Descartes, brain death and organ transplants: a Japanese view.
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Attitude to Death↗
Biomedical subjects
T Umehara
Publications and source records attributed to T Umehara.
[Study of clinical usefulness of an antiandrogen, TZP-4238, as a drug for treatment of benign prostatic hypertrophy--its influence on sexual function].
Using chlormadinone acetate (CMA) as the control drug, a double-blind study was carried out to examine not only the effects of 17 alpha-acetoxy-6-chloro-2-oxa-4,6-pregnadiene-3,20-dione (TZP-4238;) on subjective urinary symptoms but also, especially, that on the sexual function in patients with benign prostatic hypertrophy (BPH). The clinical efficacy rate in relation to the subjective urinary symptoms was about the same in the two treatment groups; 45.9% in the TZP-4238 group and 50.0% in the CMA group. However, the incidence of adverse effects on the sexual function showed a marked difference between the two groups. The TZP-4238 group revealed a lower suppressive effect on the function than the CMA group (45.1% vs. 71.4%). In relation to their causation of other adverse effects, there were no differences between the two drugs. Accordingly, in consideration of the facts that TZP-4238 with less influence on the sexual function affords a superior quality of life to elderly patients, while achieving effective treatment by means of a convenient single daily administration, TZP-4238 was surmised to be a more useful drug than CMA as an antiandrogen for the treatment of BPH.
Aged↗
[Immunohistochemical localization of transforming growth factor-beta 1 in growth plate freshly transplanted into a full-thickness defect in articular cartilage].
Transplants of the epiphyseal growth plate obtained from the proximal tibia of Lewis rats at 3 weeks of age were inserted into full-thickness defects in the patellofemoral articular surface of Lewis rats at 5 weeks of age. As controls, similar surface defects were induced but no transplants were inserted. Transplants were studied immunohistochemically at varying intervals up to 72 weeks in order to determine the effects of transforming growth factor-beta 1 (TGF-beta 1) on the repair of the articular cartilage by the epiphyseal growth plate. TGF-beta 1 was present in chondrocytes in the region corresponding to the hypertrophic zone of the transplanted growth plate at 1 week after transplantation. The distribution pattern of TGF-beta 1 in this hypertrophic zone was similar to that prior to transplantation. At 2 weeks after transplantation, TGF-beta 1 was detected in the matrix, but the hypertrophic chondrocyte cell membranes were not clear. TGF-beta 1 was undetectable in the transplanted growth plate at 4 weeks after transplantation, at which time a morphological examination revealed metaplastically-transformed articular cartilage but no hypertrophic cartilage cells. No immunostaining of TGF-beta 1 was present in the untreated articular defect. These findings suggested that TGF-beta 1 in the hypertrophic chondrocytes was probably transferred from the cytoplasm to the extracellular matrix and stimulated the ossification of the matrix with vessel induction and osteoid formation during the process of incorporation of the transplant into the articular cartilage defect.
Animals↗
[Changes in the salivary testosterone level in aged].
Measurement of the level of free testosterone is important in the evaluation of testicular function. Because most of the testosterone in the saliva is in the free form, measurement of the salivary testosterone level is considered to be effective for the evaluation of testicular function. In the present study, a commercial kit was employed to measure the salivary testosterone level, and the change in the salivary testosterone level with age was investigated. The subjects of this study were 76 males, 20-89 years of age, with no endocrinological diseases. The concentration of testosterone in the saliva was measured for each of the subjects, and for 34 of the subjects the concentrations of total testosterone and free testosterone in the serum were also measured at the same time. Standard serum was diluted to have a testosterone concentration of 50 pg/ml, and the results indicated that it was sufficiently possible to measure the salivary testosterone. The coefficient of correlation between the salivary testosterone concentration and the serum total testosterone concentration was 0.479 (p < 0.01), while the coefficient of correlation between the salivary testosterone concentration and the serum free testosterone concentration was 0.732 (p < 0.001). These findings thus indicate that the correlation between the salivary testosterone concentration and the serum free testosterone concentration is better than that between the salivary testosterone concentration and the serum total testosterone concentration. It was also demonstrated that the salivary testosterone concentration decreased significantly with aging after the fifth decade of life. The correlation coefficient for that relationship was -0.606 (p < 0.001), and the change was similar to that seen in the serum free testosterone concentration as a function of aging. The findings suggested that measurement of the salivary testosterone concentration with the commercial kit is useful for the evaluation of testicular function.
