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Biomedical subjects

M Yokokawa

Publications and source records attributed to M Yokokawa.

At least 37 records · Page 2Linked to original sources

Pharmacokinetics and safety of a new parenteral carbapenem antibiotic, biapenem (L-627), in elderly subjects.

The pharmacokinetics and tolerability of a new parenteral carbapenem antibiotic, biapenem (L-627), were studied in healthy elderly volunteers aged 65 to 74 years (71.6 +/- 2.7 years [mean +/- standard deviation], n = 5; group B) and > or = 75 years (77.8 +/- 1.9 years, n = 5; group C), following single intravenous doses (300 and 600 mg), and compared with those of healthy young male volunteers aged 20 to 29 years (23.0 +/- 3.5 years, n = 5; group A). The agent was well tolerated in all three age groups. Serial blood and urine samples were analyzed for biapenem to obtain key pharmacokinetic parameters by both two-compartment model-dependent and -independent methods. The maximum plasma concentration and area under plasma concentration-versus-time curve (AUC) increased in proportion to the dose in all three groups. Statistically significant age-related effects for AUC, total body clearance, and renal clearance (CLR) were found, while elimination half-life (t1/2 beta) and percent cumulative recovery from urine of unchanged drug (% UR) remained unaltered (t1/2 beta, 1.51 +/- 0.42 [300 mg] and 2.19 +/- 0.64 [600 mg] h [group A], 1.82 +/- 1.14 and 1.45 +/- 0.36 h [group B], and 1.75 +/- 0.23 and 1.59 +/- 0.18 h [group C]; % UR, 52.6% +/- 3.0% [300 mg] and 53.1% +/- 5.1% [600 mg] [group A], 46.7% +/- 7.4% and 53.0% +/- 4.8% [group B], and 50.1% +/- 5.2% and 47.1% +/- 7.6% [group C]). A significant linear correlation was observed between the CLR of biapenem and creatinine clearance at the dose of 300 mg but not at 600 mg. The steady-state volume of distribution tended to be decreased with age, although not significantly. Therefore, the age-related changes in parameters of biapenem described above were attributable to the combination of decreased lean body mass and lowered renal function of the elderly subjects. However, the magnitude of those changes does not necessitate dosage adjustment in elderly patients with normal renal function for their age.

Adult↗

Intravesical ureterocele presenting bladder outlet obstruction in an adult male.

Large ureteroceles in adult males causing bladder outlet obstruction are rare. We report a case of a large intravesical orthotopic ureterocele in an adult male presenting as acute urinary retention. Incisional transurethral endoscopy was successful with decompression of ureteral end obstruction, enabling smooth urination immediately and no occurrence of vesicoureteral reflux.

Adult↗

Intravesical mitomycin C and doxorubicin sequential therapy for carcinoma in situ of the bladder: a longer followup result.

A total of 43 patients with carcinoma in situ of the bladder (primary in 26 and secondary in 17) who underwent intravesical mitomycin C and doxorubicin sequential therapy for 2 multicenter studies were followed for a median period of 45 months (range 10 to 84). Of the patients 32 (74%) achieved complete response after induction therapy and underwent maintenance therapy with either mitomycin C plus doxorubicin, mitomycin C alone or observation only. Of the complete responders 13 (41%) had a local recurrence, and subsequent repeat intravesical mitomycin C and doxorubicin sequential therapy as well as bacillus Calmette-Guerin was effective in a significant proportion (75% or greater). The maintenance therapy did not have a favorable effect on the recurrence rate. In 8 patients (19%) (3 of 32 complete responders and 5 of 11 nonresponders) progression developed, including invasive cancers in 4, metastatic disease in 2 and both conditions in 2. Initial complete responders had a significantly higher progression-free rate than initial nonresponders, although there was no difference in the sites of progression between them. At the last followup 35 patients (81%) remained free of disease with 31 (72%) having a normally functioning bladder. According to these results, intravesical mitomycin C and doxorubicin sequential therapy appears to be applicable as initial treatment for carcinoma in situ of the bladder.

Administration, Intravesical↗

A study of prognosis and clinicopathology of bladder cancer to blood group type of host patients in Japan.

A total of 538 patients with transitional cell carcinoma of the bladder with a mean follow up period of 5.8 years (range 1-25) were retrospectively analysed to see if there were any associations between blood group and grade, stage, or prognosis of the tumour. In contrast to previous findings among European and Americans, there were no significant differences among blood groups for stage, histological grade, or survival rate.

ABO Blood-Group System↗

[Intra-arterial CDDP and CDDP plus THP-ADM therapy for bladder cancer].

