Mortality of rheumatoid arthritis in Japan: a longitudinal cohort study.

OBJECTIVE: To determine the mortality risk of Japanese patients with rheumatoid arthritis, taking into account lifestyle and physical factors, including comorbidity. METHODS: 91 individuals with rheumatoid arthritis were identified during screening a cohort of 16 119 Japanese atomic bomb survivors in the period 1958 to 1966. These individuals and the remainder of the cohort were followed for mortality until 1999. Mortality risk of the rheumatoid patients was estimated by the Cox proportional hazards model. In addition to age and sex, lifestyle and physical factors such as smoking status, alcohol consumption, blood pressure, and comorbidity were included as adjustment factors for the analysis of total mortality and for analysis of mortality from each cause of death. RESULTS: 83 of the rheumatoid patients (91.2%) and 8527 of the non-rheumatoid controls (52.9%) died during mean follow up periods of 17.8 and 28.0 years, respectively. The age and sex adjusted hazard ratio for mortality in the rheumatoid patients was 1.60 (95% confidence interval, 1.29 to 1.99), p < 0.001. Multiple adjustments, including for lifestyle and physical factors, resulted in a similar mortality hazard ratio of 1.57 (1.25 to 1.94), p < 0.001. Although mortality risk tended to be higher in male than in female rheumatoid patients, the difference was not significant. Pneumonia, tuberculosis, and liver disease were significantly increased as causes of death in rheumatoid patients. CONCLUSIONS: Rheumatoid arthritis is an independent risk factor for mortality. Infectious events are associated with increased mortality in rheumatoid arthritis.

[Evaluation of sternal deformity after pediatric minimally invasive cardiac surgery].

Sternal shape is one of the most important esthetic factors of the chest appearance after pediatric minimally invasive cardiac surgery (pMICS) as well as length of skin wound. We evaluated the grade of postoperative sternal deformity in 20 patients who underwent total repair of pediatric congenital heart disease [atrial septal defect (ASD): 17, ventricular septal defect (VSD): 2, partial anomalous pulmonary venous connection (PAPVC): 1] with minimal skin incision and lower partial median sternotomy. The sternum was closed with stainless wire in 3 patients, with absorbable polydioxanone (PDS) cord in 5 patients, with combined use of reabsorbable radiolucent poly (L-lactate) acid sternal pin and absorbable PDS cord in 12 patients. The evaluation of postoperative sternal deformity was made according to the vertebral index (VI) and frontosagittal index (FSI) in 3 groups with each sternal closure method. VI and FSI of the 3 groups showed no significant difference. Sternal deformity in the group with sternal closure with PDS cord group was more severe than that in other 2 groups. The combined use of sternal pin with PDS cord offered the most sufficient fixative strength for sternal closure.

Experimental study of small arterial anastomosis with gelatin-resorcin-formaldehyde glue and collagen sheet.

In cardiovascular surgery, the manual continuous suture has often been used for microvascular anastomosis, but the luminal irregularity often causes thrombotic stenosis in the anastomosis sites. The purpose of this study was to examine the feasibility of the combined use of gelatin-resorcin-formaldehyde (GRF) glue and a collagen sheet for the anastomosis of small arteries 3 to 4 mm in diameter in experimental animals. End-to-end anastomoses of the carotid and femoral arteries of mongrel dogs were carried out with the combined use of GRF glue and collagen sheet. The physical strength of the anastomosis, the histopathologic condition of the vassels, and the absorptivity and the inflammatory response of the glue were evaluated. The physical strength of the anastomosis sites was good and their flexibility optimal, the smooth luminal surface appeared excellent for preventing thrombotic stenosis in all follow-up periods, and the glue was absorbed almost completely within 12 weeks postoperatively. The combined use of GRF glue and collagen sheet would be feasible for the anastomosis of small arteries 3 to 4 mm in diameter and could substitute for the conventional suture method.

Monoclonal antibodies generated against an affinity-labeled immune complex of an anti-bile acid metabolite antibody: an approach to noncompetitive hapten immunoassays based on anti-idiotype or anti-metatype antibodies.

