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Biomedical subjects

Y Kawada

Publications and source records attributed to Y Kawada.

At least 37 records · Page 2Linked to original sources

Endocrine plus uracil/tegafur therapy for prostate cancer.

A prospective, randomized clinical trial was conducted to evaluate the efficacy of endocrine chemotherapy with uracil and tegafur (in a molar ratio of 4:1 [UFT]) in patients with prostate cancer. The study included two treatment arms: endocrine plus UFT vs endocrine-only therapy. Of the 136 patients with prostate cancer enrolled in this study from April 1990 to December 1992, 69 received endocrine plus UFT therapy and the remaining 67 received endocrine-only therapy. Among those receiving UFT therapy, eight patients had stage A2 and B prostate cancer, 11 had stage C disease, and 50 had stage D disease. In the endocrine-only group, 10 patients had stage A2 and B disease, seven had stage C disease, and 50 had stage D disease. Tumors were well differentiated in 20 patients, moderately differentiated in 38 patients, and poorly differentiated in 11 patients receiving UFT. The endocrine-only group included 29 patients with differentiated tumors, 26 with moderately differentiated tumors, and 12 with poorly differentiated carcinomas. After a mean follow-up period of 54.9 months for patients receiving endocrine plus UFT therapy and 47.8 months for patients receiving endocrine-only therapy, disease had not progressed in 53.0% of the UFT-treated patients and 43.8% of the endocrine-only-treated patients (P = .114). The 5-year cancer-specific survival rates were 67.4% for the UFT group and 49.5% for the endocrine-only group (P = .273). The 5-year survival rates were 47.4% for the UFT group and 35.4% for the endocrine-only group (P = .177). Adverse effects, such as bone marrow suppression, nausea, vomiting, and anorexia, occurred in 36 patients in the UFT group and 41 patients in the endocrine-only group. However, adverse effects were not specifically related to UFT use. It is concluded that endocrine chemotherapy plus UFT is a tolerable regimen that might be effective for patients with prostate cancer.

Adenocarcinoma↗

Prostate specific antigen density for discriminating prostate cancer from benign prostatic hyperplasia in the gray zone of prostate-specific antigen.

Serum prostate specific antigen (PSA) is currently the best blood marker for prostate cancer. However, low specificity for detection of prostate cancer, especially in the gray zone of PSA, is a problem. We evaluated the clinical significance of PSA density (PSAD) in gray zone PSA cases with conversion of serum PSA to a Stanford reference value. In a series of histologically confirmed 63 benign prostatic hyperplasia (BPH) patients and 234 prostate cancer patients, 36 BPH patients and 25 prostate cancer patients had gray zone PSA levels. Serum PSA was measured with the Markit-F or Markit-M PA assay. All data were converted to Stanford reference values. We used transabdominal ultrasound to determine prostate volume. PSAD was determined as the serum PSA/prostate volume ratio. The mean PSA values for BPH and prostate cancer were 6.42 +/- 1.80 and 7.80 +/- 2.15 ng/ml (p = 0.0116), respectively, and prostate volume was 33.4 +/- 14.1 ml and 17.1 +/- 8.2 ml, respectively (p < 0.0001). The mean PSAD for prostate cancer was 0.572 +/- 0.363 while that for BPH was 0.218 +/- 0.085 (p = 0.0001). Cut-off values with sensitivity > 90% were 0.218 for PSAD and 30 ml for prostate volume. At these cut-off values, specificity reached 56% for each marker. In discriminating prostate cancer from BPH in the gray zone of PSA, PSAD demonstrated better performance than PSA.

Aged↗

[Bacillus Calmette-Guerin intravesical instillation treatment for carcinoma in situ of the bladder. Gifu BCG Instillation Therapy Research Group].