From 1983 to 1988, 20 patients (group A: 3 stage T1, 4 stage T2 and 13 stage T3-4 tumors) with bladder cancer were treated with single injection of CDDP (150-200 mg/body), and 28 patients (group B: 4 stage T1, 9 stage T2 and 15 stage T3-4 tumors) were treated twice with injection of CDDP (100 mg/m2) and THP-ADM (40 mg/m2) mixture from the internal iliac artery. As a rule, one half of the agents was equally given for the both sides, while 75% dose was given to the tumor side to the case with unilateral localized tumors. Then total or partial cystectomy was followed. When residual invasive cancer was pathologically present in operative specimens, patients underwent three to six courses of adjuvant chemotherapy including CDDP. Clinical response rate (CR+PR) to the intra-arterial chemotherapy in group A and B were 39% and 62%, respectively. Pathological response rate (grade 3 and grade 4 by Oboshi and Shimozato classification) were 17% in both group. After total cystectomy, the 2-year cancer specific survival rates of 17 patients in group A and 22 patients in group B were 75% and 59%, respectively. The 2-year cancer specific survival rates of 8 patients in group A and 10 patients in group B with pT3b were 63% and 54%, respectively. No cancer death occurred thereafter in the patients of group A during another three years. The 3-year cancer specific survival rate of 9 patients after partial cystectomy (3 in group A, 6 in group B) was 86%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Secondary T-cell lymphoma presenting as a giant ulcer.

Secondary cutaneous T-cell lymphoma may present with various types of skin lesions, but rarely produces ulceration in contrast to primary cutaneous T-cell lymphoma. We report a case of malignant lymphoma of the tonsil that recurred as a giant cutaneous ulcer on the back of a 45-year-old man. Biopsy of the ulcer revealed a malignant lymphoma of diffuse, mixed-cell type. Surface marker analysis of the tumour cells showed suppressor/cytotoxic T-cell characteristics. The skin lesions were treated by electron beam therapy.

Humans↗

[Usefulness and safety of bunazosin hydrochloride in neurogenic bladder after prolonged administration].

Bunazosin hydrochloride (Ea-0643), a selective alpha 1-blocker, was administered to 14 patients with neurogenic bladder over prolonged periods of time in order to determine its efficacy and safety. Subjective symptoms were classified into 4 grades, and their response assessed after 12 weeks of treatment. The proportion of patients showing improvement by at least one grade was 50.0% for retarded urination, 16.7% for prolonged urination, 25.0% for urinary stream condition, 25.0% for abdominal pressure at voiding, and 28.6% for residual urine. Objective symptoms were also assessed after 12 weeks of treatment, and a statistically significant improvement was recognized in the volume of spontaneously voided urine, the maximum and mean flow rates on uroflowmetry. It should be noted that both of those flow rates had improved significantly only 2 weeks into the treatment. The degree of improvement in subjective and objective symptoms and the degree of general improvement were all higher at week 12 than at week 2 of treatment. Current knowledge of the mechanism of action of this drug, coupled with the observations made in this study, suggests that, once it has improved the urodynamics, it exhibits a sustained effect for prolonged periods of treatment. However, further studies are warranted concerning the mechanisms of the pharmacological action of the drug from a pathological viewpoint. The proportion of patients in whom Ea-0643 was judged to be useful at 12 weeks of treatment was 41.7%, but when the assessment of 'slightly useful' was taken into consideration, the usefulness rate rose as high as 91.7%. Stomatitis was observed in only one case as a side effect of this drug.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Antagonists↗

[Neoadjuvant intra-arterial chemotherapy followed by partial cystectomy for invasive bladder cancer].

From January, 1987 through January, 1990, partial cystectomy was performed for 4 (18%) of 22 patients with invasive bladder cancer who had received neoadjuvant intra-arterial chemotherapy. The criteria of patient selection for partial cystectomy were: 1) invasive bladder cancer showing good response (greater than or equal to PR) to neoadjuvant chemotherapy, 2) solitary or localized tumor that can be eradicated by segmental resection, and 3) tumor of stage T3 or less. As a rule, cisplatinum (100 mg/m2) and THP-adriamycin (40 mg/m2) were administered selectively to the internal iliac artery by one-shot infusion. Concurrently, sodium thiosulfate (10 g/m2), a neutralizing agent against cisplatinum, was administered intravenously. All four patients had achieved clinical complete responses by one or two courses of intra-arterial chemotherapy, and then underwent partial cystectomy with pelvic lymphadenectomy. Pathological examination revealed pTONO in two patients, and the remains were pT3aNO and pT3bN1. After the mean follow-up of 24 months, three of them are alive with no evidence of disease, and also with normal bladder and sexual functions. However, one with pT3bN1 tumor underwent total cystectomy 5 months later for local recurrence (pT4b) and had died of cancer 18 months later. Neoadjuvant intra-arterial chemotherapy followed by partial cystectomy should be the most applicable conservative therapy with high radicality for invasive bladder cancer, when: 1) the patient has localized invasive cancer showing good response (greater than or equal to PR) to neoadjuvant chemotherapy, 2) the tumor is stage T3a or less and without findings of tentacular invasion (INF gamma) by pre-operative biopsy, and 3) pre-operative multiple biopsy is performed as deeply as possible along the prearranged incision line.

