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Despite the outstanding results generally obtained with imatinib mesylate (IM) in the treatment of chronic myeloid leukemia (CML), some patients show a poor molecular response. To evaluate the relationship between steady-state trough plasma IM concentration (IM-C(min)) and clinical response in CML patients, we integrated data from six independent Japanese studies. Among 254 CML patients, the mean IM-C(min) was 1,010.5 ng/ml. Importantly, IM-C(min) was significantly higher in patients who achieved a major molecular response (MMR) than in those who did not (P = 0.002). Multivariate analysis showed that an MMR was associated with both age (odds ratio (OR) = 0.97 (0.958-0.995); P = 0.0153) and with IM-C(min) (OR = 1.0008 (1.0003-1.0015); P = 0.0044). Given that patients with IM-C(min) values >1,002 ng/ml had a higher probability of achieving an MMR in our large cohort (P = 0.0120), the data suggest that monitoring of IM levels in plasma may improve the efficacy of IM therapy for CML patients.

To investigate the effects of cyclosporine on spermatogenesis and endocrinological function of the testis, cyclosporine was administered subcutaneously to mature male Sprague-Dawley rats. Four and 6 weeks after the termination of cyclosporine administration (40 or 60 mg kg-1), the diameter of seminiferous tubules was diminished. The percentage of tubules with spermatozoa was decreased 6 weeks after the termination of cyclosporine treatment (20-60 mg kg-1). However, tubular wall thickness did not change throughout the experiment. Serum follicular stimulating hormone level increased significantly immediately after termination of cyclosporine administration dose-dependently, while the serum levels' luteinizing hormone and testosterone did not alter throughout the experiment. It is strongly suggested that cyclosporine impairs spermatogenesis and Sertoli cell function, although Leydig cell function is not injured.

To reduce the invasiveness of radical esophagectomy, we developed a new approach: video-assisted transsternal radical esophagectomy (VATRE). This article presents the operative techniques and our initial results. In our new procedure, cervical U-shaped and longitudinal sternoabdominal incisions are made, and a complete midline sternotomy is carried out. Lymph node clearance from the neck to the upper mediastinum and from the lower mediastinum to the upper abdomen is performed under direct vision. In the middle mediastinum, a video-assisted technique is used to dissect the lymph nodes. After esophageal resection and three-field lymphadenectomy, reconstruction is performed. One-lung ventilation is unnecessary. We have performed this procedure in two cases. These patients had no major complications and recovered more rapidly than patients undergoing conventional transthoracic esophagectomy. Our initial experience shows that VATRE is a technically feasible and less invasive procedure for cancer surgery, and it enables us to easily perform three-field lymphadenectomy.

Bilateral vasovasostomies were performed in 7 previously vasectomized patients. The method employed was a modification of a one-layer anastomotic technique. There was no correlation between the presence of absence of sperm in the vas fluid, presence or absence of sperm granuloma, and site of vasectomy. No correlation was revealed between the presence or absence of sperm in the vas fluid and the duration of obstructive period. After vasovasostomy, sperm was observed in the ejaculate in 86% of the patients. Only one patient's partner became pregnant. However, the partner of one patient with short postoperative period and good seminal finding after vasovasostomy was expected to become pregnant. This modified method of one-layer microsurgical vasovasostomy can be performed more easily and quickly, but requires further clinical experience and evaluation of usefulness.For various reasons, some men seek the reversal of prior vasectomy. Macroscopic methods to reverse vasectomy and restore fertility have achieved patency rates of 50% or higher, but reports have also indicated that final fertility is attained in only 5-25% of cases. Higher patency and pregnancy rates have been reported using a two-layer microscopic technique. This paper reports the findings obtained after performing a modification of a one-layer microsurgical vasovasostomy. Bilateral vasovasostomies were performed in seven patients vasectomized 2-12 years before; the median interval between vasectomy and vasectomy reversal was 9 years. The men were aged 33-45 years (median age, 39 years). No correlation was identified between the presence or absence of sperm in the vas fluid, presence or absence of sperm granuloma, and site of vasectomy. Furthermore, no correlation was revealed between the presence or absence of sperm in the vas fluid and the duration of obstructive period. After vasovasostomy, sperm was observed in 86% of the patients, although only one patient's partner became pregnant. The partner of one patient with short postoperative period and good seminal finding after vasovasostomy is, however, expected to become pregnant. The authors note that while the modified method of one-layer microsurgical vasovasostomy can be performed easier and quicker than the two-layer approach, it requires a higher level of clinical experience and additional evaluation of its usefulness.

We report a case of surgical treatment of pulmonary pleomorphic carcinoma invading the azygos vein. Chest computed tomography (CT) revealed a mass of 6 cm in size, in the upper lobe of the right lung. He underwent the right upper lobectomy and lymph node dissection with combined resection of the involved azygos vein. Histological examination revealed pleomorphic carcinoma (pT3N0M0, stage IIB). The postoperative course was uneventful, and he was alive without recurrence 26 months after the operation. Six cases of pleomorphic carcinoma have been surgically treated between June 2008 and August 2009 in our institute. Early diagnose with complete resection is suggested to be essential in the improvement of survival for this disease based on review of our experience.

From 1979 to January 1990, 48 patients with newly diagnosed superficial bladder tumours were treated by transurethral resection (TUR) at Toyama Medical and Pharmaceutical University Hospital. The relationship between tumour recurrence and the stage, grade, number, or size of the tumours was investigated. The 1-, 2-, 3-, 4- and 5-year non-recurrence rates were 72%, 63%, 47%, 40%, and 40%, respectively. Non-recurrence rate for pTa tumours was significantly higher than that for pT1 tumours (p

The effects of birth season on the case fatality rate (CFR) of pulmonary tuberculosis were examined in case records of 9206 patients discharged during 1937–1965 from a national hospital for tuberculosis in Tokyo. The CFR was over 60% until 1945, then it decreased down to less than 9% after 1950. Male cases had little variation in their CFR by their birth season, while female cases had a significant variation and showed a significantly higher CFR than the male cases when they were born in January–June. The results suggest that the birth season had a significant influence on the prognosis of pulmonary tuberculosis.

