Stimulation of adenosine 3',5'-monophosphate and sex steroids in the spermatic venous blood after human chorionic gonadotropin injection into human testes.

To study the participation of cAMP in the action of gonadotropin on testicular steroidogenesis in the human testis in vivo, we have measured the concentrations of cAMP, testosterone, 5 alpha-dihydrotestosterone, estrone, 17 beta-estradiol, and hCG in the spermatic venous blood of the patients with prostatic cancer after hCG injections into the testis. Five minutes after hCG administration, spermatic cAMP increased to 5 times the pretreated level, and after 30 min, it increased to 20 times the pretreated level. Testosterone increased gradually after hCG injection, and the 2-fold increase was demonstrated at 50 min. Although the pattern of the changes in spermatic 5 alpha-dihydrotestosterone was similar to that of testosterone, a statistically significant increase was not observed after hCG administration. Estrogen production was also stimulated by hCG. These results are consistent with the view that cAMP may participate in the action of hCG upon steroidogenesis in the testis of human beings in vivo, as has previously been observed with rat and human testes in vitro.

Ampicillin and cephalexin in renal insufficiency.

We analyzed the relationship between functional damage and transport processes in the kidney in patients with glomerulonephritis and renal failure by a new analytic method. In renal failure patients, there was substantial diminution of maximum transport of secretion in renal tubules. This reduction affected the urinary excretion of ampicillin and cephalexin substantially because both drugs depend on active renal tubular secretion. Our results indicate that dosage adjustment based on creatinine clearance is not appropriate for patients receiving drugs requiring active tubular secretion for urinary excretion. Our data point to a need for a prolongation of the dosage interval of cephalexin to 20 times that in normal subjects, while five times is recommended by the creatinine clearance. In these patients, it is therefore suggested that a dosage adjustment method that involves both factors--glomerular and renal tubular functions--is required.

A new dosing regimen in renal insufficiency: application to cephalexin.

We describe a new method of drug dosage adjustment. The method simultaneously considers glomerular and tubular functions as parameters, because nonparallel decreases in both functions limit the use of the conventional endogenous creatinine clearance (CLCR) method for dosage adjustment. In the new method, CLCR and the 15-minute phenolsulfonphthalein (PSP15') test were used and applied to patients with renal insufficiency with cephalexin (CEX) as a model drug for renal tubular secretion. The results clearly demonstrate good control of plasma CEX concentrations by the CLCR-PSP15' method, whereas there were marked changes in plasma CEX levels with the CLCR method alone. Our method appears to be more useful for patients with renal impairment than the conventional CLCR method for CEX, which is mainly excreted in urine by renal tubular secretion. A nomogram for the CEX dosing interval is proposed for application to clinical practice.

Androgen receptor in electroresected and cold punch-resected specimens. Usefulness of Kaplan cold punch resectoscope.

The measurement of androgen receptor and 5 alpha-dihydrotestosterone (DHT) levels in prostatic carcinoma may be of value in predicting responsiveness to anti-androgenic therapy. A sufficient amount of prostatic carcinoma tissue must be removed for measuring androgen receptor and DHT levels. We have studied the usefulness of Kaplan cold punch-resection compared with electroresection for obtaining tissue in 29 cases of enucleated benign prostatic hyperplasia. DHT level in electroresected specimens was similar to controls. However, following low, moderate, and high-power electroresection an average of total R1881 binding sites (Bmax) of electroresected specimens was reduced to 82.2, 71.9, and 52.1 per cent of corresponding controls, respectively. In contrast, the per cent decrease of Bmax of Kaplan cold punch-resected specimens was only 10 per cent of the control. From our data, Kaplan cold punch-resection of the prostate appears to be a useful tool for obtaining tissue suitable for measuring androgen receptor levels.

Muscle involvement in congenital insensitivity to pain with anhidrosis.

A patient with congenital insensitivity to pain with anhidrosis, who had characteristic clinical features and biopsied sural nerve, is presented. Nerve pathology findings indicated a loss of the small myelinated and unmyelinated fibers. Biopsied muscle disclosed a marked variation in fiber size, some small fibers with central nuclei, and a small number of small angulated fibers, consistent with neurogenic and myogenic changes. Many patients with congenital insensitivity to pain with anhidrosis had muscle weakness and absent or decreased deep tendon reflexes with normal nerve conduction velocity. We confirmed that lack of small myelinated fibers in motor neurons resulted in a striking change of muscle in our patient.

[A clinical evaluation of doxycycline in the treatment of genitourinary infections caused by Chlamydia trachomatis].