Aged↗

[Neurogenic bladder dysfunction due to spina bifida and sacral dysgenesis manifested itself in middle age. Report of a case].

Congenital neurogenic bladder dysfunction with spina bifida and sacral dysgenesis manifested itself at middle age is reported. A 48-year-old male who had urinary retention and suprapubic cystostomy one year and a half before in another hospital was seen, asking for removal of the cystostomy. He had never had any neurologic or bladder dysfunction in his childhood and adulthood. X-ray examination revealed a bifid spine and sacral dysgenesis, bilateral hydronephrosis, bilateral VUR and urethral stricture. Uroflowmetry showed a severe dysuric pattern (voided volume 5 ml, residual urine 230 ml) and the cystometrogram revealed a hyperactive bladder. Optical urethrotomy for stricture yielded some improvement i.e. recovery of voluntary voiding with large amount of residual urine. TUR of the bladder neck resulted in almost complete voiding. Cohen's antireflux operation yielded favorable improvement of hydronephrosis. The bladder and renal function remained favorable in the follow-up period of about two years. The clinical course of this patient suggested that his bladder dysfunction was due to late manifestation of congenital neurogenic bladder.

Humans↗

[Changes in lanthanum permeability of rat Sertoli cell tight junction after CDDP administration].

Using electron microscope, distribution of lanthanum tracer in the seminiferous epithelium was evaluated in adult male rats 2, 7, 25 and 53 days after single intraperitoneal injection of 3 mg/kg of CDDP. Lanthanum penetrated beyond the tight junction between Sertoli cells and the maximum penetration around the spermatid was found on the 7th day, when any degenerative changes of seminiferous epithelium were not recognized light microscopically. And 4 weeks pretreatment with Cephalantin and Kallikulein had no effects on this lanthanum tracer penetration around the spermatid. On decreasing this lanthanum tracer penetration after 7 days, some lanthanum was also found around the spermatocytes on the 53rd day but not around the spermatid. It is proposed that lanthanum tracer penetration beyond the Sertoli cell tight junction may be a morphological marker of early Sertoli cell dysfunction after CDDP administration.

Animals↗

[Apparently bladder origin signet ring cell carcinoma: a case report].

A 72-year-old woman with signet-ring cell carcinoma of the urinary bladder treated with total cystectomy is described. The bladder yielded linitis plastica pattern of infiltration similar to that seen in the gastric cancer, i.e., cancer tissue extended almost whole bladder deeply to the serosa, whilst the mucosal surface was only minimally invaded. She received no adjuvant therapy and she is alive without recurrence 8 months after the operation. We review the reported cases and shortly discuss the prognosis and treatment of primary signet-ring cell carcinoma of the urinary bladder.

Adenocarcinoma, Mucinous↗

Intravesical combination chemotherapy with mitomycin C and doxorubicin for carcinoma in situ of the bladder.

We treated 30 patients with carcinoma in situ of the bladder via intravesical combination chemotherapy. As an induction therapy 20 mg. mitomycin C on day 1 and 40 mg. doxorubicin on day 2 were instilled into the bladder once a week for 5 consecutive weeks. Patients who achieved complete response were assigned a maintenance instillation of mitomycin C alone every 2 to 4 weeks for 1 year. A total of 19 patients achieved complete response following an initial course of induction therapy and 2 partial responders to initial therapy also achieved complete response after repeated induction therapy, resulting in a 70 per cent over-all complete response rate. Toxicity was considerable with moderate to severe bladder irritation occurring in 20 patients but it was tolerable in the majority. Of 21 complete responses 13 remained free of disease for 6 to 43 months (average of 23 months), 5 had recurrent carcinoma in situ and 1 had invasive urethral cancer. In contrast, of 9 nonresponders 2 and 1 had invasive cancer of the bladder and ureter, respectively.

Administration, Intravesical↗

Intestinal absorption kinetics using a laminar flow model.

The drug concentration profile at non-steady state in the intestine was simulated using a laminar flow model. The transport equation with cylindrical coordinates was solved by a finite difference method to stimulate the concentration profile in the tube and the exit cup-mixing concentration. A drug with a various wall permeability coefficient (Pw = zero or 10(-5) to 10(-3) cm/s) and diffusion constant (D = 10(-6) to 10(-4) cm2/s) was assumed to be introduced into the tube in a pulse form. The spatial intervals of the grid and the time step were varied to yield the optimum condition for calculation. The concentration profile in the tube as the time elapsing and the exit cup-mixing concentration versus time profile were shown graphically. Pw and D influenced the concentration profiles. This suggests the possibility of the estimation of Pw and D by determining the exit cup-mixing concentration after a pulse input to a perfused intestine under a laminar flow condition.

Intestinal Absorption↗