The clinical consequences of drug acetylatoon polymorphism is reviewed for isoniazid. One controversial area was the development of hepatotoxicity when treatment (often prophylactic) was made with isoniazid alone. At first it was thought that the hepatotoxicity occurred more frequently in rapid acetylators than in slow acetylators. Now that many further studies have been performed on this issue, the consensus of opinions favors the other way, i. e., slow acetylators are more at risk to develop this particular adverse effect.
Furthermore, relations between acetylator status that involve polymorphically acetylated drugs, arylamine-induced cancer, and spontaneous disorders were dealt with. As to the latter issue, presumed relations between acetylator status and spontaneous disorders including systemic lupus, breast cancer, Gilbert's disease, Graves' disease, and leprosy were discussed. Thus, knowledge of the acetylator phenotype of a patient can help determine the relative risk for some drug-related toxic and therapeutic responses.

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Ten cases of carcinoma of the stomach after gastric surgery were examined. The average age of cases was 56.9 and the sex of them was predominantly male. Diagnosis of initial surgery were benign gastric disease (5 cases) and gastric carcinoma (5 cases). Billroth-II method without Braun anastmosis was chosen mainly for initial gastrectomy. The average interval between initial and subsequent surgery was 14.4 years in the cases of benign gastric diseases and 9.4 years in gastric carcinoma. Symptoms such as swallowing disturbances and epigastralgia were frequently seen in advanced carcinoma of the remnant stomach. Early stage of carcinoma was diagnosed by endoscope and biopsy. The methods of second operation were total resection of the remnant stomach (7 cases) and palliative surgery (3 cases): 5 cases underwent curative resection and 2 noncurative resection. Since the carcinoma of the remnant stomach was advanced, combined resection of spleen and/or tail of the pancreas was often done. Carcinomas of the resected remnant stomach were 3 early carcinomas (2 cases of type IIa, one type IIa+IIc) and 4 advanced carcinomas (2 cases of Borrmann 3, 2 cases of Borrmann 4). Cases of the curative resection survived three years and one month longer. Most of the noncurative cases and palliative surgery cases died in a year. Histologic examination of the resected remnant stomach revealed mild atrophic gastritis (all cases) and moderate intestinal metaplasia (a few cases) which were said to be precancerous changes. We conclude that several factors to improve the prognosis of surgery for carcinoma of the remnant stomach are as follows: 1) periodic follow-up and examination of diagnosis of early stage of cancer 2) total resection of the remnant stomach with combined resection of adjacent organs for complete lymphnode dissection.

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Total colonoscopy was performed in 700 cases in the 4-year-period from August 1983 to August 1987. Complete total colonoscopy was successful in 691 cases (98.7%). Serious complication was not encountered in our series. The rate of abnormality was 33.3 per cent, and neoplastic polyp (adenoma, early cancer), advanced cancer, ulcerative colitis and diverticulosis were the principal disorders. The histopathological study of the 184 cases of neoplastic polyp removed endoscopically revealed adenoma in 164 lesions (89.1%) and early cancer in 20 lesions (m: 15, sm: 5). The frequency of early cancer with adenoma was 75 per cent and that without adenoma was 25 per cent.
This result was consistent with the concept of adenoma-carcinoma sequence. The shape of the majority of early cancer was Is and the size 11 to 15mm. It was thought that symptoms other than anal bleeding were also important as indication of total colonoscopy for the detection of colorectal adenomas and early cancer. Therefore, we think that aggressive and vigorous total colonoscopy followed by endoscopic polypectomy are highly effective in the prevention and treatment of colorectal malignancy. And, from the viewpoint of the early diagnosis of de novo cancer, we colonoscopists should make every efforts to find not only elevated lesions but also flat and depressed lesions in the future.

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Fifty-three cases of bile duct carcinoma were studied. Ten of the 53 cases (18.9%) survived more than 3 years and were analyzed for prognostic factors. These patients were all treated with resection and in 9 of 10, tumor was middle and lower third lesion. Longterm survivors were the patients with nodulous type tumor, no or slightly metastasis of regional lymph node (n0 or n1) and whose tumor was no or slightly extended over the mucosal of duct (s0 or s1). Long-term survival rate was 75.0% in stage I cases, 53.8% in stage II who were treated with resection.
Patients with upper third tumor had poor prognosis and there were no long-term survivors treated with more aggressive operation (extended right hepatectomy) but with middle third tumor had good results, and 5 of 7 were long-term survivors treated with bile duct resection only.
Pancreato-duodenectomy for lower third tumor also had good results.

