Impact of Exposure of Methicillin-Resistant Staphylococcus aureus to Polyhexanide In Vitro and In Vivo.

Methicillin-resistant Staphylococcus aureus (MRSA) resistant to decolonization agents such as mupirocin and chlorhexidine increases the need for development of alternative decolonization molecules. The absence of reported severe adverse reactions and bacterial resistance to polyhexanide makes it an excellent choice as a topical antiseptic. In the present study, we evaluated the in vitro and in vivo capacity to generate strains with reduced polyhexanide susceptibility and cross-resistance with chlorhexidine and/or antibiotics currently used in clinic. Here we report the in vitro emergence of reduced susceptibility to polyhexanide by prolonged stepwise exposure to low concentrations in broth culture. Reduced susceptibility to polyhexanide was associated with genomic changes in the mprF and purR genes and with concomitant decreased susceptibility to daptomycin and other cell wall-active antibiotics. However, the in vitro emergence of reduced susceptibility to polyhexanide did not result in cross-resistance to chlorhexidine. During in vivo polyhexanide clinical decolonization treatment, neither reduced polyhexanide susceptibility nor chlorhexidine cross-resistance was observed. Together, these observations suggest that polyhexanide could be used safely for decolonization of carriers of chlorhexidine-resistant S. aureus strains; they also highlight the need for careful use of polyhexanide at low antiseptic concentrations.

Qualidade de vida relacionada à saúde de adultos após cirurgia defêmur ou quadril / Quality of life related to adults health after hip or femur surgery

Objetivo: identificar mudanças ocorridas na avaliação da qualidade de vida relacionada à saúde(QVRS) de adultos entre o terceiro e sexto mês após cirurgia de fêmur ou quadril. Métodos: abordagemquantitativa, de delineamento longitudinal realizado de junho a novembro de 2013. Aplicadoquestionário de caracterização e o Short Form Health Survey (SF-36). Realizadas análises descritivas,teste de Mann-Whitney e Wilcoxon. Adotado p=0,05, como nível de significância. Resultados:participaram 24 adultos. Houve redução das médias de pontuação em cinco dos oito domínios do SF-36, representando piora da QVRS no sexto mês. O domínio Aspecto físico foi o mais afetado. As médiasdo domínio Dor foram maiores e estatisticamente significantes para as mulheres (p=0,04), houvemelhora nas médias de Estado geral de saúde (p=0,01) e Aspecto emocional (p=0,05) no sexto mês.Conclusão: há piora da QVRS nos adultos submetidos a cirurgia de fêmur ou quadril nos seis primeirosmeses após cirurgia.

Objective: identifying changes occurred during the evaluation of health-related quality of life(HRQOL) of adults between the third and the sixth month after surgery. Methods: quantitativeapproach, longitudinal design, conducted from June to November 2013. A characterizationquestionnaire and the Short Form Health Survey (SF-36) were applied. Descriptive analyses, MannWhitneyand Wilcoxon test were carried out. Significance level p=0.05. Results: 24 adults participated. There was a reduction of average scores in five of the eight domains of the SF-36,representing worsening of HRQOL in the sixth month. The domain Physical aspect was the mostaffected. The averages of Pain domain were higher and statistically significant for women (p=0.04),there was improvement in the general health status (p=0.01) and Emotional aspect (p=0,05) in thesixth month. Conclusion: there is worsening of HRQOL between adults undergoing surgery of hip orfemur during the first six months after discharge the day of surgery.

A Human Biofilm-Disrupting Monoclonal Antibody Potentiates Antibiotic Efficacy in Rodent Models of both Staphylococcus aureus and Acinetobacter baumannii Infections.

