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Using cine magnetic resonance imaging (MRI) and echocardiography, we investigated the effects of candesartan cilexetil, a specific angiotensin II type 1 (AT1) receptor antagonist, on left ventricular (LV) mass and hemodynamics in patients with essential hypertension. Ten patients (four men and six women) with essential hypertension received candesartan cilexetil 2-8 mg/day orally for 8-12 weeks. After drug administration, systolic blood pressure (BP) decreased from 178.9 +/- 17.2 mmHg (mean +/- SD) to 150.2 +/- 14.3 mmHg (P < 0.0001) and diastolic BP from 101.4 +/- 6.5 mmHg to 87.8 +/- 11.9 mmHg (P = 0.0021). Both MRI and echocardiography revealed a significant decrease in LV mass index (LVMI) after candesartan cilexetil. MRI indicated that LVMI decreased from 111.3 +/- 31.3 g/m2 to 102.6 +/- 32.1 g/m2 (P = 0.0484) and echocardiography that LVMI decreased from 123.9 +/- 31.1 g/m2 to 115.8 +/- 31.4 g/m2 (P = 0.0316). Total systemic vascular resistance decreased significantly during treatment with candesartan cilexetil in both MRI and echocardiography assessment, from 1847.2 +/- 636.3 dynes.s.cm-5 to 1540.4 +/- 432.0 dynes.s.cm-5 (P = 0.0034) on MRI and from 1820.4 +/- 318.8 dynes.s.cm-5 to 1659.0 +/- 317.7 dynes.s.cm-5 (P = 0.0060) on echocardiography. These findings suggest that candesartan cilexetil 2-8 mg/day orally for 8-12 weeks is beneficial in the regression of cardiac hypertrophy in patients with essential hypertension.

Theophylline is widely used for treating patients with bronchial asthma. However, since the therapeutic concentration range is narrow, adverse reactions are frequent and often difficult to control, making monitoring of theophylline concentration mandatory for its efficient and safe use. In this study, we employed the AccMeter which allowed us to measure theophylline concentrations quickly and with ease, and compared it with EIA method. AccMeter is a kit which consists of two parts. One part consists of a chromatopaper with antitheophylline mouse monoclonal antibody fixed on it, on which a smaple is applied with enzyme-linked theophylline. The other part consists of a coloring solution. We used a part of arterial blood samples collected for gas analysis as trial samples. Both whole blood and plasma from 50 patients who did or did not receive theophlline were analysed. Plasma portions were also used for measurements by the EIA method. Results from all three measurements were almost identical, and showed good correlation. The time necessary for measurement using AccMeter was about 20 minutes. We consider this method to be useful for clinics due to its simplicity and ease of handling, and the accuracy of the results obtained.

We have made a new device for allergen skin testing, which can be used easily. It consists of two parts. One, several gears are fixed on a board in a row, and when one gear goes round, other gears also go round simultaneously. A disposable needle is attached to each gear. A semi-spherical hole is made in the lower surface of a disposable needle, and a sharp needle is fixed in, but not at the centre of the hole. The other, small tanks are arranged in a row at the same distance as the gears. When the disposable needles are inserted to the tanks filled with allergen extract, it is hold in a semi-spherical hole by surface tension. The allergen extracts go intradermally, when the needles move semi-circular on a human skin. We performed skin tests to 23 patients with this device, and got satisfactory results as screening tests.

Several criteria have been used for differentiating hepatic cavernous hemangioma from other tumors at magnetic resonance imaging (MRI). Included are signal intensity and lobulation of the tumor. We counted the frequency of presence of lobulation of liver hemangiomas on T2-weighted images (T2WI), and measured the signal-intensity ratio (SIR) on T1-weighted images (T1WI) and on T2WI with a 0.9 mm x 0.9 mm pixel size using a 0.5 T magnetic resonance system. Eighty-three cavernous hemangiomas in 44 patients and 67 malignant tumors in 44 patients were retrospectively studied. Seventy-five of the cavernous hemangiomas (90%) exhibited lobules of various sizes, and four of the malignant tumors (6%) exhibited lobulations. The cavernous hemangiomas had a significantly higher SIR than the malignant tumors on T2WI: 3.0 +/- 0.7 and 1.9 +/- 0.8 (p < 0.001), respectively. The presence of lobulation together with a high SIR was a useful measure for differentiating cavernous hemangiomas from other liver tumors.