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We treated 39 cases of bile duct cancer from 1974 to 1987. The lesion was found in the superior portion of the bile duct in 20 cases, middle portion in eight and inferior portion in nine. Resection was performed in 20 of the 39 cases (51%). In detail, seven (35%) of the cases with superior portion cancer, six (75%) of the cases with middle portion cancer and seven (70%) of the cases with inferior portion cancer underwent resection. Surgery was curative in ten of the 20 cases (50%). These ten cases consisted of five with middle portion cancer and five with inferior portion cancer. In cases with superior portion cancer, surgery was non-curative, and consequently, the survival rate was lower than that for cases with middle and inferior portion cancers. These results were interpreted as follows: The pancreatoduodenostomy were performed in cases with middle and inferior portion cancers, yielding favorable results. In cases with superior portion cancer, the bile duct at the porta hepatis was resected, and the surgery was non-curative in many cases because of not only retention of cancer in the hepatic side stump of the bile duct but also infiltration in the serous membrane side. It was suggested that extensive cholangectomy with resection of the liver and partial resection of portal vein and hepatic artery was necessary to improve results of treatment for bile duct cancer. Further, usefulness of external irradiation in patients not receiving resection of bile duct cancer was discussed.

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A total of 631 patients with malignant neoplasms excluding leukemia and myeloma examined with bone scintigraphy during 3 years in Kure National Hospital from 1985 to 1987 and 9 skull metastases treated in our department of neurosurgery for 10 years from 1978 to 1987 were investigated in this study. One hundred and ninety-seven (31.2%) bone metastases and 39 (6.2%) skull metastases were observed in 631 cases. There was no primary site that especially tended to metastasize to skull. The primary sites of 9 treated skull metastases were breastin 3, prostate in 2, lung, uterine cervix, malignant lymphoma and liver in one respectively. Six skull metastases were in vault and 3 in cranial base. Four cases were treated by irradiation, 2 by operation only and 3 by combination with operation and irradiation. Although 8 of 9 cases had died, there were no cases who died of skull metastases. The mean survival time from the diagnosis of primary site was 27.3 months and from skull metastases was 8.1 months. Because of cases with skull metastases often have another metastases, it is necessary to give special consideration to their treatments.

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We report 1104 cases (1140 materials) with tumors and tumor-like lesions of the soft tissue at our hospital during the period of April 1982 to March 1987. Majority of the cases were outpatients. These cases were 0.7% of 15834 cases of the department of pathology during the same period. Most of them complained of subcutaneus tumors. In our experience these tumors could occur practically in any part of the body. The majority occurred in the face, the backs, and the extremities. They increased slightly every year. There were 536 male and 568 female cases. They showed no sex preponderance and might make their appearance at any age. They occurred more commonly in the forth and fifth decades.
Histological classification was as follows. Tumors derived from skin tissue were observed in 511 cases (44.8%), tumors of connective tissue in 74 (6.5%), tumors of fatty tissue in 240 (21.1%), tumors of muscular tissue in 21 (1.8%), tumors of vascular tissue in 112 (9.8%), tumors of nervous tissue in 49 (4.3%), tumors of synovial tissue in 63 (5.5%). malignant tumors in 41 (3.6%) and others.
In accordance with WHO classification they were reclassified as follows. There were 487 materials. Tumors of connective tissue were observed in 74 cases, tumors of fatty tissue in 224, tumors of muscular tissue in 20, tumors of vascular tissue in 103, tumors of nervous tissue in 49 and malignant tumors in 17.
We discussed the clinical findings, the modes of treatment and the pathological findings of these tumors.

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One hundred and twenty-seven elderly subjects underwent operations for fractures at our hospital between 1975 and 1986. One hundred and five cases of these were studied on the basis of an inquiry by mail or telephone. There were 15 cases of fractures of the upper extremity, 90 with that of the lower extremity. Seventy-nine out of 105 had complications; some of which caused prolongation of hospitalization or death in the hospital. The average cost through the whole hospitalization for each subject was ¥1, 480, 000, ranging from 690, 000 to 3, 350, 000. The subjects going back to their own home after discharge got better in ADL than those who moved to other hospitals or institutions. As for mental condition, the result was as such. Ninety-two point four per cent of the patients answered that they were satisfied with the results.