Conventional immunoassays for haptens such as steroids and synthetic drugs are dependent on the competitive reaction between an unlabeled antigen (analyte) and a labeled antigen against a limited amount of anti-hapten antibody. Although noncompetitive immunoassay procedures such as two-site immunometric assays offer a much higher sensitivity, direct application of this principle to haptens has been difficult due to their small molecular mass precluding simultaneous binding by two antibody molecules. Here, we have attempted to develop a noncompetitive immunoassay system based on anti-idiotype or anti-metatype antibodies. Ursodeoxycholic acid 7-N-acetylglucosaminide (UDCA 7-NAG), which is a bile acid metabolite (molecular weight, 595.8), was selected as the model hapten. A/J mice were immunized with a monoclonal antibody against UDCA 7-NAG, which had been affinity-labeled with a relevant hapten derivative. The fusion between the immune spleen cells and P3/NS1/1-Ag4-1 myeloma cells yielded four kinds of alpha-type and two kinds of beta-type monoclonal anti-idiotype antibodies, each recognizing the framework region and paratope of the anti-hapten antibody. The use of a selected combination between alpha-type and beta-type antibodies together with the anti-hapten antibody provided a noncompetitive assay system with a subfemtomole order sensitivity (detection limit, 118 amol) and a practical specificity.

Prognosis and surgical treatment of gastric cancer invading the pancreas.

The clinicopathologic characteristics of gastric cancer invading the pancreas have not been determined. Gastrectomy was performed in 282 patients with gastric cancer invading adjacent organs at the Department of Surgery II, Kyushu University Hospital, between 1970 and 1987, and patient data were retrospectively analyzed using univariate and multivariate analyses. Of these patients, 150 (53.2%) had tumors invading the pancreas and 132 had tumors invading adjacent organs other than the pancreas. In both groups, the undifferentiated tissue type with infiltrative growth, lymphatic involvement and lymph node metastasis was common. In cases of pancreas invasion, the extent of lymph node metastasis was more severe, vascular involvement was more frequent and the rate of concomitant liver metastasis was higher. The survival time of the patients with pancreas invasion was shorter compared to patients with cancer invading other organs, and pancreas involvement was one of the independent factors predicting a poor prognosis. With respect to surgical treatment of gastric cancer invading the pancreas, the prognosis was better for cases treated with curative surgery and pancreas resection. Of 39 patients treated with partial resection of the pancreas, the tumor had invaded only the capsule of the pancreas in 18 and the pancreas in the other 21. Pancreas-invasive gastric cancer cells are likely to advance via lymphatic and vascular routes and survival time is shorter, but curative resection can improve the survival rate, and perioperative treatment should be appropriately designed.

A monoclonal antibody-based enzyme-linked immunosorbent assay of ursodeoxycholic acid 3-sulfates in human urine.

Sulfation of the 3-hydroxy group is assumed to be a major metabolic route of ursodeoxycholic acid (UDCA) which is used for treating various hepatobiliary diseases. We have developed a sensitive enzyme-linked immunosorbent assay (ELISA) for determining the total amount of nonamidated, glycine- and taurine-amidated ursodeoxycholic acid 3-sulfates (UDCA 3-Suls) using a newly established monoclonal antibody. In this study, 12 kinds of antibody-secreting hybridoma clones were generated by a fusion experiment between P3/NS1/1-Ag4-1 myeloma cells and the spleen cells from a BALB/c or an A/J mouse which had been immunized with a conjugate of nonamidated UDCA 3-Sul and bovine serum albumin. One of the monoclonal antibodies, Ba-10 (gamma2a, kappa), had suitable binding properties for clinical application, which was group-specific to the UDCA 3-Suls, and showed negligible cross-reactivities with various related bile acids including potentially interfering compounds, namely, the unconjugated UDCA, UDCA 7-N-acetylglucosaminide, the 3-sulfates of cholic acid, chenodeoxycholic acid and deoxycholic acid. The antibody Ba-10 allowed us to develop a sensitive competitive ELISA system whose measurable range was approximately 2-200 pg per assay. A serial dilution study indicated that the ELISA enables the direct measurement of the UDCA 3-Suls in human urine before and after the administration of exogenous UDCA. The daily urinary excretion rate of UDCA 3-Suls from healthy male volunteers (n = 5) was determined to be a mean of 131 +/- 61.2 (SD) microgram as the nonamidated UDCA 3-Sul equivalent.