Many serious bacterial infections are antibiotic refractory due to biofilm formation. A key structural component of biofilm is extracellular DNA, which is stabilized by bacterial proteins, including those from the DNABII family. TRL1068 is a high-affinity human monoclonal antibody against a DNABII epitope conserved across both Gram-positive and Gram-negative bacterial species. In the present study, the efficacy of TRL1068 for the disruption of biofilm was demonstrated in vitro in the absence of antibiotics by scanning electron microscopy. The in vivo efficacy of this antibody was investigated in a well-characterized catheter-induced aortic valve infective endocarditis model in rats infected with a methicillin-resistant Staphylococcus aureus (MRSA) strain with the ability to form thick biofilms, obtained from the blood of a patient with persistent clinical infection. Animals were treated with vancomycin alone or in combination with TRL1068. MRSA burdens in cardiac vegetations and within intracardiac catheters, kidneys, spleen, and liver showed significant reductions in the combination arm versus vancomycin alone (P < 0.001). A trend toward mortality reduction was also observed (P = 0.09). In parallel, the in vivo efficacy of TRL1068 against a multidrug-resistant clinical Acinetobacter baumannii isolate was explored by using an established mouse model of skin and soft tissue catheter-related biofilm infection. Catheter segments infected with A. baumannii were implanted subcutaneously into mice; animals were treated with imipenem alone or in combination with TRL1068. The combination showed a significant reduction of catheter-adherent bacteria versus the antibiotic alone (P < 0.001). TRL1068 shows excellent promise as an adjunct to standard-of-care antibiotics for a broad range of difficult-to-treat bacterial infections.

Local oestrogenic/androgenic balance in the cerebral vasculature.

Reproductive effects of sex steroids are well-known; however it is increasingly apparent that these hormones have important actions on non-reproductive tissues such as the vasculature. The latter effects can be relevant throughout the lifespan, not just limited to reproductive years, and are not necessarily restricted to one gender or the other. Our work has established that cerebral blood vessels are a non-reproductive target tissue for sex steroids. We have found that oestrogen and androgens alter vascular tone, endothelial function, oxidative stress and inflammatory responses in cerebral vessels. Often the actions of oestrogen and androgens oppose each other. Moreover, it is clear that cerebral vessels are directly targeted by sex steroids, as they express specific receptors for these hormones. Interestingly, cerebral blood vessels also express enzymes that metabolize sex steroids. These findings suggest that local synthesis of 17ß-estradiol and dihydrotestosterone can occur within the vessel wall. One of the enzymes present, aromatase, converts testosterone to 17ß-estradiol, which would alter the local balance of androgenic and oestrogenic influences. Thus cerebral vessels are affected by circulating sex hormones as well as locally synthesized sex steroids. The presence of vascular endocrine effector mechanisms has important implications for male-female differences in cerebrovascular function and disease. Moreover, the cerebral circulation is a target for gonadal hormones as well as anabolic steroids and therapeutic drugs used to manipulate sex steroid actions. The long-term consequences of these influences are yet to be determined.

GABAergic transmission modulates ethanol excitation of ventral tegmental area dopamine neurons.

Activation of the dopaminergic (DA) neurons of the ventral tegmental area (VTA) by ethanol has been implicated in its rewarding and reinforcing effects. We previously demonstrated that ethanol enhances GABA release onto VTA-DA neurons via activation of 5-HT2C receptors and subsequent release of calcium from intracellular stores. Here we demonstrate that excitation of VTA-DA neurons by ethanol is limited by an ethanol-enhancement in GABA release. In this study, we performed whole-cell voltage clamp recordings of miniature inhibitory postsynaptic currents (mIPSCs) and cell-attached recordings of action potential firing from VTA-DA neurons in midbrain slices from young Long Evans rats. Acute exposure to ethanol (75 mM) transiently enhanced the firing rate of VTA-DA neurons as well as the frequency of mIPSCs. Simultaneous blockade of both GABA(A) and GABA(B) receptors (Picrotoxin (75 µM) and SCH50911 (20 µM)) disinhibited VTA-DA firing rate whereas a GABA(A) agonist (muscimol, 1 µM) strongly inhibited firing rate. In the presence of picrotoxin, ethanol enhanced VTA-DA firing rate more than in the absence of picrotoxin. Additionally, a sub-maximal concentration of muscimol together with ethanol inhibited VTA-DA firing rate more than muscimol alone. DAMGO (3 µM) inhibited mIPSC frequency but did not block the ethanol-enhancement in mIPSC frequency. DAMGO (1 and 3 µM) had no effect on VTA-DA firing rate. Naltrexone (60 µM) had no effect on basal or ethanol-enhancement of mIPSC frequency. Additionally, naltrexone (20 and 60 µM) did not block the ethanol-enhancement in VTA-DA firing rate. Overall, the present results indicate that the ethanol enhancement in GABA release onto VTA-DA neurons limits the stimulatory effect of ethanol on VTA-DA neuron activity and may have implications for the rewarding properties of ethanol.