The clinical effectiveness of doxycycline (DOXY) in the treatment of chlamydial infections was studied by giving it to 14 patients composed of 9 with nongonorrheal urethritis and 5 with cervicitis, all caused by Chlamydia trachomatis. DOXY was given in an oral dose of 100 mg twice daily for 4 to 19 days. The total dosage ranged from 800 to 3,800 mg. The overall clinical efficacy as assessed on the basis of both bacterial response and relief of subjective or objective symptoms was excellent in all of 12 evaluable patients. Two patients for whom we failed to perform postdose bacteriological examinations were excluded from evaluation. No side effect related to dosing of DOXY developed.

[Double-blind comparison of cefotetan and cefmetazole in complex urinary tract infections].

For the purpose of carrying out an objective evaluation of the clinical efficacy and safety of cefotetan (CTT), a new cephamycin-type injectable antibiotic, in the treatment of complicated urinary tract infections, cefmetazole (CMZ) was employed as the control drug in a comparative study performed by the double-blind method. CTT was administered in a dose of 0.5 g or 1 g, while CMZ was used in a dose of 1 g; both of these drugs were administered by intravenous drip infusion twice a day for 5 days. The total number of treated cases was 393; 105 patients in the CTT 1 g group, 97 patients in the CTT 2 g group, and 96 patients in the CMZ 2 g group. The judgment of the clinical effects of these 3 therapeutic regimens was carried out in accordance with the criteria for evaluation of clinical efficacy of antimicrobial agents on UTI (2nd edition). The results are as follows. With regard to the overall efficacy of the drug treatments, the calculated efficacy rates were 54.3% in the CTT 1 g group, 63.9% in the CTT 2 g group and 52.1% in the CMZ 2 g group. The differences between these efficacy rates were not statistically significant. Regarding the efficacy of the treatments in terms of the bacteriuria, the bacterial cultures were seen to become negative in 40% of the cases in the CTT 1 g group, 54.6% of the CTT 2 g group and 42.7% of the CMZ 2 g group. Again, there were no statistically significant differences between the groups. Concerning the efficacy of the drugs against pyuria, by combining the cases found to be normalized and those seen to show improvement, the improvement rates were calculated to be 41.9% for the CTT 1 g group, 37.1% for the CTT 2 g group, and 37.5% for the CMZ 2 g group. These pyuria improvement rates show no statistically significant differences, respectively. The incidences of occurrence of side effects and laboratory test abnormalities thought to be caused by the drug therapy were as follows; 1.5% and 5.3% in the CTT 1 g group, 1.5% and 3.1% in the CTT 2 g group and 0% and 6.9% in the CMZ 2 g group. There were no significant differences between the groups. Based on the above clinical results, it can be concluded that, in the treatment of complicated urinary tract infections, we can expect CTT to provide the same therapeutic efficacy as CMZ when its dosage is the same or even half thereof. In addition, the safety of CTT is equal to that of CMZ. Therefore, CTT is concluded to be a useful drug.

[Efficacy of a latex Foley catheter with sustained release of chlorhexidine: 1st report: Clinical trials for the prevention of urinary tract infection].

Seventy five patients requiring urethral catheterization for over 24 hours were treated with a latex Foley catheter with sustained release of chlorhexidine in a closed drainage system. While the catheter was indwelling, urinary concentrations of chlorhexidine were maintained at the level of 1 to 2 micrograms/ml in average in almost all patients. The catheter was highly effective in preventing the acquisition of catheter-associated bacteriuria in patients with initially sterile urine without systemic antimicrobial therapy. The acquisition rate of bacteriuria was 8, 16, 23, 35 and 74% on day 3, 4, 5, 6 and 7 with the catheter indwelling, respectively. The catheter was not effective in eradicating preexisting bacteriuria. Complications of the catheter were minimal.

[Prophylactic effect of etretinate on the recurrence of superficial bladder tumors--results of a randomized control study].

