In vitro antimicrobial activity of gatifloxacin compared with other quinolones against clinical isolates from cancer patients

Owing to the predominance of gram-positive pathogens in neutropenic cancer patients, newer generation quinolones with an expanded gram-positive spectrum and enhanced potency, may have a role to play for prophylaxis and/or empiric therapy in such patients. The in vitro activity of gatifloxacin was compared with that of ciprofloxacin, levofloxacin and trovafloxacin against 848 recent clinical isolates from cancer patients. Against gram-positive organisms, gatifloxacin was the most active agent tested inhibiting all Aerococcus, Listeria monocytogens, Micrococcus, Stomatococcus mucilaginous, Bacillus, and Rhodococcus equi strains at < or =2 mg/l, its designated susceptibility breakpoint. It was also very active against methicillin-susceptible staphylococci and Streptococcus spp. (including penicillin nonsusceptible Streptococcus pneumoniae and viridans streptococci). It had moderate activity against methicillin-resistant staphylococci and Enterococcus faecalis, inhibiting 68-80% of these strains at < or =2 mg/l. Gatifloxacin also had good activity against the Enterobacteriaceae (although ciprofloxacin was more potent) inhibiting >95% of isolates at < or =1 mg/l. Nonfermentative gram-negative organisms were less susceptible to all 4 agents. Gatifloxacin was very active against Acinetobacter lwoffi (MIC100 0.12 mg/l) and had moderate activity against Acinetobacter baumanii, Chryseobacterium spp., Stenotrophomonas maltophilia, Pseudomonas aeruginosa and other Pseudomonas species. Alcaligenes xylosoxidans strains were relatively resistant to all 4 agents.     

White matter hyperintensities in subjects with cocaine and opiate dependence and healthy comparison subjects

The prevalence, severity, and location of white matter signal hyperintensities (WMH) on brain magnetic resonance images were compared in patients with cocaine or opiate dependence and healthy subjects. Patients with cocaine (n=32) and opiate dependence (n=32), whose diagnoses were confirmed with the Structured Clinical Interview for DSM-IV, and age- and sex-matched healthy subjects (n=32) were scanned using a 1.5 T whole body GE magnetic resonance scanner. Axial proton-density and T2-weighted images were obtained as well as fluid-attenuated inversion recovery axial images. The severity of WMH was assessed separately for deep (and insular) and periventricular WMH, using a modified composite version of the rating scales of Fazekas and Coffey. The cocaine-dependent group had greater severity of WMH than the opiate-dependent group, which in turn had greater severity of WMH than the healthy comparison group (odds ratios=2.54 and 2.90, respectively). The cocaine-dependent group had greater lesion severity of deep and insular WMH than the opiate-dependent group and the healthy comparison group (odds ratio>3.25 for deep WMH; odds ratio>4.38 for insular WMH). For periventricular WMH, there were no significant differences between the three groups. The frontal lobes were the predominant locations of WMH in both substance-dependent groups. The greater prevalence and severity of WMH in cocaine-dependent subjects than in opiate-dependent subjects may reflect the fact that cocaine induces more ischemia via vasoconstriction than opiates. Also, there was a trend for lower WMH severity in substance-dependent women relative to the healthy comparison group, possibly due to estrogen's protective effect against cerebrovascular accidents.     

Use of High-Dose-Rate Brachytherapy in the Management of Locally Recurrent Rectal Cancer

INTRODUCTION: Locally recurrent rectal cancer is associated with poor quality of life and has justified aggressive surgical and adjuvant approaches to control the disease. This study was designed to evaluate the use of fractionated perioperative high-dose-rate brachytherapy in association with wide surgical excision (debulking). Our hypothesis is that this combined therapy can help control locally recurrent rectal cancer. METHODS: Patients with biopsy-proven locally recurrent rectal cancer that could not be completely removed surgically were considered candidates for this procedure. All patients had abdominal exploration, aggressive tumor debulking, and placement of afterloading brachytherapy catheters. Patients underwent simulation on postoperative Day 3 and received 1,200 to 2,500 (mean, 1,888) cGy of fractionated high-dose-rate brachytherapy between postoperative Days 3 and 5. All patients had involvement of the lateral pelvic sidewall and/or the sacrum. RESULTS: Twenty-seven patients (18 males) aged 32 to 79 years underwent therapy. Follow-up ranged from 18 to 93 (mean, 50) months and was available in 27 patients. Ten patients (37 percent) were alive at the time of this report. Nine patients are without evidence of disease. Five patients (18 percent) died of non–cancer-related causes without evidence of recurrent disease. Five complications potentially related to treatment (3 abscesses, 2 fistulas) occurred in five patients. CONCLUSION: High-dose radiation brachytherapy delivers high-dose, highly controlled, focused radiation to specific sites of disease, thereby minimizing injury to normal tissues. The results in this series suggest increased local control, better palliation, and increased salvage of patients.     

