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Biomedical subjects

Masato Fujisawa

Publications and source records attributed to Masato Fujisawa.

At least 37 records · Page 2Linked to original sources

Rapid detection of the fluoroquinolone resistance-associated ParC mutation in Neisseria gonorrhoeae using TaqMan probes.

BACKGROUND: In fluoroquinolone-resistant Neisseria gonorrhoeae, the amino acid mutations in the fluoroquinolone-resistant determining region (QRDR) of the parC gene are an important factor. The aim of the present study was to develop a rapid detection method of a serine 88 to proline substitution in parC which we previously showed as having significantly higher fluoroquinolone minimal inhibitory concentrations (MIC) using the TaqMan discrimination system. METHODS: We extracted DNA from 90 urine or urethral swab samples obtained from male patients with urethritis caused by N. gonorrhoeae. After DNA extraction, they were subjected to real-time polymerase chain reaction (PCR) using a TaqMan discrimination system and compared with the results of conventional DNA sequencing. RESULTS: Of the 90 samples, the TaqMan technique result showed 13 samples that were classified as having a serine 88 to proline mutation in parC, and 77 samples that did not have a serine 88 to proline mutation in parC. The classifications of all samples completely corresponded to those determined by conventional DNA sequencing. We also found that N. gonorrhoeae with a serine 88 to proline mutation in parC have a significantly higher MIC to ciprofloxacin than that without a serine 88 to proline mutant in parC. CONCLUSIONS: The present genotyping method of real-time PCR using a TaqMan discrimination system could be applied to the rapid detection of a serine 88 to proline amino acid mutation in parC of N. gonorrhoeae. This point mutation is significant for the determination of fluoruquinolone resistance. This rapid detection system may lead to the prevention of use of noneffective antimicrobial agents and a decrease of resistant strains.

DNA Topoisomerase IV↗

A case of Sweet's syndrome following septic pulmonary emboli after high-dose chemotherapy for advanced testicular cancer.

A 33-year-old man with advanced testicular cancer underwent high-dose chemotherapy combined with peripheral blood stem cell transplantation. After administration of granulocyte colony-stimulating factor (G-CSF), multiple infiltrative erythema was identified on the face, thigh, and lower leg. A dermatologist diagnosed this as Sweet's syndrome caused by G-CSF; consequently G-CSF administration was stopped. When the skin lesions had improved, phlebitis was found at the injection site of the peripheral vein catheter. The patient then suffered from sudden left chest pain and dyspnea. Chest computed tomography showed the characteristic findings of septic pulmonary emboli (SPE). He was treated by the administration of vancomycin, fluconazole, and pazufloxacin mesilate. Although Sweet's syndrome and SPE are rare diseases, the presence of these diseases must be considered when performing chemotherapy for urological malignancy.

Adult↗

Complicated urinary tract infection caused by Pseudomonas aeruginosa in a single institution (1999-2003).

BACKGROUND: Pseudomonas aeruginosa has been an important uropathogen that causes complicated urinary tract infection. We investigated the clinical characteristics of complicated urinary tract infection caused by Pseudomonas aeruginosa in a single institution. METHODS: We studied those patients who had basal disease in their urinary tract that was diagnosed as urinary tract infection caused by more than 10(4) colony forming units (CFU)/mL of Pseudomonas aeruginosa isolated from their urine. In those patients, we analysed infectious risk factors, treatment methods including the use of antimicrobial agents, the presence of a urinary tract catheter, and the relationship between febrile infection and urinary tract catheter. In addition, we examined the various antimicrobial susceptibilities against Pseudomonas aeruginosa. RESULTS: We studied 76 patients (59 men and 17 women). Of their basal diseases of the urinary tract, bladder tumor was the most prevalent (42.1%). Of the 39 patients who had an indwelling urinary tract catheter, 26 (66.7%) experienced a high-grade fever, a higher rate than that of the 37 patients who were not catheterized (40.5%). Seven patients were treated with anticancer chemotherapy drugs and 31 cases of urinary tract infection caused by Pseudomonas aeruginosa were diagnosed in the perioperative period. Piperacillin showed lower susceptibility against Pseudomonas aeruginosa in these 2 years (P<0.05). CONCLUSIONS: Our results indicated that those patients with urinary tract catheterization had a higher incidence of fever than patients without catheterization. Therefore, we must improve not only the antimicrobial treatment of Pseudomonas aeruginosa but also our management of catheters.