We report a novel missense mutation of the Notch3 gene in a Japanese family with CADASIL. The Cys49Gly mutation in this family is located in exon 2 of the Notch3 gene. Most of the documented Notch3 gene mutations occur in exons 3 or 4. On the other hand, there are few reports around the world of mutations in exon 2 of the Notch3 gene, and this is the first report of a mutation in exon 2 of the gene in a Japanese family. In general, CADASIL mutations involve a cysteine residue. Such mutations may influence the tertiary structure of the Notch3 protein, resulting in protein dysfunction. Thus, the CADASIL in the present case may be a consequence of the mutation in exon 2 causing a structural change in the Notch3 protein.

Cardiac (123)I-meta-iodobenzylguanidine (MIBG) uptake was measured in 11 patients with dementia with Lewy bodies (DLB), 10 patients with Alzheimer's disease (AD), and 10 age matched control subjects. The severity of cognitive impairment and duration of symptoms in patients with DLB matched that in the patients with AD. The heart/mediastinum (H/M) ratio of MIBG uptake in the patients with AD was indistinguishable from that in the control subjects. However, the H/M ratio in all patients with DLB was significantly lower than that in the patients with AD and control subjects (p0.001). These findings indicate that local myocardial sympathetic nerves are affected in DLB and that cardiac (123)I-MIBG scintigraphy may provide a means of differentiating DLB from AD.

A 68-year-old male was admitted for interstitial pneumonia associated with scleroderma. High-dose methylprednisolone was administered for treatment of the pneumonitis. Two weeks later, anemia, thrombocytopenia and progressive increase in BUN, creatinine and LDH were observed. Although the blood pressure remained normotensive, renal biopsy showed thrombosis of the polar arterioles and glomerular capillaries. The affected interlobular artery included concentric intimal thickening and thrombosis in the lumen. Our findings suggested that the antecedent use of high-dose corticosteroids is involved in precipitating normotensive renal crisis. Corticosteroids should be used in low doses and with great caution in scleroderma patients.

Until recently, most published reports on phytic acid (myo-inositol hexaphosphoric acid, IP6) have focused on the possible decreased mineral bioavailability. Because myo-inositol is known to function as a lipotropic factor, studies in my laboratory were conducted to investigate whether dietary IP6 also reduces excessive liver lipids. Male Wistar rats were fed sucrose or corn starch diets, supplemented with myo-inositol or IP6 for 12-14 days. Equimolar myo-inositol and IP6 similarly depressed the rises in hepatic levels of lipids and in hepatic activities of lipogenic enzymes due to sucrose feeding. However, dietary myo-inositol and phytate did not prevent orotic acid-induced hepatic lipid accumulation, which is known to be caused by severe inhibition of hepatic lipoprotein secretion. These results suggest that myo-inositol and phytate might both protect against fatty liver resulting from elevated hepatic lipogenesis.

Seventeen patients with hydrocele of the testis were treated by aspiration of fluid and substitution with tetracycline supplemented with 1% lidocaine. In 15 patients (88%) symptoms disappeared by sclerotherapy. After sclerotherapy scrotal ultrasonography was useful to diagnose either relapse or thickened tunica vaginalis. No side effect was noticed.

Ultrasonograms of the carotid artery were compared with the intraoperative finding of atheroma plaque in terms of stenosis, fragility, ulceration and calcification. Soft type, intermediate type and these mixed type plaques were fragile plaques in almost all cases. All hard type plaques were tough plaques. The detection of stenosis and calcification was satisfactory, however that of ulceration was not sufficient. The stenotic lesions frequently existed in bilateral carotid arteries and the intima was easy to become thick even after the endoarterectomy. The ultrasonogram was thought to be the essential study for the carotid artery lesions.

1. National survey on died patients with active tuberculosis (tbc) or tbc sequelae had been held in national hospitals every five year from 1959 (3433 cases) to 1994 (688 cases). In 1994, 330 patients died due to pulmonary tbc. Recent study revealed the decreased rate of death due to operation, or far advanced cavitary cases, and the increased rate of nontuberculous death, aged people (60 yrs), and nontuberculous complications. Main causes of death in pulmonary tbc were lung insufficiency (about half) and general weakness (almost one fifth) in any survey. Rapid progression of pulmonary tbc had been increased cause of death (20.9% in 1994). Main attributable factors of death in 1994 in pulmonary tbc cases were severe condition on admission (38.4%), disturbed lung function (31.2%) and old age (33.2%). Delayed treatment (13.9%) and complications (12.1%) were increasing factors. Early death within 3 months from onset in 1994 was seen in patients60 yrs as well as in patients80 yrs. Severity due to delayed treatment and rapid progression were supposed to the causes of early death. 2. During 1994 to 1997, mechanical ventilation (MV;24 hours) was applied to 18 patients with active pulmonary tuberculosis; 10 acute respiratory failure (ARF), 5 chronic respiratory failure (CRF), 2 central nervous system tbc and 1 hemoptysis. Only one ARF case and three CRF ones survived. ARF cases had low PaO2/FIO2 (about 100), low albuminemia, short MV period (7 cases:7 days) and steroid therapy (9 cases). CRF cases had higher PaO2/FIO2 (294), longer MV period (4 cases:30 days) and all CO2 narcosis. 3. Noninvasive positive pressure ventilation (NIPPV) was applied to 23 patients with pulmonary tbc sequelae. In 13 patients with stable chronic respiratory failure (mean PaO2 91 mmHg, PaCO2 82 mmHg) 10 continued NIPPV and started home mechanical ventilation (HMV). In 10 patients with acute on chronic respiratory failure (mean PaO2 61 mmHg, PaCO2 92 mmHg) 2 patients fell into tracheal intermittent positive pressure ventilation (TIPPV). Eight patients recovered with NIPPV and 5 started HMV. NIPPV is supposed to be very effective to treat severe chronic hypercapmic respiratory failure.

