Changes in thyroid volume of patients with various thyroid diseases were evaluated and compared with those in circulating thyroid parameters. Studies were conducted on 160 patients with Graves' disease, 20 patients with Hashimoto's thyroiditis, 25 patients with simple goiter and 25 patients with thyroid tumor. Thyroid volume was measured by ultrasonography (thyroid volume = πabc/6, a : length, b : width, c : depth).
In normal subjects (n=-20), thyroid volume ranged from 2.9 to 11.3ml (mean, 6.8ml). In simple goiter, thyroid volume ranged from 4.2 to 13.7ml (mean, 9.7ml). In untreated Graves' disease, thyroid volume ranged from 6.9 to 66.7ml (mean, 27.0ml). In untreated Hashimoto's thyroiditis, thyroid volume ranged from 4.3 to 120.0ml (mean, 31.8ml). In thyroid tumor, thyroid volume ranged from 7.4 to 25.8ml (mean, 13.5ml).
In all the patients with Graves' disease as well as untreated patients, thyroid volume was significantly correlated with TBII (p<0.01) and Tg (p<0.01), but not with TSH, TSAb, MCHA or TGHA. In 11 patients, the mean thyroid volume decreased significantly after 1 year of therapy with methimazole (MMI, p<0.01), which is associated with decreasing serum TB II levels. Ten patients went through transient hypothyroidism due to overdoses of MMI, and the mean thyroid volume increased significantly (p<0.01) with increasing serum TSH levels. The mean thyroid volume of patients with sustained remission (n= 7) was significantly less than that of patients with relapse (n = 5) at the time MMI was stopped (p<0.05).
Six patients with Hashimoto's thyroiditis were treated with T₃, while 14 patients were treated with T₄. In patients given T₃ or T₄ therapy, the mean thyroid volume decreased significantly after 6 months (p<0.01). In patients with euthyroid Hashimoto's thyroiditis, as well as those with hypothyroidism, the mean thyroid volume decreased significantly after thyroid hormone therapy (p<0.01).
In conclusion, it is suggested that TSH and TSH receptor antibodies (TRAb) may stimulate thyroid growth. In addition, circulating Tg levels reflect thyroid volume in Graves' disease. It is also suggested that measurement of thyroid volume is useful in predicting remission in Graves' disease. In both patients with euthyroid Hashimoto's thyroiditis and hypothyroidism, thyroid volume decreased significantly after T₃ or T₄ therapy.

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The author proposed improvement of the criteria for the effects of transcatheter therapy for hepatocellular carcinoma. 104 patients were treated by transcatheter therapy. Their responses were determined by the usual criteria. Next, they were classified and evaluated in 3 groups, with the area of lipiodol deposition on CT for over 4 weeks regarded as necrosis. The result was determined, and its relationship to prognosis was studied in light of the repeated therapy.
1. By the usual criteria, only 10% of patients were judged as PR, and there were no differences between therapies. Many of the NC cases had low AFP levels with therapy.
2. At the initial therapy, the ratio of cases with low AFP levels was higher and the survival time was longer in the A group. So the A group was judged as most effective. Clinically, 10 patients were considered most benefitted by therapy. They were considered the A group, but all were judged as NC.
3. Considering the effects of repeated therapy, 10 patients with NC were judged as the A-max group. Prognosis was poor in patients of the B-max and C-max groups. These results indicate that judgement by the usual criteria was inconsistent with clinical condition. It was improved by regarding the area of lipiodol deposition on CT for over 4 weeks as necrosis. Estimations of effects and prognosis were made more accurate by considering repeated therapy. Thus, the proposed improvement of the criteria by CT is more useful to estimate of transcatheter therapy of the hepatocellular carcinoma.