Adult↗
Clinical study of bone-related relapse in prostate carcinoma.
Prostate carcinoma is usually highly responsive to initial endocrine therapy. However, when relapse occurs, the subsequent clinical course is very poor. In this study, we tried to reveal the clinical aspects of bone-related relapse in 392 patients who received endocrine therapy for prostate carcinoma. In 17 stage B patients who had relapsed, 76% experienced relapse within 4 years following the start of treatment, 76% within 3 years in 27 stage C patients, and 71% within 2.5 years found in 45 stage D patients. Pre-treatment levels of serum enzymes and initial response of the primary lesion and of serum enzymes failed to predict relapse. The Gleason sum tended to be correlated with relapse. In particular, patients with a Gleason sum of 9-10 had a lower non-relapse rate during the follow-up period than patients with lower sums. With the recent use of more sophisticated measurements of PSA and/or PAP, the reduction rate or interval to normalization of the markers must be more relevant to predicting relapse.
Acid Phosphatase↗
[Dose finding study of sparfloxacin in single-dose therapy for female acute uncomplicated cystitis].
Sparfloxacin (SPFX) is a new quinolone compound with a long half-life of 16 hours and a potent antibacterial activity (MIC90: < or = 0.025 micrograms/ml against Escherichia coli), suggesting that the agent can be effectively used in single-dose therapy for acute uncomplicated cystitis in female patients. To find the optimum dose, the present dose-finding study was conducted. A dose of either 100 mg or 200 mg of SPFX was selected by the double-blind method, and was administered only once (single dose therapy). The clinical efficacy was judged on day 3, 7 and 14 after administration. On day 3, of the 49 pts. in the 100 mg-group, the efficacy rate was 95.9% (excellent rate: 79.6%), and of the 42 pts. in the 200 mg-group, it was 100% (excellent rate: 88.1%). On day 7, of 38 pts. in the 100 mg-group, it was 94.7% (excellent rate: 78.9%), and of 28 pts. in the 200 mg-group, it was 100% (excellent rate: 92.9%). On day 14, of 27 pts. in the 100 mg-group, it was 92.6% (excellent rate: 66.7%), and of 26 in the 200 mg-group, it was 96.2% (excellent rate: 84.6%). Recurrence was observed in 4.8% (1/21) in the 200 mg-group. Therefore, there was no significant difference in the efficacy rate between the two groups, but the rate of excellent responses was higher in the 200 mg-group. Otherwise, the efficacy was estimated to be insufficient in 3 pts. and recurrent in 1 pt. they were examined the findings of detailed urological intractableness. Among 2 pts. in whom the external genitalia and urethra were closely examined, a urethral caruncle was noted in 1 pt. The results of our study indicate that 200 mg of SPFX is recommended as a single dose therapy for acute uncomplicated cystitis in females.
Acute Disease↗
[Dopaminergic control of gonadotropin secretion in male senescence].
To verify the role of the dopaminergic mechanism in the control of gonadotropin secretion and aging of this mechanism in men, we studied serum gonadotropin response to LH-RH (100 micrograms i.v.) in basal condition and during dopamine infusion (DA 4 micrograms/kg/min). Seven young males (24-29yr.) and twenty aged males (50-80yr.) without endocrinological diseases were included in the present study. Aged male subjects were divided into hyperresponders, in whom maximal LH response to LH-RH without DA infusion exceeded 153.5mIU/ml (mean + 2SD of young male subjects), and non-hyperresponders, in whom maximal LH responses to LH-RH without DA infusion were less than 153.5mIU/ml. In hyperresponders, serum LH response at 30 minutes after LH-RH administration was significantly (p less than 0.05) suppressed by DA infusion. In non-hyperresponders and young male subjects, however, serum LH response to LH-RH was not affected by DA infusion. Basal levels of serum LH and FSH in hyperresponders tended to be higher than that of non-hyperresponders. Total serum testosterone, free testosterone and estradiol levels of hyper and non-hyperresponders failed to reveal any significant differences. These observations suggest that 1) DA directly suppresses gonadotroph responsiveness to LH-RH, 2) in aging men, inhibitory tone imposed on gonadotrophs by DA is decreased, and 3) this decline of DA system can cause hypergonadotropism in aging men, independent of serum sex steroids levels.