Health-related quality of life plays an important role in assessing the effectiveness of health care. The EuroQol is a generic instrument for describing and valuing health-related quality of life. To elicit health state descriptions and their preferences among the general public in Japan and compare them with cross-national data, a feasibility study for applying the EuroQol to the general public in Japan was carried out.The subjects were 120 people aged 40s-60s randomly selected in a suburban area at Aichi Prefecture in Japan. In assessing health states and their preferences, the EuroQol valuation instrument (version 12, 1991) translated into Japanese was used. The questionnaires were distributed and collected by public health nurses. The valid responses (rate) were 89 (74%).The mean scores (raw scores) using the visual analogue scale (VAS) for one's own health was 89.2. No statistically significant difference in VAS scores was observed for both sex and age. The contribution ratio of own health status, sex and age was 0.326 (p0.0001). The main independent variables were three dimensions of health status. Valuations for core health states varied from 96.3 (no problem in each health status) to 6.8 (dead). These VAS scores in Japan were correlated with those from other countries (p0.001). A multivariate analysis indicated that bias from own health status on preference valuations for core health states was not observed.The health states and their preferences among the general public in Japan were estimated by using the EuroQol. The results show the feasibility of evaluation for health states quantitatively. Moreover, this study suggested cross-national and cross-cultural applicability of the EuroQol.

There is an increasing incidence of the evolution of myelodysplastic syndrome (MDS) from aplastic anaemia (AA) with immunosuppressive treatment. In paediatric patients G-CSF is also reported to increase MDS evolution, but this process is not precisely understood in children or in adults. Therefore risk factors of MDS evolution in adults are evaluated here. Of 72 patients, five developed MDS. In 47 patients without cyclosporine (CyA) or antithymocyte globulin (ATG) therapy, only one developed MDS with trisomy 8, 242 months after diagnosis. But of 25 patients treated with either CyA or ATG, four developed monosomy 7 MDS within 3 years. Of these 25 patients, 18 were treated with G-CSF and the four patients (22.2%) who developed MDS were found in this group. The cumulative dose and the duration of G-CSF administration were significantly elevated in patients who developed MDS when compared with those who did not, 822.3 +/- 185.0 v 205.4 +/- 25.5 microg/kg (P0.05) and 187.5 +/- 52.5 v 72.0 +/- 24.6 d (P0.002), respectively. However these two values for CyA did not differ significantly. Statistically, treatment with CyA, G-CSF and combined G-CSF and CyA were significantly related to MDS evolution. The administration of G-CSF for more than a year was the most important factor (P=0.00). These results suggested that a close relationship exists between G-CSF and subsequent monosomy 7 MDS from AA in adults who receive immunosuppressive therapy. Long-term administration of G-CSF should be prohibited in order to prevent MDS evolution.

Mutations in the sterol 27-hydroxylase gene (CYP27) cause cerebrotendinous xanthomatosis (CTX). Early diagnosis of CTX is crucial because treatment with chenodeoxycholic acid can prevent or reverse some of the neurologic disability associated with the disease. We report the identification of three types of mutations (Arg441Trp, Arg372Gln, and Arg441Gln) in the CYP27 gene in five patients with suspected CTX from four unrelated families by restriction endonuclease analysis.

T-794 is a new reversible inhibitor of MAO type A. In order to predict its clinical utility as an antidepressant, we examined its pharmacological profile (i.e., MAO inhibitory activity, antidepressant-like activity and safety) in vivo in rodents. The p.o. administration of T-794 potentiated L-5-hydroxytryptophan-induced symptoms with ED50 = 1.01 mg/kg (mice) or 1.15 mg/kg (rats), and L-dopa-induced behavior with ED50 = 5.90 mg/kg (mice), whereas it did not alter the effect of beta-phenylethylamine even at 100 mg/kg (mice). In the L-5-hydroxytryptophan test in rats, the activity of T-794 (at twice the dose of ED50) disappeared by 8 h; the duration of action was similar to that of moclobemide. These results confirm the previous biochemical results that MAO-A inhibition by T-794 is highly selective and of short duration. T-794 was effective in three animal models of depression: reserpine reversal (mice, rats), behavioral despair test (mice) and learned helplessness (rats). In these tests, it had potency similar to or greater than moclobemide, tranylcypromine or imipramine. The p.o. administration of T-794 (30 mg/kg) did not affect the pressor effect of tyramine in anesthetized rats, whereas moclobemide (30 mg/kg) and tranylcypromine (6 mg/kg) potentiated the effect. Acute toxicity of T-794 proved to be very low (maximal tolerated dose2 g/kg p.o.) in contrast to brofaromine (maximal tolerated dose = 150 mg/kg p.o.). Unlike tricyclic antidepressants, T-794 did not prevent the oxotremorine-induced tremor even at 100 mg/kg p.o.; in this it demonstrated a lack of the anticholinergic activity. These results suggest that T-794 is an effective and particularly safe antidepressant and that it may make an important contribution in the treatment of depressive disorders.

Coronary flow reserve is used as an indicator to assess coronary microvascular function in the absence of obstructive coronary atherosclerosis. Diabetic patients, even with angiographically normal coronary arteries, show significantly reduced coronary flow reserve. This study evaluated coronary microcirculation in coronary artery disease complicated by glucose intolerance. Thirty-three patients with coronary artery disease were divided into three groups: Fourteen patients without glucose intolerance (control group), 8 with impaired glucose tolerance (IGT group), and 11 with noninsulin dependent diabetes mellitus (DM group). A Doppler guide wire was used to measure phasic coronary blood flow velocity in the left anterior descending artery without significant stenosis (or = 40% diameter narrowing). Coronary flow reserve was determined by intracoronary 10 mg papaverine hydrochloride administration which induced maximal hyperemia. Coronary flow reserve was decreased in the DM group compared with the control group (2.1 +/- 0.6 vs. 3.1 +/- 0.9, p = 0.004), and that in the IGT group (2.5 +/- 0.9) did not show a significant difference compared with the other two groups. Vessel characteristics, such as infarct- or noninfarct-related artery and previous coronary angioplasty, did not have an influence on the results. Other coronary risk factors, left ventricular function, and hemodynamic findings were comparable in the three groups. This study demonstrates that diabetes mellitus may cause functional microvascular abnormalities in coronary artery disease.