Transcranial application of low-energy laser irradiation improves neurological deficits in rats following acute stroke

BACKGROUND AND OBJECTIVES: Low-level laser therapy (LLLT) has been shown to have beneficial effects on ischemic skeletal and heart muscles tissues. The aim of the present study was to approve the effectiveness of LLLT treatment at different locations on the brain in acute stroked rats. STUDY DESIGN/MATERIALS AND METHODS: Stroke was induced in 169 rats that were divided into four groups: control non-laser and three laser-treated groups where laser was employed ipsilateral, contralateral, and both to the side of the induced stroke. Rats were tested for neurological function. RESULTS: In all three laser-treated groups, a marked and significant improvement in neurological deficits was evident at 14, 21, and 28 days post stroke relative to the non-treated group. CONCLUSIONS: These observations suggest that LLLT applied at different locations in the skull and in a rather delayed-phase post stroke effectively improves neurological function after acute stroke in rats.     

Performance on the Stroop predicts treatment compliance in cocaine-dependent individuals.

Treatment dropout is a problem of great prevalence and stands as an obstacle to recovery in cocaine-dependent (CD) individuals. Treatment attrition in CD individuals may result from impairments in cognitive control, which can be reliably measured by the Stroop color-word interference task. The present analyses contrasted baseline performance on the color-naming, word-reading, and interference subtests of the Stroop task in CD subjects who completed a cocaine treatment trial (completers: N=50) and those who dropped out of the trial before completion (non-completers: N=24). A logistic regression analysis was used to predict trial completion using three models with the following variables: the Stroop task subscale scores (Stroop model); the Hamilton depression rating scale (HDRS) scores (HDRS model); and both the Stroop task subscale scores and HDRS scores (Stroop and HDRS model). Each model was able to significantly predict group membership (completers vs non-completers) better than a model based on a simple constant (HDRS model p=0.02, Stroop model p=0.006, and Stroop and HDRS model p=0.003). Models using the Stroop preformed better than the HDRS model. These findings suggest that the Stroop task can be used to identify cocaine-dependent subjects at risk for treatment dropout. The Stroop task is a widely available, reliable, and valid instrument that can be easily employed to identify and tailor interventions of at risk individuals in the hope of improving treatment compliance.     

Effects of food or protein restriction on plasma volume expansion in pregnant rats.

The effects of either food restriction or a low protein diet on the plasma volume expansion of pregnancy was determined in Sprague-Dawley rats. Rats fed ad libitum a standard diet or fed a 25% casein diet were used as controls. Both the food restricted and protein restricted rats had a significant reduction in body weight and fetal and placental weights. The total plasma volumes were also significantly lower in the restricted groups. Plasma volume expressed per 100 g of maternal net body weight or 100 g of conceptus weight was significantly reduced only in the rats fed the 6% casein diet. Correlations between plasma volume and maternal net body weight or conceptus weight in the control groups suggested that although the conceptus can influence the degree of expansion of maternal plasma volume, maternal factors such as net body weight are more important determinants of plasma volume expansion.     

Vitamin B12 malabsorption associated with a normal Schilling test result.

A patient with vitamin B12 deficiency and a true normal Schilling test result is presented. This patient could absorb chemically pure vitamin B12 normally but could not absorb protein-bound vitamin B12.     

Angiogenesis in bladder cancer--prognostic marker and target for future therapy

Angiogenesis is the process by which tumours induce a blood supply, crucial for growth and metastasis. Evidence for its role in bladder carcinogenesis, its usefulness as a marker of patient prognosis, and potential anti-angiogenic therapies for future development are discussed in this chapter.     