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Activation of the hypothalamus-pituitary-adrenal axis and decreased gastric mucosal microcirculation are considered central factors in the pathogenesis of cinchophen-induced acute gastric mucosal lesions (AGML) in rats and dogs (Nagamachi, 1982). The present study was undertaken to elucidate the effects of truncal vagotomy (vagotomy) on gastric mucosal micro blood flow (GMBF), hepatic micro blood flow (HBF), potential difference (PD) and hexosamine content in gastric mucosa in cinchophen-administered rats. The effects of vagotomy and vagal stimulation by 2 -deoxy-D-glucose on cinchophen-induced AGML development were also studied.
The results were as follows : (1) Vagotomy did not affect GMBF in control rats and could not prevent the decrease in GMBF caused by cinchophen-induced stress. (2) Vagotomy reduced HBF significantly in the course of cinchophen-induced stress period. (3) Vagotomy did not affect PD in control rats and did not prevent the decrease in PD induced by cinchophen-induced stress. (4) A large dose of cinchophen reduced hexosamine content in gastric mucosa. Vagotomy prevented the recovery of mucosal hexosamine content caused by administration of the drug. (5) Vagotomy did not stimulate or prevent cinchophen-induced AGML in the rats.
Conclusion : It is therefore considered that vagotomy is not a suitable treatment for AGML in the physical stress period.

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The relationship between acid secretion, interdigestive migrating contractions (IMC) in the stomach, and gastrointestinal hormones in the dog was investigated. Heidenhain pouches and Pavlov pouches were perfused with saline (1.3 ml/min) and pH changes in the perfusate were recorded continuously by means of an indwelling pH sensor. Force transducers were used to detect contractions. The pH value started to increase 3.2min after a bolus injection of cimetidine, and decreased 3.1min after the administration of betazole hydrochloride. Seventy percent of all registered IMC cycles obtained from Pavlov pouch dogs showed a decrease in pH values from 4.2±0.1 to 1.7±0.1 (mean±S.E.) corresponding to phase II contractile activity. The other 30% of the cycles did not demonstrate any changes in pH value. Acid outputs during 10min, including the minimum pH value, were 29.9±4.6% of those observed 30-40min after feeding. The decrease in pH values during phase II was also recognized in Heidenhain pouch dogs. The serum gastrin concentration during the pH-decreasing phase (40.8±4.5pg/ml) was significantly higher (p<0.05) than that in the pH-increasing phase (23.0±3.4), and significantly lower (p<0.01) than that (141 8±10.6) obtained at 30min after feeding. The serum concentration of motilin during the pH-decreasing period (265.3±49.3pg/ml) was significantly lower (p<0. 05) than that during the increasing phase (430.8±34.3). Administration of exogenous motilin induced phase III-like contractile activity and significantly elevated the pH value from 3.9±0. 1 to 4.6 ± 0.3. Cimetidine increased pH values significantly from 4.0 ± 0.3 to 5.5 ± 0.1 (p<0. 01), and the duration of an IMC cycle (101.8±4.5min) was not significantly different from that of the control (103.5±6.5). These data indicate that a simple device used in these experiments detects changes in acid secretory activity in the canine gastric pouch within 3 min. Acid secretion during fasting is activated in association with phase II contractile activity in 70% of IMC cycles in the stomach. Gastrin and motilin are likely to be involved in controlling the activity. The H₂ receptor blocker (cimetidine) suppresses acid secretion during phase II, but does not affect the IMC cycle.

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In order to evaluate neural control of airway goblet cell secretion in guinea pigs in vivo, we have developed a new morphometric method in which mucus score (MS) was employed as a parameter of discharge. Tissue slides of trachea and main bronchi from guinea pigs with or without vagal nerve stimulation were stained with alcian blue pH 2.5/periodic acid Schiff. At a magnification of × 400, epithelial cells which were positive for the staining were divided into two grades according to the size of the positive area in the cell. MS was then calculated by adding the number of these cells using following formula : 1 × (total number of small sized-cells) + 2 × (total number of large sized-cells). Intra-observer error or intra-animal variability in MS was very small, indicating that MS was highly reproducible. Further, the total in MS at main bronchi was significantly correlated with that at trachea. MS was inversely well correlated with secretory ratio, a parameter for goblet cell secretion independent on the total number of positive cells. MS in animals with nerve stimulation was significantly low compared with those with sham stimulation, indicating the presence of neural control on goblet cell secretion in guinea pig airways. MS seemed to be a simple and reproducible parameter to evaluate goblet cell secretion.