[A case of Churg-Strauss syndrome presented as right thalamic hemorrhage].

Intracerebral hemorrhage is an uncommon sequel of Churg-Strauss syndrome (CSS). We report the first case of CSS accompanied by right thalamic hemorrhage. The patient was 59-year-old male who experienced a sudden onset of left hemiplegia. Magnetic resonance imaging of the brain revealed right thalamic hemorrhage. Although several reports had pointed out a close relationship between hypertension and cerebral hemorrhage in patients with CSS, this patient had no apparent prior history of hypertension. The cause of thalamic hemorrhage in this patient might be probably due to cerebral vasculitis and an effect of abnormal coagulation and fibrinolytic agents.

Characterization of cholyl-adenylate in rat liver microsomes by liquid chromatography/electrospray ionization-mass spectrometry.

The cholyl-adenylate, covalently bound 3alpha, 7alpha, 12alpha-trihydroxy-5beta-cholanoic acid (cholic acid) with adenosine 5'-monophosphate having an acid anhydride linkage, has been characterized by means of liquid chromatography/mass spectrometry in an incubation mixture with a rat liver microsomal fraction. The authentic specimen of cholyl-adenylate was synthesized using the carbodiimide method and the structure was confirmed by MS and nuclear magnetic resonance spectroscopy. After incubation of cholic acid with a hepatic microsomal fraction in the presence of adenosine 5'-triphosphate, bile acids were extracted and purified by solid-phase extraction on a Sep-Pak C18 cartridge and then subjected to a LC/MS analysis, where cholyl-adenylate and a CoA thioester of cholic acid (cholyl-CoA) were monitored with characteristic negative ions of m/z 736 and 577, respectively. Cholyl-adenylate was definitely characterized and preferential biotransformation into the acyl-adenylate prior to formation of cholyl-CoA was noted. The nonenzymatic formation of taurine-conjugated cholic acid by incubation of cholyl-adenylate with taurine in a buffer solution was also demonstrated.

[Successful removal of a left ventricular fibroma in a 10-year-old patient].

A 10-year-old girl with negative T wave in leads I, II, III, aVF, and V2-6 in the ECG was examined. The two-dimensional echocardiogram and the MRI revealed that she had a tumor in the free wall near the apex of the left ventricle. We removed the intramural fibroma (50 x 35 x 30 mm) of the left ventricle under cardiopulmonary bypass very carefully not to perforate the left ventricular cavity. After the removal, the defect was repaired by the sutures of the myocardial layers so that the volume inside the left ventricle could be kept and its shape could be maintained. She has been doing well without any trouble for 5 months after the operation.

Production and characterization of group-specific monoclonal antibodies recognizing nonamidated, glycine- and taurine-amidated ursodeoxycholic acid 7-N-acetylglucosaminides.

Ursodeoxycholic acid 7-N-acetylglucosaminides (UDCA 7-NAGs) are novel conjugated metabolites whose urine levels are expected to be a specific diagnostic index for primary biliary cirrhosis. To obtain a specific antibody which is useful for developing immunochemical analytical methods of UDCA 7-NAGs, a variety of monoclonal antibodies have been generated. Spleen cells from an A/J mouse, which had been immunized with a conjugate of nonamidated UDCA 7-NAG and bovine serum albumin, were fused with P3/NS1/1-Ag4-1 myeloma cells. After screening by an enzyme-linked immunosorbent assay (ELISA) using a beta-galactosidase-labeled antigen, thirteen kinds of antibody-secreting hybridoma clones were established. Binding properties of these monoclonal antibodies were investigated in detail by ELISA. One of these antibodies, Ab-#8 (gamma1, kappa) had the most favorable characteristics for clinical application, which was group-specific to the 7-NAG conjugates of nonamidated, glycine- and taurine-amidated UDCAs providing a highly sensitive dose-response curve for each conjugate (midpoint 17 pg per assay for nonamidated UDCA 7-NAG). Cross-reactivities with eleven kinds of bile acids, including some potential interfering metabolites as UDCA 3-sulfate, were negligibly low. By using direct ELISA based on Ab-#8, daily urinary excretion rates of UDCA 7-NAGs of two healthy subjects were determined to be 1030 and 469 microg as GUDCA 7-NAG equivalent.