TRIDENT high-energy-density facility experimental capabilities and diagnostics.

The newly upgraded TRIDENT high-energy-density (HED) facility provides high-energy short-pulse laser-matter interactions with powers in excess of 200 TW and energies greater than 120 J. In addition, TRIDENT retains two long-pulse (nanoseconds to microseconds) beams that are available for simultaneous use in either the same experiment or a separate one. The facility's flexibility is enhanced by the presence of two separate target chambers with a third undergoing commissioning. This capability allows the experimental configuration to be optimized by choosing the chamber with the most advantageous geometry and features. The TRIDENT facility also provides a wide range of standard instruments including optical, x-ray, and particle diagnostics. In addition, one chamber has a 10 in. manipulator allowing OMEGA and National Ignition Facility (NIF) diagnostics to be prototyped and calibrated.

The shell of the nucleus accumbens has a higher dopamine response compared with the core after non-contingent intravenous ethanol administration.

Dopamine increases in the nucleus accumbens after ethanol administration in rats, but the contributions of the core and shell subregions to this response are unclear. The goal of this study was to determine the effect of various doses of i.v. ethanol infusions on dopamine in these two subregions of the nucleus accumbens. Male Long-Evans rats were infused with either acute i.v. ethanol (0.5, 1.0, 1.5 g/kg), repeated i.v. ethanol (four 1.0 g/kg infusions resulting in a cumulative dose of 4.0 g/kg), or saline as a control for each condition. Dopamine and ethanol were measured in dialysate samples from each experiment. The in vivo extraction fraction for ethanol of probes was determined using i.v. 4-methylpyrazole, and was used to estimate peak brain ethanol concentrations after the infusions. The peak brain ethanol concentrations after the 0.5, 1.0 and 1.5 g/kg ethanol infusions were estimated to be 20, 49 and 57 mM, respectively. A significant dopamine increase was observed for the 0.5 g/kg ethanol group when collapsed across subregions. However, both the 1.0 g/kg and 1.5 g/kg ethanol infusions produced significant increases in dopamine levels in the shell that were significantly higher than those in the core. An ethanol dose-response effect on dopamine in the shell was observed when saline controls, 0.5, 1.0, and 1.5 g/kg groups were compared. For the cumulative-dosing study, the first, second, and fourth infusions resulted in significant increases in dopamine in the shell. However, these responses were not significantly different from one another. The results of this study show that the shell has a stronger response than the core to i.v. ethanol, that dopamine in the shell increases in a dose-dependent manner between 0.5-1.0 g/kg doses, but that the response to higher ethanol doses reaches a plateau.

City tuberculosis control coordinators' perspectives of patient adherence to DOT in São Paulo State, Brazil, 2005.

SETTING: Thirty-six priority cities in São Paulo State, Brazil, with a high incidence of tuberculosis (TB) cases, deaths and treatment default. OBJECTIVE: To identify the perspectives of city TB control coordinators regarding the most important components of adherence strategies adopted by health care teams to ensure patient adherence in 36 priority cities in the State of São Paulo, Brazil. DESIGN: Qualitative research with semi-structured interviews conducted with the coordinators of the National TB Control Programme involved in the management of TB treatment services in the public sector. RESULTS: The main issues thought to influence adherence to directly observed treatment (DOT) by coordinators include incentives and benefits delivered to patients, patient-health care worker bonding and comprehensive care, the encouragement given by others to follow treatment (family, neighbours and health professionals), and help provided by health professionals for patients to recover their self-esteem. CONCLUSION: The main aspects mentioned by city TB control coordinators regarding patient adherence to treatment and to DOT in São Paulo are improvements in communications, relationships based on trust, a humane approach and including the patients in the decision-making process concerning their health.

Short pulse laser train for laser plasma interaction experiments.