The recurrence preventing effect of Etretinate on 174 superficial bladder tumors was examined by a randomized study using the envelope method. After transurethral resection of the bladder tumor, the tumor-free patients were divided into two groups, one administered one 10 mg capsule of Etretinate once a day, and the other group untreated (control group). As a rule, the patients were examined for recurrence every 3 months. There were 9 drop outs (9.6%) in the Etretinate group, and 8 (10%) in the control group. Therefore, 85 subjects in the Etretinate group and 72 patients in the control group were analyzed for statistics. The recurrence rate during the observation period of over 2 years was 38% in the control group and 18% in the Etretinate group, the number of relapsing cases in the latter group tending to be decreased (P less than 0.1). The cumulative recurrence inhibition rate for cases observed over one year tested by the Kaplan Meier method tended to be higher in the Etretinate group compared to the control group (P less than 0.1). Etretinate administration had a high recurrence inhibitory effect (P less than 0.05) in the cases of relapse, multiple tumors, and tumors less than 1 cm. Side effects of Etretinate administration were seen in 21 cases (22.3%). The major symptoms were dry lips, cheilitis, stomatitis, dermal desquamation, etc., and drug use was discontinued in 7 cases (7.4%). The symptoms all disappeared after drug administration was discontinued.

[Clinical effects of terodiline hydrochloride for urinary frequency and sense of residual urine].

The clinical effects of terodiline hydrochloride were evaluated in forty-four patients with urinary frequency and/or sense of residual urine. After a four-week treatment with 24 mg terodiline hydrochloride once daily, subjective symptoms were improved and micturition frequency was decreased significantly. Slight dysuria was reported as a side effect only in one patient. Terodiline hydrochloride is considered to be superiorly effective and safe for the treatment of urinary frequency and sense of residual urine.

[Clinical studies of antimicrobial prophylaxis of recurrent urinary infection in women. Long-term, low-dose pipemidic acid for prophylaxis].

The prophylactic efficacy of long-term, low-dose antimicrobial treatment in urinary tract infection (UTI) was studied. Fifty-eight female adult patients with a history of at least two recurrent episodes of UTI in the past year were entered into this study, and the prophylactic regimen was not started until the existing UTI had been eradicated. Patients took 250 mg of pipemidic acid (PPA) daily at bedtime after voiding for 6 consecutive months. Incidence of recurrence of UTI in 48 patients with uncomplicated UTI and 10 patients with complicated UTI decreased to 0.15 and 0.29 per year, respectively, during the treatment compared with 3.5 per year before the treatment. At the end of the 6 months of prophylactic treatment, the patients were divided into two groups by the envelope method. Seventeen patients were treated for a further 6 months and 11 patients were followed up without further medication. Prophylactic efficacy of UTI was obtained in both groups, and there was no significant difference in the incidence of recurrence between the two groups. These findings suggest that the 6-month period of prophylaxis might be sufficient. Examination of the periurethral swab showed that E. coli and Klebsiella sp. were decreased during the treatment. This prophylactic treatment produced no resistant strains. Urinary levels of PPA in the morning urine of patients administered 250 mg of PPA at bedtime averaged 513 micrograms/ml. These values were about 2 times higher than those found in the evening urine after administration of the same dose in the morning.

[Clinical experience with oxendolone for treatment of benign prostatic hyperplasia. Clinical efficacy and effects on serum lipid and lipoprotein fraction levels].

Forty-three patients with benign prostatic hyperplasia were treated with weekly i.m. injections of 400 mg oxendolone for 12 weeks. The subjective symptoms were improved in 83% of these patients. Residual urine was decreased significantly and Qmax was increased by this treatment. Serum VLDL level was suppressed significantly, whereas the levels of LDL, total cholesterol, HDL-cholesterol and triglycerides were changed little. Atherosclerotic index and the ratio of (total cholesterol--HDL-cholesterol) to (HDL-cholesterol), was not influenced by the treatment. No severe side-effect was found. These findings suggest that oxendolone is the drug of choice for non-surgical treatment of benign prostatic hyperplasia.

[A study of combination chemotherapy with cis-diamminedichloroplatinum for advanced genitourinary carcinoma].

The patients with advanced testicular tumors and bladder carcinoma were treated by combination chemotherapies including cis-diamminedichloroplatinum. Four patients with advanced testicular tumors were treated with a combination chemotherapy, consisting of cis-diamminedichloroplatinum, vinblastine, and bleomycin or pepleomycin according to Einhorn's regimen. Three patients with advanced bladder carcinoma were treated with a combination chemotherapy consisting of cis-diamminedichloroplatinum, cyclophosphamide, and adriamycin according to Yagoda's regimen. These chemotherapy regimens produced 25% complete and 75% partial responses in testicular tumors and 100% of no change in bladder carcinoma. Although an overall response rate of three patients with bladder carcinoma was 0%, one patient was plateaustable for more than three months. We believe that the combination chemotherapy including cis-diamminedichloroplatinum is promising in the management of patients with advanced testicular tumors or bladder carcinoma.