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We reviewed the results of treatment of 86 patients with trochanteric fracture of the femur. The patients were treated for the first time at National Medical Center Hospital from 1974 to 1986. Twenty-nine patients were male and 57 were female with a mean of 72 years. Fifty-six patients (65%) had had other diseases, physically or psychiatrically, before the fracture. According to the classification of trochanteric fracture by Evans, 32 cases (37.2%) belonged to the stable type and 54 (62.8%) belonged to the unstable type. Our surgical methods of treatment consisted of Jewett nail plate in 44 cases (51.2%), McLaughlin nail plate in 11 cases (12.8%), compression hip screw in 11 cases (12.8%), and pinning or others in 9 cases. Conservative method was applied in 11 cases (12.8%).
Of all cases (86 cases), 7 (8.1%) failed to heal, namely, 3 showed malunion, 3 showed remaining unacceptable varus deformity, and 1 case developed late infection. All failed cases belonged to “unstable type”.
Sex, age, previous diseases and methods of treatment gave little influence on the results of healing of the fracture. To the contrary, types of fracture, that is “stable” or “unstable”, were revealed to be a most important factor. It should also be noted, however, that 47 cases (87%) of the unstable type showed excellent bony union. These cases were treated successfully by experienced surgeons. So it would also be important to perform surgery skillfully.
Of the 6 cases who died during the admission, 4 died from the conditions unrelated to the fracture, while 2 died from postoperative complications. Those diseases that had affected the patients before or after the fracture did not give much influence to the results of fracture healing, but they gave some problems for general control of the patients during the hospitalization, as well as for the length of admission.

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Histochemical analysis of the paraspinal muscles was conducted in 44 patients clinically suspected of idiopathic scoliosis. They consisted of 16 male and 28 female cases, and were 4 to 22 years of age with the mean of 14.5 years. In these cases the right and left paraspinal muscles were sampled during operation and frozen-sectioned. Sections were subjected to the following histologic and histochemical staining procedures: Hematoxylin-Eosin, Gomori-Trichrome, NADH and ATP-ase. Of the 41 cases three were classified as nonspecific myopathy, two as central core disease, two as mitochondrial myopathy, two as chronic polymyositis, one as nemaline myopathy, one as Kugelberg-Welander disease and one as motor neuron disease on the basis of the pathological findings of the muscle. The remaining 32 cases were considered to be so-called idiopathic scoliosis. No clear histological abnormalities were found in any of them. Histochemically, however, target fibers or type grouping which were neurogenic changes were found in 18 (56.3%) of the 32 cases. The etiology of idiopathic scoliosis is still unsolved and various theories have been proposed. The present results support the neurogenic theory, although the possibility of secondary changes due to scoliosis could not be denied.
In addition, relatively rare diseases such as central core disease and nemaline myopathy have been included in scoliosis. Therefore, histochemical examination of the paraspinal muscles is of great value in the diagnosis of scoliosis.

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We studied the hormonal aspects and the prognosis of 44 anovulatory patients with high luteinizing hormone (LH) level in serum. The following results were obtained.
1. There were few patients with hirsutism.
2. Hyperprolactinemia were seen in 27.30 of all.
3. Hyper-testosterone level in serum were in 47.6%.
4. Patients with relatively lower LH level ovulated spontaneously.
5. The oral administration of Shakuyaku-kanzo-to (Kanpo) resulted in the ovulatory rate of 58.3%.
6. The oral administration of bromocriptine was effective in patients with hyper-PRL level in serum.
7. Most patients had ovulation by treatment with clomiphene citrate or HMG-HCG.
8. Resection of tunica albuginea ovarii was a very effective procedure for the induction of ovulation but few patients needed surgical therapy.

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We conducted a practical survey on TDM at the dispensaries in 46 National Hospital and Sanatoriums in the Kyushu district. The following results were obtained:
a) Twenty-one dispensaries (46%) measured the drug concentration in blood. The actual measurement was conducted in the dispensary.
b) Fourteen dispensaries (30%) performed the measurement outside of the dispensary.
c) Eleven dispensaries (24%) did not perform the measurement.
d) Twelve dispensaries (48%) out of the 25 in which the measurement was not done had a plan of conducting the measurements in the near futre.
e) Nine dispensaries (36%) did not intend to any future plans to do so.
f) Four dispensaries (16%) remained unknown.
The conditions of those dispensaries with a lower ratio of measurement-taking were as follows: less than 300 beds or less than 2 pharmacists.
The following number of dispensaries intended to study TDM: 29 (63%) of the total number of dispensaries, and 19 (66%) of those dispensaries in which the measurement was not currently performed.
The results of a questionnaire from the 21 dispensaries in which measurement was performed on-site were as follows: 20 dispensaries (96%) had a form for comments, 9 (43%) dispensaries participated in a suitable plan of administration in accordance with drug concentration in blood. Eight (38%) dispensaries selected a few patients for comments. In 7 (33%) medical facilities, doctors selected a few patients for comments. Six (29%) dispispensaries had comments on all patients. Eighteen (86%) dispensaries had a concrete counter-measure for infection.
The dispensaries in a considerable number of medical facilities intended to measure the drug concentration in blood, and to study TDM and its practice, and 9 dispensaries had already participated in the administration plan which will bring future development to TDM.

