Biomedical subjects
Publications and source records attributed to M Tani.
We report a case of acute generalized exanthematic pustulosis induced by 2 different drugs, cefaclor and acetazolamide. The diagnosis was confirmed by challenge tests, and these 2 drugs respectively were proven to be responsible for the patient's pustular eruptions.
We compared survival patterns in 61 medically treated and 78 surgically treated patients at a Japanese community hospital. The 2 groups were matched for presence of significant 3 vessel disease, resting ejection fraction of more than 40%, a bypassable left anterior descending artery, sex, and age. All surgical patients received saphenous vein grafts. The patients treated surgically had better 5 and 9 years survival rates than the medically treated patients (93% and 85% vs 74% and 55%, respectively; p < 0.01 by Cox-Mantel analysis). Five and 9 years rates of absence of ischemic events (non-fatal myocardial infarction and primary cardiac death) were also better in the surgical group than the medical group (92% and 87% vs 66% and 52%, respectively; p < 0.001). Of the surgically treated patients, 5 died perioperatively, 3 had late cardiac deaths and 2 had a nonfatal infarction. Among the medically treated patients, 16 had cardiac deaths, and 6 had non-fatal infarctions. Although our study was non-randomized, we have shown an advantage for surgical treatment of patients with 3-vessel coronary disease.
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Based on the pathophysiology of Bell's palsy that edema as well as ischemia lead to both compression and hypoxia, Stennert employed high doses of cortisone and dextran and reported a high recovery rate. In the past 5 years, we have been treating patients with Bell's palsy and Hunt syndrome with a high dose of steroids or low-molecular dextran (SD therapy). SD therapy was administrated in 71 cases of Hunt syndrome, and the results were compared with those of a group of 36 patients who had been treated with orally administrated low-dose steroids. All patients with incomplete palsies recovered completely, regardless of the mode of treatment. In cases of complete palsy, 62% of patients recovered completely when treated with SD therapy. In contrast, 29% of the patients treated with orally administrated steroids recovered completely. These results indicate that for patients with complete palsy SD therapy is more effective than oral steroid therapy, while patients with incomplete palsy recover completely with oral steroids. On the basis of this study, oral steroids are best used in cases of incomplete palsy unless complete palsy develops. In these latter cases, we now believe that SD therapy should be started immediately.
A 59-year-old male took total cystourethrectomy on July, 1991, since the bladder tumor recurred 2 years and 4 months after transurethral resection. Six months after total cystourethrectomy, an abnormal mass shadow appeared on the right lower lung field. Metastatic lung tumor was strongly suspected from CT scan. Despite chemotherapy, the pulmonary lesion grew rapidly and the patient died. From the autopsy, metastatic lesions were found in the bilateral lung fields, skin (face, head and abdominal wall), pleura, bilateral kidneys, small intestine and lymph nodes (para-aortic and mesenteric). The primary bladder tumor contained histologically transitional cell carcinoma as the epithelial element and sarcomatous changes with osteoid formation as the non-epithelial elements. Thus, the primary lesion was diagnosed as a malignant mesodermal mixed tumor. However, all of the metastatic lesions showed only sarcomatous changes. Only 10 cases of malignant mesodermal mixed tumor of the bladder have been reported in Japan since Fujita's report. In general, total cystectomy is necessary for the treatment of this disease. It has a poor prognosis; 5 of the 10 patients died within one year after operation.
