Nonsteroidal antiinflammatory drugs (NSAIDs) have been shown to cause mucosal injury in the gastrointestinal tract as a side effect, occasionally turning out to be severe complications such as bleeding and perforation. So far NSAIDs-caused mucosal injury was attributed to their inhibitory effects on the activity of cyclooxygenase-1 (COX-1) which is expressed and shown to play a crucial role for the mucosal protectoin via producing prostaglandin E2 in the stomach. However, a recent progress of the understaining about COX physiology has revealed that NSAIDs cause gastric mucosal injury by inhibiting not only COX-1 but also COX-2 in the stomach. COX-1 inhibition alone has been demonstrated not to cause gasric mucosal injury. In addition, a selective COX-2 inhibitor which is demonstrated to have much less harmful effect in the stomach is now widely used as a safer NSAID in USA. Moreover, a selective COX-2 inhibitor is recently considered to have an inhibitory effect on growth of a certain type of cancers, thereby being in the spotlight as a chemopreventive agent.

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Purpose: To search for methods of improving the excretion of injected gadolinium contrast medium (GdCM) in hemodialysis (HD) patients, we investigated the effect of the surface potential of HD membranes and the electrical charge of GdCM on the dialyzability of GdCM.Materials and Methods: Ionic (Gd-DTPA) or non-ionic (Gd-DO3A) GdCM solutions were dialyzed using a clinical HD unit. Two types of HD membranes, AN69 with a surface potential and PMMA without, were used. GdCM clearance was then calculated.Results: Gd-DTPA clearance was significantly higher for PMMA membranes than for AN69 membranes. Gd-DO3A clearance was slightly higher for AN69 membranes than for PMMA membranes. The difference in Gd-DTPA and Gd-DO3A clearance values was not significant when PMMA membranes were used.Conclusion: These data indicate that non-ionic GdCM is preferable to ionic GdCM in patients receiving dialysis through an electrically positive membrane. Either ionic or non-ionic GdCM can be used when a normal dialysis membrane is being used.

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Proinflammatory cytokines have been implicated in mediating respiratory failure associated with major surgery. We investigated the effect of giving glucocorticoids preoperatively for the prophylaxis of surgical stress and the association of cytokine levels, such as interleukin-6 (IL-6) and interleukin-8 (IL-8), with oxygenation after esophagectomy. We studied 17 patients who underwent subtotal esophagectomy. Seven patients (steroid group) were chosen at random to be given methylprednisolone (10 mg/kg) and 10 patients (control group) to be given saline intravenously before operation. Plasma and bronchoalveolar lavage fluid (BALF) IL-8 levels in the control group were significantly higher than those in the steroid group. In both groups, plasma IL-6 levels were significantly higher than those in BALF, but in contrast, BALF IL-8 levels were significantly higher than plasma levels of IL-8 postoperatively. The PaO₂/FiO₂ ratio was significantly reduced in the control group. The PaO₂/FiO₂ ratio of the control group had significantly lower values than that of the steroid group. There was significant correlation between BALF IL-8 levels and the PaO₂/FiO₂ ratio postoperatively. We conclude that preoperative administration of methylprednisolone may attenuate postoperative reduction of arterial oxygen saturation by suppressing the release of cytokines.

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Cardiac ruptures after myocardial infarction are classified as ventricular free wall ruptures (FWR), ventricular septal ruptures (VSR), and papillary muscle ruptures (PMR). A combination of any two types of rupture is called "ventricular double rupture;" (VDR) and shows a specific clinical course.3,284 patients with acute myocardial infarction (AMI) were admitted to the CCU of our hospital between April, 1973 and December, 2001, and 10 patients (8 males and 2 female, aged 54∼82 years) with VDR were clinicopathologically evaluated. All were diagnosed as VDR consisting of FWR and VSR. VDR was observed in 0.30% of all patients with AMI, in 3.0% of those with FWR, and in 16.1% of those with VSR. The infarct site was anteroseptal in 3 patients, anterolateral in 3, inferior in 3, and posterolateral in 1. Two patients with inferior infarction complicated RV infarction and a patient with posterolateral infarction had healed inferior infarction.The risk factors related to VDR were age, a history of hypertension, increased sympathetic tone to improve hemodynamic aggravation after perforation, cardiotonic agents, thrombolytic agents, delayed reperfusion, right ventricular volume overload by shunt and re-infarction. However, these factors might have played only a subsidiary role. The most important factor in VDR was the pathological findings. The site of septal perforation was the apex close to the septum-free wall junction in 9 patients and the site of rupture was also apical in 8 patients.Four patients already had VSR on admission to our CCU. FWR developed soon after VSR was demonstrated in 4 patients. FWR and VSR occurred simultaneously in one patient. These results suggest that VSR in the apical region is a precursor of VDR and requires the earliest surgical treatment.Surgical treatment was carried out in the operating room in 5 patients and 3 (60.0%) of them survived for 4 months or more. Two patients with rupture incidentally detected during operation for VSR were discharged and are still alive, though another one with free wall blow out rupture died 129 days after operation. Bedside thracotomy was performed in 3 patients and all of them died.