Adult↗
[Salivary testosterone levels in normal boys at puberty].
Salivary testosterone (Salivary-T) was measured in 133 normal boys at puberty (8-14 years old) and 21 adult males (24-36 years old) by using radioimmunoassay. Also, a simultaneous measurement was performed on salivary-T and serum total testosterone (Total-T) and free testosterone (Free-T) in order to study the correlation between saliva and serum. The results were summarized as follows: (1) Good correlations were observed in the values between Salivary-T and Total-T or Free-T. The correlation coefficient value was 0.54 between Salivary-T and Total-T, 0.84 between Salivary-T and Free-T when measured by DPC kit. Correlation coefficient value was 0.59 between Salivary-T by Wien kit and Total-T by DPC kit, also 0.77 between Salivary-T by Wien kit and Free-T by DPC kit. (2) Salivary-T, in the mean level, increased by age. The most rapid increase of Salivary-T was observed at 13 years of age. (3) Diurnal change of Salivary-T was observed at 13 years of age through adult age. Salivary-T level was highest in the morning and declined toward evening. (4) These results suggest that Salivary-T measurement was highly reliable and applicable for use in the monitoring of androgen status.
Adolescent↗
The assessment of bioavailable androgen levels from the serum free testosterone level.
Recently, it has been concluded that measurement of the serum free testosterone level is crucial for evaluating male gonadal function. However, the extent of the decline of serum free testosterone levels with aging and the actual levels in male infertility have not yet been clearly defined. In this study, the clinical significance of serum free testosterone levels was evaluated in a total of 248 subjects, including 120 healthy adult males (54 males aged 20-39, 26 males aged 40-59 and 41 males aged more than 60), 94 infertile males, 28 male hemodialysis patients, and 6 patients with Klinefelter's syndrome. Since the serum free testosterone levels correlate significantly with serum LH and FSH levels among 120 normal adult males, it appears that free testosterone has a biological action on the organ. In the subjects aged over 60, serum free testosterone levels were significantly decreased compared with the decrease of serum total testosterone. Thus, biologically active androgen levels decreased with aging. Serum free testosterone levels tended to decrease significantly from 40 years onwards. In infertile males, serum total testosterone levels were equal to those in normal adult males, but their serum free testosterone levels were significantly lower. This decrease of serum free testosterone may be one of the causes of their hypospermatogenesis. In male hemodialysis patients, serum total and free testosterone levels were not lower than in normal adult males. It is considered that the decline of percentage of serum free testosterone levels in aged males and infertile males was caused by increased serum sex hormone binding globulin (SHBG) levels. Several workers have shown that the production of SHBG is regulated by sex steroid hormones. In this study, however, serum SHBG levels were not correlated with the E2/T ratio. We concluded that measurement of the serum free testosterone level is of value in the endocrinological evaluation of male gonadal function.
Adult↗
[Study on frequency of prostate carcinoma and benign prostatic hypertrophy by mass screening in Hokkaido].
