QuEChER method for air microbiological monitoring in hospital environments.

INTRODUCTION: Nosocomial pathogens have become a priority issue for public health, since they are responsible for increased morbidity and mortality in hospitalized patients and the development of multi-resistant microorganisms, as well. Recent studies found strong evidence that airborne transmission plays a key role in many nosocomial infections. Thus, we aim to develop a QuEChER methodology for the characterization of airborne microbial levels, analyzing potential variables that modify the air microbiological load. METHODOLOGY: Particulate matter levels and suspended and settled bioaerosols were determined simultaneously employing optical sensors, Harvard impactors and settle plates, respectively. Environmental variables were also measured at different sites during different working shifts and seasons. RESULTS: We found a straightforward relationship between airborne particles, air exchange rates, and people influx. Levels of suspended microorganisms were related to fine particulate matter concentration, CO2 and ambient temperature. A positive linear relationship (R2 = 0.9356) was also found between fine particulate matter and CO2 levels and air microbial load. CONCLUSION: The QuEChER methodology is an effective methodology that could be used to improve the surveillance of nosocomial pathogens in developing countries hospitals where air quality is scarcely controlled.

Platelets Promote Macrophage Polarization toward Pro-inflammatory Phenotype and Increase Survival of Septic Mice.

We investigated the contribution of human platelets to macrophage effector properties in the presence of lipopolysaccharide (LPS), as well as the beneficial effects and time frame for platelet transfusion in septic animals. Our results show that platelets sequester both pro-(TNF-α/IL-6) and anti-(IL-10) inflammatory cytokines released by monocytes. Low LPS concentrations (0.01 ng/mL) induced M2 macrophage polarization by decreasing CD64 and augmenting CD206 and CD163 expression; yet, the presence of platelets skewed monocytes toward type 1 macrophage (M1) phenotype in a cell-contact-dependent manner by the glycoprotein Ib (GPIb)-CD11b axis. Accordingly, platelet-licensed macrophages showed increased TNF-α levels, bacterial phagocytic activity, and a reduced healing capability. Platelet transfusion increased inducible nitric oxide synthase (iNOS)+ macrophages, improving bacterial clearance and survival rates in septic mice up to 6 h post-infection, an effect that was abolished by CD11b and GPIb blockade. Our results demonstrate that platelets orchestrate macrophage effector responses, improving the clinical outcome of sepsis in a narrow but relevant time frame.

An optimised protocol for platelet-rich plasma preparation to improve its angiogenic and regenerative properties.

Although platelet-rich plasma (PRP) is used as a source of growth factors in regenerative medicine, its effectiveness remains controversial, partially due to the absence of PRP preparation protocols based on the regenerative role of platelets. Here, we aimed to optimise the protocol by analysing PRP angiogenic and regenerative properties. Three optimising strategies were evaluated: dilution, 4 °C pre-incubation, and plasma cryoprecipitate supplementation. Following coagulation, PRP releasates (PRPr) were used to induce angiogenesis in vitro (HMEC-1 proliferation, migration, and tubule formation) and in vivo (chorioallantoic membrane), as well as regeneration of excisional wounds on mouse skin. Washed platelet releasates induced greater angiogenesis than PRPr due to the anti-angiogenic effect of plasma, which was decreased by diluting PRPr with saline. Angiogenesis was also improved by both PRP pre-incubation at 4 °C and cryoprecipitate supplementation. A combination of optimising variables exerted an additive effect, thereby increasing the angiogenic activity of PRPr from healthy donors and diabetic patients. Optimised PRPr induced faster and more efficient mouse skin wound repair compared to that induced by non-optimised PRPr. Acetylsalicylic acid inhibited angiogenesis and tissue regeneration mediated by PRPr; this inhibition was reversed following optimisation. Our findings indicate that PRP pre-incubation at 4 °C, PRPr dilution, and cryoprecipitate supplementation improve the angiogenic and regenerative properties of PRP compared to the obtained by current methods.

Schedule-Dependent Antiangiogenic and Cytotoxic Effects of Chemotherapy on Vascular Endothelial and Retinoblastoma Cells.