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Pulmonary adenocarcinoma composed of pure or predominant solid components is reported to be a highly malignant tumor. However, the existence of solid components and its connection with biological behavior have not been well documented. To answer this question, we histologically subclassified poorly differentiated adenocarcinoma (P/D Ad Ca) into solid type and non-solid type, and compared the biological behavioral characteristics.Material and Methods: All histological specimens of surgically resected primary lung carcinoma diagnosed as P/D Ca or large cell carcinoma in Nippon Medical School Hospital were re-evaluated according to the 1999 WHO manual. The cases re-evaluated as P/D Ad Ca were further divided into solid type and non-solid type according to our original definition: the solid type contains solid components where a glandular structure is not recognized in more than one high-power field, while in the non-solid type, a small glandular structure is observed in every high-power field. The differences in the occurrence of lymph node metastasis were assessed by Fisher's exact test.Results: Among 109 cases satisfying both histological and clinical investigation, 45 cases were re-evaluated as P/D Ad Ca; solid type (n=22), and non-solid type (n=23). Lymph node metastases occurred at a higher rate in the solid type than in the non-solid type (p<0.01).Conclusion: Patients with solid type Ad Ca have reached a more advanced stage than patients having non-solid type due to high metastatic rate to lymph nodes. These results suggest that we should not overlook solid components even if the solid components are the focal lesion. This sub-typing alerts clinicians to survey metastases, and may contribute to therapeutic strategies in the future.

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Hashimoto's thyroiditis (HT) is usually considered to be manageable by levothyroxine (L-T4) administration, which can reduce the thyroid volume and supplement the lack of hormone. However, we sometimes encounter a huge goiter that has not shrunk in response to L-T4therapy. These goiters continue to produce symptoms of compression and an unsightly appearance. Here we discuss the surgical indication and procedure for HT.Thirteen patients with clinically diagnosed Hashimoto's thyroiditis involving a huge diffuse goiter that produced pressure symptoms or nodular lesions were treated with surgery. The gender, age distribution, total dose and period of L-T4 administration prior to the operation, and clinical symptoms caused by the large goiter were evaluated in each case.The titer of antibodies was extremely elevated in 8 HT patients with a diffusely enlarged goiter. The total period of L-T4 medication ranged from 6 to 25 years. A subtotal thyroidectomy in which a small amount of thyroid was left in the posterior area of the bilateral lobes was performed in the 8 cases of diffusely enlarged goiter. Pressure symptoms and the unsightly appearance caused by the goiter were relieved by the surgery in all cases. No surgical complications developed.In conclusion, the surgery is an effective therapy for HT patients who have persistent compression symptoms and/or an unsightly neck appearance due to a large goiter despite long-term L-T4 treatment.

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Understanding of the relationship between tumor infiltrating cytotoxic T lymphocytes (CD 8⁺TILs) and tumor cells as well as tumor-associated antigens is important and may reflect the extent of immune response of the patient to the tumor, thus providing a useful clue relevant to the prognosis. The purpose of this study was to determine the relationship between the expression of HLA-DR and CA-125 antigens and the presence of CD 8⁺TILs with regard to the established clinicopathological factors of ovarian carcinomas using immunohistochemical methods. Thirty-one ovarian carcinomas consisting of 20 serous, 7 mucinous, and 4 clear cell types were examined. Of these, 18 (58%) and 22 (71%) were positive for HLA-DR and CA-125 antigens respectively, and the overall mean number of the CD 8⁺TILs was 7.2±2.9. A significant association was observed between the mean number of CD8⁺TILs and tumor grade (P=0.01), disease stage (P=0.003), and patient outcome (P=0.01). The mean number of CD 8⁺TILs in HLA-DR positive (8.6±2.2) or CA-125 positive (8.4±2.1) tumors was significantly higher than that in HLA-DR negative (5.2±2.5; P=0.0003) or CA-125 negative (4.2±2.2; P=0.00002) tumors. These signifcant levels were further enhanced by one order of magnitude when the mean number of CD 8⁺TILs in tumors postive for both HLA-DR and CA-125 antigens (9.1±1.7) was compared to that in HLA-DR negative or CA-125 negative tumors. The frequency of cancer-related deaths in HLA-DR and CA-125 positive tumors was significantly lower than in the negative tumors (P=0.01). These data suggest that concurrent expression of HLA-DR and CA-125 antigens may augment the immune response of the patient to the tumor, thus providing a potential clue relevant to the prognosis.

