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Biomedical subjects

Y Aso

Publications and source records attributed to Y Aso.

At least 217 records · Page 12Linked to original sources

Measurement of inhibin concentrations in men: study of changes after castration and comparison with androgen levels in testicular tissue, spermatic venous blood, and peripheral venous blood.

We measured serum inhibin levels in eight untreated patients with prostatic cancer undergoing castration by RIA using an antiserum against 31-kDa bovine follicular fluid inhibin. The inhibin concentrations in testicular tissue and spermatic venous blood were also measured in six of these patients. Serum inhibin levels (mean +/- SD, 377.8 +/- 212.1 U/L), declined rapidly after castration (15 min after, 233 +/- 171.4; 30 min, 224.6 +/- 156.6; 1 h, 181.5 +/- 95.9; 2 h, 174.3 +/- 69.4; 4 h, 122 +/- 6.4; 6 h, less than 120). High concentrations of inhibin were detected in testicular tissue (31,360 +/- 15,180 U/kg), and the levels in spermatic venous blood (3,178.3 +/- 1,386.8 U/L) were approximately 10 times greater than those in peripheral blood (385.5 +/- 233.1 U/L). Testosterone levels were 1,968.2 +/- 992.3 nmol/kg in testicular tissue and approximately 100 times greater in spermatic venous blood (1,631.6 +/- 389.7 nmol/L) than in peripheral blood (18.0 +/- 4.4 nmol/L). These results suggest that circulating inhibin in men mainly originates from testis and that one of the routes of secretion is via the bloodstream.

Aged↗

Statistical evaluation of accelerated stability data obtained at a single temperature. I. Effect of experimental errors in evaluation of stability data obtained.

Accelerated stability data obtained at a single temperature is statistically evaluated, and the utility of such data for assessment of stability is discussed focussing on the chemical stability of solution-state dosage forms. The probability that the drug content of a product is observed to be within the lower specification limit in the accelerated test is interpreted graphically. This probability depends on experimental errors in the assay and temperature control, as well as the true degradation rate and activation energy. Therefore, the observation that the drug content meets the specification in the accelerated testing can provide only limited information on the shelf-life of the drug, without the knowledge of the activation energy and the accuracy and precision of the assay and temperature control.

Drug Stability↗

Statistical evaluation of accelerated stability data obtained at a single temperature. II. Estimation of shelf-life from remaining drug content.

Accelerated stability data obtained at a single temperature (40 degrees C) is statistically evaluated and the utility of the actual value of remaining drug content observed in the test for estimation of shelf-life is discussed. The distribution of the time required for 10% degradation at 25 degrees C, t90(25), is calculated from the observed drug content, taking the experimental errors into consideration. The probability that the t90(25) is longer than a specified shelf-life, which is calculated from the distribution, is represented as a function of the observed drug content. The probability was found to depend on the experimental errors in the assay and temperature control as well as in the activation energy of degradation (Ea). The relationship between the observed drug content and the shelf-life assured with a certain probability is shown graphically, so that one can reasonably predict the expected shelf-life as a function of Ea if the accuracy and precision of the assay and temperature control are known.

Drug Stability↗

Epimerization and racemization of some chiral drugs in the presence of human serum albumin.

Epimerization and racemization of carbenicillin, ethiazide, etoposide and oxazepam acetate were examined kinetically in the presence of human serum albumin (HSA). The concentration of both optical isomers of each drug was determined by stereospecific high-performance liquid chromatography. The apparent rate constants of epimerization or racemization and hydrolysis were estimated from the concentration-time data. HSA retarded the racemization of ethiazide and the epimerization of etoposide. The binding of the drugs to HSA may inhibit the attack of hydroxy ion and/or water molecule and thus retard the epimerization and the racemization. HSA accelerated the epimerization of carbenicillin, which is charged at the pH studied. Ion-ion and ion-dipole interactions between carbenicillin and HSA activate the carbenicillin molecule favorable for the attack of hydroxy ion and/or water molecule. The hydrolysis rates of ethiazide, carbenicillin and oxazepam acetate were increased by the addition of HSA. The hydrolysis rate of d-oxazepam acetate enantiomer bound to HSA was twice that of the l-enantiomer, which suggests that the esterase-like activity of HSA is enantioselective. Differences in the binding affinities of the drug's enantiomers to HSA may account for the selectivity.