To identify the effect of chronotropic responsive cardiac pacing on ventilatory responses to exercise, 9 patients with chronotropic incompetence underwent paired cardiopulmonary exercise tests with fixed demand rates (AAI, VVI) and chronotropic responsive (AAIR, VVIR, DDD) pacing modes. Compared with fixed rate pacing, chronotropic responsive pacing increased peak oxygen uptake and delayed the attainment of the anaerobic threshold (AT) with a higher level of oxygen consumption (p < 0.01). Dyspnea was a major symptom that limited exercise time in 7 patients with fixed rate pacing, which was prominent with chronotropic responsive pacing. Ventilation (VE) and the ratio of ventilation to CO2 production (VE/VCO2) were consistently higher with fixed rate pacing during exercise. To compare the responses between the 2 pacing modes with the same work loads under aerobic conditions, we measured ventilatory variables one min prior to the AT as obtained with fixed rate pacing. When switching the pacing mode from fixed rate pacing to chronotropic responsive pacing, VE and VE/VCO2 decreased significantly from 22.0 +/- 7.8 to 19.8 +/- 6.8 l/min, and from 37.4 +/- 5.4 to 33.6 +/- 5.2, respectively. Tidal volume did not change, but respiratory frequency decreased more with chronotropic responsive pacing (p < 0.05). Although peak VE did not differ between the 2 pacing modes, VE/VCO2 decreased more with chronotropic responsive pacing (p < 0.01). Respiratory frequency decreased and tidal volume increased more with chronotropic responsive pacing (p < 0.05). This study suggests that chronotropic responsive cardiac pacing attenuates exertional dyspnea by improving ventilatory responses to exercise as well as increasing the cardiac output in patients with chronotropic incompetence.
To elucidate the role of increased basal vagal activity in vasovagal syncope, we compared patients with bradyarrhythmia due to increased vagal tone and patients with vasovagal syncope using an upright-tilt (60 degrees) positioning test with isoproterenol infusion. Eight patients with unexplained recurrent syncope after clinical and electrophysiological investigations and 5 patients without syncope who had bradyarrhythmias due to increased vagal tone were studied. All 8 patients with recurrent syncope had some prodrome suggestive of vasovagal syncope. The upright-tilting test was considered positive if syncope developed in association with hypotension or bradycardia, or both. If 10 min of control tilting was negative, the patient was lowered to the supine position. Upright-tilting was then repeated during continuous intravenous isoproterenol infusion at successive incremental doses of 0.01 to 0.03 microgram/kg/min. During the control upright-tilting test, none of the patients had positive responses. During the upright-tilting with isoproterenol infusions, all patients with vasovagal syncope had positive responses; whereas, all patients with bradyarrhythmia due to increased vagal tone had negative responses. In patients with vasovagal syncope, the heart rate (HR) and the mean blood pressure (mBP) were higher at the time of supine positioning than at the time of syncope (HR: 109 +/- 16-->88 +/- 16 bpm, p < 0.05) (mBP: 86 +/- 5-->53 +/- 6 mmHg, p < 0.01). However, in patients with bradyarrhythmia there was no significant change in HR and mBP between the supine and 10 min of the upright-tilting with isoproterenol infusion.(ABSTRACT TRUNCATED AT 250 WORDS)
Effect of ursodeoxycholic acid (600 mg/day 12 weeks) on liver function tests and bile acid metabolism were investigated in 6 patients with compensatory liver cirrhosis (CLC) and 6 with chronic active hepatitis (CAH). Serial determination of serum GOT, GPT and gamma-GTP after the initiation of UDCA revealed significant reduction in mean levels of these enzymes after 4 weeks, and further improvement was observed at the end of the 12-weeks treatment regimen (CLC: 79.3%, 81.1%, 51.5% of initial values, respectively, CAH: 61.2%, 59.3%, 42.8%). On the other hand, after UDCA administration, serum total bile acid increased and UDCA became the predominant bile acid in CLC and CAH patients. Other endogenous bile acids decreased in both groups, but reduction rate of serum chenodeoxycholic acid level in CLC was smaller than that in CAH group (CLC: 86.1% of initial values, respectively, CAH: 54.2%). During UDCA treatment, apparent side effect was not observed. We suggest that UDCA administration might constitute effective treatment for compensatory liver cirrhosis as well as chronic hepatitis.