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As ulcerous lesions in the ileo-cecal region, Crohn's disease, tuberculosis, and Behret's syndrome are known, but recently, simple ulcer has been established as an independent disease entity. We recently treated two patients with simple ileo-cecal ulcer. We would like to report the details of these cases in this paper together with a review of the literature.
Case 1 was a 56-year-old man with a chief complaint of right lower quadrant pain. Past medical history revealed occasional oral aphtha beginning one year earlier. Barium enema and colonic endoscopy showed a deep-seated ulcer with an irregular shape, accompanied by an accumulation of mucosa was noted just above the ileo-cecal valve. To rule out malignant lesions, angiography and endoscopic biospy were performed, but no evidence of cancer was found. Simple ulcer or Behcet's syndrome was most likely, but the diagnosis of simple ulcer was clinically made. A right hemicolectomy was carried out, and the final histological diagnosis was a simple ulcer. However, since intestinal symptoms might precede Behcet's syndrome, and it is difficult to discriminate between these two diseases either macroscopically or histologically, this patient has been being followed in our clinic.
Case 2 was a 48-year-old man with a chief complaint of ileo-cecal pain. A 2×3cm mass was felt in the ileo-cecal region on abdominal examination. Since the WBC was increased slightly to 9300mm³, the diagnosis of acute appendicitis was made, and an emergency laparotomy was carried out. On surgery, the ileo-cecal region formed a single mass, and the cecum could not be identified. Macroscopically this was judged to be an inflammatory tumor, and the ileo-cecal region was resected. The histological examinations revealed simple ulcer of the cecum.

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The patient was an 8-year-old girl, who suffered from Kawasaki disease at the age of 4 years and 5 months. After the acute stage of the disease, she had been well and enjoying her daily life without any complaints. When she became 6 years old, she developed an acute myocardial infarction. She was treated with aspirin, dipyridamole and Ca antagonist. The anginal episodes did not disappear after the acute stage of myocardial infarction. Recently, dipyridamole-induced myocardial ischemia has been demonstrated in animals and humans with coronary artery disease. After administration of the dipyridamole was discontinued, her angina pectoris decreased in frequency. The so-called “coronary steal phenomenon” may play some important roles in the dipyridamole-induced ischemia in this patient. Based on our experience, there may be some possibilities that dipyridamole would not be effective in patients with multiple branch lesions in Kawasaki disease.

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An 81-year-old male was admitted to this hospital in June 1986 because of precoma, superior alternating hemiplegia. On the 1st hospital day, his body temperature was high and γ-hemolytic streptococcus was found in blood cultures on the 2nd and 3rd hospital day. This patient did not response to many antibiotic therapy and on the 20th hospital day, his consciousness level became worse and on the 24th hospital day, apnea appeared and he suddenly died.
His main pathological findings were endocarditis with bacterial vegetation on aortic valve, midbrain infarction with arch-shaped softening extending from oculomotor nerve to crus cerebri, meningoencephalitis, infarction of spleen and bronchopneumonia. The cause of death in this patient was an extensive cerebral infarction in the region of the left middle cerebral artery and uncal herniation.
In conclusion, we think that this is a case of superior alternating hemiplegia due to midbrain embolism resulting from endocarditis by γ-hemolytic streptococcus.