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Interlobular bile ducts in thirty-one liver biopsy specimens from 31 patients with drug-induced intrahepatic cholestasis were morphologically investigated.
1. Several changes in interlobular bile ducts were found under light microscopy in 29 of the 31 specimens. Prominent histological features were inflammatory cell infiltration in the epithelial layer and vacuolation of the cytoplasm of epithelial cells. Cell swelling, flattening and/or karyopyknosis were often found in affected bile ducts. Cellular debris was also seen in the lumen. Destruction of the ductal wall was sometimes observed in a few cases that underwent liver biopsy in the early stage.
2. Loss of interlobular bile ducts was observed in drug-induced cholestasis. A decreased number of bile ducts was observed in drug-induced cholestasis, and the grade was between those of primary biliary cirrhosis and the hepatocellular type of drug-induced liver injury. There was a good correlation between the number of bile ducts per portal area and maximum serum total bilirubin level or duration of jaundice.
3. In 13 liver biopsy specimens, 32 interlobular bile ducts were investigated by electron microscopy. Most of the epithelial cells had deposits of bile pigment in cytoplasm. The appearance of dark cells, clear cells and multilayered basement membrane and infiltration of lymphocytes into the epithelial layer were occasionally observed. In some cases damaged epithelial cells were in contact with infiltrating lymphocytes.
4. These results suggest that damage to interlobular bile ducts plays an important role in drug-induced intrahepatic cholestasis. It may be possible to predict the prognosis of drug-induced cholestasis by estimating the number of bile ducts per portal area.

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This study was undertaken to investigate the effects of histamine and its receptor antagonists and agonists on IgE antibody production in mice.
BALB/c mice were immunized intraperitoneally with 1mg alum plus 30μg of Ag90, an antigen prepared from the water soluble fraction of “Konnyaku Maiko” precipitated by 90% saturated ammonium sulfate. Histamine receptor antagonists were administered before immunization and histamine at sensitization ; histamine receptor agonists were administered at sensitization. The mice were bled 14 days after immunization and anti-Ag 90 IgE antibody titers were measured by passive cutaneous anaphylaxis reaction in Sprague-Dawley rats.
The titers were expressed as a reciprocal of the highest dilution that yielded a positive reaction.
Treatment with histamine did not affect the level of specific IgE antibody. Prior administration of the H₁ antagonist to histamine suppressed IgE production significantly ; H₂ agonist also suppressed it. In contrast, pretreatment with H₂ antagonist or administration of H₁ agonist augmented IgE antibody production. Treatment with H₁ + H₂ antagonists prior to histamine had no effect on antibody production.
These results suggested that histamine, in the induction phase, suppressed specific IgE antibody production via the H₂ receptor and enhanced it through the H₁ receptor.

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To clarify the roles of H₁ and H₂ receptors in the airways of asthmatic patients, we studied the effects of the administration of a histamine H₁ receptor antagonist, an H₂ receptor antagonist and a combination of both on bronchial constriction induced by histamine inhalation and allergen inhalation in patients with asthma.
We also examined the effects of H₁ and H₂ antagonists on bronchial response induced by histamine inhalation in normal guinea pigs.
Chlorpheniramine (H₁ antagonist) raised the threshold of histamine-induced bronchoconstriction in asthmatic patients compared with that at no medication. In contrast, cimetidine (H₂ antagonist) augmented histamine-induced bronchospasm. The combination of both produced inhibitory effects similar to those of chlorpheniramine alone.
These findings imply that in asthmatic patients histamine induces bronchial constriction predominantly via H₁ receptors in the airways, but H₂ receptors may function to induce bronchodilation.
In guinea pigs, histamine-induced bronchial response was reduced after the administration of H1 antagonist, but no effects of H₂ antagonist were observed.
Chlorpheniramine alone also had an inhibitory effect on the immediate asthmatic response (IAR) of the allergen inhalation test. Cimetidine did not have any clear influence on IAR.
It is suggested that both H₁ and H₂ receptors are present in the airways of humans, and histamine action via the H₁ receptors plays the main role in the development of bronchoconstriction.