Adult↗

Progress report on phase I/II clinical trial of Ad-OC-TK plus VAL therapy for metastatic or locally recurrent prostate cancer: Initial experience at Kobe University.

There is no effective therapy for hormone-refractory prostate cancer and a novel therapeutic modality, such as a gene therapy, should be actively pursued. Previously, Gardner and Chung conducted a phase I clinical trial of Ad-OC-TK (recombinant adenoviral vector containing osteocalcin promoter-driven herpes simplex virus thymidine kinase gene) plus VAL (valacyclovir) for the treatment of hormone-refractory prostate cancer at the University of Virginia. We report on our ongoing phase I/II clinical trial of Ad-OC-TK plus VAL for the treatment of advanced prostate cancer at the Kobe University Hospital, Japan.

Acyclovir↗

Effect of sildenafil on arterial stiffness, as assessed by pulse wave velocity, in patients with erectile dysfunction.

BACKGROUND: The problems of patients with erectile dysfunction have been recognized, leading to the emergence of sildenafil, which has led to successful treatment in many cases. The purpose of this study is to examine the effect of sildenafil on the pulse wave velocity of patients with erectile dysfunction. METHODS: Fifteen patients with erectile dysfunction were enrolled for this study. The brachial/ankle pulse wave velocity was determined before dosing and at 30, 60, 120, and 180 min after dosing with 25 or 50 mg of sildenafil citrate. Concurrently, the changes in blood pressure, heart rate, and brachial/ankle pulse wave velocity were measured. For the consideration of revised brachial/ankle pulse wave velocity by blood pressure, the systolic blood pressure-derived brachial/ankle pulse wave was also investigated, and we classified and examined those results with and without risk factors for arteriosclerosis. RESULTS: The systolic blood pressure decreased significantly at 60 min after dosing compared with the placebo control. The heart rate decreased at 120 min after dosing compared with the placebo control but that decrease was not significant. The brachial/ankle pulse wave velocity transiently decreased at 30 or 60 min after dosing compared with the placebo control, but the decrease was not significant; however, the systolic blood pressure-derived brachial/ankle pulse wave velocity decreased significantly. In those patients with risk factors for arteriosclerosis, the pulse wave velocity decreased significantly. CONCLUSION: In patients with erectile dysfunction who were administered sildenafil, the pulse wave velocity, along with blood pressure, tended to decrease transiently after dosing. There is a possibility that sildenafil affects the improvement of erectile dysfunction via the decrease of pulse wave velocity, especially in patients with risk factors for arteriosclerosis.

Adult↗

High-dose chemotherapy for male germ cell tumor.

Today, 20-30% of male patients with advanced germ cell tumor (GCT) do not have durable, complete remission in spite of cis-platinum (CDDP)-based chemotherapy. High-dose chemotherapy (HDCT) has been tried in CDDP refractory GCT patients. Initially HDCT was performed with autologous bone marrow transplantation in heavily treated patients. However, the clinical outcome was not good and the treatment-related death rate was not ignorable. Therefore, earlier introduction of HDCT with peripheral blood stem cell transplantation was preferable as it renders HDCT more effective and less toxic, and multicycle HDCT is feasible. The durable free rate of recent HDCT for refractory GCT patients is 32-65%. HDCT is also performed as first line chemotherapy for poor prognosis GCT patients. Induction chemotherapy followed by multicycles of HDCT was tried. The durable free rate of recent HDCT as first line chemotherapy is 43-73%. Although previous reports suggest the superiority of HDCT, one recent randomized controlled trial (RCT) failed to show an improvement with one cycle of HDCT followed by three cycles of standard-dose chemotherapy (SDCT) compared with four cycles of SDCT. Ongoing RCT comparing multicycles of HDCT with SDCT for poor prognostic GCT patients will clarify the role of HDCT. Recently, new regimens of HDCT containing paclitaxel have been devised. In this review, the history, current status and future of HDCT for advanced or refractory GCT will be discussed.