We present three patients with Creutzfeldt-Jakob disease (CJD). They lived in Fuji city and its neighboring towns in the eastern part of Shizuoka prefecture. Patient 1 and patient 2 were cousins. Patient 1 developed the illness at the age of 50 in 1987 and died 13 months later. Patient 2 became ill at the age of 73 in 1989 and died seven months later. Patient 3 was related to a familial CJD cases in Yamanashi prefecture, known as Akai's "H" family (Akai et al in 1979, Yamamoto et al in 1986). She became ill at the age of 78 in 1990 and died four months later. Their clinical features were common; rapidly progressive dementia, generalized myoclonus, and periodic synchronous discharges on electroencephalographies. They were autopsied and neuropathologically diagnosed as typical CJD. Molecular genetic analysis of the prion protein (PrP) gene was performed on patient 2 and patient 3 using their frozen brain sections. The results showed a point mutation in the PrP gene at codon 200; GAG to AAG (Glu-->Lys). The eastern part of Shizuoka prefecture is adjacent to Yamanashi prefecture where a large number of patients with CJD including familial cases has been found during the recent 15 years. This study suggests that the patients with CJD in both Yamanashi and Shizuoka prefecture should be re-evaluated by analysis of the PrP gene.

Magnetic resonance (MR) angiographic studies of 14 patients with intracranial aneurysms (AN) were analyzed retrospectively as compared with contrast angiographic studies. Eighteen of 19 (95%) lesions were detected, and the relation between AN and their parent vessels was precisely assessed. The diameter of the smallest aneurysm detected in our case was 3 mm. However, small vessels around AN were not visualized. Therefore, MR angiography (MRA) is definitely not a substitute for preoperative contrast angiography. MRA is a useful screening tool for nonruptured AN, but further refinement is required to evaluate emergency ruptured AN.

We measured and compared left ventricular mass in 20 patients by ultrafast computed tomography (UFCT), magnetic resonance imaging (MRI), and contrast left ventriculography (LVG). Left ventricular mass was calculated by UFCT and MRI in two ways: (1) excluding papillary muscles and trabeculae (LV mass), and (2) including papillary muscles and trabeculae (LV mass + PM&T) by Simpson's method. Left ventricular mass excluding papillary muscles and trabeculae (LV mass) in LVG was calculated by Rackley's method by biplane angiocardiography. LV mass was significantly larger in LVG than in MRI and UFCT (p < 0.01). Although LV mass was significantly larger in MRI than in UFCT (p < 0.01), there was no significant difference in LV mass + PM&T between UFCT and MRI. Interobserver and intraobserver variability showed good correlation of coefficient in both UFCT and MRI. We therefore conclude that left ventricular mass is best measured by including papillary muscles and trabeculae by Simpson's method in UFCT or MRI.

Staphylococcus aureus S704 and 8325MMT7 show constitutive resistance to macrolide antibiotics such as erythromycin (EM), oleandomycin, spiramycin, rosamicin and josamycin, except for tylosin, rokitamycin (RKM), and mycinamicin as well as lincosamide and streptogramin type B antibiotics (PM-resistance). Whenever 70S ribosomes from either of them were dissociated into 30S and 50S subunits in a 10-28%(W/W) linear sucrose gradient, the latter subunit was further cleaved into two small apparently equal particles (about 40S). RKM could no longer bind to either of the small particles. A prior exposure of 8325MMT7's 50S subunit to RKM (except EM) did not cause cleavage in any small particles. The largest component (M.W. 33.0kDa) of 50S ribosomal proteins was absent in at least the small particles. The first finding suggests that the lability of the 50S ribosome may be responsible for PM-resistance.

In the management of patients with acute cerebral disturbances, it is essential to determine precisely the degree of impaired consciousness. In order to secure the accuracy of observations, one must use a reliable coma scale. We have evaluated the Edinburgh 2 coma scale (E2CS) and explored the relationship between levels of the E2CS and the final outcome. Case notes and observation charts of the past 7 years were reviewed, covering neurosurgical operations on 406 patients, in each of whom the postoperative course was evaluated periodically by the E2CS and the outcome was determined by the Glasgow outcome scale. By matching the outcome with each level of impaired consciousness, about 22,000 pairs of data were obtained. In order to quantify the morbidity rate, different stages of the Glasgow outcome scale were rated from 100 through 0, arbitrarily. It was proved that levels of the E2CS were arranged in the correct order in respect to both mortality and morbidity rates. It was shown at the same time that each level has different prognostic significance and that the distance between each level is not identical. The recommendation is made to separate the levels on a chart not by an ordinal number but by the distance calculated on the basis of either mortality or morbidity rates. This will make it possible to get a rough estimate of the patients' prognoses by simply looking at a daily clinical chart.