A 42-year-old man was admitted to the hospital because of sudden left-lateral chest pain and dyspnea. The chest roentgenogram on admission showed a string-like shadow and pleural effusion, and analysis of arterial blood gases revealed hypoxemia. Many bilateral segmental defects were seen on a radioisotope perfusion scan of the lungs, and the chest CT scan showed a low-density area in the trunk of the pulmonary artery. From these findings, pulmonary thromboembolism was diagnosed. The serum antithrombin III (ATIII) activity and the antigen value were low, and the patient's son's serum ATIII level was also low. Both the patient and his son were given the diagnosis of congenital ATIII deficiency. Gene analysis revealed two point mutations in exon 6 of the ATIII gene, so we classified this case as type IIc. The patient was treated with intravenous urokinase and heparin, and was then given warfarin. The arterial blood gas tensions improved, and the low-density area of the pulmonary artery on the CT scan disappeared, as did the pulmonary perfusion defect on the radioisotope scan. The clinical manifestations of members of 28 families with congenital ATIII deficiency reported in Japan were reviewed. Patients in whom many point mutations were detected in the ATIII gene were rare.

Prevention of cellular damage after warm ischemia is of major importance in liver transplantation. In this study, we determined the extent to which lipid peroxides contribute to the pathogenesis of hepatic cell damage induced by transient warm ischemia with subsequent reperfusion. In addition, the function and immunohistochemical features of glutathione peroxidase, a potent physiological lipid peroxide scavenger of the liver, was assessed. Reperfusion following 15 or 30 minutes of warm ischemia resulted in a significant elevation in serum and liver lipid peroxidase (LPO) levels. In addition, necrosis of the hepatic periportal area accompanied with remarkable rises in serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were observed. In contrast, 30 min of ischemia without reperfusion caused minimal hepatocellular damage. The adverse changes after ischemia/reperfusion were minimized by pretreatment with superoxide dismutase (SOD). These results indicate that increased lipid peroxidation by production of radicals after reperfusion caused the liver cell damage. After ischemia/reperfusion, liver glutathione peroxidase (GSH-PO) activity was significantly decreased and its location altered in the damaged liver. These findings suggest that GSH-PO contributes significantly to the protection against hepatic reperfusion injuries.

Six men (mean age: 36.3 +/- 29 years) infected with the human immunodeficiency virus (HIV), four Japanese and two from Myammar, were admitted to our hospital for treatment of tuberculosis. In five, HIV positivity on serologic testing was first found when tuberculosis was diagnosed. The mean CD4 cell count was 37.3 +/- 29.6/microliters. Results of tuberculin skin tests were negative in 5 patients. One patient had pulmonary tuberculosis and 5 had miliary tuberculosis. Hilar and mediastinal lymphadenopathy was found on chest X-ray films in 4 patients and superficial lymphadenopathy was found in all patients. All patients had positive mycobacterial cultures of sputum and 2 patients had positive tests for acid-fast bacilli on smears of lymph-node aspirates. In one patient with tuberculosis meningitis, a culture of cerebrospinal fluid for acid-fast bacilli was positive. Epithelioid cell granulomas were found in samples of lung, liver, and bone marrow from 4 patients. Mycobacterium tuberculosis was isolated from all patients, and was not resistant to isoniazid, rifampicin, ethambutol, or streptomycin. Therefore all patients responded well to treatment of tuberculosis.

We have been conducting surgical therapy for patients with atypical pulmonary mycobacteriosis (AM) since 1965 and have reported on the outcome of this approach to treatment. We have found that chemotherapy is not adequately efficacious against type III Mycobacterium avium complex (MAC), which suggests that surgical intervention may be the optimum approach for MAC. Among MAC patients who were treated surgically at our hospital in the period between 1966 and 1994, 74 cases on whom postoperative follow-up observation was possible served as the subjects of the present investigation. We report here on the outcome of treatment and related problems in these patients. Thirty-nine patients gave positive results for bacterial discharge on smear tests and all were positive on culture. Operation was performed on the right lung in 46 patients and on the left lung in 16. Pneumonectomy was conducted in 10 patients and lobectomy in 20. Other operative modes used included segmental resection in 9, pyothorax in 7, and thoracoplasty in 5 patients. Postoperative bacterial excretion was observed in 15 patients and was persistent bacterial discharge were advanced cases with lesions in another lobe, cases with a past history of tuberculosis, cases of cavitation with lesions on the contralateral side or cases with massive bacterial discharge prior to surgery. Postoperative death occurred in 5 patients: the cause of death was lung cancer in 1 case, serum hepatitis in 1 case, and respiratory failure evidenced by enlarged shadows in 3 cases. These findings pointed to a marked significance of surgical therapy for MAC patients. However, recurrent bacterial discharge has been observed occasionally in some patients even 5 years after surgery. This suggests the need for careful ongoing assessment of the efficacy of surgical therapy and long-term postoperative follow-up.