Chromatography, High Pressure Liquid↗

[A trial of combination chemotherapy. Cis-platinum, peplomycin and adriamycin for advanced prostatic cancer].

Between September 1982 and May 1984, combination chemotherapy with cis-platinum, peplomycin and adriamycin was administered to 12 patients with histologically confirmed adenocarcinoma of the prostate and progressive disease with evaluable parameters. Cis-platinum (CDDP) 20 mg/sqm was administered intravenously on Days 1-5, peplomycin 5 mg/sqm by 24-hour continuous drip infusion on day 1-5 and adriamycin 25 mg/sqm on Day 1. This course was repeated every 28 days. The dose and schedule were modified by hematologic toxicity or other side effects. One patient refused therapy because of severe nausea and vomiting; therefore 11 patients were eligible for response evaluation. Of the 11 patients, two had a documented PR, five had SD and four had PD. Ten patients whose disease eventually progressed received a second line of therapy consisting either of estramustine or estrogen. Of these ten patients, 6 had a documented PR, one had SD and three had PD. It is concluded that this combination chemotherapy regimen may prime advanced prostatic cancer to respond to hormonal therapy, even though it has only a limited effect on advanced prostatic cancer.

Adenocarcinoma↗

[The clinical efficacy of outpatient extracorporeal shock wave lithotripsy].

From March 1989 through December 1989, 123 patients, 9 to 78 years old, were treated by extracorporeal shock wave lithotripsy (ESWL) with the Wolf Piezolith device. Outpatient treatment was performed routinely. Anesthesia was not required in all of the patients. No analgesia or sedation was given routinely. When pyuria had been found before treatment, a course of prophylactic oral antibiotics was given. Treatment consisted of 2000 to 6000 shocks in adults. The need for re-treatment was decided on the basis of the follow up X-rays. Fragmentation into particles 5 mm in size or less occurred in 144 of the 149 renoureteral units (96.6%). Unfragmented stones were treated successfully by the combination therapy of ESWL and fiberoptic transurethral nephroureterolithotripsy (f-TUL). Of 144 renoureteral units, 3-month follow-up data are available for 96. Among the 96 units, the rate of being free of stones was 67 per cent for renal stones and 96 per cent for ureteral stones treated in situ. The over-all rate of being free of stones was 80.2 per cent. There were no significant complications. Ultrasound imaging has proved to be as effective as X-ray imaging. Outpatient ESWL with the Wolf Piezolith device is considered to be safe and efficient for the initial treatment of urinary stones. On the other hand, ESWL monotherapy is not sufficient for the treatment of complete staghorn calculi or long-term impacted ureteral calculi. We think that the combination use of ESWL and f-TUL is the most effective procedure for treatment of complicated stones.

Adolescent↗

[Histological and flow cytometric analyses of carcinogenesis of rat prostate cancer].

Histological and flow cytometry (FCM) analyses were performed of carcinogenesis of rat prostate cancer induced with N-Nitroso-N-methylurea (NMU). Ten-week-old rats were inoculated intravenously (i.v.) with twice injections of NMU (30 mg/kg body weight) and then, divided into 3 groups; Group 1: the rats were injected subcutaneously with LH-RH analogue (100 micrograms/kg b.w.) every 4 weeks. Group 2: the rats were injected subcutaneously with testosterone enanthate (10 mg/body) every 2 weeks and Group 3: the rats were untreated to serve as controls. We further divided Groups 1 and 2 into (+) and (-) subgroups at 34 weeks after initial injection. Group 1 (+) or 2 (+) rats were continuously given the drug and in Group 1 (-) or 2 (-) rats the drug was suspended. At 44 or 53 weeks after initial injection, we removed the prostate and seminal vesicles of all rats and performed histological and FCM analyses of them. Histological analysis of rat prostates revealed hyperplasia in each group, and both Groups 2 (+) and 2 (-) showed an incidence as high as 87.5%. Atypical hyperplasia was sometimes observed in each group and its incidence was not significantly different between any 2 groups. At 51 weeks after initial injection, a macroscopic adenocarcinoma (weighing about 11 g) was found in the prostate of a dead rat of Group 2 (+). Histological analysis of rat seminal vesicles revealed hyperplasia in each group, in particular in Groups 2 (+) and 2 (-). In these groups all rats showed hyperplasia.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Histological effects of endocrine therapy on prostatic cancer].