A rare case of malignant melanoma metastatic to the cavernous sinus and skull, with an unknown primary origin, is reported. A 46-year-old man noticed diplopia, lt. ptosis and swelling in the parietal and maxillary regions. The parietal skull tumor and the maxillary lymph node were excised and histological examination revealed malignant melanoma. Because of its roentogenological characteristics, the lesion of the cavernous sinus was also thought to be the site of metastasis of malignant melanoma. This case is rare because the initial symptom was cavernous sinus syndrome, and no involvement of brain parenchyma was observed.

A cell line was established from an anaplastic astrocytoma from a 69-yr-old female. The cells have been serially subcultured over 300 times for 6 yr without showing any sign of cell senescence. Their doubling time is about 36 h. The cells are fusiform and often hexagonal in sparse culture, but become spindle-shaped and formed mosaic structure in confluent culture. Under electron microscopy, intermediate filaments were randomly distributed in the cytoplasma, especially in the perinuclear space. The chromosome number was near tetraploid and varied from 86 to 94 chromosomes with a modal number of 91. The alpha and beta subunits of S-100 protein, vimentin, and glial fibrillary acidic protein (GFAP), which are reliable markers of astrocytic cells, were demonstrated in a large number of cells by immunoperoxidase staining. The results of immunoblotting showed that the expression of vimentin was much higher than that of GFAP. The tumorigenicity of the cells was revealed by xenografting into nude mice, which were X-irradiated before inoculation. Culture medium conditioned by the cells promoted growth of these cells in serum-free conditions and of normal rat glial cells in serum-depleted culture. The growth-promoting effect of conditioned medium was lost by trypsinization and reduced by boiling. These findings suggest that these cells are derived from neoplastic astrocytic cells and secrete a self-acting polypeptide growth-promoting factor into the culture medium.

Surgical repair of the mixed type total anomalous pulmonary venous connection (TAPVC) in infancy is known to be difficult. In this report, experience of two infants with the mixed type TAPVC with the left upper pulmonary vein (PV) draining into the innominate vein and the other PVs into the coronary sinus (IIa + Ia (left upper PV) type TAPVC) is presented. In such cases, it has been said that the left upper PV should be left uncorrected, but we anastomosed the left upper PV, that was thin and fragile, to the left atrium and corrected all the other anomalous PVs. The results were satisfactory. Recently, Extra-Corporeal circulation, microsurgery, and other techniques have significantly progressed, so we consider that the anastomosis is possible in most infants with IIa + Ia (left upper PV) type TAPVC. In the future, careful clinical follow-up and repeat catheterizations should be done, and we'd like to examine the long term patency of the left upper PV.

The antitumor compound ACNU (1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitroso ure a hydrochloride) is widely used for treatment of malignant brain tumors. The authors have investigated the mechanism of acquisition of ACNU resistance at the cellular level by isolating ACNU-resistant mutants from V79 Chinese hamster cells and C6 rat glioma cells after treatment of the cells with ACNU or other alkylating agents. In V79 Chinese hamster cells, ACNU at 1 to 4 micrograms/ml caused dose-dependent induction of drug-resistant mutants to ACNU (10 micrograms/ml) and 8-azaguanine (20 micrograms/ml), but not to ouabain (1 mM). Values for the mean lethal dose of ACNU-resistant mutants were 2.4 to 17.2 times those of the parent V79 cells. The ACNU-resistant phenotype was stable during an observation period of 13 weeks. The ACNU seemed to have a specific effect in inducing ACNU-resistant mutations, because no ACNU-resistant mutations were induced by treatment of the cells with other known mutagens, such as N-methyl-N'-nitro-N-nitrosoguanidine, methylmethanesulfonate, and ethylmethanesulfonate. The C6 rat glioma cells also showed a significant mutagenic response to ACNU, producing ACNU- and 5-fluorouracil-resistant mutants. The present results have the important therapeutic and mechanistic implication that ACNU is a potent mutagen and induces mutants that are resistant to ACNU and to other drugs.

FT-207 rectum suppository at a daily dose of 1 g was repeatedly administered to patients with squamous cell carcinoma of the uterine cervix. Total doses ranged from 7 to 41 g. The following pharmacokinetic results were obtained in comparison with single administration. The blood level of FT-207 showed its peak of 35 to 37 mcg/ml at 4 hours after administration, of which half-time was 11 to 12 hours. The blood level of 5-FU showed its peak of 0.038 to 0.041 mcg/ml at 2 to 4 hours after administration, of which half time was more than 24 hours. Inter-individual differences were less than those of single administration. The level of FT-207 in tumor tissue was 14.2 mcg/g which was 15 times higher than that single administration. The level in healthy uterine cervix was 18.1 mcg/g which was 12 times higher that of single administration. The level of 5-FU in tumor tissue was 0.359 mcg/g which was 5 times than that of single administration. The level in normal tissue was 0.15 mcg/g which was 3 times higher than that of single administration. The level of 5-FU in tumor tissue was 7.8 to 8.4 times higher than that in blood. There was no difference in concentrations of both FT-207 and 5-FU between metastatic and non-metastatic lymph nodes.