We conducted mass screenings for prostate diseases on male subjects over fifty years of age in three separate areas in Hokkaido. Prostate carcinoma and benign prostatic hypertrophy were searched in the 1,764 participants. Histopathologically proven prostate carcinoma was found in twenty-two (1.25%) of the 1,764 participants. This frequency of carcinoma was higher than any other carcinoma found in the mass screenings for gastric, uterine, breast and lung carcinoma in Hokkaido. Of the 22 prostate carcinomas found, 68% were in the early stage (stage B). This stage distribution was clearly distinct from that of prostate carcinoma found on the hospital visit, most of which had already progressed to an advanced stage. These results indicate that mass screening for prostate carcinoma on greater than or equal to 50 year old-male subjects is efficient in finding carcinoma of all stages but, in particular, carcinoma of early stage, when compared with mass screening for other carcinomas. BPH, defined as a moderately or markedly enlarged prostate on rectal palpation, was found in 10% of the participants. Questionnaire on subjective symptoms of voiding disturbance in the participants has confirmed that these symptoms, mainly elicited by BPH, become manifested in fifties and more frequent with age. Of thirteen patients with prostate carcinoma who received both rectal examination and prostate-related markers measurement in serum at the time of mass screening, three without induration of the prostate were diagnosed as having carcinoma from an abnormal value of the serum markers. This result suggests that the marker(s) is one of the useful screening tests for detecting carcinoma.(ABSTRACT TRUNCATED AT 250 WORDS)
Acid Phosphatase↗
[Histopathological findings of prostate carcinoma--nuclear anaplasia (NAN) and structural atypism (SAT)].
Most of the previous publications have focused mainly on structural atypism (SAT) or differentiation in the studies on histopathological findings of prostate carcinoma. We studied nuclear anaplasia (NAN) as well as SAT in prostate carcinoma, comparing with differentiation grade or Gleason's pattern, to find NAN's clinical implication. We also compared histopathological findings of prostate carcinoma in our cases with those in U.S.A. Analysis of NAN grade and SAT grade distribution in stages revealed a correlation between the grades and the stages, in which SAT1 or NAN1 decreased while SAT3 or NAN3 increased in their frequencies as stage progressed. A similar correlation was found between mean value of SAT + NAN grade and stage. While NAN grade and SAT grade agreed with each other in 70% of the patients with prostate carcinoma, that was not the case in the remaining patients. This suggested a complementary relationship between NAN grade and SAT grade in some patients. A similar relationship was found between NAN grade and Gleason's pattern. These results suggest that, in a non-negligible number of patients, the NAN grade does not agree with the SAT grade or Gleason's pattern which is defined by atypism in the glandular structure. Disease-specific survival in each SAT grade could be further defined by the NAN grade. For example, in both SAT2 and SAT3, NAN3 tended to have a poorer prognosis than NAN2. Thus, NAN grading system would furnish more accurate information to predict the patients' clinical course.(ABSTRACT TRUNCATED AT 250 WORDS)
Anaplasia↗
[Clinical studies on endocrine therapy for prostatic carcinoma (4): Initial response to endocrine therapy and prognosis].
We have already pointed out by the use of multivariate analysis that local response of the prostate is one of the important prognostic factors in patients receiving endocrine therapy. Herein, we investigated how the local response to endocrine therapy affects the survival rate or the survival period. We also studied the relationship between the local response and histopathological findings. The local response of prostate was not correlated with the stage progression. Sixty-seven percent of the patents in each stage had an initially favorable local response of the prostate, in which the primary tumor became flattened or reduced by endocrine therapy. By contrast, the local response of the prostate was well correlated with the prognosis in each stage. Patients with a flattened or reduced primary lesion following endocrine therapy showed a higher survival rate or a longer survival period than those with the unchanged lesion. This result has confirmed that the local response of prostate to endocrine therapy is useful in predicting clinical courses of patients. Grade of structural atypism (SAT), one of the pathological findings, had a correlation with local response of the prostate. With an elevation of the SAT grade, the proportion of patients with unchanged primary lesion was increased.
Humans↗
[Clinical studies on endocrine therapy for prostatic carcinoma (5): Analyses of relapse from endocrine therapy].