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We report a floppy infant with Werdnig-Hoffmann disease (spinal muscular atrophy: SMA type 1) and Klinefelter syndrome. After genetic counseling with parents, a genetic diagnosis using DNA from the infant's peripheral blood mononuclear cells was performed. The parents' deletion of exons 7 and 8 of the survival motor neuron (smn) gene and exons 4 and 5 of the neuronal apoptosis inhibitory protein (naip) gene were noted in the infant, so he was confirmed to have SMA type 1. The parents wanted to receive a prenatal diagnosis on the next pregnancy. However this genetic test is achieved by confirming that a specific band can not be detected by PCR. Therefore, this method should be applied with great care to prenatal diagnosis using chorionic villi, which may be contaminated with maternal tissue.

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We report here a case of Behçet's syndrome. The patient was suddenly affected by chest pain during the clinical course of the disease and developed abdominal pain and melena after 5 weeks. The diagnosis of acute anteroseptal myocardial infarction was made on the basis of the electrocardiography findings, and many perforated ulcers were confirmed in specimens of the resected colon. Coronary angiography showed constriction by 50% of the left anterior descending artery. There were no atherosclerotic changes. Pulse therapy was performed using sodium methylprednisolone succinate at a dose of 1,000 mg for 3 days, followed by oral administration of prednisolone at a dose of 60 mg/day, leading to improvement of all the symptoms after 3 weeks. The electrocardiogram findings at that time were normal. Prompt resolution of the symptoms provided by corticosteroid therapy supports the conclusion of previous studies that myocardial infarction in Behçet's syndrome may possibly be due to vasculitis of the coronary arteries.In Behçet's syndrome, myocardial infarction is rare but should be considered as one of the most important lesions that determine the prognosis.

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The aim of the present study was to ascertain the pharmacoeconomical efficacy of a clinical pathway (CP) employing medication management and instruction tasks (i. e. pharmaceutical care and counseling for inpatients) in gastrectomy patients. Pharmaceutical services of a uniform quality were provided. These included a CP check sheet, medication management, and a history of the drugs chiebly prescribed by pharmacists. As a result, the average number of hospitalized days among the patients who were offered pharmaceutical care compared with those who were not was significantly shortened from 35.4 days to 26.1 days (P<0.001). Moreover, the average cost of medication was also significantly reduced from 270,631 yen to 190,331 yen (P<0.05). These data provide the first evidence that a CP employing medication management and instruction tasks for gastrectomy patients may play a substantial role in saving on medical costs.

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Thyroid disease is comparatively prevalent, and it is important to perform careful palpation of the anterior neck when patients are first examined. In this paper, the latest data on and clinical characteristics of the epidemiology of thyroid carcinoma are described.According to Japanese cancer statistics, in 1996, the number of cases of thyroid carcinoma was 1,390 men and 5,437 women. The female to male ratio was 3.91: 1. The crude rate of thyroid carcinoma per 100,000 population was 2.3 men and 8.5 women. The age-adjusted incidence rate showed a gradual increase with age, and the peak of the age-adjusted incidence rate was over 80 years old among men, and from 70 to 80 years old among women.According to the Japanese Thyroid Cancer Registration Committee, from 1977 to 1999, papillary thyroid carcinoma accounted for more than 85% (30,256) of thyroid carcinomas among 35,312 patients. Medullary thyroid carcinoma (1.4%) and anaplastic thyroid carcinoma (1.6%) were rare. The female to male ratio of thyroid carcinoma was 6.1: 1. Registration was made in accordance with the general rules issued by the Japanese Society of Thyroid Surgery. According to the vital statistics, mortality related to thyroid carcinoma among all cancer-related deaths was 0.23% among men (411) and 0.76% among women (887) in 2000. The female to male ratio of mortality was 2.16: 1. The peak of mortality was from 70 to 80 years old among men, and from 80 to 90 years old among women.Most patients with differentiated thyroid carcinoma had a low mortality rate, but anaplastic carcinoma had a poor prognosis. Lung and bone were the main distant metastatic sites, and respiratory insufficiency was the most common specific fatal condition.

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Erythromelalgia is a rare condition that is characterized by the triad of redness, increased temperature, and intense pain of feet or hands. This syndrome was first described in 1878, however, universal classification, precise mechanism and successful medical treatment of erythoromelalgia have not been described. We experienced 3 cases of erythomelalgia in our outpatient pain clinic that showed the different progress. One patient experienced the long-term pain complicated with neuropathic pain. The pain of other two patients was eliminated early by nerve block treatments, and they did not showed chronic pain. From the prophylactic viewpoint of chronic pain, the most considerable matter is early and certain elimination of severe pain under certain diagnosis. In this article, the mechanisms of passing into the chronic pain state as well as the efficacy of neural blockade for intractable pain such as erythromelalgia are discussed.

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