Retrospective study for risk factors for febrile UTI in spinal cord injury patients with routine concomitant intermittent catheterization in outpatient settings.

STUDY DESIGN: Retrospective study. OBJECTIVES: The objective of this study was to investigate the clinical risk factors for febrile urinary tract infection (UTI) in spinal cord injury-associated neurogenic bladder (NB) patients who perform routine clean intermittent catheterization (CIC). SETTING: Rehabilitation Hospital, Kobe, Japan. METHODS: Over a 3-year period, we retrospectively assessed the clinical risk factors for febrile UTI in 259 spinal cord injury patients diagnosed as NB and performing routine CIC with regard to the factors such as gender, the presence of pyuria and bacteriuria, and the categories of the American Spinal Injury Association (ASIA) impairment scale. RESULTS: A total of 67 patients had febrile UTI in the follow-up period, with 57 cases of pyelonephritis, 11 cases of epididymitis and 2 cases of prostatitis, including the patients with plural infectious diseases. The causative bacteria were ranked as follows: Escherichia coli (74 cases), Pseudomonas aeruginosa (17 cases), Enterococcus faecalis (14 cases) and Klebsiella pneumoniae (12 cases). Antibiotic-resistant E. coli were seen, with 10.5% instances of extended-spectrum ß-lactamase (ESBL) production and 23.8% of fluoroquinolone resistance. Multivariate analyses of clinical risk factors for febrile UTI showed that gender (male, P=0.0431), and ASIA impairment scale C or more severe (P=0.0266) were significantly associated with febrile UTI occurrence in NB patients with routine CIC. CONCLUSION: Our data demonstrated gender (male) and ASIA impairment scale C or more severe were significantly associated with febrile UTI occurrence in NB patients using routine CIC. Further prospective studies are necessary to define the full spectrum of possible risk factors for febrile UTI in these patients.

Emergence and prevention measures for multidrug resistant Pseudomonas aeruginosa in catheter-associated urinary tract infection in spinal cord injury patients.

OBJECTIVE: To evaluate measures for preventing multidrug resistant Pseudomonas aeruginosa (MDRP) in catheter-associated urinary tract infection (CAUTI) in spinal cord injury patients. SETTING: Spinal Cord Injury Unit of Hyogo Prefectural Hyogo Prefectural Rehabilitation Center, Kobe, Japan. METHODS: We defined MDRP as resistance to amikacin, imipenem and levofloxacin. We had eight cases of MDRP-causing CAUTI in hospitalized neurogenic bladder patients caused by spinal cord injury in 2 months. Pulse-field gel electrophoresis (PFGE) was performed for epidemiological studies. We assessed prevention measures against MDRP emergence from the 2nd month, such as surveillance of CAUTI and infection control, and evaluated the outcomes of these measures over a total of 8 months. RESULTS: Our PFGE results showed that these eight MDRP isolates could be considered as closely related strains. We concluded that this was an MDRP outbreak that was causing CAUTI. The isolated ratio of MDRP began to decrease over 4 months of surveillance and significantly decreased in the 4th quarter (7th and 8th months) compared with the 1st quarter (1st and 2nd months) (P=0.021) even though urinary tract device usage significantly increased over the same period (P<0.001). CONCLUSION: We experienced an outbreak of emergent MDRP causing CAUTI in neurogenic bladder patients with spinal cord injury. Our preventive measures for isolating the outbreak, including surveillance, may have led to the decrease we observed in the ratio of MDRP isolated.

E10A, an adenovirus-carrying endostatin gene, dramatically increased the tumor drug concentration of metronomic chemotherapy with low-dose cisplatin in a xenograft mouse model for head and neck squamous-cell carcinoma.