In Japan there are about 40,000 patients under home oxygen therapy (HOT), of whom about 30 to 40% are pulmonary tuberculosis sequelae (TBS). These patients can be divided into three groups depending on the treatments they had, Group 1: those who had medical treatments only, Group 2: those who had artificial pneumothorax, and Group 3: those who had thoracoplasties or other surgical treatments. The purpose of this study was to observe the distributions and possible differences in the survival rates among these groups. The study included 1537 patients with TBS under HOT followed at National Hospitals and Sanatoriums nationwide in Japan. In 819 patients the treatments were specified and of those 354 were in Group 1, 29 in Group 2, and 436 in Group 3, so that the proportion of surgically treated patients in PTS was estimated between 28.4% (436/ 1537) to 53.2% (436/819). The ages at the onset of tuberculosis, at the start of HOT and the intervals in between were 36.6, 66.2 and 29.8 in Group 1, and 26.8, 65.5, and 38.1 in Group 3 respectively. Though the ages at the start of HOT were the same, those at the onset of tuberculosis were about ten years younger in Group 3 than in Group 1. Comparing Group 1 and 3, the survival rates after the initiation of HOT (Kaplan-Meier method) was better in Group 2 (surgically treated) than in Group 1 (medically treated). It is speculated that the reason could be a better preservation of the function of the remaining lung in the surgically treated and a higher incidence of obstructive impairments in the medically treated patients.

We studied 266 patients with drug-resistant pulmonary tuberculosis at national sanatoria in Japan. The patients included 218 men (mean age, 58 years) and 48 women (mean age, 62 years). The levels of isoniazid and rifampicin resistance were determined at 1 mcg/mL and 50 mcg/mL, respectively. The results were as follows. (1) Most patients with drug-resistant pulmonary tuberculosis were middle-aged or past middle-aged. (2) There were many cases of drug-resistant pulmonary tuberculosis in previously treated tuberculosis patients with active disease and several cases in previously untreated pulmonary tuberculosis patients. However, in some previously untreated patients active tuberculosis was convert relatively easily to inactive tuberculosis. (3) Concerning life style, bachelors who drank heavily were more likely to develop drug-resistant pulmonary tuberculosis. (4) Most cases of drug-resistant pulmonary tuberculosis had at least one cavity on chest radiographs. (5) Several patients with drug-resistant tuberculosis left the hospital against the advice of their attending doctors; therefore, it was difficult to treat their illnesses. (6) In more than half the cases in which Mycobacterium tuberculosis was resistant to isoniazid and rifampicin, tolerance to streptomycin and ethanbutol was also seen. (7) When patients with drug-resistant pulmonary tuberculosis continued to have tuberculous bacilli in their sputum after 3 months of chemotherapy, there was a tendency for them to expectorate tuberculous bacilli in their sputum. For these drug-resistant tuberculosis patients, we must pay attention not only to the medical aspects but also to the social aspects of their disease.

A case with autoimmune hemolytic anemia (AIHA) induced by interferon-alpha (IFN-alpha) is presented. A 40-year-old male who had a previous history of autoimmune hemolytic anemia, agranulocytosis and thrombocytopenia was admitted to our hospital because of chronic C type hepatitis. Liver biopsy was performed, which diagnosed chronic active hepatitis and IFN-alpha was administrated at a dose of 3 Meg unit per day. 11 days after the initiation of the therapy he developed hemolytic anemia, but Coombs tests were negative. Although IFN was withdrawn 15 days later, anemia became progressively more serious. 20 days later, both direct and indirect Coombs tests became positive. He was diagnosed as AIHA and treated with methylprednisolone pulse therapy, then he recovered soon afterward. Further analysis of Coombs tests revealed that he had both cold type and warm type (IgG) autoantibodies which was the same type of antibodies for AIHA he suffered 10 years ago. In conclusion, latent AIHA may be reactivated by the treatment with IFN-alpha.

The immunopathology of human T cell lymphotropic virus type 1 (HTLV-I) uveitis was addressed by using T cell clones (TCC) established from the intraocular fluid of patients with HTLV-I uveitis. Proviral DNA of HTLV-I was identified in 55 out of 94 (59%) or 13 out of 36 (36%) TCC from the ocular fluid or the peripheral blood of these patients, respectively. Most of HTLV-I-infected TCC had a CD3+ CD4+ CD8- phenotype. HTLV-I infection on TCC was confirmed by analysis of the viral mRNA, nucleotide sequence, virus-associated proteins, and virus particles. HTLV-I-infected TCC, but not HTLV-I negative TCC, constitutively produced high amounts of IL-6 (1,336 +/- 1,050 pg/ml) and TNF-alpha (289 +/- 237 pg/ml) in the absence of any stimuli. HTLV-I-infected TCC from the ocular lesion also constitutively produced high amounts of IL-1 alpha (12,699 pg/ml), IL-2 (61 pg/ml), IL-3 (428 pg/ml), IL-8 (1,268 pg/ml), IL-10 (28 pg/ml), IFN-gamma (5,095 pg/ml), and GM-CSF (2,886 pg/ml). Hydrocortisone, a drug effective in vivo for the treatment of HTLV-I uveitis, severely depressed cytokine production in vitro in most cases. In summary, the results demonstrated direct evidence of HTLV-I infection of the eye and suggest that cytokines produced by HTLV-I-infected T cells are responsible for the intraocular inflammation in patients with HTLV-I uveitis.

To elucidate the relationship between the clinical manifestations and pathologic findings of the lung in patients with cryptococcosis, we reviewed 14 autopsied cases of cryptococcosis. Five patients had pulmonary cryptococcosis and 9 had disseminated cryptococcosis. Patients with pulmonary cryptococcosis showed granulomatous reactions of the lung, such as fibrocaseous cryptococcoma (n = 2), discrete granuloma (n = 2), and granulomatous pneumonia (n = 1). Patients with disseminated cryptococcosis showed intracapillary/interstitial involvement (n = 2), mucoid pneumonia (n = 3), histiocytic pneumonia (n = 1), and granulomatous pneumonia (n = 3). There was a distinct difference between pulmonary cryptococcosis and disseminated cryptococcosis in lung pathology. Intracapillary/interstitial involvement and mucoid pneumonia were fatal because of extensive hematogeneous dissemination to other organs. Hilar lymph node involvement of cryptococcosis was found in all of the nine patients with disseminated cryptococcosis and in one of the five patients with pulmonary cryptococcosis. Pleural involvement of cryptococcosis was found in six of the nine patients with disseminated cryptococcosis. We conclude that the clinical manifestations of cryptococcosis are closely associated with the variety of lung pathology of cryptococcosis. Clinicians should understand the morphologic features to cope with patients with cryptococcosis.