We studied the effects of coronary collaterals on exercise capacity in relation with the coronary flow reserve. Thirty-one patients with single vessel disease of the left anterior descending artery (LAD) were selected using coronary angiography. Thirteen of them had angiographical collaterals. A Doppler coronary catheter was positioned in the proximal portion of the LAD, and the resting and peak coronary flow velocity was measured using an intracoronary injection of 6 ml of contrast material. Peak to resting velocity ratio was calculated as an index of the coronary flow reserve. Multi-stage treadmill exercise ECG test was performed, and the end point of the exercise was 0.1 mV depression of ST segment. The exercise capacity was expressed as the ratio of maximal to resting double product. In patients without collaterals, peak to resting coronary flow velocity ratio was correlated with double product ratio (r = 0.94, p less than 0.01). But in patients with collaterals, double product ratios were higher than those in patients without collaterals. We conclude that coronary collaterals preserve exercise capacity in spite of the low coronary flow reserve in the recipient coronary artery.
Transvaginal sonographic endometrial images and endometrial biopsies were obtained during the luteal phase (L5-L10) from 31 patients with normal menstrual cycles. The Hyperechoic Endometrial Area (HEA) ratio was used as the index of sonographic endometrial dating, and 12 glandular and/or stromal parameters were used as the index of histological endometrial dating. The day of ovulation was determined with sequential transvaginal sonography. In 20 patients with a typical sonographic image, 80% of the HEA ratio was equal to L6 based on the histological endometrial dating, and 90% was equal to L9. These results suggested the efficacy of the sonographic endometrial dating. The remaining 11 patients with an atypical sonographic endometrial image were classified into 3 groups (hyperechoic, spotted and hypoechoic type). Two characteristic features, delayed glandular element and increased stromal cell density, were observed in the hyperechoic group. On the other hand, dissociation between glandular and stromal dating was observed in the spotted group. Hypoplastic glands and insufficient secretion were characteristic of the hypoechoic group. These results show that sonographic endometrial dating has clinical efficacy. This dating has enough coincidence with endometrial histology. Moreover, two advantages were recognized in the sonographic dating over the histological dating. One is the non-invasive examination, and the other is the real-time evaluation of the endometrium.
The synergy of cytotoxic activity by interleukin 2 (IL-2) and interferon gamma (IFN-gamma) was evaluated in human peripheral blood mononuclear cells (PBMC) and spleen cells. PBMC incubated with IL-2 (10 IU/ml) and IFN-gamma (200 IU/ml) for 4 days showed the stronger cytotoxic activity against K562, MOLT-4 and Daudi cells. Combination with IL-2 and IFN-gamma induced stronger activity than IL-2 or IFN-gamma alone. In order to investigate the sequential roles of IL-2 and IFN-gamma in the killer cell function, the cells were stimulated with IFN-gamma after washing of IL-2 or stimulated by IFN-gamma at various timing and duration without washing of IL-2. IL-2 was essential to induce the synergistic effect of IL-2 and IFN-gamma to cytotoxic activity. The similar augmentation of cytotoxic activity was observed by the addition of IFN-gamma at any incubation periods with IL-2, compared with stimulation with IL-2 or IFN-gamma alone. The phenotypes of the killer cells by stimulation with IL-2, IFN-gamma alone or IL-2 plus IFN-gamma were mainly CD2+, CD16+, indicating the activated natural killer cells.
A major problem associated with the succinate dehydrogenase inhibition (SDI) test using tetrazolium dye (MTT) as a cancer chemosensitivity testing is the contamination of non-malignant cells in the tumour tissues. Highly purified fresh human tumour cells from 44 solid tumours and 24 malignant ascites were used for the MTT assay. The purity of tumour cells was greater than 90% after separation on Ficoll-Hypaque and Percoll discontinuous gradients. The OD570 obtained from tumour cells alone was higher than that from non-malignant cells. The chemosensitivity of tumour cells was distinct from that of non-malignant cells. Moreover, the chemosensitivity of highly purified tumour cells was also distinct from that of non-purified cells just separated from tumour tissues. 31 of the 68 patients had evaluable lesions, and received cancer chemotherapy according to the results of MTT assay using highly purified tumour cells. A clinical response was obtained in 10 of the 31 patients (response rate = 32.3%, 5 complete responses, 5 partial responses).