Optimizing Caco-2 cell monolayers to increase throughput in drug intestinal absorption analysis

INTRODUCTION: The aim of this investigation was to evaluate methods for increasing Caco-2 cell throughput for assessing drug intestinal absorption. The use of 6-, 12-, and 24-well membranes and the effect of membrane size on permeability and the integrity of the Caco-2 cell monolayer were assessed. In an effort to optimize the assessment of drug permeability, increased throughput was investigated by testing compounds singly or as mixtures of analytes. METHOD: The transepithelial electrical resistance (TEER) of cell monolayers was measured on 0.33, 1.0, and 4.7 cm2 polycarbonate membranes using EVOM, over a 25-day period. Absorptive transport was determined on all compounds tested using LC-MS/MS assays, or liquid scintillation spectrometry. RESULTS: The effect of multiple compounds in one well compared to single compounds was assessed with atenolol, nadolol, metoprolol, and propranolol for mixtures of four compounds and with RWJ-53308, atenolol, terbutaline, propranolol, naproxen, piroxicam, topiramate, and furosemide for mixtures of eight compounds. The apparent permeability (Papp) values correlated well between single analytes and mixtures of four and eight analytes in each well. Drug permeability decreased slightly with an increase in well size. The TEER value increased with the number of days in culture for each of the 6-, 12-, and 24-well sizes. DISCUSSION: It was demonstrated that the 24-well format system is ideal for high-throughput assessment. Furthermore, the approach of mixing four or eight analytes in each well to further increase throughput was also demonstrated to be valid.     

Nonrandomized comparison of surgery with and without adjuvant pelvic irradiation for patients with pT3N0 adenocarcinoma of the prostate.

The purpose of this study was to evaluate the outcome of radical prostatectomy alone and compare it with that of surgery followed by planned adjuvant radiotherapy in patients with pT3N0 prostate cancer (CaP). A total of 402 patients with CaP were treated with prostatectomy, including 311 (77%) who received a planned course of adjuvant radiotherapy (RT) (surgery [S] + RT) to the prostatic fossa (median dose: 48 Gy) and 91 (23%) who had surgery alone. Patients in the former group had worse risk factors than those in the latter group, such as a higher clinical and pathologic stage (p = 0.001), higher Gleason score (p = 0.09), and higher preoperative prostate-specific antigen (PSA) level (p = 0.0001). PSA failure was defined as more than 0.05 ng/ml. Median follow-up was 59 months. The 5- and 10-year overall survival for the 311 S+RT patients was 91% and 81%, respectively, and it was similar for those 91 in the surgery-alone group, p = 0.59. The 5- and 10-year probability of freedom from PSA and/or clinical failure for the former group was 70% and 53%, respectively, whereas it was 66% and 46%, respectively, for the latter group, p = 0.72. Any recurrence developed in a total of 96 (31%) patients in the S+RT group as compared with 23 (25%) in the surgery-alone group. Local recurrence was noted in 10 (3.2%) S+RT and in 6 (6.6%) surgery-alone patients (N.S.). The time to clinical or chemical recurrence was also similar for both treatment groups (median time: 3.0 versus 3.8 years). Patients with pT3b tumors had relatively poor 5- and 10-year disease-free survival (53% and 32%, respectively, for S+RT and 38% and 0%, respectively, for surgery alone, p = 0.82). In multivariate analyses, pathologic stage and Gleason score were independent predictors of recurrence, each with p < 0.001 after controlling for the other. The worst prognostic category included patients with pT3bN0, Gleason score 7-10 disease who had 5.0 times the risk of recurrence as compared with pT3aN0, Gleason score 2-6 patients. No significant difference in disease-free survival by the treatment group was seen in Cox regression analysis controlling for pathologic stage (p = 0.59), Gleason score (p = 0.99), and PSA (p = 0.28). S+RT patients were predicted to have disease recurrence at 83% the rate of surgery-alone patients, p = 0.42. Preoperative PSA (>25 ng/ml) was predictive of recurrence (2.0 x risk) in univariate analysis, but it was not a significant predictor in multivariate analysis. It appears that moderate-dose, localized fields postoperative irradiation reduced the incidence of local recurrence in patients who were at a higher risk of recurrence as compared with those treated with surgery alone. New treatment strategies need to be developed to manage pT3bN0, Gleason score 7-10 patients whose 10-year disease-free survival was poor.