We performed a retrospective long-term study to evaluate the efficacy of intravesical instillation of Tokyo 172 strain Bacillus Calmette-Guerin (BCG) on carcinoma in situ (CIS) of the bladder. Between 1989 and 1998, 42 patients with CIS of bladder underwent intravesical instillation of BCG. In the follow-up period from 6 to 116 months (mean: 37.3 months), the efficacy rate of intravesical BCG instillation for CIS of the bladder was 81.0%. Two patients died from the bladder cancer. The non-recurrence rate in patients with grade 2 carcinoma (19 cases) was not significantly different from that in those with grade 3 carcinoma (23 cases). However, the recurrence rate in patients with secondary CIS (15 cases) was significantly higher than in those with primary CIS (27 cases). The recurrence of CIS was observed in 7 of 42 cases. In 6 of 7 patients, CIS recurred within one year after treatment. Total cystectomy was performed in 10 of 42 patients, and pathological findings of muscle layer invasion were detected in 8 patients. Although side effects occurred in 33 patients (77.5%), no clinically significant side effects were observed. Our results suggest that intravesical BCG therapy may be useful for the treatment of CIS of the bladder.

Adjuvants, Immunologic↗

[Clinical evaluation of biapenem in various infectious diseases].

The clinical usefulness of injectable biapenem (BIPM) was examined for various infectious diseases in the fields of internal medicine, urology, surgery, orthopedics, obstetrics and gynecology, otorhinolaryngology, ophthalmology, dermatology, oral surgery, and plastic surgery. BIPM was administered by intravenous drip infusion at a dose of 150, 300, or 600 mg twice a day. The concentrations in various body fluid and tissues were also examined. 1. In the total enrollment of 256 cases, the numbers subjected to the analyses for clinical efficacy, bacteriological efficacy, side effects and abnormal laboratory findings were 214, 170, 252 and 251 cases, respectively. 2. The clinical efficacy rate was 85.5% (183/214 cases) as a whole, being 2/2 for sepsis, 6/8 for cellulitis and lymphangitis, 76.2% (16/21) for traumatic, operative wound and burn infections, 4/6 for osteomyelitis and arthritis, 92.9% (13/14) for peritonsillar abscess and peritonsillitis, 83.3% (15/18) for chronic lower respiratory tract infection, 7/7 for pneumonia, 83.3% (30/36) for complicated urinary tract infection, 100% (14/14) for cholecystitis and cholangitis, 88.2% (15/17) for peritonitis, 86.5% (32/37) for internal genital infection, 8/9 for pelvic peritonitis, 2/4 for corneal ulcer, orbital infection and panophthalmitis, 1/2 for otitis media, 4/4 for sinustitis, 93.3% (14/15) for osteitis of jaw and cellulitis of mouth floor. The efficacy rate in the poor responders to the pretreatment by other antibiotics was 86.4% (70/81). 3. 300 strains of causative organisms were isolated from 170 cases which contained polymicrobial infections. The elimination rate of causative organisms was 85.3% (256/300 strains), in terms of bacteriological efficacy. 4. Side effects were noted in 11 of 252 cases (4.4%) with 11 events. The signs and symptoms were the skin symptoms (5 cases), gastro-intestinal symptoms (3 cases), interstitial pneumonia (2 cases), and feeling bad (1 case), all of which disappeared during treatment or after the discontinuation of treatment. The abnormal laboratory findings were observed in 31 of 251 cases (12.4%) with 50 events, and major ones were an increase in eosinophils, and elevations of AST, ALT, gamma-GTP and Al-p. 5. The concentrations of BIPM in body fluid and tissues were determined in 46 cases (212 samples) most of which were administered 300 mg of BIPM by intravenous drip infusion for 60 minutes. The concentrations in the sputum within 6 hours after administration were 0.1-2.5 micrograms/g. The maximum concentrations in body fluid and tissues were 0.2-1.8 micrograms/g or ml in the bile, middle ear mucosa, tonsillar tissue, aqueous humor and bone tissues and were 2.0-5.7 micrograms/g or ml in the gallbladder, maxillary sinus mucous membrane, ethmoidal sinus mucous membrane, oral tissues, skin, woman genitals, synovia, joint tissue, and the eschar. The concentrations in the uterine arterial plasma and retroperitoneal fluid were almost similar to those in the cubitl vein plasma. From the above-mentioned results of clinical efficacy, bacteriological efficacy, and safety, injectable BIPM was confirmed to be useful in the treatment of moderate, severe and/or refractory infections in various fields.

