efficacy rate of the ABK therapy was 62% (good, 13; fair, 4; ineffective, 4; unknown, 3). The bacteriological efficacies were: eradicated, 7 (44%); decreased, 4; no change, 5; unknown, 8. Side effects were found in 3 patients (oliguria, 2; eruption due to drug, 1) and one case resulted in serious renal disorder. Abnormal laboratory data were found in 7 cases. Above results have indicated that ABK is a useful antibiotic in chemotherapy of MRSA-infections.

[Clinical studies of cefpodoxime proxetil in respiratory tract infections].

Twelve patients with respiratory tract infections were treated with cefpodoxime proxetil (CS-807, CPDX-PR), a new cephem antibiotic. It was given orally at a dose of 200 mg 2 times a day for 4 approximately 15 days. Its clinical effects were evaluated as excellent in 1 case, good in 9 cases and poor in 2 cases. The efficacy rate was 83.3%. Its bacteriological effects were evaluated as eradication in 5 strains and decrement in 1 strain. The eradication rate was 83.3%. No adverse reactions and disorder of laboratory findings due to CPDX-PR were observed.