International project--MGTX study]

MGTX Study is a multi-center, international, single-blinded, randomized trial to determine whether extended transsternal thymectomy (ETTX) for patients with myasthenia gravis receiving the prednisone protocol confers added benefits to the prednisone protocol alone. The aims of the study are answering following three questions. 1) Does ETTX combined with prednisone result in a greater improvement in myasthenic weakness, compared to prednisone alone? 2) Does ETTX combined with prednisone result in a lower total dose of prednisone, thus decreasing the likelihood of concurrent and long-term toxic effects, compared to prednisone alone? 3) Does ETTX combined with prednisone enhance quality of life by reducing adverse events and symptoms associated with the therapies, compared to prednisone alone? Primary outcome measure is consists with 1) Comparison of the prednisone protocol alone to prednisone protocol plus ETTX, based on the clinical response to therapy measured over the 3 year trial period by the Area Under the Quantitative Myasthenia Gravis (QMG) Weakness Score (AUQMG), and 2) Testing the difference in the total prednisone used over the 3 year trial period measured by pill count from blister packs (Area Under the Prednisone Dose Time Curve, AUDTC), conditional on the results of comparing AUQMG.     

Clinical study of recombinant hepatitis B vaccine

The efficacy and safety of a recombinant yeast-derived hepatitis B vaccine were evaluated in 209 subjects after three administrations at 0, 4 and 20 weeks. Subjects were divided into four groups given 5 micrograms vaccine subcutaneously, 10 micrograms subcutaneously, 10 micrograms intramuscularly and 20 micrograms subcutaneously to define the effective dose and to compare the effect of administration. Seroconversion of the antibody to hepatitis B surface antigen after the third vaccination reached 96.6% in the group given 5 micrograms vaccine subcutaneously and 100% in the other groups. The final geometric mean antibody titres were 700 IU/l in subjects given 5 micrograms subcutaneously, 2004 IU/l in those given 10 micrograms subcutaneously, 4674 IU/l in those given 10 micrograms intramuscularly and 3342 IU/l in those given 20 micrograms subcutaneously. In the groups given 10 micrograms, the early seroconversion rate of the antibody to hepatitis B surface antigen and the geometric mean antibody titres after the third vaccination were significantly higher in subjects administered intramuscularly than subcutaneously (P less than 0.05). No major adverse effects were observed and minor reactions were the same as, or less than, those reported for the plasma-derived vaccine. Before and after administration, no significant fluctuation in the yeast antibody titre was observed. These results demonstrate the efficacy and safety of the yeast-derived vaccine, and show that 10 micrograms was the effective dose.     

A study on the development of a filing system for funduscopic images with a personal computer for Twin AMHTS

A filing system for ocular fundscopic image data was developed by using a personal computer for the Twin AMHTS. The development of the system was tried as one of the data transfer system including image data between two similar AMHTSs named the Twin AMHTS through the information network system. The filing system is capable of storing 26782 data of ophthalmoscopic pictures with a data compression mode by using a magneto-optical disk (MOD) whose storage capacity of both sides is 616 MB. It takes no long time for retrieval and display of the image data in the filing system. Good quality of compression and decompression obtained and reproducibility of the ocular fundus picture is favorable regardless of normal or abnormal cases. As a result, it is suggested that the developed system has practical utility although it requires more improvement.     

Effect of natural panting frequency and cheek support on the plethysmographic determination of thoracic gas volume in patients with chronic obstructive pulmonary disease]

The authors studied the effects of natural panting frequency (NF) and the cheek support on the plethysmographic measurement of thoracic gas volume (TGV) in 8 normal subjects (non-smokers) and 46 patients with chronic obstructive pulmonary disease (COPD). The patients were divided into 2 groups according to the degree of airway obstruction (group I; specific airway conductance (SGaw) greater than 0.1 (n = 18), group II; SGaw less than 0.1 (n = 28)). TGV was measured with a pressure-type body plethysmograph (BP). NF was 2.00 +/- 0.43 Hz (mean +/- SD) in control subjects, 1.92 +/- 0.78 Hz in group I, and 1.39 +/- 0.59 Hz in group II, respectively, indicating lower NF in the patients with severe airway obstruction. In control subjects and group I, the differences between TGV at NF and at 0.5-1.0 Hz (TGVNF-TGV1.0) were -0.01 +/- 0.07L, and -0.06 +/- 0.16L, respectively, and cheek support did not alter the difference. On the other hand, in group II, the difference was slightly larger than other groups in spite of the lower NF, and this overestimation was abolished by cheek support (0.13 +/- 0.25L-----0.06 +/- 0.27L, p less than 0.05). These results suggest that, in patients with severe airway obstruction, TGVNF may be overestimated even if NF is relatively low. This overestimation may be mainly due to the extrathoracic airway compliance including the cheek.     