In the isolated papillary muscle of the rabbit the time course of the effects of selective beta- and alpha-adrenoceptor stimulation by isoprenaline and methoxamine, respectively, on the contractile force and on the level of 3',5'-cyclic AMP (cAMP) was determined. 1. Isoprenaline (3 times 10(-7) M) increased significantly the content of cAMP at 15 sec and elevated it to the maximal level-about twice the control value-at 30 sec after its administration, while the developed tension of the papillary muscle was also increased significantly at 15 sec and reached gradually its maximum at 90 sec. 2. Compared with isoprenaline methoxamine (10(-4) M) increased the developed tension very slowly: the maximal response was reached after 20 min. The level of cAMP, on the other hand, was changed neither before nor during the induction of the positive inotropic effect of methoxamine. 3. The phosphodiesterase inhibitor papaverine (10(-5) M) inhibited the PDE activity of the papillary muscle by about 40% after an incubation of 1 hr, and increased the level of cAMP significantly. The effects of isoprenaline on the contractile forced and on the level of cAMP were considerably enhanced by papaverine: the content of cAMP was increased by isoprenaline (3 times 10(-7) M) to about 3 times the control value and also its positive inotropic effect was significantly greater than in controls without papaverine. On the other hand, the positive inotropic effect of methoxamine (10(-4) M) was not affected by papaverine (10(-5) M). Furthermore, in the papillary muscle treated with papaverine the level of cAMP was significantly reduced by methoxamine: the papaverine-induced increase of cAMP was abolished by methoxamine. 4. The present results are compatible with the hypothesis that cAMP is involved as a mediator in the positive inotropic effect induced by beta-adrenoceptor stimulation, and indicate further that the stimulation of alpha-adrenoceptors evokes its positive inotropic effec through a mechanism other than that elicited by beta-adrenoceptor stimulation, i.e., independent of cAMP.

A 1-year-and 4-month-old girl with giant choroid plesux carcinoma was reported from a viewpoint of surgical treatment. As this tumor develops in the ventricular system, rapid deterioration of the general condition due to marked intracranial hypertention is seen especially in children. Therefore, the first aid of the surgical treatment is the control of the intracranial pressure by continuous ventricular drainage in an attempt to improve the general condition of the patient. Because the tumor is very bloody, applying of the temporary clip on the feeding artery such as the anterior choroidal artery should be recommended prior to the dissection of the tumor during surgery.

We have treated 2 cases of simultaneous bilateral breast cancer by intra-arterial infusion chemotherapy (IA) and transcatheter arterial chemo-embolization (TAC-E), respectively. In the former case treated by I. A., both the treated tumor and the contralateral mass were remarkably regressed and necrotized. However, serious systemic side effects due to the intraarterially infused drug were observed. In the latter case treated by TAC-E, chemo-embolic effects were selectively observed in the treated tumor, and side effects were slight. On the other hand, a non-treated mass showed no changes. From these findings, we concluded that I. A. serves as a semisystemic therapy, and that TAC-E, at least in our subjects, works as a loco-regional cancer chemotherapy.

The purpose of this study was to examine the effects of N-(2,6-dimethylphenyl)-8-pyrrolizidineacetamide hydrochloride hemihydrate (SUN 1165), a newly developed antiarrhythmic agent belonging to class Ic, on the ventriculoatrial (VA) conductivity of accessory pathways and paroxysmal supra-ventricular tachycardia (PSVT). Twelve patients with accessory pathways were examined by standard electrophysiologic technique before and after a single oral dose of SUN 1165 (100 mg). 1 h after administration, SUN 1165 blocked VA conduction of the accessory pathway in six of twelve patients and prevented the induction of PSVT in six of seven cases. In the cases in which VA block did not occur, the VA interval prolonged (from 178 +/- 7 to 190 +/- 11 ms, p less than 0.05), and the effective refractory period of VA conduction was also increased (from 273 +/- 10 to 318 +/- 15 ms. p less than 0.05). SUN 1165 also prolonged the conduction time in normal conduction systems (AH and HV intervals and QRS duration), but the degree of the prolongation was moderate and not dangerous. There was no adverse effect. These results indicate that SUN 1165 is a potent and safe antiarrhythmic agent, and useful for preventing or stopping PSVT by blocking or depressing VA conduction through accessory pathways.