Effect of hyperbaric oxygen on intercellular adhesion molecule-1 (ICAM-1) expression in murine lung.

BACKGROUND: The lung is one of the most susceptible organs to the toxic effect of high pressure oxygen. However, the contribution of the cellular adhesion molecules and inflammatory leukocytes in the pulmonary oxygen toxicity, especially in an acute exudative phase, is not well understood. In the present study we have investigated the toxic effect of hyperbaric oxygen (HBO) expressed by the analysis of the intercellular adhesion molecule-1 (ICAM-1) on the pulmonary vascular endothelial cells and leukocyte function. METHODS: Mice were exposed to HBO at 3 ATA of PO2 for 3, 4, or 6 h. Expression of ICAM-1 was serially observed by immunohistochemical analysis. The oxidative metabolic activity of the leukocytes was measured after HBO exposure. RESULTS: After HBO exposure an increase in the number of pulmonary interstitial leukocytes (PIL) and bronchoalveolar lavage (BAL) was observed at 72 h and 48 h, respectively. The expression of ICAM-1 was strongly enhanced immediately after HBO exposure and this enhancement lasted for 24 h. This suggests the importance of enhanced expression of adhesion molecules in the generation of pulmonary oxygen toxicity. However, we could not detect increased chemiluminescence activity in the early phase in the BAL cells and PIL. CONCLUSION: Expression of ICAM-1 was enhanced from the very early stage after HBO, but neither accumulation of leukocytes in the lung nor increase in the chemiluminescence activity were observed in this phase. Therefore, activation of inflammatory leukocytes in the pulmonary oxygen toxicity may occur only after prolonged (more than 4 h) or repetitive exposures to HBO.

Overexpression of p53 is associated with growth pattern and prognosis in advanced gastric cancer.

BACKGROUND/AIMS: The growth pattern of advanced gastric carcinoma, based on volumetric analysis, is closely associated with the biological characteristics of tumors, including DNA ploidy, and is an important prognostic factor. Abnormality of the p53 tumor suppressor gene plays an important role in alteration of cells and possibly leads to cancer development. MATERIALS AND METHODS: Expression of tumor suppressor gene p53 was investigated immunohistochemically in the primary lesion of 196 patients with advanced gastric cancers, and the relationship of p53 immunopositivity with the growth pattern and prognosis was analyzed. RESULTS: Positive p53 staining was found in 94 (48%) of the 196 primary carcinomas. Vessel invasions were more frequent and lymph node metastasis was more extensive in p53-positive tumors (p < 0.05), whereas p53 immunopositivity was not associated with depth of cancer invasion nor with the stage of cancer. In the column and mountain type tumors, characterized by vertical or penetrative growth, positive p53 staining was found in 53.8% and 52.9%, respectively. In the funnel type tumor, characterized by superficially spreading growth, positive p53 staining was found in significantly lower incidence (28.9%, p < 0.05). The 5-year survival rates were 44.2% and 25.4% for patients with p53 negative and positive gastric carcinomas, respectively (p < 0.01). Multivariate analysis showed that p53 overexpression was an independent prognostic factor of patients with advanced gastric cancer. CONCLUSIONS: These findings suggest that p53 gene alteration is associated with less favorable prognosis of advanced gastric cancer, possibly by providing tumors with a potential of vertical growth into the gastric wall.

[Two cases of the successful treatment of TAPVR with asplenia syndrome in neonates and infants].