Adult↗

Association study of structural mutations of the tyrosine hydroxylase gene with schizophrenia and Parkinson's disease.

Tyrosine hydroxylase (TH) gene is the rate-limiting enzyme in the synthesis of catecholamines. Functional polymorphisms of the TH gene may be involved in the pathogenesis of neuropsychiatric diseases such as schizophrenia, affective disorders, and Parkinsonism. This study examined a possible association of two polymorphisms, both of which result in an amino acid change of the TH protein, with schizophrenia and Parkinson's disease (PD). The Val81Met polymorphism is a common variation, although its effect on the enzyme expression is unclear. Leu205Pro polymorphism is a rare mutation that is reported to cause Parkinsonism in infancy for individuals who are homozygous for the mutated type. We genotyped a Japanese sample of 194 schizophrenics, 99 patients with PD, and 161 controls for the Val81Met polymorphism by using mis-match PCR and digestion by the restriction enzyme BalI. There was no significant allelic or genotypic association of the Val81Met polymorphism with schizophrenia or PD. The Leu205Pro polymorphism was examined by using PCR and digestion by AluI; however, there was no individual who carried the mutated type of Pro205 among 50 schizophrenics or 50 patients with PD. Thus we obtained no evidence for the involvement of the two structural mutations of the TH gene in the pathogenesis of schizophrenia or PD.

Alleles↗

Cellular basis of skin allograft rejection in mice: specific lysis of allogeneic skin components by non-T cells.

BACKGROUND: It has been generally assumed that CD8+ T cells mediate direct lysis of allografts and that their growth, differentiation, and activation are dependent upon cytokine production by CD4+ T cells. However, both the generation of CD4- or CD8-deficient mice and adoptive transfer experiments with CD4+ T cells from CD8-deficient mice demonstrate that noncytotoxic CD4+ T cells alone are sufficient to induce skin or organ allograft rejection. Furthermore, we have reported that the major effector cells responsible for allografted-tumor (e.g., Meth A) rejection are allograft-induced macrophages (AIM) with MHC haplotype specificity. METHODS: We characterized the macrophages migrating into the rejection site of allografted skin by immunohistochemical and in situ hybridization analyses using an antibody (K16.5) specific for AIM and a cDNA (pK30) encoding the antigen. To determine the in situ effector cells responsible for the rejection, we prepared both effector cells and target cells from the graft-graft bed border. RESULTS: The macrophages seemed to be morphologically (monocytic), phenotypically (K16.5+/pK30+), and functionally (cytotoxic against Meth A cells) AIM. The AIM population in bulk infiltrates taken from the rejection site was cytotoxic against allografted, but not self, skin components (e.g., fibroblasts, myocytes, endothelial cells, and epithelial cells). In contrast, other types of infiltrating cells including lymphocytes and granulocytes were virtually inactive toward these targets, and NK-1.1+ cells hardly infiltrated into the rejection site. CONCLUSIONS: These data suggest that the major effector cells mediating allografted skin rejection are AIM and not T cells.

Animals↗

Detection of Mycoplasma genitalium in patients with urethritis.