Histological effects of endocrine therapy were evaluated in one hundred and four prostatic cancer patients by new criteria presented by the committee of "General Rule for Clinical and Pathological Studies on Prostatic Cancer". Route and time of biopsy, clinical stage and histological grade were related to histological effects. Biopsy specimens taken within three months from the start of the therapy tended to score rather low marks and this tendency is especially apparent with low grade cancers. Histological effects evaluated by the present method correlated well with prognosis in localized stages (stage B, C and D1). In metastatic cases, however, local effects were not related to the prognosis.

Aged↗

[In situ hybridization study of human papillomavirus from the penile cancer].

The histochemical detection of human papillomavirus (HPV) was performed using the technique of in situ hybridization from the formalin fixed paraffin embedded specimens of penile carcinoma and condylomata+ acuminata . One of 19 penile cancer cases (5.3%) revealed the positive staining on the nuclei of the tumors for HPV type 16/18. However, the positive nuclei were scattered and localized in small part of the tumor which showed no koilocytosis. On the contrary, 11 of 12 condyloma acuminata cases (91.7%) showed positive staining on the nuclei of the tumors for HPV type 6/11, also 5 of the 11 cases (45.5%) revealed cross reaction for other type of HPV. The HPV types 6/11, 16/18 and 31/33/35 may be unrelated to the pathogenesis of the Japanese penile carcinoma. However, further study is necessary to evaluate that the number of HPV-DNA copy in our cases is too small, or the other type of HPV is responsibility.

Adult↗

[Four cases of bladder replacement by enterocystoplasty after radical cystectomy for bladder cancer].

Four male patients with invasive bladder cancer, 44 to 68 years old in age, underwent bladder replacement with ileum after radical cystectomy. In three patients an ileal segment alone was isolated for construction of neobladder, and in the fourth patient, the terminal portion of the ileum, the cecum and the proximal part of the ascending colon were isolated for the bladder replacement. In all the cases isolated segments were detubularized for obtaining a low pressure reservoir. All the patients, except one who had a past history of cerebro-vascular disease and was performing intermittent self-catheterization because of a kind of detrusor-sphincter dyssynergia of the ileal-neobladder, are now enjoying almost the same voluntary urination as before the operation. Serum creatinine, BUN and electrolytes are all normal during the postoperative observation period, although a very slight metabolic acidosis was observed in 3 patients. Ten to 16 months have passed without any complications and all the patients are alive without any sign of tumor recurrence or metastatic involvement.

Aged↗

[Infiltration and tissue concentration of intravesically instilled (2"R)-4'-O-tetrahydropyranyladriamycin or adriamycin in rat bladder tumor induced by BBN].