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Recently, understanding of the factors that control ductus arteriosus closure after birth has advanced dramatically. In 1975, prostaglandin E₁ (PGE₁), an effective vasodilator of the ductus arteriosus, was administered to a neonate with congenital heart disease for the first time. As PGE₁ was very useful to maintain a patent ductus arteriosus (PDA), it be came widely used in infants in whom pulmonary or systemic hood flow depends on a PDA.
This is a report of our clinical assessment of PGE₁ in patients with congenital heart disease. Seventy-two infants were examined. PGE₁ was effective in 61 (84.7%) infants, and they could survive until the shunt operation or total correction. In eleven (15.3%) patients PGE₁ was useless, and they died before the operation.
We divided the 72 infants into three groups. The first group consisted of congenital heart disease in which all or almost all pulmonary blood flow was supplied through the PDA. This group included pulmonary atresia with intact ventricular septal defect or other combinations such as ventricular septal defect (extreme tetralogy of Fallot, double outlet right ventricle etc.), tricuspid atresia, single ventricle, transposition of great artery and so on.
The second group consisted of patients in whom all or almost all systemic blood flow was supplied through the PDA. This group included hypo-plastic left heart syndrome (aortic atresia, mitral atresia, etc), interruption of the aortic arch and severe coarctation of the aorta.
Those with transposition of the great artery formed the third group. PGE₁ dilates the PDA and pulmonary vascular bed and thus increase pulmonary blood flow and interatrial mixing. PGE₁ is effective to maintain the patients condition and enable balloon atrio-septostomy to be done more safely.
Of these three groups, PGE₁ was most useful in the first and third groups.

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Ten cases of malignant hepatic tumor (3 hepatic metastases and 7 primary hepato-cellular carcinomas) were treated by partial Lipiodol/transcatheter arterial embolization, in which lipiodol and anticancer drug mixed with gelfoam powder were administered alternately. The hepatic blood flow was not blocked completely by embolization. All cases were followed for more than one year.
1) The changes in hepatic function were similar to those with conventional TAE.
2) The one-year survival rate was 70.0%, and two-year survival rate was 52.9%.

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It is important to investigate the types of branching of the portal vein in the human caudate lobe when radical operation is performed in patients with such conditions as cholangiocarcinoma in hepatic hilum.
Thirty-six caudate lobes were dissected. Many types of portal vein branching (from 1 PV to 6 PV but not 5 PV) were observed. The total number of branches was 74 (2.0/caudate lobe). Many caudate portal branches ramified from the portal trunc, bifurcation and left portal vein, but no caudate branches from the right portal vein were observed. Spiegel's lobe is a main part of the caudate lobe and its portal branches also ramified from the portal trunc, bifurcation and left portal vein but not from the right portal vein. The portal branches of the paracaval portion ramified from every side of the portal vein. The portal branches of the caudate process portion mainly ramified from the right portal vein, and its independent portal branches were recognized in 3 or more portal vein types of the caudate lobe.
The results showed that the portal branches of the caudate lobe have a certain regularity in types of branching.

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During the fourteen years from January 1975 to December 1989, 61 patients underwent resection of gastric cancer with cancer cell invasion at the oral and anal surgical stump. Thirty-four of the 61 patients were non-curative operation because of metastasis to the liver, peritoneum and distant lymph nodes. Though the remaining 27 undergone radical resection, the operation was non-curative due to histological cancer cell invasion at the surgical stump of the specimen. Of the 27 patients, 14 have survived more than five years, and 7 died within five years. The surviving patients included not only stage III and stage IV but stage I and stage II. In contrast, the latter were all stage III and stage IV.
The patients who underwent reoperation due to cancer invasion at the oral surgical stump have survived without recurrence.

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1) The isolation frequency of clinical pathogen and their drug-resistances were surveyed by 8 public hospitals in Gunma Prefecture in Japan in 1989. 15604 strains were identified and 16942 strains were examined for 22 kinds of drug-resistances.
2) Among clinical isolates, 47% were Gram-negative rods and 42% were Gram-positive cocci. S. aureus (13.2%), E. coli (7.9%), P. aeruginosa (8.8%), and coagulase-negative staphylococci (8.1%) were the major bacterial species. Isolation frequency of these isolates were different in different clinical sources and in different hospitals.
3) Seventeen kind of species whose isolation frequency was more than 1 % were surveyed for their drug-resistances. Both the 3rd-generation cephems and new quinolones were losing their antibacterial effect, especially in Pseudomonas and S. aureus.
4) Identified species were different between inpatients and outpatients. Development of drug-resistances is more marked in inpatients than in out-patients. In some case hospital infections were suggested.