A joint multi-institution study was conducted on the efficacy of Sairei-to, centering on urinary tract fibrosis. The subjects consisted of 18 patients with retroperitoneal fibrosis (including 3 women), 77 patients with plastic induration of penis, 5 patients with sclerotic lipogranuloma (all men), and 67 patients with hemorrhagic cystitis (including 6 men). As a rule, Sairei-to was administered in monotherapy for periods of 4 weeks or longer. Efficacy was most pronounced in the patients with sclerotic lipogranuloma and plastic induration of penis, with overall improvement rates (percentage of patients with ratings of effective or better) of 80% in the former and 77.9% in the latter group. The overall improvement rate in the patients with retroperitoneal fibrosis was 61.1%. In the above diseases, there were numerous patients concurrently administered drugs such as antiinflammatory enzyme preparations and corticoid preparations, and the improvement rates were somewhat higher in these patients treated concurrently with other drugs. Outstanding efficacy was also seen in hemorrhagic cystitis. Dividing the patients into irradiation and non-irradiation groups, respective overall improvement rates of 77.8% and 82.8% were obtained, with the non-irradiation group showing a slightly higher rate. The non-irradiation group showed slightly higher improvement rates in the subjects treated concurrently with drugs such as antibacterial drug. Conversely, the irradiation group showed significantly superior rates for monotherapy. Side effects such as mild gastrointestinal disturbances were seen in only 13 of 167 patients (7.8%), and the utility of this drug in treatment of the above diseases should be held in high regard.

A questionnaire survey of blood donors at Santa Cruz General Hospital, Bolivia, showed that while there were no seropositive cases of syphilis, HBsAg, and HIV, the prevalence of Chagas' disease was very high (23%) among the 225 blood donors who responded to this questionnaire. Actual cases of Chagasic seropositive blood being used for blood transfusion were seen, including the urgent need for a program for Chagas' disease in Bolivia. From the results of this study, it is recommended that for blood donors from South American countries, the presence/absence of Chagas' disease should be confirmed.

Thirty five patients with renal pelvic and ureteral tumors were treated at our hospital between 1979 and December 1992. Thirty patients were male and five were female. They ranged in age from 44 to 80 years old (average 67.4 years). The most frequent symptoms were hematuria that was found in 31 cases (24 gross hematuria and 7 microscopic hematuria). Histopathologically, there were 30 transitional cell carcinomas (TCC), 1 squamous cell carcinoma (SCC), 2 TCCSCC and 1 papillary adenocarcinoma. As to staging, 1 was pTis, 5pTa, 11pT1, 3pT2, 11pT3 and 4pT4. As to grading, 9 were G1, 16 G2 and 9 G3. The incidence of cancerous vessel invasion was noted in 8 of the 29 patients. The 5-year survival rate (Kaplan-Meier's method) was 44.9% for all of the patients. The 5-year survival rate according to staging and according to grading were as follows: 76.7% for low stage (pTis, pTa, pT1, pT2), 24.9% for high stage (pT3, pT4), and 83.3% for G1, 59.9% for G2 and 0% for G3. The 5-year survival rate was 20.8% and 68.7% in the patients with and without vessel invasion, respectively. Grade, stage and cancerous vessel invasion was suggested to be associated with the prognosis in renal pelvic and ureteral tumors.

In order to identify the most appropriate time for lung transplantation, we examined the natural courses of eight patients who died of idiopathic interstitial pneumonitis (IIP). Five of eight patients died within two years after they were diagnosed as IIP and six died within one year after the last admission. As the disease progressed, arterial oxygen pressure tended to decrease and serum LDH level to increase. But no parameter was able to predict the natural courses of patients. We conclude that it is very difficult to identify the most appropriate time for lung transplantation and the prognosis of IIP patient is very poor. Therefore as soon as patients are diagnosed as IIP, it is mandatory to assess their eligibility for lung transplantation.

We reviewed our experience of using double Malecot polyurethane intraurethral catheters (IUC). Ten patients with dysuria were treated between April 1991 and April 1993. Seven patients with benign prostatic hypertrophy (BPH) were judged as in a high risk group for operation. The three other patients had neurogenic bladder (two had underactive bladder and 1 had overactive bladder). Under local anesthesia, 150 ml of 0.1% Povidone iodine solution was infused into the bladder through a Nelaton catheter. Under guidance by ultrasonography, an IUC was placed into the bladder neck and posterior urethra using the specially designed introduction set. An long-term follow up of the BPH patients, two IUCs were removed for operation and one was exchanged for an indwelling catheter because of deterioration in general condition. In the neurogenic bladder patients, all IUC were removed because of the increase of residual urine, formation of a pseudourethra, or dislocation into the bladder. Side effects were observed in 6 patients such as, urethral bleeding and stone formation in the stent. Erosion and bleeding tendency in the urethral mucosa were shown in the prolonged duration cases. We conclude that a urethral stent is an effective devise for a high risk patient with benign prostatic hypertrophy but we must keep each patient under strict observation for complications during IUC placement.

We induced intraocular inflammation by foot pad injection of lipopolysaccharide (LPS) in rats to investigate the inflammatory effects of the various doses of the LPS and the anti-inflammatory effects of prostaglandin (PG) synthetase inhibitor. The aqueous protein concentration curve showed two peaks, an early one at 3 hours and another at 24 hours after the injection, at doses higher than 12.5 micrograms per rat. The PG synthetase inhibitor reduced the aqueous protein concentration by 30 to 60% at both of the two peaks. These results suggest the involvement of PG in the mechanism of the endotoxin-induced uveitis.