Antineoplastic Agents↗

Papillary renal cell carcinoma: a clinicopathological study of 35 cases.

AIM: The objective of the present study was to characterize the clinicopathological features of histologically defined papillary renal cell carcinoma (RCC). METHODS: The present study included a total of 35 patients who were treated by radical surgery and subsequently diagnosed as having papillary RCC between April 1995 and June 2004. Clinicopathological data of these patients were retrospectively reviewed according to the previously reported classification system (Mod. Pathol. 1997; 10: 537-44). RESULTS: Of these 35 patients, 23 (65.7%) and 12 (34.3%) were diagnosed as type 1 and type 2 papillary RCC, respectively. Despite the lack of significant differences in clinical parameters between these two groups, including age, gender, clinical stage and metastasis, the incidence of symptomatic disease in patients with type 2 papillary RCC was significantly higher than that in those with type 1 papillary RCC. Pathological examinations demonstrated that there were no significant differences between these two groups in pathological stage, tumor grade or vascular invasion. Furthermore, there was no significant difference between these two groups in overall or recurrence-free survival. CONCLUSIONS: Although the present study included a small number of patients with short follow-up period, the clinicopathological features including prognoses were almost similar between patients with type 1 and type 2 papillary RCC; therefore, careful postoperative follow-up should be considered for patients with papillary RCC irrespective of morphological subtype.

Aged↗

Hydronephrosis caused by intra-abdominal abscess from cecal perforation by an ingested fish bone.

A patient was treated for hydronephrosis caused by an intra-abdominal abscess arising from cecal perforation by an ingested fish bone. To the authors' knowledge there is no previous report of such ureteral obstruction. Ureteral stenting, drainage of the abscess, and ileocecal resection were performed. Six months of stenting were required to attain ongoing ureteral patency following removal.

Abdominal Abscess↗

Analysis of factors predicting intravesical recurrence of superficial transitional cell carcinoma of the bladder without concomitant carcinoma in situ.

BACKGROUND: The objective of this study was to investigate risk factors for intravesical recurrence in patients with superficial bladder cancer without concomitant carcinoma in situ (CIS). METHODS: In this series, we analyzed data from patients with newly diagnosed superficial Ta or T1 transitional cell carcinoma (TCC) of the bladder without concomitant CIS who underwent complete transurethral resection (TUR) without any adjuvant intravesical instillation therapies. Multivariate analysis was used to determine significant risk factors affecting intravesical recurrence after TUR. Differences in clinicopathological features between primary and recurrent tumors were also characterized. RESULTS: Among 341 patients undergoing TUR of Ta or T1 bladder cancer, 187 diagnosed as having concomitant CIS and/or treated with adjuvant intravesical therapy were excluded, and the remaining 154 were evaluated. Intravesical recurrence was detected in 64 of the 154 patients, showing a 5-year recurrence-free survival rate of 58.3%. Among several factors examined, only tumor size was significantly associated with intravesical recurrence. Multivariate analysis identified tumor size as an independent predictor for intravesical recurrence irrespective of other parameters including age, gender, multiplicity, growth pattern, grade and stage. Recurrent tumors were significantly smaller and of a lower grade and lower stage than primary tumors, despite the absence of differences in growth pattern and the multiplicity between them. CONCLUSIONS: These findings suggest that primary tumor size could be used as a potential risk factor for predicting intravesical recurrence following TUR of superficial TCC of the bladder without concomitant CIS, and that the pathological characteristics of recurrent tumors are more favorable than those of primary tumors.