A multiframe, high-time resolution pump-probe diagnostic consisting of a consecutive train of ultrashort laser pulses (approximately ps) has been developed for use with a chirped pulse amplification (CPA) system. A system of high quality windows is used to create a series of 1054 nm picosecond-laser pulses which are injected into the CPA system before the pulse stretcher and amplifiers. By adding or removing windows in the pulse train forming optics, the number of pulses can be varied. By varying the distance and thickness of the respective optical elements, the time in between the pulses, i.e., the time in between frames, can be set. In our example application, the CPA pulse train is converted to 527 nm using a KDP crystal and focused into a preformed plasma and the reflected laser light due to stimulated Raman scattering is measured. Each pulse samples different plasma conditions as the plasma evolves in time, producing more data on each laser shot than with a single short pulse probe. This novel technique could potentially be implemented to obtain multiple high-time resolution measurements of the dynamics of physical processes over hundreds of picoseconds or even nanoseconds with picosecond resolution on a single shot.

Tratamiento de las fracturas de cóndilo mandibular en la IAHULA: 1999-2004 / Treatment of the fractures of cóndilo mandibular in the IAHULA: 1999-2004

Se realizó un estudio observacional descriptivo tipo serie clínica en 44 pacientes con fractura de cóndilo mandibular que ingresaron al área de emergencia del Hospital Universitario de Los Andes entre 1999 y 2004. El grupo estaba constituido por 36 hombres (81.8 por ciento) y 8 mujeres (18.2 por ciento). La edad de los pacientes osciló de 7 a 76 años, de ellos el grupo de 20-29 años fue el más afectado reportando el 40.9 por ciento (18 casos). Las fracturas simples representaron 12 casos (27.3 por ciento). Las fracturas combinadas correspondieron a 32 pacientes (72.7 por ciento). El mecanismo traumático fue colisión vehicular con 17 casos (38.6 por ciento). El 50 por ciento (6) de las fracturas condilares simples fueron manejadas sin tratamiento quirúrgico. Por el contrario 22 pacientes (68.75 por ciento) de las fracturas compuestas ameritaron al menos algún tipo de osteosíntesis. El seguimiento de los pacientes fue en promedio de 26 meses (9-60 meses). Se obtuvieron 24 (55 por ciento) excelentes resultados, 16 (36 por ciento) buenos resultados y 4 (9 por ciento) malos resultados. Las complicaciones encontradas fueron: Maloclusión 4 (9 por ciento), laterodesviación mandibular 6 (3 por ciento), hipomovilidad mandibular 4 (9 por ciento). Los resultados en nuestro servicio inclinan la balanza hacia la osteosíntesis con miniplacas como tratamiento para manejar las fracturas condilares cuando éstas tienen indicación quirúrgica.

Simultaneous quantitation of dexmedetomidine and glucuronide metabolites (G-Dex-1 and G-Dex-2) in human plasma utilizing liquid chromatography with tandem mass spectrometric detection.

Dexmedetomidine (Dex) (Precedex) is a novel lipophilic imidazole derivative with a high affinity for alpha-2 adrenergic receptors, which exhibits sedative, analgesic-sparing, and sympatholytic properties. The pharmacological effects and therapeutic benefits of this drug have drawn continued interest from the medical community. Here we report a liquid chromatography/tandem mass spectrometry (LC/MS/MS) method to simultaneously measure the concentrations of dexmedetomidine and its glucoronide metabolites, G-Dex-1 and G-Dex-2, in human plasma samples. A solid-phase extraction method was developed to effectively extract Dex, G-Dex-1, and G-Dex-2 from plasma matrices. An isocratic chromatographic method was developed to achieve baseline separation of G-Dex-1 and G-Dex-2. The linear dynamic range evaluated was 19.08-1908.56 pg/mL for Dex, 65.17-6518.17 pg/mL for G-Dex-1, and 29.42-2943.28 pg/mL for G-Dex-2. The linear correlation coefficient (r) ranged from 0.9944-0.9979 for Dex, from 0.9966-0.9984 for G-Dex-1, and from 0.9939-0.9966 for G-Dex-2. The intra-assay coefficient of variation (CV) was between 2.5-12.5% for Dex, between 5.2-11.0% for G-Dex-1, and between 3.5-12.1% for G-Dex-2. The inter-assay precision of QC samples give % CV ranges from 6.5-9.3% for Dex, from 7.1-10.6% for G-Dex-1, and from 8.2-10.2% for G-Dex-2. The inter-assay accuracies ranged from 102.0-109.3% for Dex, from 95.4-105.6% for G-Dex-1, and from 98.7-115.0% for G-Dex-2.