Interleukin-1 beta (IL-1 beta) is an inflammatory cytokine. We measured its production in 21 Behçet's disease patients, 4 healthy controls, and 4 sarcoidosis patients, by enzyme-linked immunosorbent assay (ELISA) after stimulation with lipopolysaccharide from peripheral blood monocytes. IL-1 beta production of the posterior segment type was significantly greater (p0.001) than in healthy controls, sarcoidosis patients, and anterior segment type. In all posterior segment type cases, IL-1 beta production in the active period was greater than in the remission period. IL-1 beta production is considered to be related to posterior segment type attacks of Behçet's disease.

We experienced 20 cases of methicillin-resistant Staphylococcus aureus (MRSA) infection from April 1991 to September 1992. Of them, 9 showed substantial morbidity and their clinical courses are herein reported. The clinical presentations of these cases were wound infection and enterocolitis. Although in 8 cases MRSA was eradicated in 14 to 160 days by effective antibiotics administration, one had a fatal outcome. All strains isolated showed similar drug-sensitivity pattern suggesting hospital infection. Sensitivity to vancomycin and arbekacin, however, remained high and these drugs were effective clinically. It should be stressed that treatment strategy of MRSA infection should consist of isolation of patients with MRSA from other patients, use of disposable equipment and products, and serious and continuing concerns of medical personal on communicability of MRSA.

An 81-year-old male patient visited our hospital on November 13, 1992 for the treatment of penile edema that had been caused by a metallic ring which he placed for fun 4 days prior to the visit. He had placed the metallic ring on the base of the penis and subsequent penile edema made it impossible to remove the ring. He had no problem with urination. The ring was successfully removed with a metal-cutting tool. But 3 days later, infected penile ulceration occurred at the base of the penis and the necrotic tissue was resected. It took 25 days for the wound to heal. It is stressed that penile strangulation is a serious injury and prompt removal is necessary.

To compare the hypoosmotic swelling test (HOST) with other sperm function assays.The HOST was performed on 105 patients with idiopathic infertility. The results were compared with those of various other sperm function tests, including the sperm penetration assay (SPA), triple-stain technique for evaluating acrosomal reactions, and the in vitro cervical mucus penetration test (Penetrak).A strong positive correlation was observed between percent sperm motility and the percent swollen sperm, between the motile sperm concentration and sperm swelling, and between sperm swelling and penetration values. Only a weak correlation was detected between sperm swelling and the percent sperm penetration. However, most of the cases with a sperm swelling percentage of 50% or more had good sperm penetration into ova.The HOST was useful to evaluate sperm tail function and was found valuable as a screening test prior to the SPA.

To investigate genetic polymorphism of N-acetylation in Japanese population we measured isoniazid (INH) and acetylisoniazid (AcINH) in the urine of 340 unrelated Japanese subjects. For the detection of polymorphism, we used probit analysis, logit analysis, and arcsine transformation of the logarithm of molar acetylation ratio (log (INH/AcINH)). The observed antimodes were -0.85 and -0.325 for the probit, 4.899 and 7.154 for the logit, 43.85 and 71.57 for the arcsine analysis plot. Probit and arcsine analysis were sensitive for the separation of intermediate from slow acetylators, while logit analysis was sensitive for the separation of rapid from intermediate acetylators. Clinically it is important to know to which genetic group the patient belongs because we may have to increase the dosage for the rapid acetylators to achieve the desired therapeutic effect, while we may have to reduce the dosage for slow acetylators in whom the incidence of side effect is high.

The ability of pentoxifylline to stimulate sperm motility characteristics was assessed. The effect of pentoxifylline was immediate and lasted for 240 min. The percent motility was increased 1.5-fold when compared with the control at 120, 180, and 240 min after pentoxifylline treatment. Significant increases in velocity and amplitude of lateral head displacement by the agent were observed at 120 min after the start of incubation. Conversely, linearity was reduced by pentoxifylline. Beat-cross frequency did not show any significant change by the agent at any time point. Sperm swelling was not influenced by pentoxifylline throughout the experiment. It would appear that pentoxifylline stimulates sperm motion in vitro with no change of the sperm membrane.

We studied 2247 patients with pulmonary tuberculosis who were hospitalized for the initial course of chemotherapy under the provision of the revised Tuberculosis Prevention Law issued by Japanese Ministry of Welfare. The results were as follows. 1) There were more males than females with a ratio of 2.6: 1. 2) There were two peaks in their ages, 20s and 60s. 3) The average admission periods were 5.2 +/- 2.7 months for men and 5.1 +/- 2.8 months for women. 4) The average compulsory admission periods were 6.8 +/- 2.5 months for men and 6.4 +/- 2.3 months for women, so that the actual admission periods were shorter in the majority of the patients. 5) The sputum cultures were converted negative in three months in about 80 percent of the patients who were smear and/or culture positive on admission. 6) The appearance rate of INH-resistant and RFP-resistant strains were 2% and 1.4% respectively. 7) Most of the death from tuberculosis was observed in the early stages of admission. 8) With regards to the cost, there seemed to be no difference whether treated under the new or the old provisions. 9) The newly approved extension of the admission periods for those who had complications such as diabetes mellitus or pneumoconiosis and those who had INH and/or RFP positive bacilli seemed to be appropriate.

The resazurin reduction test was performed on semen samples from 83 untreated infertile and 9 pregnancy-confirmed fertile males, and the results were compared with other sperm parameters. The highest correlations with resazurin grade were found for motile sperm concentration (r = 0.65, P0.001), per cent motility (r = 0.58, P0.01), and percentage of swollen sperm (r = 0.57, P0.01). There were also significant but weak correlations between resazurin grade and both sperm concentration and linearity. There was a significant difference in the rate of positive tests between samples from normozoospermic and fertile males, and samples from patients exhibiting abnormal semen parameters (P0.001). These findings indicate that the resazurin test may be able to predict those males who may be fertile despite an abnormal semen analysis, and therefore, the test may be useful in the evaluation of the infertile patient as a part of a comprehensive male fertility assessment.