Adolescent↗

Clinical study of complicated urinary tract infection using 'The UTI Criteria (Draft Fourth Edition)': measurement methods for pyuria.

OBJECTIVE: To evaluate the influences the change of the measurement method of pyuria from conventional centrifuged sediment to microchamber uncentrifuged urine for the results of evaluation of antimicrobial agents in clinical study against complicated urinary tract infections. From the viewpoint of international harmonization of judgement criteria, the recent method for counting white blood cells (WBC) in urine has changed from using uncentrifuged urine to using a microchamber in all countries. METHODS: Targeted diseases were non-catheterized complicated urinary tract infection, and cefcapene pivoxil hydrochloride or levofloxacin were used as antimicrobial drug. Pyuria was examined using the counting chamber method, a quantitative method using uncentrifuged urine with a microchamber, and the sedimentation method. RESULTS: Overall clinical efficacy in early evaluation by the two methods in measuring pyuria was evaluated as different in eight patients (7.3%). It was rated excellent in 63 (52.9%), moderate in 32 patients (26.9%) and poor in 24 (20.2%) with an efficacy rate of 79.8% using the counting chamber method, and excellent in 68 (57.1%), moderate in 27 (22.7%) and poor in 24 (20.2%) with an efficacy rate of 79.8% using the conventional sedimentation method CONCLUSION: No significant difference was seen between the two methods of WBC count in urine.

Adult↗

Limited significance of routine excretory urography in the follow-up of patients with superficial bladder cancer after transurethral resection.

OBJECTIVES: To evaluate the utility of routine excretory intravenous urography (IVU) for detecting subsequent upper urinary tract cancer (UUTC) during the follow-up of patients with superficial bladder cancer. PATIENTS AND METHODS: The study included 413 patients who had transurethral resection (TUR) of superficial bladder cancer between January 1986 and December 2003, and were followed for at least 1 year. After TUR, patients were followed by periodic cystoscopy, urinary cytology and IVU. The risk factors for UUT recurrence after TUR were analysed, and based on this outcome, we then determined whether routine IVU should be used for patients with superficial bladder cancer. RESULTS: During the observation period, UUTCs developed in 20 of the 413 patients (4.8%) within a median of 33 months from the initial TUR to the detection of UUTCs. Among several factors examined, only multiplicity was significantly associated with UUT recurrence after TUR. Of the 20 patients with secondary UUTCs, only two, who had multiple superficial bladder cancers at initial presentation, were diagnosed as having UUTCs by routine IVU, while the remaining 18 presented with symptoms suggesting possible UUT recurrence before IVU, including macrohaematuria (10 patients), intravesical recurrence (five), positive urinary cytology (five), abdominal pain (three) and high fever (two). CONCLUSIONS: Most patients with recurrent UUTCs presented with some subjective and/or objective symptoms, and routine IVU failed to detect recurrent diseases in such patients. Therefore, routine IVU may not be required for all patients who have TUR of superficial bladder cancer.

Aged↗

Larger prostate causes higher frequency of infectious complications in prostate biopsy.