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Mass screening for detecting breast cancer was performed from 1974 to 1989 in and around Ota city. The total number of subjects during these 15 years was 40, 519 at the first screening with physical examination. Breast cancer was detected in 36 cases, a detection rate of 0.089%. The detection rate was higher at the initial screening than at the subsequent one. Thus, the number of initial examinees is expected to be increased. Patients with breast cancer detected by mass screening showed an earlier stage and better prognosis the ordinary outpatients in Gunma Cancer Center. However, interval breast cancer was also found in 5 cases (stage I : 3, stage II : 2). This study indicated that mass screening for breast cancer is a useful means for early discovery and early treatment of breast cancer, and it is also important to educate woman about the practice of breast self-examination. In future, more effective, economical and safer screening instruments are expected to be used at the first examination.

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Mass screening to detect both breast and thyroid cancer at the same time was conducted between April 1980 and March 1990 in Gunma Prefecture with the cooperation of the Gunma Cancer Society. The total number of subjects during these ten years on the first screening with physical examination alone was 273, 964. Of these, 24, 587 women (9.0%) were advised to undergo a second examination. Breast cancer was detected in 218 women, a detection rate of 0.08% and thyroid cancer in 276 women (0.10%). The detection rate for breast cancer was approximately twice as high at the initial screening than at the subsequent screening. The breast cancer detected by mass screening was in an earlier stage of disease and showed better prognosis than that of ordinary outpatients in our hospital. The 10-year survival rate was 95. 3% for the mass screening group and 76.8% for the outpatients group. Interval breast cancer was found in 24 cases and the prognosis was very favorable. Each physician obtained a different rate at the second examination. This mass screening program is a useful means for the early discovery and treatment of breast cancer. Hereafter, the number of initial examinees and women aged 60 or more should be increased. Mammography and ultrasonography should be introduced into the first examination. It is important to train physicians participating in the screening and to educate women about practicing breast self-examination.

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A 66-year-old male with the symptoms of fever and abdominal pain was referred to our hospital. The patient had undergone aortic replacement with a Y-shaped vascular prosthesis for abdominal aortic aneurysm 18 months previously. Blood culture revealed the presence of Enterobacter aerogenes and a diagnosis of prosthetic vascular infection was made.
On laparotomy the right leg of the vascular prosthesis was found to adhere to the jejunum and, moreover, emerge in the jejunal lumen, indicating so-called Graft-Enteric Erosion (GEE). The operative treatment consisted of removal of the infected graft, closure of the intestinal wound and insertion of a vascular prosthesis from the right axillary to the bilateral femoral arteries to bypass the infected aortic segment. The postoperative course was uneventful, with fever and abdominal pain disappearing soon after the operation. Now, 2 months after the operation, he is progressing favorably.
GEE following prosthetic replacement of vessels, though of rare occurrence, is important as one of the graft infections that carries a high mortality rate. Bunt et al. reported that the mortality rate of GEE was 20% with appropriate surgical measures, while it was 100% with conservative therapy alone. In the treatment of GEE, early diagnosis, removal of the infected graft and non-anatomical reconstruction of circulation are of major prognostic importance.

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We experienced two patients with heart diseases complicated by ischemic intestinal disease. A 65-year-old man was admitted to hospital because of acute myocardial infarction. Three days after coronary angiography, he suddenly had abdominal pain, nausea and melena. Fiberoptic colonoscopy revealed extensive ischemic change of the mucosa. A 44-year-old woman with combined valvular disease and atrial fibrillation, who had had several episodes of abdominal pain of unknown origin, was admitted to hospital because of abdominal pain. Renal scintigraphy revealed a wedge-shaped defect in the right kidney. Angiographic examination showed multiple avascular areas in the bilateral kidneys, as well as complete occlusion of the jejuno-ileal artery.
We recommend that abdominal angiography, as well as barium enema and colonoscopy, be included in the list of diagnostic procedures for abdominal pain among patients with heart diseases in whom the risk of symptomatic thromboembolism is high.

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