Most cancer chemotherapeutic agents are administered at the maximum-tolerated dose (MTD) in short cycles with treatment breaks. However, MTD-based chemotherapies are often associated with significant toxicity and treatment breaks allow the opportunity for tumor regrowth and acquisition of chemoresistance. To minimize these drawbacks, a metronomic strategy, in which chemotherapeutics are administered at doses significantly below the MTD without treatment breaks, has been suggested by many investigators. The antitumor effect of metronomic chemotherapy may be partially due to inhibition of tumor angiogenesis, and it could be enhanced by a combination therapy, including antiangiogenic agents. In this study, we evaluated the synergistic effect of E10A, an adenovirus carrying the endostatin gene, the most potent inhibitors of tumor angiogenesis, in combination with weekly low-dose cisplatin in a xenograft mouse model for head and neck squamous-cell carcinoma. The E10A induced mRNA and protein expressions of endostatin in H891 cells in vitro. E10A significantly enhanced the in vivo tumor growth inhibitory effect of cisplatin. Immunohistochemical analysis with a TUNEL (terminal deoxynucleotidyl transferase-mediated nick-end labeling) assay and anti-CD31 antibodies revealed that the combination of E10A and cisplatin induced high levels of cell apoptosis and inhibited tumor angiogenesis. Importantly, E10A increased the platinum concentrations in tumors to fivefold higher than that induced by cisplatin alone.

In vitro and in vivo inhibitory effect of three Cox-2 inhibitors and epithelial-to-mesenchymal transition in human bladder cancer cell lines.

BACKGROUND: Although the anti-tumour effect of cyclooxygenase-2 (Cox-2) inhibitors in invasive bladder cancer has been confirmed, its mechanisms of action are unclear. Recently, the concept of an epithelial-to-mesenchymal transition (EMT) promoting carcinoma progression has been suggested, and a key feature of the EMT is the downregulation of E-cadherin. In this study, we investigated the effect of Cox-2 inhibitors on reversal EMT and tumour growth inhibition in bladder cancer cells. METHODS: We used three Cox-2 inhibitors, etodolac, celecoxib and NS-398 and three human bladder cancer cell lines, T24, 5637 and KK47, in this study. T24 xenograft tumour mouse model was used in the in vivo study. RESULTS: Within the clinical drug concentrations, only etodolac showed the in vitro growth inhibition in T24 not in the other cell lines. Etodolac reduced SNAIL mRNA and vimentin cell surface expression, and induced E-cadherin mRNA and E-cadherin cell surface expression, in T24. Etodolac also most strongly inhibited the cell migration of T24 in vitro and showed the highest tumour growth inhibition in T24 tumour in vivo. CONCLUSION: Etodolac at clinical doses exhibited induced in vitro and in vivo anti-tumour effects and reversal effect of EMT in T24. These results suggest that etodolac is a good candidate for an anti-tumour or chemopreventive reagent for high-grade bladder cancer.

Rapid detection and differentiation of Gram-negative and Gram-positive pathogenic bacteria in urine using TaqMan probe.

Urinary tract infection has been shown to be quite complicated and often difficult to diagnose and treat. For appropriate diagnosis, it is very important to find the correct Gram stain classification as soon as possible, especially in severe cases where there is a possibility of severe sepsis developing. In order to solve this problem, we developed a new method to detect a Gram stain of bacteria obtained from 1 ml of urine from urinary tract infection patients using a consensus real-time PCR protocol with a TaqMan probe that allows detection of spiked bacterial 16S DNA from urine. We extracted DNA of 55 urine samples obtained from patients with complicated urinary tract infection and at the same time performed urine culture testing. After DNA extraction, they were subjected to real-time PCR using a TaqMan discrimination system. Sixteen kinds of bacteria were cultured from the urine culture testing. Of these bacteria, eight were classified as Gram-positive bacteria and the other eight were classified as Gram-negative bacteria. Of the 55 samples, the TaqMan technique result showed 27 samples that were classified as Gram-negative bacteria; 11 samples that were Gram-positive, 10 that included both Gram-negative and -positive bacteria, and 7 that showed no amplification. The classifications of all samples corresponded exactly to those determined by urine culture testing. The present genotyping method of real-time PCR using a TaqMan discrimination system could be applied to the rapid detection of Gram-positive or -negative bacteria in urine of urinary tract infection patients. This assay can differentiate those species tested, but whether the presence of other (untested) bacteria could lead to misinterpretation is unknown. For further investigation, it is important to test other (untested) bacteria in the near future.