PURPOSE: We attempted to detect Mycoplasma genitalium in urethral swab specimens by a polymerase chain reaction based assay to determine the prevalence of M. genitalium in patients with urethritis. MATERIALS AND METHODS: We examined a total of 171 Japanese men who presented to our hospital from February 1995 through January 1997. Of these men 150 had symptoms and signs compatible with acute urethritis and 21 had no symptoms or signs of urethritis. Urethral swab specimens were used to culture Neisseria gonorrhoeae, to detect Chlamydia trachomatis by an enzyme immunoassay and to detect M. genitalium by a polymerase chain reaction based assay. RESULTS: Gonococcal urethritis was diagnosed in 74 symptomatic men, and nongonococcal urethritis was diagnosed in 76 symptomatic men. Of the 74 cases of gonococcal urethritis 3 (4.1%) were positive for M. genitalium, and 14 (18.9%) were positive for C. trachomatis. Of the 76 cases of nongonococcal urethritis 10 (13.2%) were positive for M. genitalium, and 42 (55.2%) were positive for C. trachomatis. While only 1 of the 42 cases with chlamydial nongonococcal urethritis (2.4%) was positive for M. genitalium, 9 of the 34 chlamydia negative nongonococcal urethritis cases (26.5%) were positive for the mycoplasma. In contrast, all 21 cases men were negative for N. gonorrhoeae, M. genitalium, and C. trachomatis. CONCLUSIONS: The prevalences of M. genitalium in patients with gonococcal urethritis and nongonococcal urethritis who attended our clinic were 4.1 and 13.2%, respectively. M. genitalium was detected significantly more often in men with nongonococcal urethritis than in asymptomatic men. In addition, its prevalence in men with chlamydia negative nongonococcal urethritis (26.5%) was significantly greater than in those with chlamydia positive nongonococcal urethritis (2.4%). These findings suggest that M. genitalium may be associated with the development of nongonococcal urethritis independent of C. trachomatis.

Adolescent↗

Significance of free to total PSA ratio in men with slightly elevated serum PSA levels: a cooperative study.

BACKGROUND: The ratio of free PSA in total PSA (f/t) has been reported to improve the diagnostic accuracy of prostate cancer in the group with slightly elevated serum PSA values. In Japanese cases, the clinical significance of f/t is still controversial. METHODS: The diagnostic significance of f/t in serum for prostate cancer was evaluated in a cooperative study. A total of 77 cases with prostate cancer and 224 with non-prostate cancer showing less than 20 ng/ml of total PSA were evaluated. RESULTS: Serum total and free PSA values were not affected by storage at 25 degrees C for 2 days. The determination of f/t was useful in the cases with a serum total PSA of 5.1-10 ng/ml; the specificity was 60% with a sensitivity of 90% at an f/t of 0.148. The positive predictive value for diagnosis of prostate cancer also increased to 54% from 34% of that in total PSA alone. In the range of 4.1-10 ng/ml, the cut-off value of f/t was 0.155 for obtaining relatively high specificity; sensitivity was 85% and specificity was 56.5%. CONCLUSIONS: Thus, the determination of f/t was considered to be an effective tool for discriminating the non-prostate cancer cases from those of prostate cancer.

Humans↗

Clinical evaluation of serum prostate-specific antigen-alpha1-antichymotrypsin complex values in diagnosis of prostate cancer: a cooperative study.