INTRODUCTION: Prostate biopsy (PBX) is being performed more often than ever before for the early detection of prostate cancer, but some patients may have febrile infectious complications after biopsy. The risk factors of infectious complications need to be considered. METHODS: We investigated the pre-biopsy risk factors and febrile infectious complications in 120 patients who underwent PBX in our institution. The pre-biopsy risk factors set were prostate volume (> or = 40 ml), transitional zone (TZ) volume (> or = 20 ml), core number of biopsy (> or = 10 cores), and additional performance of TZ biopsy. We analyzed statistically the correlations between these risk factors and C-reactive protein and peripheral white blood cell (WBC) count elevation on day 1 and day 7 after biopsy. RESULTS: Our results showed that a prostate volume > or = 40 ml and a TZ volume > or = 20 ml caused a significantly higher elevation of the C-reactive protein level compared with a prostate volume < 40 ml (p = 0.0055 on day 1 and p = 0.0225 on day 7, respectively) on day 1 and day 7, and a TZ volume < 20 ml (p = 0.0008) on day 1. Regarding WBC count, those patients with a prostate volume > or = 40 ml and a TZ volume > or = 20 ml had a tendency to have an elevated WBC count on day 1 compared with those patients with a prostate volume < 40 ml and a TZ volume < 20 ml, and however these changes were not significant. CONCLUSIONS: This study showed that a larger prostate volume and a larger TZ volume may possibly be risk factors in infectious complications after PBX, although we can perform additional TZ biopsy and increase biopsy core number safely if necessary.

Aged↗

The limited significance of a longer duration of neoadjuvant hormonal therapy prior to radical prostatectomy for high-risk prostate cancer in Japanese men.

INTRODUCTION: The objective of this study was to evaluate the therapeutic significance of a longer duration of neoadjuvant hormonal therapy (NHT) followed by radical prostatectomy (RP) in Japanese men with high-risk prostate cancer. MATERIALS AND METHODS: This study included a total of 42 patients with high-risk prostate cancer who were treated with NHT for >or=8 months prior to RP. In this series high-risk prostate cancer was defined as clinical stage T2c or T3, pretreatment serum prostate-specific antigen (PSA) >20 ng/ml and/or a biopsy Gleason score of 8-10. Biochemical recurrence was defined as a serum PSA level of >or=0.2 ng/ml. The data of these patients were retrospectively reviewed to clarify the relationships between treatment outcomes and various clinicopathological parameters. RESULTS: The clinical stage was T2c in 13 patients and T3 in 29, the median value of pretreatment serum PSA was 43.3 ng/ml (range 9.7-322.2), and the biopsy Gleason score was 6 in 3 patients, 7 in 16 and >or=8 in 23. Following NHT (median 12 months, range 8-27), the median value of serum PSA decreased to 0.05 ng/ml (<0.01-18.3 ng/ml), and 15 patients (35.7%) were pathologically downstaged. During the median follow-up of 38 months (range 8-58), 11 patients (26.2%) developed biochemical recurrence, and the multivariate analysis identified pretreatment serum PSA, biopsy Gleason score and percentage of positive biopsy core as independent predictors of biochemical recurrence. The 3-year biochemical recurrence-free survival rate of the 42 patients was 68.3%, which was not significantly different from that of 34 patients who underwent RP for high-risk prostate cancer without NHT during the same period. CONCLUSION: A longer duration of NHT followed by RP for patients with high-risk prostate cancer resulted in a comparatively favorable outcome. However, despite the nonrandomized retrospective analysis, the present findings suggest no significant impact of long-term NHT on biochemical recurrence. Longer follow-up is needed to determine whether this therapeutic strategy is beneficial for high-risk prostate cancer patients.

Aged↗

Clinicopathological features of patients with biochemical recurrence after radical prostatectomy without progressive rise in serum prostate-specific antigen.