Two cases of hypereosinophilic syndrome (HES) that seemed to be myeloproliferative disorders were treated with interferon-alpha (IFN-alpha). Case 1 was a 45-year-old man with HES who was unresponsive to prednisolone. Because Flaum's hematologic grading score was 8 points, he was diagnosed as a myeloproliferative variant of HES. Although his condition was well controlled by hydroxyurea (HU), cardio-pulmonary insufficiency with refractory eosinophilia developed after 4 years. Instead of HU, IFN-alpha dramatically decreased eosinophil counts, and the clinical situation has stabilized since. Case 2 was a 30-year-old man with HES whose grading score was 9 points. IFN-alpha therapy was started when an accelerated phase of neutrophil dominant with chromosomal abnormality (8 trisomy) occurred. However, he died because of no response to IFN-alpha and other chemotherapy. In both cases, studies of eosinophil colony formation revealed no excess of eosinophil colony-stimulating factor from their lymphocytes. Flaum's hematologic grading score was useful for the diagnosis of myeloproliferative variants of HES. IFN-alpha successfully induced hematologic remission in one case, and this therapy may be beneficial for these patients as a first line agent.

To evaluate the effects of TPN on the hepatic function, the changes in hepatic energy charge levels, oxidative and phosphorylative activities of mitochondria and serum transaminase were studied, using male Sprague-Dawley rats 240 to 250 g in weight. The rats were randomized into three groups. The first group (TPN-V group, n = 6) was infused with TPN solution via the right jugular vein. The number of calories of TPN solution infused daily was adjusted to provide each rat with 80 kcal/kg/day on the 1st day, 160 kcal/kg/day on the 2nd day and 240 kcal/kg/day on the 3rd day. After the 4th day, 240 kcal/kg/day was given to both groups. The second group (TPN-G group, n = 5) was infused with the same solution via an intragastric route and was given the same calories as the TPN-V group. The third group (control group, n = 6) was given a chow diet with the same calories as the TPN group. At the 13th day, all groups were sacrificed, and the hepatic energy charge (EC) and phosphorylation rate (PR) of hepatic mitochondria were measured, and liver function tests were done. PR was 101.2 +/- 5.0 nmol/mg protein/min in control group, 120.8 +/- 2.7 in TNP-G group and 136.5 +/- 6.2 in TPN-V group. EC was 0.906 +/- 0.006, 0.889 +/- 0.008, 0.831 +/- 0.010, respectively. The liver function tests of all group were normal. In both TPN groups, despite evidence that liver function tests were normal, enhanced mitochondrial phosphorylative activity was observed during the early stage of TPN.(ABSTRACT TRUNCATED AT 250 WORDS)

Ciclosporine (CS) caused rapid improvement of anemia and increase of CD 4/8 ratio in two patients with pure red cell aplasia (PRCA). One case was a 45 year old female who were unresponsive to steroids, plasmapheresis and high dose cyclophosphamide, and another was a 61 years old man with diabetes mellitus (DM) without any treatment for PRCA. In both cases hemoglobin increased soon after the initiation of CS and CD 4/8 ratio also rose from 0.80 to 1.47 and 1.78 to 1.98, respectively. There was no side effects to interrupt the course of the therapy. CS seems to inhibit the production of cytokines such as IL-2 and IFN-gamma, and it damages the activated suppressor/cytotoxic T cells. CS is an effective drug for not only refractory cases but the first step therapy for the untreated patients.

Protection of the spermatogenic cells against anticancer drugs can be performed by temporarily interrupting testicular blood flow during drug administration. In our study we investigated the effect of ischaemia on spermatogenesis, using mature male Sprague-Dawley rats. Eight and 16 weeks after a 1 h period of left testicular ischaemia, left testicular weights significantly decreased compared with the controls (both, p0.05). The decreased testicular weights returned to almost normal values at 24 weeks. Sperm counts in the left cauda epididymis were significantly reduced 8, 16 and 24 weeks after ischaemia (p0.01, p0.01 and p0.05, respectively). Sperm motility also decreased 8 and 16 weeks after the procedure (both, p0.01). These parameters returned to normal at 48 weeks. The diameter of seminiferous tubules in the left testis was diminished 8 and 16 weeks after testicular ischaemia, and increased tubular wall thickness on the left side was demonstrated 8 weeks after ischaemia (each, p0.05). No changes in the parameters at any interval after ischaemia were observed in the right testis. The serum levels of LH, FSH and testosterone showed no alteration throughout the experiment. The present study reveals that testicular damage induced by ischaemia up to 1 h is completely reversible and no contralateral orchiopathy is produced by this procedure.

Eight patients with benign prostatic hypertrophy (BPH), considered as a high risk for an operation because of severe accompanying disease, were treated with a self-retaining intraurethral catheter set. Two patients were judged unfit for operation (one because of severe cardiac failure, the other because of severe respiratory failure) and 1 patient rejected an operation. The BPH surgery was postponed in the others because of recent operations for such diseases as gastric cancer or because of severe gastric ulcer. All patients voided freely after stent placement and were continent. The device was left in place for 1 to 16 weeks. The chief complaint was frequency of voiding, with intervals of 1 to 2 hours. Some micturition discomforts such as urgency were recognized in 2 patients, but disappeared within 1 to 2 days. Pyuria observed before treatment disappeared in all but 1 patient. Average residual urine volume calculated on ultrasonograms was 54 ml. Stone formation was demonstrated in 1 patient 9 weeks after placement. We concluded that the intraurethral stent is an effective device for high-risk patients with BPH. However, a longer follow-up study will be needed to exclude late side effects.