Accumulating evidence suggests an important role of vascular renin-angiotensin system (RAS) in the local control of arterial tone. To further gain insight into the significance of vascular RAS in hypertension, we investigated the relationship between the antihypertensive action of delapril, a newly developed converting enzyme inhibitor (CEI), and its effects on vascular angiotensin II (Ang II) release in spontaneously hypertensive rats (SHR). Male SHRs were given delapril or its active metabolite (5-hydroxydelapril diacid; 5-hydroxy-DPD) orally (10 mg/kg/day) for 2 weeks. Isolated hind legs of these rats were perfused with angiotensinogen-free Krebs-Ringer solution, and Ang II released into the perfusate was directly determined by extraction with Sep-Pak C18 cartridges connected to the perfusion system. Both delapril and 5-hydroxy-DPD produced a sustained antihypertensive action. The spontaneous release of Ang II from isolated perfused hind legs of control SHRs was about 50 to 110 pg during the first 30 min of perfusion, and it remained stable up to 3 h. Another active metabolite, delapril diacid (DPD), when added to the perfusion medium (10(-9) to 5 x 10(-5) mol/L), suppressed the Ang II release in a dose-dependent manner. The maximal percent inhibition of Ang II released evoked by DPD (5 x 10(-6) mol/L) was approximately 51%. Oral pretreatment of either delapril or 5-hydroxy-DPD for 2 weeks suppressed the Ang II release by 61% and 73% for delapril and 5-hydroxy-DPD, respectively. These results suggest the presence of a functional RAS in vascular tissues, and that delapril exerts its antihypertensive effect through inhibition of vascular Ang II release in SHRs.
Previously we reported that immunoreactive angiotensin II (Ang II) release from isolated perfused human umbilical veins was inhibited by the angiotensin-converting enzyme inhibitor captopril. To further investigate the mechanism by which Ang II is generated in the blood vessels of humans, we examined the effects of various inhibitors of the renin-angiotensin system (captopril, delapril, N-acetyl-pepstatin, and human renin inhibitor KRI-1314) on Ang II release from perfused human umbilical cord veins in vitro. Isolated human umbilical veins were perfused with Krebs-Ringer solution, and immunoreactive Ang II released into the perfusate was measured directly by using a Sep-Pak C18 cartridge connected to the perfusion system. Both captopril and delapril diacid (10(-9) to 5 x 10(-6) mol/L), an active metabolite of delapril hydrochloride, suppressed the Ang II release in a dose-dependent fashion; the maximal percent suppression of Ang II release evoked by these inhibitors (5 x 10(-6) mol/L) was 56% and 64%, respectively, for captopril and delapril. Both N-acetyl-pepstatin (10(-9) to 10(-5) mol/L) and KRI-1314 (10(-9) to 10(-6) mol/L) suppressed Ang II release in a dose-related manner. At a 10(-6) mol/L concentration, KRI-1314 produced a 74% reduction in the basal rate of Ang II release, and a reduction threefold greater than the maximal reduction in basal Ang II release produced by N-acetyl-pepstatin.(ABSTRACT TRUNCATED AT 250 WORDS)
1. In view of a recent interesting hypothesis that the vascular renin-angiotensin system (RAS) plays an important role in the maintenance of hypertension, we examined the effect of delapril (DP), a newly developed angiotensin converting enzyme inhibitor (ACEI), on angiotensin II (Ang II) release from isolated perfused hind legs of spontaneously hypertensive rats (SHR) in comparison with normotensive rats of Wistar-Kyoto strain (WKY). 2. Male SHR and WKY were given DP orally (10 mg/kg per day) for 2 weeks. Isolated hind legs of these rats were perfused with angiotensinogen-free Krebs-Ringer solution, and Ang II released into the perfusate was determined directly by extraction with Sep-Pak C18 cartridges connected to the perfusion system. 