BACKGROUND: We studied the clinical significance of serum prostate-specific antigen bound to alpha1-antichymotrypsin (PSA-ACT) values determined with a newly developed enzyme immunoassay. METHODS: Serum PSA-ACT values were determined in a total of 652 sera. Clinical utility for the diagnosis of prostate cancer was compared to that of Tandem-R PSA and gamma-seminoprotein (gamma-Sm). The new enzyme immunoassay is based on the use of the Stanford reference as an international standard for PSA assays. RESULTS: Serum PSA-ACT values ranged from less than 0.10 to 1.4 ng/mL in healthy males (n = 100) while values in patients with benign prostatic hyperplasia (n = 155) averaged 3.4 +/- 3.8 ng/mL (mean +/- SD). In patients with prostate cancer, serum PSA-ACT values increased significantly with progression of the clinical stage and there were statistically significant differences between benign prostatic hyperplasia and each stage of prostate cancer except for stage A. Using BPH levels as controls (4.8 ng/mL for PSA-ACT, 7.2 ng/mL for PSA, 3.8 ng/mL for gamma-Sm, and 2.4 ng/mL for the complexed/free PSA ratio of PSA-ACT/gamma-Sm), specificity was 80%. The sensitivity of prostate cancer detection was 79% for PSA-ACT, 77% for PSA, 57% for gamma-Sm, and 46% for the ratio between PSA-ACT/gamma-Sm. CONCLUSION: Although the determination of serum PSA-ACT showed essentially the same utility as that of PSA for the diagnosis of prostate cancer, PSA-ACT may allow prediction of the clinical stage. The PSA-ACT assay may therefore replace PSA in the detection of prostate cancer.

Disease Progression↗

Alteration in the GyrA subunit of DNA gyrase and the ParC subunit of DNA topoisomerase IV in quinolone-resistant clinical isolates of Staphylococcus epidermidis.

We examined 22 clinical isolates of Staphylococcus epidermidis to analyze the association of alterations in GyrA and ParC with fluoroquinolone resistance. The simultaneous presence of GyrA and ParC alterations was associated with a high level of fluoroquinolone resistance in the clinical isolates of S. epidermidis.

4-Quinolones↗

Alterations in the GyrA subunit of DNA gyrase and the ParC subunit of DNA topoisomerase IV associated with quinolone resistance in Enterococcus faecalis.

The gyrA and parC genes of 31 clinical isolates of Enterococcus faecalis, including fluoroquinolone-resistant isolates, were partially sequenced and analyzed for target alterations. Topoisomerase IV may be a primary target in E. faecalis, but high-level fluoroquinolone resistance was associated with simultaneous alterations in both GyrA and ParC.

4-Quinolones↗

[Changes in blood polyamine levels following chemotherapy in patients with invasive urinary bladder carcinoma].

BACKGROUND: Polyamines are recognized as cell growth factors. We attempted to determine whether blood polyamines are useful biochemical makers for monitoring the efficacy of the chemotherapy on bladder tumors. METHODS: The blood concentrations of three polyamines, diamine, spermidine and spermine, were determined in 31 patients with invasive urinary bladder carcinoma, following chemotherapy with cisplatin, methotrexate and pirarubicin. Clinical response was evaluated by CT after 3 weeks. In 26 patients who underwent subsequent surgical therapy, the effectiveness of the chemotherapy were histopathologically evaluated by a pathologist according to the response criteria for bladder cancer treatment. RESULTS: Mean regression rate in the size of the tumor after the chemotherapy was 40.8%. Of 31 patients, clinical CR was observed in 2, PR in 11, and NC in 18. Of 26 patients who were histopathologically evaluated, grade 3 was observed in 5, grade 2 in 4, grade 1b in 4, grade 1a in 12, and grade 0 in 1. One week after chemotherapy, the levels of spermine and total polyamine in the patients with CR and PR were significantly lower than those in the patients with NC. Similarly one week after chemotherapy, the levels of spermine and total polyamine in the patients with grade 3 and grade 2 were significantly lower than those in the patients with grade 1b, grade 1a and grade 0. CONCLUSION: The study suggested that the levels of blood polyamines could be used as biochemical markers for monitoring the efficacy of the chemotherapy on bladder tumors.

Adenocarcinoma↗

[Intraarterial chemotherapy via reservoir system for far-advanced bladder and prostate cancer].