INTRODUCTION: The objective of this study was to characterize clinicopathological features of patients with biochemical recurrence after radical prostatectomy who did not exhibit a progressive rise in serum prostate-specific antigen (PSA) during the follow-up period. MATERIALS AND METHODS: We analyzed data from 162 consecutive patients who underwent radical prostatectomy for clinically organ-confined prostate cancer without neoadjuvant hormonal therapy and were followed postoperatively for at least 1 year. The serum PSA value was measured using an ultrasensitive PSA assay system (Roche Diagnostics, Mannheim, Germany), and biochemical recurrence was defined as a serum PSA of >or=0.1 ng/ml. RESULTS: A total of 32 patients (19.8%) were diagnosed as having biochemical recurrence. Among these patients, we identified 10 (31.3%) with a serum PSA>0.1 ng/ml who had not shown PSA or clinical progression during a median follow-up of 34 months after radical prostatectomy. In these 10 patients, the median time to biochemical recurrence was 17 months, the median PSA velocity after biochemical recurrence was 0.034 ng/ml/year, and there was no patient whose serum PSA value became >0.4 ng/ml. There were no clinicopathological parameters except for PSA velocity that were significantly associated with the features of these 10 patients. CONCLUSION: Because of the presence of a subset of patients with biochemical recurrence after radical prostatectomy who will not show a progressive increase in serum PSA value, the indication for adjuvant therapy for such patients should be cautiously determined considering several factors, such as PSA kinetics.

Aged↗

The potential of clusterin inhibiting antisense oligodeoxynucleotide therapy for prostate cancer.

This review summarise the authors' recent experience in the development of antisense (AS) oligodeoxynucleotide (ODN) therapy that targets a cytoprotective gene, clusterin, for the treatment of prostate cancer. The acquisition of resistance to a wide variety of proapototic stimuli was initially demonstrated by introducing the clusterin gene into prostate cancer cells. Furthermore, silencing clusterin expression using AS ODN synergistically enhanced the effects of several conventional therapeutic modalities through the effective induction of apoptosis in prostate cancer xenograft models. Based on these outcomes, Phase I clinical trials were conducted using AS clusterin ODN incorporating 2'-O-(2-methoxy)ethyl-gapmer backbone (OGX-011), and the optimal dose of OGX-011 capable of inducing </= 90% suppression of clusterin in human prostate cancer tissue was determined. Collectively, these findings suggest the utility of inactivating clusterin function using AS ODN technology as a novel therapeutic strategy for prostate cancer treatment. There have been four kinds of Phase II studies that have begun to further evaluate the efficacy of OGX-011 in patients with prostate, breast and lung cancers.

Animals↗

[Pathological prognostic factors of renal pelvic and ureteral cancer].

OBJECTIVE: To determine the pathologic risk factors after nephroureterectomy in patients with urothelial carcinoma of the renal pelvis and ureter. PATIENTS AND METHODS: We investigated the clinicopathological features of 131 patients (94 males and 37 females) with urothelial carcinoma of the renal pelvis and ureter who underwent nephroureterectomy at our department and related facilities from August, 1994 to August, 1997. The mean age of the patients was 68 years, ranging from 24 to 86 years. RESULTS: The 1-, 3- and 5-year cause-specific survival rates (Kaplan-Meier's method) for all of the patients were 91.8%, 76.7%, and 67.8%, respectively. The significant prognostic factors for survival rates by univariate analysis using the log rank test were tumor stage, infiltration pattern, lymphatic invasion, vessel invasion and lymph node metastasis. On the other hand, multivariate analysis using Cox proportional hazards regression model showed the most influential prognostic factors to be vessel invasion and tumor stage. CONCLUSIONS: From these results, in urothelial carcinoma of the renal pelvis and ureter underwent nephroureterectomy, we suggested that vessel invasion and tumor stage were the independent prognostic factors.

Adult↗

[A case of retroperitoneal malignant peripheral nerve sheath tumor in a patient with neurofibromatosis].

We report a case of retroperitoneal malignant peripheral nerve sheath tumor (MPNST) in a patient with neurofibromatosis 1. A 42-year-old woman was admitted because of a palpable left abdominal mass. Her mother, son, and daughter had neurofibromatosis 1. Computed tomography and magnetic resonance imaging revealed a 73 x 76 mm retroperitoneal mass. We performed complete resection of the tumor, confirming the margin status by frozen section examination intraoperatively. The histopathological examination revealed MPNST. Although no further therapy was performed, she is alive with no evidence of disease 11 months after surgery.

Adult↗