Activities of beta-lactams, fluoroquinolones, amikacin and fosfomycin alone and in combination against Pseudomonas aeruginosa isolated from complicated urinary tract infections.

Using the checkerboard titration method as well as the time-kill curve technique, we investigated the activities of beta-lactams, fluoroquinolones, amikacin, and fosfomycin alone and in combination against Pseudomonas aeruginosa isolated from patients with complicated urinary tract infections. In the checkerboard titration studies, none of 21 combinations demonstrated antagonism against 26 strains tested, and the mean fractional inhibitory concentration (FIC) indices for these combinations ranged between 0.4694 and 0.9828. Corresponding to the respective FIC indices, the bactericidal activity determined in combinations of meropenem with ciprofloxacin or amikacin and ceftazidime with ciprofloxacin at sub-minimum inhibitory concentrations (MICs) produced a great reduction in bacterial counts (>/=2 log10 CFU/ml) within 6 h of administration against most of the strains, including strains resistant to one or both drugs, and these synergistic effects were confirmed morphologically by scanning electron microscopy. In time-lag combinations, the first administration of ciprofloxacin or amikacin supplemented by meropenem with 1-h lag diminished bactericidal activity, in comparison with the simultaneous administration of the drugs. These results suggest that simultaneous combinations of beta-lactams with fluoroquinolones or amikacin may be useful alternatives for the treatment of serious infections due to P. aeruginosa.

[A case of metastatic carcinoma to the retina].

The authors report a case of metastatic carcinoma to the retina. The patient was a 61-year-old man who had an operation for a well-differentiated adenocarcinoma of the rectum. Ophthalmoscopic examination disclosed a single, white, elevated mass lesion surrounded by serous retinal detachment located in the upper part of the macula of the right eye. A few retinal hemorrhages existed around the lesion. Fluorescein angiography revealed partially obscured retinal vessels due to compression by the tumor and arteriovenous anastomosis. Postmortem pathologic examination confirmed metastases to the brain, lung and retina. Microscopic examination showed a retinal lesion and tumor cells in the right eye. Tumor cells, similar to the carcinoma of the rectum, were present only in the neurosensory retina and did not invade the pigmented epithelium or choroid.

Comparative study of single-dose and three-day therapy for acute uncomplicated cystitis.

To assess the efficacy and safety of a single-dose therapy for acute uncomplicated cystitis (AUC), we compared 4 treatment regimens in 120 women. Patients eligible for the study were randomly assigned to one of four treatment groups: Ciprofloxacin (CPFX) 200 mg in a single oral dose (group A); 200 mg once daily for 3 days (group B); 200 mg twice daily for 3 day (group C); and cefpodoxime-proxcetil (CPDX-PR) 200 mg once daily for 3 days (group D). The efficacy was evaluated 3 days after the single-dose therapy or at the end of a three-day therapy according to the criteria proposed by the Japanese UTI Committee. The overall clinical efficacy in a total of 107 patients was evaluated to be excellent, moderate, and poor in 72 (67.3%), 35 (31.8%), and 1 (0.9%), respectively. The causative organisms were eradicated in 88.0, 85.2, 85.2, and 82.1% of the patients in groups A, B, C, and D, respectively. Recurrence was identified in 3 (2 in group A and one in group D) of 16 patients who were followed at 2 to 3 weeks after the treatment. No adverse reactions related to the antibiotics were recognized in the study. There were no significant differences in the clinical efficacy or recurrence rate among these four treatment regimens. These results indicate that the single-dose therapy of CPFX is the treatment of choice in women with AUC.

[A study of the simulation model of the lower urinary tract for urodynamics--(the first report)--theoretical evaluation of hydrodynamic model].

From the view point of urodynamics, the lower urinary tract might be able to be simulated by a hydrodynamic model, consisting of a spherical balloon corresponding to the bladder and a circular tube to the urethra. In this hydrodynamic model, the diameter of the tube corresponding to the posterior urethra was assumed to become smaller with increase of the prostatic pressure according to the development of BPH. On this assumption, Bernoulli's equation might be adopted. Because of the turbulent flow in the tube, the velocity of flow was expressed as a function of the invariants, which indicated the pressure in the balloon, the respective lengths and diameters of narrow tube and wide tube, coefficients due to pipe friction, pipe fitting and pipe enlargement. The findings suggested that the smaller the diameter of the narrow tube, the smaller the flow volume showed with the development of BPH. In conclusion the urodynamics in the lower urinary tract could be simulated quantitatively by this model. The study may lead to the development of the urodynamic simulation model for the lower urinary tract.

[Anesthetic management for AICD (automatic implantable cardioverter defibrillator) implant surgery].

We studied anesthetic management and monitoring during AICD (automatic implantable cardioverter defibrillator) implantation. For anesthetic management, complete sedation and amnesia are needed during implantation procedures with rapid awakening and extubation after the surgery. We chose inhalation anesthesia supplemented with small doses of fentanyl or thiamylal. Monitoring for AICD implantation should be less invasive, continuous and rapid in responsiveness. For brain and cardiac monitoring, a combination of near infrared spectroscopy and transesophageal echocardiography was quite useful.

[Effect of nafamostat mesilate on the renin-aldosterone system].

