The increased prevalence of multidrugresistant bacterial pathogens motivated us to attempt to enhance the therapeutic efficacy of bacteriophages. The therapeutic application of phages as antibacterial agents was impeded by several factors: (i) the failure to recognize the relatively narrow host range of phages; (ii) the presence of toxins in crude phage lysates; and (iii) a lack of appreciation for the capacity of mammalian host defense systems, particularly the organs of the reticuloendothelial system, to remove phage particles from the circulatory system. In our studies involving bacteremic mice, the problem of the narrow host range of phage was dealt with by using selected bacterial strains and virulent phage specific for them. Toxin levels were diminished by purifying phage preparations. To

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Colonization of the gastrointestinal tract with vancomycin-resistant Enterococcus faecium (VRE) has become endemic in many hospitals and nursing homes in the United States. Such colonization predisposes the individual to VRE bacteremia and/or endocarditis, and immunocompromised patients are at particular risk for these conditions. The emergence of antibiotic-resistant bacterial strains requires the exploration of alternative antibacterial therapies, which led our group to study the ability of bacterial viruses (bacteriophages, or phages) to rescue mice with VRE bacteremia. The phage strain used in this study has lytic activity against a wide range of clinical isolates of VRE. One of these VRE strains was used to induce bacteremia in mice by intraperitoneal (i.p.) injection of 10 9 CFU. The resulting bacteremia was fatal within 48 h. A single i.p. injection of 3 ؋ 10 8 PFU of the phage strain, administered 45 min after the bacterial challenge, was sufficient to rescue 100% of the animals. Even when treatment was delayed to the point where all animals were moribund, approximately 50% of them were rescued by a single injection of this phage preparation. The ability of this phage to rescue bacteremic mice was demonstrated to be due to the functional capabilities of the phage and not to a nonspecific immune effect. The rescue of bacteremic mice could be effected only by phage strains able to grow in vitro on the bacterial host used to infect the animals, and when such strains are heat inactivated they lose their ability to rescue the infected mice.Isolates of vancomycin-resistant Enterococcus faecium (VRE) from patients in the United States, France, and England were first reported in 1989 (9, 19). By 1998, the U.S. National Nosocomial Infections Surveillance System had reported that 20% of nosocomial isolates of enterococci were resistant to vancomycin (12). Individuals with compromised immune systems, such as AIDS patients, cancer patients undergoing chemotherapy, postsurgical patients, transplant recipients, and the elderly in general, are particularly prone to develop VRE infections. While the antibiotic quinupristindalfopristin (Synercid; Rhone-Poulenc Rorer, Collegeville, Pa.) has recently been licensed for clinical use, its efficacy for VRE infections may be limited because (i) it is bacteriostatic, and (ii) one of its two components is an analog of virginiamycin, which has been used as an additive in hog and poultry feed for the past 2 decades. Quinupristin-dalfopristin-resistant bacteria have been isolated from turkeys fed virginiamycin, suggesting that the use of virginiamycin has created a reservoir of enterococci resistant to the analog in quinupristin-dalfopristin (5). Linezolid (Zyvox; Pharmacia and Upjohn), another recently introduced antibiotic, is also described as bacteriostatic for VRE, and resistance to it appeared during clinical trials even though it is the first member of a new class of agents (the oxazolodinones).Early applications of antibacterial phage therapy (1920s to 1950s) were impeded by...

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Colonization of the gastrointestinal tract with vancomycin-resistant Enterococcus faecium (VRE) has become endemic in many hospitals and nursing homes in the United States. Such colonization predisposes the individual to VRE bacteremia and/or endocarditis, and immunocompromised patients are at particular risk for these conditions. The emergence of antibiotic-resistant bacterial strains requires the exploration of alternative antibacterial therapies, which led our group to study the ability of bacterial viruses (bacteriophages, or phages) to rescue mice with VRE bacteremia. The phage strain used in this study has lytic activity against a wide range of clinical isolates of VRE. One of these VRE strains was used to induce bacteremia in mice by intraperitoneal (i.p.) injection of 10 9 CFU. The resulting bacteremia was fatal within 48 h. A single i.p. injection of 3 ؋ 10 8 PFU of the phage strain, administered 45 min after the bacterial challenge, was sufficient to rescue 100% of the animals. Even when treatment was delayed to the point where all animals were moribund, approximately 50% of them were rescued by a single injection of this phage preparation. The ability of this phage to rescue bacteremic mice was demonstrated to be due to the functional capabilities of the phage and not to a nonspecific immune effect. The rescue of bacteremic mice could be effected only by phage strains able to grow in vitro on the bacterial host used to infect the animals, and when such strains are heat inactivated they lose their ability to rescue the infected mice.

Eleven women and seven men with moderate to severe chronic hyperventilation and idiopathic seizures refractory to therapeutic serum levels of anticonvulsant medication were given diaphragmatic respiration training with percent end-tidal CO2 biofeedback. The training had a rapid correcting effect on their respiration, making it comparable to that of 18 asymptomatic control subjects. Ten of the seizure-group subjects were in the study at least 7 months and following treatment, 8 showed EEG power spectrum "normalization", restoration of cardio-respiratory synchrony (RSA), and their seizure frequency and severity were significantly reduced.

Breathing rate (RR), end-tidal percent CO2, and EEG were obtained in three groups: psychiatric referral subjects presenting with anxiety, panic phobia, depression and migraine; a group of idiopathic seizure sufferers; and a group of asymptomatic controls. Virtually all the noncontrol subjects were found to show moderate to severe hyperventilation and the accompanying EEG dysrhythmia. The seizure group subjects were taught diaphragmatic respiration with end-tidal percent CO2 biofeedback. The training normalized their respiration and altered their EEGs and seizure frequency.

A201nosed and treated for BC with and without metastases. METHODS: Retrospective data from 2 large integrated claims databases spanning July 2008 to December 2010 were used to identify adult patients with a diagnosis of malignant neoplasm of the bladder (ICD-9 188.0-188.9; ICD-10 C67.0-67.9). Patients were included if they (1) had continuous eligibility for 6 months prior to at least 6 months following their index diagnosis, (2) had no diagnosis of any other cancer in the pre-period, and (3) received no chemotherapy in the pre-period. Patients were stratified into 2 cohorts based on the presence of metastatic disease within 180 days of diagnosis: non-metastatic (NM) and metastatic (M). Resource use and all-cause costs (2013 USD) were evaluated after cancer diagnosis. RESULTS: There were 10,250 (9,268 NM, 982 M) and 22,965 (20,786 NM, 2,179 M) patients in each of the databases meeting all inclusion criteria, respectively. Mean follow-up was 35.1 months and 38.6 months in the 2 datasets.