Susceptibilities of Neisseria gonorrhoeae to fluoroquinolones and other antimicrobial agents in Hyogo and Osaka, Japan.

OBJECTIVES: Decreasing susceptibility of Neisseria gonorrhoeae to fluoroquinolones has been reported in several countries. Knowledge of local N gonorrhoeae susceptibilities to various antimicrobials is important for establishing a rational treatment strategy in each region. METHODS: Isolates of N gonorrhoeae from male urethritis patients attending four urological clinics in Hyogo and Osaka prefectures in Japan were collected during 2002. The MICs for nine antimicrobials: penicillin G, tetracycline, cefixime, ceftriaxone, levofloxacin, gatifloxacin, ciprofloxacin, moxifloxacin, and spectinomycin were determined for each isolate. All isolates were also tested for beta lactamase producing profiles. RESULTS: Among the 87 isolates obtained, only one isolate was revealed to produce beta lactamase. MIC90 values for ciprofloxacin, levofloxacin, gatifloxacin, and moxifloxacin were over 8 microg/ml, over 8 microg/ml, 4 microg/ml, and 2 microg/ml, respectively. The proportion of isolates resistant to fluoroquinolones was over 60% (ciprofloxacin, 70.1%; levofloxacin, 65.5%; gatifloxacin, 70.1%). Chromosomally mediated penicillin and tetracycline resistance was identified in 12.6% and 33.3% of the isolates. MIC90 values for cefixime and ceftriaxone and were 0.5 microg/ml and 0.0063 microg/ml. All isolates were sensitive to ceftriaxone and 90.8% of them were sensitive to cefixime. MIC90 for spectinomycin was 32 microg/ml and all isolates were sensitive to it. Fluoroquinolone resistance correlated significantly with MICs for penicillin G but not tetracycline. CONCLUSION: Ceftriaxone and spectinomycin demonstrated lower MICs and so are recommended for N gonorrhoeae. Susceptibilities of N gonorrhoeae should be monitored periodically by region.

Different beta-adrenergic regulation of myocardial contraction and relaxation between apical and nonobstructive hypertrophic cardiomyopathy.

BACKGROUND: The impaired adrenergic control of both inotropic and lusitropic reserves has been evaluated in patients with hypertrophic cardiomyopathy (HCM) but not in those with apical HCM (APH). OBJECTIVES: We examined the influence of increases in heart rate and adrenergic stimulation on inotropic and lusitropic reserves in HCM and APH with normal resting left ventricular (LV) systolic function. METHODS: We evaluated LV isovolumic contraction and relaxation during atrial pacing and during supine leg exercise in 7 patients with APH and in 8 patients with HCM. RESULTS: Heart rate was significantly correlated with LV isovolumic contraction and relaxation during pacing and exercise in all patients. In all patients with APH, the increase in LV isovolumic contraction was greater during exercise (101%) than pacing alone (27%) for similar increase in heart rate. In 5 patients with HCM, the increase in LV isovolumic contraction was greater during exercise (83%) than pacing alone (24%), whereas in 3 patients with HCM the increase in LV isovolumic contraction was similar between during exercise (25%) and during pacing alone (22%). In all patients with APH, relaxation was shorter during exercise (39%) than pacing alone (16%). Conversely, in patients with HCM relaxation was similarly shortened between during pacing alone (20%) and during exercise (19%). CONCLUSIONS: The force-frequency and the relaxation-frequency relations were well-preserved in all patients. In patients with HCM, the adrenergic enhancement of force-frequency relation and/or relaxation-frequency relation was impaired. In patients with APH, however, adrenergic control of both force-frequency and relaxation-frequency relations was well-preserved, which may indicate a preserved beta-adrenergic signaling pathway.