Two patients of asplenia syndrome with pulmonary venous obstruction underwent TAPVR repair in the period of neonate (14 days) and infant (49 days). Associated procedures were necessary to adjust pulmonary blood flow (central shunt in 1, PA banding in 1). Both patients required subsequent surgical procedures; right modified BT shunt, due to kinking of central shunt in one patient and rePA banding for reduction of pulmonary blood flow in another patient. One patient died 4 months after the first operation of arrhythmia. Another patient is doing well in 7 months after the first operation. The TAPVR repair in the early period of infant or naonate is necessary to prevent progress of pulmonary venous obstruction. Adjustment of pulmonary blood flow is important for management of patients of asplenia syndrome after TAPVR repair.

Macroscopic intraoperative diagnosis of serosal invasion and clinical outcome of gastric cancer: risk of underestimation.

Data on 715 Japanese patients with gastric cancer were studied retrospectively with regard to the relationship between macroscopic and microscopic diagnoses of serosal invasion and clinicopathological factors affecting the accuracy of the macroscopic diagnosis. Although there was no macroscopic evidence of serosal invasion intraoperatively (S0 or S1), there was histological evidence of cancer cells on the serosal surface in 69 patients (9.7%). In these serosal invasion-positive cases, the tumors were larger; were located more commonly in the upper third, lesser and greater curvatures of the stomach; were Borrmann type 3 or type 4 tumors, and of an undifferentiated histologic type with an infiltrative growth pattern more commonly, and had more extensive lymphatic and vascular vessel invasion and lymph node metastasis (P < 0.01). Total gastrectomy was done more often for the serosal invasion-positive group, but the extent of lymph node dissection was comparable. Cases of a noncurative resection because of a positive surgical margin were more frequent in the serosal invasion-positive group (8/69 vs. 14/646, P < 0.01), and most had undifferentiated and infiltrative cancers. The 10-year survival rates were 49.2% and 85.5% for patients with and without serosa invasion, respectively. These findings clearly show that the serosal surface, especially in cases of the undifferentiated or infiltrative type of gastric cancer, must be closely inspected intraoperatively.

Clinicopathologic characteristics and outcome of adenocarcinoma of the human gastric cardia in comparison with carcinoma of other regions of the stomach.

BACKGROUND: Carcinoma arising in the cardioesophageal junction is a distinct clinical entity compared with tumors located in other regions of the stomach. This study was done to analyze the biologic characteristics of carcinoma of the gastric cardia compared with other gastric carcinomas. STUDY DESIGN: Clinicopathologic features and postoperative prognosis of 68 cases of carcinoma of the cardia were evaluated, in comparison with findings of tumors in other regions of the stomach. RESULTS: From 1975 to 1992, 68 (6.5 percent) of 1,042 patients with carcinoma of the stomach had adenocarcinoma of the cardia. Carcinoma of the cardia was characterized by a more advanced stage compared with carcinoma of other regions of the stomach. The incidence of early stage carcinoma (limited to the submucosal layer) was 11.8 percent in the cardia, 15.8 percent in the upper one-third, and 42.2 percent in the remaining middle and lower thirds of the stomach. When compared to carcinoma in other regions of the stomach, tumors of the cardia had a significantly poorer prognosis and there was a higher incidence of lymph node and hepatic metastasis. The five-year survival rates in patients with adenocarcinoma in the cardia, the upper one-third, and the remaining middle and lower thirds of the stomach were 35.3, 43.7, and 61.9 percent, respectively. Especially for patients with stage II and stage III disease, the prognosis was significantly worse with adenocarcinoma of the cardia than with carcinomas of the other regions of the stomach. CONCLUSIONS: Early detection is crucial to improve the survival of patients with carcinoma of the gastric cardia. Extended dissection of lymph nodes and aggressive postoperative chemotherapy in an attempt to prevent hepatic metastasis are highly recommended.

Growth pattern and p53 overexpression in patients with early gastric cancer.

