Phenotypic resistance of Staphylococcus aureus, selected Enterobacteriaceae, and Pseudomonas aeruginosa after single and multiple in vitro exposures to ciprofloxacin, levofloxacin, and trovafloxacin

The phenotypic resistance of selected organisms to ciprofloxacin, levofloxacin, and trovafloxacin was defined as a MIC of > or =4 microg/ml. The dynamics of resistance were studied after single and sequential drug exposures: clinical isolates of methicillin-susceptible and methicillin-resistant Staphylococcus aureus (MSSA and MRSA), Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Serratia marcescens, and Pseudomonas aeruginosa were utilized. After a single 48-h exposure of a large inoculum to four times the initial MIC for the organism, the frequency of selection of resistant mutants of MSSA was greater for trovafloxacin than levofloxacin (P = 0.008); for E. cloacae, the frequency was highest for ciprofloxacin and lowest for levofloxacin and trovafloxacin; for S. marcescens, the frequency was highest for trovafloxacin and lowest for ciprofloxacin (P = 0.003). The results of serial passage experiments were analyzed both by the Kaplan-Meier product-limited method as well as by analysis of variance of mean inhibitory values. By both methods, MSSA and MRSA expressed mutants resistant to ciprofloxacin after fewer passages than were required for either levofloxacin or trovafloxacin. For the aerobic gram-negative bacilli, two general patterns emerged. Mutants resistant to trovafloxacin appeared sooner and reached higher mean MICs than did mutants resistant to levofloxacin or ciprofloxacin. Mutants resistant to ciprofloxacin appeared later and reached mean MICs lower than the MICs of the other two drugs studied. Even though individual strain variation occurred, the mean MICs were reproduced when the serial passage experiment was repeated using an identical panel of E. coli isolates. In summary, the dynamic selection of fluoroquinolone-resistant bacteria can be demonstrated in experiments that employ serial passage of bacteria in vitro.     

An overview of neuropathic pain: syndromes,symptoms, signs,and several mechanisms

OBJECTIVE: An overview is presented of neuropathic pain syndromes, their characteristic symptoms and signs, and recent approaches to identifying their pathophysiologic mechanisms. DESIGN: The results of recent clinical studies of neuropathic pain are reviewed. Chronic neuropathic pain syndromes are emphasized because these long-lasting and often disabling conditions present a much greater challenge for the clinician than acute pain. Peripheral neuropathic syndromes have received greater attention in the research literature than central pain, and studies of syndromes such as postherpetic neuralgia and painful diabetic neuropathy provide the basis for current knowledge of neuropathic pain. CONCLUSIONS: Precise estimates of the prevalence of neuropathic pain are not available, but chronic neuropathic pain may be much more common than has generally been appreciated and its prevalence can be expected to increase in the future. There is considerable agreement that both peripheral and central processes contribute to many chronic neuropathic pain syndromes, and that these different mechanisms may explain the qualitatively different symptoms and signs that patients experience. The limitations of existing treatments for neuropathic pain and the inability to provide relief for many patients has stimulated ongoing studies that examine different approaches to preventing neuropathic pain.     

Glomerular injury in uninephrectomized spontaneously hypertensive rats. A consequence of glomerular capillary hypertension.

Micropuncture and/or morphologic studies were performed in intact Wistar-Kyoto rats (WKY) (group 0), intact spontaneously hypertensive rats (SHR) (groups 1 and 5), uninephrectomized (UNX) WKY (groups 2 and 6), and UNX SHR (groups 3 and 4, 7 and 8). UNX was performed when rats were 5 wk of age. Groups 0-4 were observed for 34 wk after which whole kidney clearance and morphologic studies were performed. Groups 5-8 underwent micropuncture study at 10 wk of age. Groups 4 and 8 were fed a diet containing 6% protein. All other rats ingested standard laboratory diet. 5 wk after UNX, normotensive group 6 had higher single nephron glomerular filtration rate (SNGFR) and initial glomerular plasma flow rate (QA) than intact, hypertensive group 5. Glomerular transcapillary hydraulic pressure difference (delta P) was similar in these two groups. Hypertensive group 7 exhibited less elevation in SNGFR and QA than group 6, but delta P was significantly increased. The presence of glomerular capillary hypertension in UNX SHR at 10 wk was associated with the development of significant proteinuria and an increased incidence of mesangial expansion and glomerular sclerosis at 7 mo (group 3) as compared with groups 0, 1, and 2. Protein restriction prevented the development of increased delta P in UNX SHR (group 8) and also conferred long-term protection from increased urinary protein excretion and glomerular injury (group 4). These studies suggest that glomerular capillary hypertension predisposes to glomerular injury in this model of hypertension with reduced renal mass.     

Mode of regulation of natural killer cell activity by interferon

Whereas xenogeneic tumors such as baby hamster kidney or HeLa cells grow in nude mice, the same cells persistently infected with a variety of viruses are rejected. Spleen cells from normal nude mice were found to be induced to produce interferon and to exert natural killer (NK) activity on virus persistently infected (PI) tumor cells, and not on uninfected parental cells in vitro. The phenotype of the interferon-producing cells and the NK effector cells was found to be the same namely, Qa 5(+), Ly 5(+), ganglio-N- tetraosylceramide, with 35 percent of the NK cells also expressing Thy 1.2. NK activity against virus PI tumor cell lines could be nonspecifically augmented both in vivo and in vitro by prior contact with virus PI tumor cells. It was unambiguously demonstrated with chemically homogeneous mouse interferon that interferon, and not a contaminant, was responsible for the augmentation of NK activity in vitro. Studies on the mode of interferon action in augmenting NK activity revealed that the target cell for interferon action was serologically distinct from the NK effector cell. Anti-Ly 5 + complement (C)-treated spleen cells were depleted of NK activity and the ability to produce interferon, but, upon incubation with interferon for 1-3 h, regained both NK activity and susceptibility to anti-Ly 5 + C. Treatment with anti-Qa 5 + C eliminated NK activity, which could not be restored by the addition of interferon. We conclude that interferon produced by Ly 5(+) cells in response to virus PI tumor cells acts on Ly 5(-) precursor cells and induces their differentiation into functional Ly 5(+) NK effector cells.     