It has been reported that continuous intravenous infusion of nafamostat mesilate (FUT) produces hyperkalemia due to reduced urinary excretion of potassium. The present study was performed to see whether renin-aldosterone effect is involved in this inhibition of potassium excretion. Ten patients were studied who had been given this drug (4 mg.hr-1) to prevent postsurgical pancreatitis or DIC. Urine potassium output decreased significantly from 44 +/- 5 microEq.min-1 prior to administration of FUT to 18 +/- 4 microEq.min-1 in 3 hours, sodium/potassium ratio increased significantly from 1.7 +/- 0.7 prior to administration of FUT to 5.4 +/- 3.3 in 5 hours; and plasma aldosterone decreased significantly from 92 +/- 24 pg.ml-1 prior to administration of FUT to 63 +/- 22 pg.ml-1 in 6 hours. The results suggest that hyposecretion of aldosterone may be one of the main causes of hypokalemia. Reduced secretion of aldosterone may be due to other factors than the suppression of renin-angiotensin system.

Effects of magnesium on polymorphic ventricular tachycardias induced by aconitine.

We examined the effects of Mg2+ on aconitine-induced polymorphic ventricular tachycardias (PVT) in excised rabbit hearts under Langendorff perfusion and in Purkinje-muscle preparations. Local electrograms using bipolar electrodes and transmembrane potentials with the microelectrode technique were recorded from Langendorff hearts and Purkinje-muscle preparations, respectively. In Langendorff preparations, intracoronary application of 0.1 microM aconitine induced PVT 28.8 +/- 3.4 min after development of regular monomorphic ventricular tachycardias (MVT) in all 18 preparations. Application of 5 and 10 mM Mg2+ restored aconitine-induced PVT to sinus rhythm after 26.8 +/- 3.4 min (n = 9), but < 3 mM Mg2+ was not effective in restoring of sinus rhythm. Increased Mg2+ concentrations < or = 5 mM in the coronary perfusate prevented development of PVT by aconitine. Intracoronary application of 10 microM tetrodotoxin (TTX) also restored aconitine-induced PVT to sinus rhythm after 3.2 +/- 0.8 min (n = 4). Although applications of 50 microM lidocaine, 10 microM flecainide, or 1 microM verapamil could change PVT to MVT, they were not effective in restoring sinus rhythm. In Purkinje-muscle preparations, spontaneous action potentials (AP) from slow diastolic depolarization appeared after aconitine at the maximum diastolic potential of -75.0 +/- 3.7 mV in Purkinje fibers and were conducted to ventricular muscles (n = 5). Spontaneous activity gradually increased in rate and then developed triggered activity arising from early after depolarization (EAD). EAD induced by aconitine always appeared first in Purkinje fibers and later in muscle fibers. Once triggered activities started from EAD, rate, rhythm and amplitudes of APs became fast and variable.(ABSTRACT TRUNCATED AT 250 WORDS)

Detection and identification of mutagens and carcinogens as their adducts with guanosine derivatives.

For use in screening for environmental mutagens and carcinogens, a highly fluorescent derivative of guanosine, 2'-deoxy-2'-(2",3"-dihydro-2",4"-diphenyl-2"-hydroxy-3"-oxo-1"-pyrrol yl) guanosine (FG), was synthesized. When incubated with FG in aqueous solution, mutagens form adducts that can be analyzed with an HPLC-fluorescence detector-system. By this method, mutagens such as glyoxal, methylglyoxal, 2-(2-furyl)-3-(5-nitrofuryl) acrylamide and 4-nitroquinoline-N-oxide, used as model compounds, were detected rapidly with high sensitivity. Reaction with isopropylideneguanosine (IPG), followed by isolation and characterization of the mutagen-IPG-adduct was found to be a useful method for identifying unknown mutagens in crude samples. This method was successfully applied in identification of the mutagens in heated glucose (200 degrees C, 20 min); glyoxal-IPG and 8-hydroxy-IPG were identified in the reaction mixture.

Non-invasive transgastric detection of ultrasonic Doppler signals from canine renal vessels.

We successfully obtained ultrasonic Doppler signals from canine renal vessels non-invasively by the transgastric approach. An outline of the method and newly developed transgastric probe is presented in this preliminary report.

Synthesis and antitumor activities of alkyl-1,4-butanediamine Pt(II) complexes having seven-membered ring structure.

Novel alkyl-1,4-butanediamine Pt(II) complexes having a seven-membered ring structure were synthesized and characterized by fast atom bombardment mass and infrared spectra and elemental analysis. Their antitumor activities in vivo toward lymphoid leukemia L1210 and Lewis lung carcinoma LL were studied in the case where the leaving group was either dichloride or cyclobutane-1,1-dicarboxylate. 1,4-Butanediamine Pt(II) complexes (seven-membered ring) showed higher antitumor activities than those of ethylenediamine Pt(II) (five-membered ring) and 1,3-propanediamine Pt(II) (six-membered ring) complexes toward L1210 for both leaving groups. Alkyl-1,4-butanediamine Pt(II) complexes showed high antitumor activities toward L1210, except for 1,1-dimethyl-1,4-butanediamine Pt(II) complexes. In particular, 2,2-dimethyl-1,4-butanediamine and 2,3-dimethyl-1,4-butanediamine Pt(II) complexes exhibited excellent antitumor activities with T/C% values higher than 300. None of the dichloro Pt(II) complexes showed antitumor activities toward LL, but the cyclobutane-1,1-dicarboxylato Pt(II) complexes, which were moderately active toward L1210 with T/C% values around 200, also showed high antitumor activities toward LL with T/C% values of more than 200. Alkyl-1,4-butanediamine Pt(II) complexes with a seven-membered ring structure were found to be stable and to have antitumor activities in vivo.