Rats with bladder tumor induced by BBN were treated by intravesical instillation of 0.8 mg of (2"R)-4'-O-tetrahydropyranyladriamycin (THP) (9 rats) or adriamycin (ADM) (8 rats) dissolved in 0.2 ml of distilled water. Thirty minutes later, the bladder was removed surgically. Rats without the tumor received the same treatment of THP (8 rats) or ADM (9 rats). THP and ADM infiltrations to the normal bladder tissue and the tumor were estimated by the use of the photonic microscope system, since both drugs were known to emit characteristic fluorescence. It was found that infiltration of THP to the tumor tissue was more prominent in amounts and deeper than that of ADM, while smaller amounts of THP infiltrated into the normal mucosa compared to ADM. The fact might explain the clinical finding that THP instilled intravesically in half a concentration of ADM showed the same effect on the tumor as ADM. Subsequently, tissue concentrations of THP and ADM were estimated by high performance liquid chromatography. Either THP or ADM was instilled intravesically for 30 minutes to 6 rats with bladder tumor. Similarly, either THP or ADM was instilled in 5 rats without the tumors. Contrary to the result of the photonic microscope system, the tissue concentration of THP was not different from that of ADM not only in the tumor tissues but also in the normal bladder ones. Furthermore, the tissue concentration of both drugs in the normal bladder was higher than that in the bladder tumor.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Intravesical↗

[Adrenal surgery].

In adrenal surgery, of note are increase of the incidence of incidentaloma because of a rapid advance of various image diagnostic procedures, change of the approach of choice due to the more accurate preoperative localization of the adrenal lesions, and the treatment of bilateral lesions. Additionally, the treatments of adrenocortical carcinoma and malignant pheochromocytoma and the method of cortisol withdrawal in Cushing's syndrome were reviewed and discussed. It is important for urologists to perform adrenal surgery appropriately by preoperatively elucidating the full picture of adrenal disorder.

Adrenal Gland Diseases↗

[A clinical study of 124 cases of renal cell carcinoma].

One hundred twenty-four cases of renal cell carcinoma treated at Department of Urology, The University of Tokyo were analyzed for their clinical characteristics and prognosis. To be noted were the recent increase of incidentally detected cases, kidney-sparing technique in curative surgery and adjuvant therapy using biological response modifiers. Prognosis was more favorable in cases with incidental detection, normal ESR or cystic pattern in pathological architecture, whereas that of cases with metastatic lesions or Grade 3 tumors was ominous. Tumor stage as TUMV or Robson stage was useful to predict the prognosis, although one stage contained cases of considerably different survival periods. These results suggested that the efforts to improve prognosis in the present practice should include early detection of renal cancer by promoting health check-up and development of preventive measure of postoperative recurrence. A more proper staging system might also be needed to analyze clinical studies.

Carcinoma, Renal Cell↗

[Expression of endocrine-paracrine cells in prostatic carcinoma].

Endocrine-Paracrine cells (EP cells) in prostatic carcinomas were screened by immunohistochemical tests for neuron specific enolase, chromogranin, and serotonin and by Grimelius method. Formalin fixed, paraffin-embedded sections from 60 prostatic carcinomas were used. EP cells were detected in 16 cases (27%). The number of EP cells in hormone independent prostatic carcinomas were significantly larger than hormone dependent (p less than 0.05) and latent prostatic carcinomas (p less than 0.01). Five cases of prostatic carcinomas with abundant EP cell proliferation died of widespread metastases within 4 years, irrespective of hormone treatment. The pathologic finding was classified into the category of adenocarcinoma, partly showing carcinoid or small cell carcinoma-like features. EP cells were found in perineural invading cancer cells and also immunoreactive to both prostate specific antigen and prostate specific acid phosphatase. It is suggested that the proliferation of EP cells in prostatic carcinomas is related with the sensitivity to hormone treatment.

Acid Phosphatase↗

[Clinical evaluation of bunazosin hydrochloride for the treatment of voiding disturbances due to neurogenic bladder--a double-blind study].