3. Delapril produced a sustained antihypertensive action in SHR but not in WKY. The spontaneous release of Ang II in SHR was 112.9 +/- 17.6 pg during the first 30 min of perfusion, which was somewhat greater than that in WKY (96.5 +/- 9.8 pg). An active metabolite of DP, delapril diacid (DPD), when added to the perfusion medium, suppressed the Ang II release in a dose-dependent manner in the two strains. Oral pretreatment of DP for 2 weeks suppressed the Ang II release by 60% in WKY and more pronouncedly by 73% in SHR. 4. These results suggest the presence of a functional RAS in vascular tissues which contributes to the maintenance of vascular tone of SHR, and that ACEI including DP exerts their antihypertensive effect through inhibition of vascular Ang II release in this animal model of human hypertension.
Increasing evidence in recent years suggests an important role of the central renin-angiotensin system in cardiovascular regulation. Although angiotensin-converting enzyme (ACE) is a pivotal element in this system, little is known about the enzyme in human brain. Thus, the regional distribution and biochemical properties of ACE were investigated in human brain. The highest activity was found in the hypothalamus (1.23 +/- 0.22 units/mg protein), followed by the caudate nucleus (1.06 +/- 0.23), substantia nigra (0.97 +/- 0.20), medulla oblongata (0.59 +/- 0.17), cerebral cortex (0.30 +/- 0.07), and cerebellum (0.08 +/- 0.02). A high activity was also detected in the pituitary (0.66 +/- 0.12). This enzyme activity was almost completely (70-90%) suppressed by a specific antibody raised against pure human kidney ACE, indicating that the majority of the activity measured is due to true ACE. The molecular weight of the enzyme was 290,000 on gel-exclusion chromatography, 152,000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and 158,000 by an immunoprecipitation technique coupled with SDS-PAGE. The optimum pH was 8.0-8.5. The enzyme activity was elevated by increasing concentrations of NaCl, indicating a chloride ion dependency of the enzyme. Most of the enzyme (greater than 80%) was bound to concanavalin A, suggesting the presence of carbohydrate residues. These findings provide evidence for the presence of specific ACE in discrete areas of human brain and suggest that angiotensin II could be generated locally in these structures to exert cardiovascular effects in humans.
We investigated whether tumor cell lysis by lymphokine-activated killer (LAK) cells was enhanced by treatment of the tumor cells with cisplatin (CDDP) in vitro. Tumor cells were treated with CDDP in vitro, and the cytotoxic activity for LAK cells was measured by 4-h 51Cr-release assay. The alterations of succinate dehydrogenase (SD) activity, and DNA,RNA synthesis of tumor cells were analysed. The susceptibility of CDDP-treated (2 micrograms/ml, 2h) Daudi and KATO-III cells to lysis by short term-cultured LAK cells was enhanced, as was the susceptibility of CDDP-treated (2 micrograms/ml, 12h) autologous tumor and Daudi cells to lysis by long term-cultured LAK cells. SD activity and DNA synthesis in tumor cells were impaired by 12-h treatment with 2 micrograms/ml of CDDP, whereas those were not altered by 2-h treatment with 2 micrograms/ml of CDDP. The enhancement of the susceptibility of CDDP-treated tumor cells to long term-cultured LAK cells was thus elucidated; it was shown to be due to alterations of the tumor cells with regard to their SD activity and DNA synthesis. It is suggested that the combined therapy with CDDP and LAK cells offers hope for increasing the response rate and the long-term survival of cancer patients.