BACKGROUND: The growth pattern of early gastric carcinoma, based on a volumetric analysis, reflects well biologic characteristics of the tumor. The penetrating growth (Pen) type tumor has an unfavorable prognosis, compared with a superficially spreading (Super) type. Abnormality of the p53 suppressor gene plays an important role in alteration of cells leading to development of cancer. p53 point mutations are present even in an early stage of carcinoma. METHOD: In 159 patients with early gastric carcinoma, overexpression of p53 was studied immunohistochemically, using a monoclonal antibody (PAb 1801), and the relationship between growth pattern and p53 overexpression was analyzed. RESULTS: Early gastric carcinoma was grouped into 43 of the Super type, 37 of the expansively penetrating growth (Pen-A) type, 16 of the infiltratively penetrating growth (Pen-B) type, and 63 of the Small mucosal type limited to the mucosal layer. The Pen-A type tumors were characterized by the highest incidence of p53 positive expression and poorest postoperative course. Between the Pen-A type and the Super type, there were significant differences in the incidence of the p53 positive expression (43% vs. 16%), the frequency of recurrence (16% vs. 7%), and disease free interval (574 days vs. 2926 days). CONCLUSION: The authors' observations show that the p53 gene plays an important role in expansion of gastric carcinoma, even in the early stages.

Gastric carcinoma in patients over 70 years of age.

The clinicopathological features and prognosis of gastric cancer in 344 patients aged 70 years or older who underwent gastrectomy between 1965 and 1990 were determined. Over the years the mean size of the tumour decreased, differentiated tumour tissue was more common, depth of penetration was less prominent, lymphatic and vascular involvement was less frequent, and the rate of lymph node metastasis and peritoneal dissemination decreased. Extensive lymph node dissection was more frequently carried out and the rate of curative resection rose. Survival rates improved with early detection of gastric cancer and there was no increase in operative morbidity and mortality rates. As age alone is not a contraindication to surgery for patients with gastric carcinoma, early detection of the lesion and surgical treatment are expected to increase the survival of elderly patients with this malignancy.

[Pulsatile total cavopulmonary shunt for hypoplastic right heart syndrome with abnormal systemic venous return--a case report].

A pulsatile total cavopulmonary shunt was successfully performed on a 5-year-old girl with hypoplastic right heart syndrome associated with abnormal systemic venous return; at the same time, modified mitral valve replacement was performed for mitral regurgitation. The right atrium, tricuspid valve and right ventricle were all extremely dimunitive. The diameter of the tricuspid valve was 50% of normal and the volume of the right ventricle was 8.6% of normal. In addition, there were severe subpumonary stenosis, a restrictive ventricular septal defect (VSD) and an atrial septal defect (ASD). The bilateral superior venae cavae (SVCs) and the hepatic vein drained to the left atrium, and the inferior vena cava was infrahepatically interrupted with a hemiazygos connection to the left superior vena cava. At the operation, each SVC was anastomosed end-to-side to each branch of the pulmonary artery (PA). The restrictive ventricular septal defect and stenotic subpulmonary lesion were left. The diameter of the ASD was reduced from 12 mm to 7 mm. The main PA was neither divided nor banded. The pulsatile blood flow from the left heart to the PA was regurated by a native restrictive VSD and stenotic subpulmonary lesion, and that from the right heart via the ASD was limited by reducing the size of the ASD. These described anatomic arrangements produced adequate antegrade pulsatile flow in the PA, which might prevent the development of pulmonary arteriovenous fistulae and, besides permit transfer of drainage of the hepatic vein from the left to the right atrium via the ASD in future.

Surgical treatment and prognosis for patients with gastric cancer lesions larger than ten centimeters in size.

In 323 of 1,620 patients with gastric cancer, the lesion was > or = 10 cm in maximum diameter. Studies were done with respect to clinicopathologic features and the prognosis. Patients with tumors > or = 10 cm were younger and women patients were more numerous compared to those with tumors < 10 cm. Tumors were more advanced and noncurative resection was usually done for these patients. A multivariate analysis showed that serosal invasion, liver metastasis, lymph node metastasis, operative curability, tissue differentiation, and extended lymph node dissection to be independent prognostic factors. This retrospective study showed that patients with a larger tumor are at an increased risk for tumor advancement and that they will benefit from curative resection and extended lymph node dissection.