DARPP-32 and regulation of the ethanol sensitivity of NMDA receptors in the nucleus accumbens.

The medium spiny neurons of the nucleus accumbens receive both an excitatory glutamatergic input from forebrain and a dopaminergic input from the ventral tegmental area. This integration point may constitute a locus whereby the N-methyl-D-aspartate (NMDA)-subtype of glutamate receptors promotes drug reinforcement. Here we investigate how dopaminergic inputs alter the ethanol sensitivity of NMDA receptors in rats and mice and report that previous dopamine receptor-1 (D1) activation, culminating in dopamine and cAMP-regulated phosphoprotein-32 kD (DARPP-32) and NMDA receptor subunit-1 (NR1)-NMDA receptor phosphorylation, strongly decreases ethanol inhibition of NMDA responses. The regulation of ethanol sensitivity of NMDA receptors by D1 receptors was absent in DARPP-32 knockout mice. We propose that DARPP-32 mediated blunting of the response to ethanol subsequent to activation of ventral tegmental area dopaminergic neurons initiates molecular alterations that influence synaptic plasticity in this circuit, thereby promoting the development of ethanol reinforcement.

Brote epidémico de acarosis en una unidad de cuidados intensivos por exposición ocupacional / Epidemic bud of acarosis in an intensive unit of cares by exposition occupational

El presente estudio muestra la experiencia de un brote epidémico intrahospitalario en trabajadores de salud por exposición al S.scabiei, a partir de un caso de Sarna Costrosa, diagnosticado tardíamente en nuestra Unidad de Cuidados Intensivos; las medidas que se tomaron para el control de la propagación, las fallas en la bioseguridad y las consecuencias que de ella derivan, la importancia de la vigilancia epidemiológica y la experiencia en el uso de permetrina 5 por ciento en un brote de acarosis.

Bartonelosis (fiebre de la Oroya o verruga peruana): reporte de un caso-revisión de la literatura / Bartonellosis(Oroya fever or verruga paruana): a case report and literature review

Se presenta un caso típico de verruga peruana atendido en el Servicio de Dermatología del Hospital Alberto Sabogal Sologuren, y a raíz de ello revisamos esta interesante enfermedad emergente mundial. La bartonelosis humana al principio fue asociada básicamente a la especie Bartonella bacilliformis, pero hoy en día se han descubierto hasta 18 Bartonellas que afectan al humano y a varios animales domésticos. La Bartonella bacilliformis es una parásito bacteriano intracelular facultativo de los eritrocitos humanos y de las células endoteliales. La enfermedad de Carrión, fiebre de la Oroya y verruga peruana son todos términos que describen las consecuencias patológicas de la infección humana por Bartonella bacilliformis. Aunque las infecciones que involucran especies de Bartonella, tales como Bartonella henselae quintan, ocurren en todo el mundo, la enfermedad de Carrión es endémica únicamente en Sudamérica. Las infecciones por B. bacilliformis son un problema de salud en numerosas áreas rurales de Sudamérica y para los viajeros que visitan estas regiones montañosas de Perú, Ecuador y Colombia. La Lutzomya verrucarum es el principal vector para la transmisión de la bacteria al ser humano; la hembra del mosquito transmite el patógeno durante su alimentación nocturna de sangre humana. Presumiblemente el insecto se alimenta de la sangre de un individuo infectado y disemina el patógeno por medio de su saliva durante la siguiente ingesta de sangre. La bacteria no es contagiosa entre humanos.

The relationship between the clinical features of pharyngitis and the sensitivity of a rapid antigen test: evidence of spectrum bias.