Early gastric cancer manifested as brain metastasis: Report of a case

A case of early gastric cancer, limited to submucosal layer, which was manifested as cerebral metastasis is presented herein. A 47-year-old man was admitted to Nagaoka Chuo General Hospital with convulsions and a disturbance in consciousness, where a computed tomography (CT) scan revealed a cerebral tumor in the left temporal lobe. The resected tumor was identified as a metastatic adenocarcinoma. Further investigation revealed gastric cancer involving the posterior wall of the cardia. At laparotomy, multiple and small metastases of the liver and a jejunal metastasis were found, and a palliative total gastrectomy was performed. The surgical specimen revealed a protruding, poorly differentiated medullary adenocarcinoma, with invasion of the submucosal layer. The patient died 4 months after undergoing the laparotomy. This case report is presented to make clinicians aware of the possibility that early gastric cancers may present as brain metastasis.     

Brain MR imaging in patients with hepatic cirrhosis: relationship between high intensity signal in basal ganglia on T1-weighted images and elemental concentrations in brain

In patients with hepatic cirrhosis, the globus pallidus and putamen show high intensity on T1-weighted MRI. While the causes of this high signal have been thought to include paramagnetic substances, especially manganese, no evidence for this has been presented. Autopsy in four cases of hepatic cirrhosis permitted measurement of metal concentrations in brain and histopathological examination. In three cases the globus pallidus showed high intensity on T1-weighted images. Mean manganese concentrations in globus pallidus, putamen and frontal white matter were 3.03 ± 0.38, 2.12 ± 0.37, and 1.38 ± 0.24 (μg/g wet weight), respectively, being approximately four- to almost ten-fold the normal values. Copper concentrations in globus pallidus and putamen were also high, 50 % more than normal. Calcium, iron, zinc and magnesium concentrations were all normal. The fourth case showed no abnormal intensity in the basal ganglia and brain metal concentrations were all normal. Histopathologically, cases with showing high signal remarkable atrophy, necrosis, and deciduation of nerve cells and proliferation of glial cells and microglia in globus pallidus. These findings were similar to those in chronic manganese poisoning. On T1-weighted images, copper deposition shows no abnormal intensity. It is therefore inferred that deposition of highly concentrations of manganese may caused high signal on T1-weighted images and nerve cell death in the globus pallidus. Received: 12 August 1996 Accepted: 17 December 1996     

Are cytokines possible mediators of cancer cachexia?

The possible role of cytokines in the development of cancer cachexia was reviewed from the literature. Tumor necrosis factor (TNF)-alpha, interleukin (IL)-1, IL-6, interferon (IFN)-gamma and leukemia inhibitory factor (LIF) can elicit many but not all host changes seen in cancer cachexia, including loss of appetite, loss of body weight, and the induction of acute-phase protein synthesis. However, these cytokines are not always demonstrated in the circulation of the cancer patients. The inability to detect circulating cytokines may be due to their low rate of production, their short half-life and rapid clearance from plasma, or their mode of action (autocrine or paracrine). Different cytokines are induced to stimulate the same response. This is very different from hormonal regulation, where a hormone acts on a cell directly through a specific receptor without depending on other mediators. Specific antibodies including anti-IFN-gamma, anti-TNF and anti-IL-6 antibodies, as well as the cyclooxygenase inhibitor indomethacin, have been used to reverse cancer cachexia. Overlapping physiologic activities make it unlikely that a single substance is the sole cause of cancer cachexia. It is hoped that further investigation on other cytokines and their possible relationships with hormones will help to clarify the mechanisms of cancer cachexia in the near future.This work was supported by a grant from the Japan-Sweden Foundation in 1991.     

Overexpression of p53, c-erbB-2 and epidermal growth factor receptor in human breast carcinomas

Overexpression of p53 protein, epidermal growth factor receptor (EGF-R), and c-erbB-2 protein was assessed by immunohistochemical staining of formalin-fixed, paraffin-embedded tissue from 64 invasive breast tumors. The correlation between abnormal expression of each protein and various disease parameters, including lymph node metastasis and histopathologic type and grade was analyzed. Despite the previous proposal, no significant correlation was found between lymph node metastases and overexpression of each gene in the primary tumors. In addition, some metastatic lesions did not always exhibit overexpression, even if it was evident in the primary tumors. Overexpression of c-erbB-2 protein correlated well with Bloom's histological grading. p53 expression was detected most often in tumors with hyperchromatism and more frequent mitosis. Overexpression of c-erbB-2 protein occurred more frequently in p53-positive tumors. The results indicate that abnormal expression of p53 protein causes genetic instability in the early stage of tumor development, resulting in subsequent overexpression of other oncogenes.