Predicting treatment response in depressed and non-depressed chronic pain patients

Although it has often been observed that chronic pain and depression are associated, there have been few systematic comparisons of chronic pain patients with and without depression. In the study reported in this article, depressed and non-depressed chronic pain patients were found to be quite similar with respect to demographic, pain-related, and treatment response variables. The primary aim of the study, however, was to examine the hypothesis that treatment response in these two groups of patients would be predicted by different patterns of variables. In non-depressed patients, beneficial response to treatment was related to a greater number of treatment visits, not receiving workmen's compensation, fewer previous types of treatment, and low back pain. As predicted, a different pattern of predictors of treatment response was found for the depressed patients, who were more likely to benefit when they were employed at the beginning of treatment and when their pain was of shorter duration. These results suggest that activity and active involvement in treatment are particularly important with chronic pain patients who are depressed. In addition, they suggest that the best prediction of treatment response in future research on chronic pain patients may be achieved by dividing patients into groups based on psychological characteristics.     

Binding of type 3 reovirus by a domain of the sigma 1 protein important for hemagglutination leads to infection of murine erythroleukemia cells.

The recognition of cellular receptors by the mammalian reoviruses is an important determinant of cell and tissue tropism exhibited by reovirus strains of different serotypes. To extend our knowledge of the role of reovirus-receptor interactions in reovirus tropism, we determined whether type 1 and type 3 reovirus strains can infect cells derived from erythrocyte precursors. We found that reovirus type 3 Dearing (T3D), but not type 1 Lang, can grow in murine erythroleukemia (MEL) cells. This difference in growth was investigated by using reassortant viruses and we found that the capacity of T3D to infect MEL cells is determined by the viral cell-attachment protein, sigma 1. In experiments using murine monoclonal antibodies (mAbs) that bind to different sigma 1 regions, we show that T3D binding to MEL cells is inhibited by a mAb that identifies a domain important for hemagglutination (HA). We also determined that type 3 strains that can infect murine L cells but do not produce HA do not infect MEL cells. These results suggest that type 3 reovirus binds to and infects erythrocyte precursor cells via a sigma 1 domain important for HA. Moreover, this study suggests that different domains of some viral cell-attachment proteins are used to initiate productive infections of different types of cells.     

Temporomandibular disorders. Variation in clinical practice

This research describes the extent of variability in diagnosis and treatment of temporomandibular disorders (TMD) and relates this variability to treatment outcomes. A health maintenance organization sequentially referred 145 patients with orofacial pain and dysfunction to two TMD clinics. The two clinics differed substantially in their use of tomography (applied to 28% vs. 64% of all patients), and varied moderately in diagnoses assigned to the patient groups. There was large variation in selection of treatments including appliances for bruxism (64% vs. 5%), mandibular repositioning (10% vs. 25%), and joint stabilization (3% vs. 30%); anti-inflammatory medications (44% vs. 19%) and analgesics (16% vs. 2%); and subsequent referral for dental or orthodontic treatment (1% vs. 42%). The differences in diagnostic and therapeutic practice that were found were not associated with important differences in patient-reported pain and dysfunction at 1-year follow-up. These data indicate the need for systematic approaches to identifying, evaluating, and modifying variation in health care practices for common presenting problems lacking reliable methods of evaluation and generally accepted clinical standards for choice of treatments.     

Suicidal ideation, plans, and attempts in chronic pain patients: factors associated with increased risk

This study describes suicidal behavior in a cross-sectional sample of chronic pain patients and evaluates factors associated with increased risk for suicidal ideation. One hundred-fifty-three adults with nonmalignant pain (42% back pain) who were consecutively referred to a tertiary care pain center completed a Structured Clinical Interview for Suicide History, the McGill Pain Questionnaire, and the Beck Depression Inventory. Nineteen-percent reported current passive suicidal ideation (PSI), 13% had active thoughts of committing suicide (ASI), 5% had a current suicide plan, and 5% reported a previous suicide attempt. Drug overdose was the most commonly reported plan and method of attempt (75%). Thirteen-percent reported a family history of suicide attempt/completion. Pain-specific and traditional suicide risk factors were evaluated as predictors of current PSI and ASI. Logistic regression analyses revealed that a family history of suicide attempts/completions was associated with a 7.5 fold increase in risk of PSI (P=0.001) and a 6.6 fold increase in ASI (P=0.003), after adjusting for significant covariates. Having abdominal pain was associated with an adjusted 5.5 fold increase in PSI (P=0.05) and a 4.2 fold increase in ASI (P=0.10). Neuropathic pain significantly reduced risk for both PSI (P=0.002) and ASI (P=0.01). Demographics, pain severity, and depression severity were not associated with suicidal ideation in multivariate analyses. These findings highlight the need for routine evaluation and monitoring of suicidal behavior in chronic pain, especially for patients with family histories of suicide, those taking potentially lethal medications, and patients with abdominal pain.     

The Efficacy of an Event-Specific,Text Message,Personalized Drinking Feedback Intervention

Prevention Science - Tailgating drinking prior to a football game is a type of event-specific drinking associated with increased alcohol use and related problems. Personalized drinking feedback...