Prostate carcinomas are well known to be initially responsive to endocrine therapy. However, a significant number of the patients experience a relapse from endocrine therapy during the follow-up period. We clinically analyzed various aspects of the relapse which indicate a limitation in the effectiveness of endocrine therapy for prostate carcinoma. In a total of 372 patients, 117 (31.5%) had some evidence of local relapse such as regrowth of the primary lesion, or a generalized relapse such as re-elevation of total acid phosphatase, reactivation of previously present metastasis or the new appearance of metastasis, during endocrine therapy. Of these, one-fourth had local relapse alone and the remainder showed generalized relapse. The interval from the start of the treatment to the time of relapse tended to become shorter; 45.9 months (mean) in stage B, 36.8 in stage C and 29.3 in stage D, according to the stage progression. As to the non-relapse rate of the primary lesion, no differences were found among the stage, with the rate being approximately 90% at the fifth year in each stage. However, the generalized relapse-rate tended to increase with the stage progression. In the generalized relapse, the patients of stage C or D showed a non-relapse rate of 71.7% or 67.4%, respectively. Most of the generalized relapse appeared within five years following start of endocrine therapy in these advanced stages. The interval from relapse to prostate carcinoma-related death in patients with the generalized relapse was 9 approximately 21 months, and those in stage D tended to show a a poorer prognosis.(ABSTRACT TRUNCATED AT 250 WORDS)
Humans↗
Dielectric study on hydration of B-, A-, and Z-DNA.
Dielectric relaxation peak due to bound water was found around 100 MHz in poly(dG-dC).poly(dG-dC) and calf thymus DNA in water-ethanol mixtures with NaCl buffer. Relaxation time and strength show a transition for poly(dG-dC).poly(dG-dC) at an ethanol composition Cw = 0.45 (w/w) where the structural transition from B- to Z-DNA takes place. It has been suggested that the transition is caused by removal of the bound water molecules preferentially from the phosphate groups. If the bound water molecules are removed equally from the phosphate groups and the grooves, the structural transition from B to A takes place. By analogy with hydration of tropocollagen, it was found that 19 water molecules per one nucleotide are at least necessary to keep B-DNA. Thirteen molecules are bound to A-DNA and 9 molecules to Z-DNA. Stringlike multimers are proposed as available structures of the bound water.
Animals↗
[Mass screening of prostate in Shiribeshi area in Hokkaido--incidence and clinical symptoms of benign prostatic hypertrophy and prostatic carcinoma].
A prostate mass screening was performed in 6 towns in Shiribeshi area in Hokkaido Prefecture on 384 males who were over 50 years old. The screening included digital palpation, uroflowmetry, blood sampling for tumor markers, questionnaire for voiding disturbances and transrectal sonography. Prostatic carcinoma was found in 9 (2.3%) of 384 males. An incidence of benign prostatic hypertrophy was 15.6% in 384 males. Atypical hyperplasia was found in 4 among 35 biopsied cases. Incidence of voiding disturbance such as retardation, prolongation and nocturia significantly increased with age as well as prostate size.
Aged↗
[Clinical studies on endocrine therapy of prostatic carcinoma (1): Multivariate analyses of prognostic factors in patients with prostatic carcinoma given endocrine therapy].
The general trend on the treatment for prostatic carcinoma has been changing from endocrine therapy alone to an alternative type according to stage. We evaluated clinically the favorable and unfavorable outcome of endocrine therapy in Japan, so that others will be appropriately evaluated. In a cooperative study made by members of five universities, 572 patients with clinically or histologically reconfirmed prostatic carcinoma were entered in this retrospective study. We studied the true influence of prognostic factors on the prognosis of 497 patients with prostatic carcinoma who had received endocrine therapy, employing multivariate analyses, such as quantification method II, multiple regression analysis and Cox's proportional hazard model. Twelve factors were considered in the study; "age", "stage", "histological findings (structural atypism = SAT, nuclear anaplasia = NAN, Gleason's primary and secondary pattern)", "pretreatment level of total acid (ACP) and of alkaline phosphatase (ALP)", "castration performed or not performed", "doses of estrogen", "type of response of local prostatic tumor and of ACP to endocrine therapy". Analysis of the "importance" of a prognostic factor by a partial correlation determined by quantification method II, revealed "stage" to have the greatest "importance" on prognosis throughout the entire period. "Response of local prostatic tumor", "response of ACP" and "Gleason's primary pattern" tended to be important factors for prognosis, in particular, in the first half period, and "age" and "Gleason's secondary pattern" were important in the latter half. Multiple regression analysis revealed the "stage", once again to be the most influential factor on the prognosis for the entire observation period. Also "response of local prostatic tumor", "SAT" and "Gleason's primary pattern" affected the patients' prognosis in the first half of the observation period. In the latter half, "age" became more of an influential factor than "histological findings". Analysis with Cox's proportional hazard model revealed that "response of ACP", "stage", "age", "Gleason's primary and secondary pattern", and "response of local prostatic tumor" were definitely the more influential prognostic factors, of which chi-square values (or t values) were statistically significant. Comparison of the significant factors in each multivariate analysis revealed that common influential prognostic factors, such as "age", "stage", "histological findings (mainly Gleason's primary and secondary pattern)", "response of local prostatic tumor" and "response of ACP" were coincident to the clinical impression. The clarification of these factors would be clinically beneficial when treating patients with endocrine therapy.