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About 10% of patients suffering from Duchenne muscular dystrophy (DMD) died of left heart failure at relatively younger age, however there have been few reports on the treatment of left heart failure in DMD. Thus we studied the cardiac functions and their responses to vasodilators and catecholamine preparations in 4 DMD patients with left heart failure. All cases were autopsied and the results indicated that they had cardiomyopathy.
These 4 patients had dyspnea, edema in the lower extremities, discomfort and palpitation, and their chest roentogenograms showed marked cardiomegaly. Out of these 4 patients with DMD (mean age 17 years), 2 had also mitral regurgitation (MR). Digitalis and diuretics were clinically effective in the initial stage of the heart failure, but these drugs became gradually ineffective as heart failure aggravated. On the results of the Swan-Ganz catheterization (SGC), they belonged to Forrester's subset 4, the mean values of pulmonary capillary wedge pressure and cardiac index were 31mmHg and 1.61/min/m², respectively. The results of the tests indicated that all of them had severe left heart failure.
Hemodynamic data showed the improvement of cardiac function after administration of isosorbide dinitrite tapes as a vasodilator. Since their symptoms became worse with the passage of time, dopamine in 3 patients and dobutamine in 1 patient was also given, resulting in temporary improvement of the cardiac function to Forrester's subset 1 or 2. However they died within a short period after the treatment, one year and 3 months from the beginning of subjective symptoms.
In recent years, vasodilators and catecholamine preparations have been used for the treatment of heart failure together with digitalis and diuretics. Based on our experience, even in the case that digitalis and diuretics became ineffective, vasodilators and catecholamine preparations were temporarily effective. Especially dobutamine seemed to be more effective, since we observed an increase in cardiac output. We propose that the usefulness of the vasodilators and catecholamines remains to be further determined.

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A 54-year-old woman suffering from myasthenia gravis for four years was transferred to the orthopedic section on June 10 1986 because of backache of six months' duration and development of paraplegia. On X-ray examinations including CTs, it was revealed that the seventh thoracic vertebra was collapsed togehter with paravertebral shadows. Thymoma was also noted in the anterior mediastinum. She had been treated with corticosteroid hormone for myasthenic disease till about six months before her admission. Diagnosis was made as paraplegia due to tuberculous spondylitis (Pott's paraplegia) and myasthenia gravis associated with thymoma.
After thymectomy via transsternal approach was done on September 3 1986 and myasthenic symptoms decreased, anterior decompression of the spinal cord followed by interbody fusion from the 6th to the 8th thoracic vertebrae through an extrapleural dissection was done on October 14 1986. Myasthenic crisis occurred on the fourth postoperative day, it was chiefly due to intramuscular injections of streptomycin.
Recovery from paraplegia was good and she could walk with minimal support six months postoperatively but myasthenic symptoms such as upper arm weakness, difficulty in swallowing became worse. Antiacetylcholine-receptor antibody titer was measured up to 400 nanomols per liter (normal:>0.6) 14 months postoperatively. On reexamination of the CTs, there was no evidence of recurrence of thymoma. So immunosuppressant therapy consisting of intravenous cyclophosphamide, adriacin and vincristine and high doses of oral prednisolone was done at intervals of every three weeks starting on December 22 1987 and showed some degree of improvement. She died suddenly on February 14 1988 probably due to acute heart failure.
It might be considered that it was better to use plasmapheresis or hemodyalysis instead of immunosuppressant drugs.

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Three patients, aged between 71 and 83 years, with cervical myelopathy due to calcification of the ligamenta flava are presented here.
Radiological examinations showed that calcified nodules were located paramedially in the posterior spinal canal.
Results of the operative treatment carried out in two cases were satisfactory.
The calcium deposit was analyzed by X-ray diffraction in one case and proved to be a mixture of hydroxyapatite and calcium pyrophosphate dihydrate (CPPD).
A total of 56 cases including ours were reported in detail in the literatures.
These studies showed the following noteworthy findings:
1. The majority of the patients were elderly and the ages ranged between 39 and 83, with a mean of 66.1 years old.
2. It was found predominantly in women (46 of 56 cases).
3. The calcified lesions were mainly observed at multiple lesions of the middle and lower cervical spine.
4. Calcification at other locations occurred in 20 cases (meniscus, pubic symphysis. and coxal labrum).
5. Ossification at other locations was observed in 12 cases (OPLL, and OYL).
6. X-ray diffraction and infrared absorption analysis were performed in 20 cases to determine the components of the calcified substances. CPPD was detected in 8, hydroxyapatite in 8, both CPPD and hydroxyapatite in 2 and calcium phosphate dibasic in 2 cases.

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A 62-year-old housewife lost consciousness on March 6 1985. She was admitted to the emergency clinic of our hospital because of disturbances of consciousness. On March 10, she developed anogenital and facial skin rash and she was referred to us on March 15. Herpes simplex virus (HSV) infection was suspected. Anti-viral agent, Ara A was administered for 8 days. Skin rash became dry with an elevation of HSV-CF antibody titre from 16× to 64× in 4 weeks, which confirmed the diagnosis of HSV infection, although recovery of her conscionsness impairment was delayed and partial.

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