The therapeutic utility of bunazosin hydrochloride was evaluated by a multi-center (67 hospitals) double-blind controlled study in patients who complained of voiding disturbances due to neurogenic bladder. For means of comparison, bethanechol chloride and placebo were used as reference drugs. Bunazosin hydrochloride was orally administered 1.5 mg per day for the first week and 3.0 mg per day for two weeks thereafter (Group E). Bethanechol chloride 15 mg (Group B) and placebo (Group P) were orally administered three times daily for three weeks. Three hundred and twenty-three cases were subjected to this study. The global improvement rating was analyzed for 244 cases (83 in Group E, 78 in Group B and 83 in Group P). The global utility rating (GUR) was analyzed for 252 cases (84 in Group E, 81 in Group B and 87 in Group P). Three hundred and twenty cases (107 in Group E, 104 in Group B and 109 in Group P) were analyzed with respect to overall safety rating (OSR). The global improvement ratings (excellent and good) were 32.5% in Group E, 28.2% in Group B and 21.2% in Group P. In the evaluation of GUR, Group E was superior to Group P. In addition, the incidence judged to be useless in Group E was significantly lower than that in Group B. There were no differences in OSR among these three groups. In the total evaluation of the subjective symptoms, the rates of improvement were not different among these three groups. In the total evaluation of the objective findings, the improvement rate in Group E was significantly higher than that in Group P. In addition, the deterioration rate in Group E was significantly lower than that in Group B. In objective findings before and after administration of bunazosin hydrochloride (Group E), the volume of residual urine, the rate of residual urine and the average flow rate improved significantly However, the bladder capacity, the maximum resting bladder pressure and the maximum urethral pressure did not change significantly. Bunazosin hydrochloride improved the objective findings regardless of the bladder capacity and the maximum resting bladder pressure. These significant improvements were marked in the neurogenic bladder patients who were able to urinate and in the patients whose urethral pressure was high. There were no differences in the incidence of side effects or in the appearance of abnormal values of laboratory findings in these three groups. Neither specific signs nor serious clinical side effects except those reported previously were observed.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenergic alpha-Antagonists↗

[Clinical phase I and phase II study on a sustained release formulation of leuprorelin acetate (TAP-144-SR), an LH-RH agonist, in patients with prostatic carcinoma. Collaborative++ Studies on Prostatic Carcinoma by the Study Group for TAP-144-SR].

TAP-144-SR is a sustained release formulation of an LH-RH agonist, leuprorelin acetate (TAP-144), that has been newly developed in Japan. As a phase I study, a single subcutaneous dose of TAP-144-SR was given to 15 patients with prostatic cancer to investigate the safety, endocrinological effects, and serum levels of the drug. The patients were divided into four groups according to the dosage levels of 1.88 mg, 3.75mg, 7.5 mg and 15 mg. No serious side effects were noted in any of the patients treated with any dose. No patients exhibited signs of a local reaction at the site of injection. In two patients transient exacerbation of clinical symptoms owing to "flare up" was observed. Serum testosterone levels decreased to the castration level (less than 1.0 ng/ml) in all of the patients, although the time required to attain the castration level tended to be longer in the patients receiving 1.88 mg. Serum TAP-144 levels increased on the first day and gradually decreased thereafter. In the groups of patients that received 3.75 mg or more of TAP-144-SR, TAP-144 was detected in the serum up to 4 weeks after administration. Based on the results of the phase I study, 3.75 mg and 7.5 mg of TAP-144-SR were selected as the doses for the phase II study. The phase II study was carried out as a multi-center open trial. Patients with stage B-D prostatic cancer received subcutaneously either 3.75 mg (3.75 mg group) or 7.5 mg (7.5 mg group) of TAP-144-SR once every 4 weeks for a total of 3 doses over a period of 12 weeks. TAP-144-SR 3.75 mg was administered to 51 patients and 7.5 mg to 50 patients. Both of these doses were adequate to suppress serum LH and FSH levels. Serum testosterone was decreased to the castration level within 22 days after the first dose, and this suppression was maintained throughout the treatment period. Clinical response rate (CR + PR) was 21% in the 3.75 mg group and 22-24% in the 7.5 mg group according to the Criteria for Evaluating the Direct Response to Chemotherapy in Solid Carcinomas and NPCP criteria. The response rate by the criteria of Japanese Prostatic Cancer Study Group was 51% in the 3.75 mg group and 62% in the 7.5 mg group. Adverse reactions were noted in 26% of patients in the 3.75 mg group and 34% in the 7.5 mg group.(ABSTRACT TRUNCATED AT 400 WORDS)

Aged↗