Estrogens↗
[Clinical studies on endocrine therapy of prostatic carcinoma (2): Prognosis of patients with prostatic carcinoma given endocrine therapy, and analyses of causes of death and side effects of endocrine therapy].
Of 572 patients with prostatic carcinoma, 497 received endocrine therapy as the initial treatment. These patients were surveyed in a cooperative research study by members from five universities. Prognosis, causes of death and side effects of estrogen therapy were studied. The prognosis of patients who had received endocrine therapy became worse, as the stage progressed. The prognosis of those who had received a combination of estrogen therapy with castration tended to be better than that of those who had received estrogen therapy alone. Similarly, the prognosis of those who had received a combination of progesterone therapy with castration tended to be better than that of those who had had progesterone therapy alone. No relationship was found between estrogen doses (low, medium and high) and prognosis, although a precise comparison among the three could not be made because of the smaller number of patents with low doses. A high dose of estrogen may not always be the indication, rather a medium dose such as 300 mg diethylstilbestrol diphosphate may be clinically appropriate. The cause of death could be identified in 303 patients who had received endocrine therapy. Cancer-related death was the most frequent (63.7%), and cardio- or cerebrovascular death accounted for only 14.2% of the cases. When this analysis was confined to the patients who had received estrogen therapy, estrogen administration seemed to be the cause of cardio- or cerebrovascular death of 16.1% of the patients. Daily dosing of estrogen was not definitely related to the incidence, or the interval to cardio- or cerebrovascular death. However, among the patients who had died of cardio- or cerebrovascular disease, 50% of the patients who had received a medium or high dose of estrogen tended to die within two years after treatment, while 50% of those who had received a low dose died within three years.
Cause of Death↗
[Clinical studies on endocrine therapy of prostatic carcinoma (3): Histopathological features of prostatic carcinoma and its prognosis].
We investigated how histopathological features, such as structural atypism (SAT), nuclear anaplasia (NAN) and Gleason's pattern, influence the prognosis of patients receiving endocrine therapy. Patients with SAT 3 or NAN 3 clearly had a lower survival rate and a shorter survival period than those with other grades of SAT or NAN and this tendency was more prominent in the high stage than low stage. Patients with a higher grade of SAT or NAN had a poorer prognosis as well, when only cancer-related death was considered in the calculation of survival and survival period. The results described above suggest that the grade of SAT and NAN is one of most influential factors for prognosis. In the analysis for the prognosis of patients according to grade of mean value of SAT + NAN, there were differences in prognosis among mean value of SAT + NAN 2-4, 5 and 6. This indicated that the combined grading system would provide more information to the prediction of prognosis. Patients with Gleason's primary (or secondary) pattern 1 and 2, or 3 and 4 had a better survival than those with pattern 5 in the analysis when only cancer-related death was considered. This was coincident with the result that the survival rate for each Gleason's sum 2-3, 4-5, 6, 7-8 and 9-10 was different. Consequently, Gleason's pattern influenced the rate of cancer-related deaths, and this pattern may be another important factor for predicting the prognosis.
Estrogens↗