A clinical study was performed on the efficacy of intraarterial chemotherapy using reservoir system for far-advanced urological malignancy. The reservoir system was indwelled in the femoral subcutaneous layer using Seldinger's method. Fifteen cases with inoperable complicated advanced bladder cancer and ten cases with postoperative local recurrent bladder cancer received intraarterial chemotherapy using the reservoir system. Then, 23 cases with local relapsed prostate cancer and two cases with endocrine-resistant prostate cancer received chemotherapy. The administered anti-cancerous agents were methotrexate, cis-platinum and adriamycin, and 5-FU or carboplatin were administered as maintenance therapy. The mean courses of chemotherapy were six for bladder cancer and four for prostate cancer. During stabilization of the local lesion, no distant deterioration was recognized. Overall clinical efficacy was as follows: PR:18 cases and NC:7 cases for bladder cancer; then, PR:11 cases and 14 cases for prostate cancer. The median duration of stabilization was as follows: 23 months for bladder cancer and 12 months for prostate cancer. Complications were fewer than with systemic chemotherapy.

Adenocarcinoma↗

[Fleroxacin treatment for acute uncomplicated cystitis in women: comparison of 3-day and 7-day therapy].

The clinical efficacy of fleroxacin (FLRX), a new fluoroquinolone, for acute uncomplicated cystitis (AUC) in women was assessed. Two regimens, 3-day and 7-day courses of FLRX, 200 mg once a day, were compared. Clinical and bacteriological efficacy were evaluated after the therapy, and recurrence rate was evaluated 1 week and 4 weeks after termination of the therapy. Of 136 registered subjects, 35 in the 3-day group and 47 in the 7-day group were evaluated. According to the criteria of Japanese UTI Committee (3rd edition), the rate of excellent results was significantly higher in the 7-day group (78.9%) than in the 3-day group (48.6%), but the overall clinical efficacy rate was similar being 100% and 97.9%, respectively. Although no recurrence was seen 1 week after the therapy in either group, recurrence was seen in 14.3% and 7.4% of the cases in the 3-day and 7-day groups, respectively, 4 weeks after the therapy. Adverse reactions were observed in 2 and 3 cases in the 3-day and 7-day groups, respectively. Both 3-day and 7-day regimens of FLRX treatment showed good efficacy. Although the 7-day treatment was superior to the 3-day treatment as to high rate of excellent results and low rate of recurrence, the 3-day treatment was concluded to be sufficient for AUC.

Adult↗

Chemopreventive effects of diosmin and hesperidin on N-butyl-N-(4-hydroxybutyl)nitrosamine-induced urinary-bladder carcinogenesis in male ICR mice.

The chemopreventive effects of 2 flavonoids (diosmin and hesperidin) on N-butyl-N-(4-hydroxybutyl)nitrosamine (OH-BBN)-induced urinary-bladder carcinogenesis were examined in male ICR mice. Animals were divided into 11 groups, and groups 1 to 7 were given OH-BBN (500 ppm) in the drinking water for 6 weeks. Groups 2 to 4 were fed diets containing the test compounds (group 2, 1000 ppm diosmin; group 3, 1000 ppm hesperidin; group 4,900 ppm diosmin + 100 ppm hesperidin) for 8 weeks during the initiation phase, while groups 5 to 7 were fed these diets, respectively, for 24 weeks during the post-initiation phase. Groups 8 to 11 were controls, given only the test compounds or untreated basal diets throughout the experiment (weeks 1 to 32). The incidence of bladder lesions and cell-proliferation activity estimated by enumeration of silver-stained nucleolar-organizer-region-associated proteins (AgNORs) and by the 5-bromodeoxyuridine (BUdR)-labeling index was compared among the groups. Feeding of the test compounds, singly or in combination, during both phases caused a significant reduction in the frequency of bladder carcinoma and preneoplasia. Dietary administration of these compounds significantly decreased the AgNOR count and the BUdR-labeling index of various bladder lesions. These findings suggest that the flavonoids diosmin and hesperidin, individually and in combination, are effective in inhibiting chemical carcinogenesis of the bladder, and that such inhibition might be partly related to suppression of cell proliferation.

Administration, Oral↗