STUDY OBJECTIVE: We evaluate the test characteristics and test for spectrum bias of a rapid antigen test for group A beta-hemolytic streptococcal (GABHS) pharyngitis among adults. METHODS: Medical record and laboratory results of consecutive adult patients receiving a rapid antigen test for GABHS in the emergency department or urgent care clinic of an urban teaching hospital between August 1999 and December 1999 were analyzed. Patients were stratified according to the number of clinical features present using the following modified Centor criteria: history of fever, absence of cough, presence of pharyngeal exudate, and cervical lymphadenopathy. The sensitivity of the rapid antigen test was defined as the number of patients with positive rapid antigen test results divided by the number of patients with either positive rapid antigen test results or negative rapid antigen test results and positive throat culture results. RESULTS: In the study sample of 498 patient visits, the prevalence of GABHS pharyngitis was 28% (95% confidence interval [CI] 24% to 32%). The prevalence of GABHS pharyngitis increased as modified Centor scores increased: 0 or 1=14%, 2=20%, 3=43%, and 4=52%. An increased number of modified Centor criteria (0 or 1, 2, 3, 4) was associated with increased rapid antigen test sensitivity (61%, 76%, 90%, and 97%, respectively) (Mantel-Haenszel trend test; P =.001). CONCLUSION: The sensitivity of the rapid antigen test for GABHS is not a fixed value but varies with the spectrum of disease. Among adults with 3 or 4 clinical criteria for GABHS pharyngitis, further study may reveal that culture confirmation of negative rapid antigen test results are not necessary.

Excessive antibiotic use for acute respiratory infections in the United States.

Estimating the amount and cost of excess antibiotic use in ambulatory practice and identifying the conditions that account for most excess use are necessary to guide intervention and policy decisions. Data from the 1998 National Ambulatory Medical Care Survey, a sample survey of United States ambulatory physician practices, was used to estimate primary care office visits and antibiotic prescription rates for acute respiratory infections. Weight-averaged antibiotic costs were calculated with use of 1996 prescription marketing data and adjusted for inflation. In 1998, an estimated 76 million primary care office visits for acute respiratory infections resulted in 41 million antibiotic prescriptions. Antibiotic prescriptions in excess of the number expected to treat bacterial infections amounted to 55% (22.6 million) of all antibiotics prescribed for acute respiratory infections, at a cost of approximately $726 million. Upper respiratory tract infections (not otherwise specified), pharyngitis, and bronchitis were the conditions associated with the greatest amount of excess use. This study documents that the amount and cost of excessive antibiotic use for acute respiratory infections by primary care physicians are substantial and establishes potential target rates for antibiotic treatment of selected conditions.

Impact of reducing antibiotic prescribing for acute bronchitis on patient satisfaction.

CONTEXT: Using a patient and clinician educational intervention, we successfully reduced antibiotic use for uncomplicated acute bronchitis. The impact of this intervention on patient satisfaction is not known. OBJECTIVE: To evaluate whether a strategy for reducing antibiotic use in acute bronchitis affects satisfaction among adult patients. DESIGN: Telephone survey administered 1 to 4 weeks after an office visit for acute bronchitis. SETTING: Two outpatient clinics belonging to a group-model HMO in the Denver, Colorado, metropolitan area. The intervention clinic had received a patient and office-based educational intervention that successfully reduced antibiotic prescribing for acute bronchitis during the previous winter. The control clinic received only the office-based materials, an intervention that did not reduce antibiotic prescribing. OUTCOME: Overall satisfaction with the episode of care. RESULTS: Antibiotics were prescribed to 64% and 85% of survey respondents at the intervention (n = 102) and control clinics (n = 164), respectively (P < 0.001). Patient satisfaction with the visit did not differ between intervention and control clinics (69% of intervention and 63% of control clinic patients reported very good or excellent satisfaction, P > 0.2). After adjustment for patient age, sex, duration of illness before the visit, reason for visit, and clinician specialty, there was no difference between intervention and control clinics in the proportion of patients reporting very good or excellent satisfaction (adjusted relative risk for high satisfaction at the intervention clinic, 1.1 [95% CI, 0.81 to 1.3]). CONCLUSION: A patient- and clinician-oriented educational intervention that reduces antibiotic treatment of adults with uncomplicated acute bronchitis does not appear to reduce satisfaction with care.