Current treatment of retinoblastoma involves using the maximum dose of chemotherapy that induces tumor control and is tolerated by patients. The impact of dose and schedule on the cytotoxicity of chemotherapy has not been studied. Our aim was to gain insight into the cytotoxic and antiangiogenic effect of the treatment scheme of chemotherapy used in retinoblastoma by means of different in vitro models and to evaluate potential effects on multi-drug resistance proteins. Two commercial and two patient-derived retinoblastoma cell types and two human vascular endothelial cell types were exposed to increasing concentrations of melphalan or topotecan in a conventional (single exposure) or metronomic (7-day continuous exposure) treatment scheme. The concentration of chemotherapy causing a 50% decrease in cell proliferation (IC50) was determined by MTT and induction of apoptosis was evaluated by flow cytometry. Expression of ABCB1, ABCG2 and ABCC1 after conventional or metronomic treatments was assessed by RT-qPCR. We also evaluated the in vivo response to conventional (0.6 mg/kg once a week for 2 weeks) and metronomic (5 days a week for 2 weeks) topotecan in a retinoblastoma xenograft model. Melphalan and topotecan were cytotoxic to both retinoblastoma and endothelial cells after conventional and metronomic treatments. A significant decrease in the IC50 (median, 13-fold; range: 3-23) was observed following metronomic chemotherapy treatment in retinoblastoma and endothelial cell types compared to conventional treatment (p<0.05). Metronomic topotecan or melphalan significantly inhibited in vitro tube formation in HUVEC and EPC compared to vehicle-treated cells (p<0.05). Both treatment schemes induced apoptosis and/or necrosis in all cell models. No significant difference was observed in the expression of ABCB1, ABCC1 or ABCG2 when comparing cells treated with melphalan or topotecan between treatment schedules at the IC50 or with control cells (p>0.05). In mice, continuous topotecan lead to significantly lower tumor volumes compared to conventional treatment after 14 days of treatment (p<0.05). Continuous exposure to melphalan or topotecan increased the chemosensitivity of retinoblastoma and endothelial cells to both chemotherapy agents with lower IC50 values compared to short-term treatment. These findings were validated in an in vivo model. None of the dosing modalities induced multidrug resistance mechanisms while apoptosis was the mechanism of cell death after both treatment schedules. Metronomic chemotherapy may be a valid option for retinoblastoma treatment allowing reductions of the daily dose.

Pharmacokinetics, Safety, and Efficacy of Intravitreal Digoxin in Preclinical Models for Retinoblastoma.

PURPOSE: To assess in vitro cytotoxic activity and antiangiogenic effect, ocular and systemic disposition, and toxicity of digoxin in rabbits after intravitreal injection as a potential candidate for retinoblastoma treatment. METHODS: A panel of two retinoblastoma and three endothelial cell types were exposed to increasing concentrations of digoxin in a conventional (72-hour exposure) and metronomic (daily exposure) treatment scheme. Cytotoxicity was defined as the digoxin concentration that killed 50% of the cells (IC50) and was assessed with a vital dye in all cell types. Induction of apoptosis and cell-cycle status were evaluated by flow cytometry after both treatment schemes. Ocular and systemic disposition after intravitreal injection as well as toxicity was assessed in rabbits. Electroretinograms (ERGs) were recorded before and after digoxin doses and histopathological examinations were performed after enucleation. RESULTS: Digoxin was cytotoxic to retinoblastoma and endothelial cells under conventional and metronomic treatment. IC50 was comparable between both schedules and induced apoptosis in all cell lines. Calculated vitreous digoxin Cmax was 8.5 µg/mL and the levels remained above the IC50 for at least 24 hours after intravitreal injection. Plasma digoxin concentration was below 0.5 ng/ml. Retinal toxicity was evident after the third intravitreal dose with considerable changes in the ERG and histologic damage to the retina. CONCLUSIONS: Digoxin has antitumor activity for retinoblastoma while exerting antiangiogenic activity in vitro at similar concentrations. Metronomic treatment showed no advantage in terms of dose for cytotoxic effect. Four biweekly injections of digoxin led to local toxicity to the retina but no systemic toxicity in rabbits.

[Shigelosis outbreak in the city of Lujan, Argentina]. / Brote de shigelosis en la ciudad de Luján, Argentina.

The aim of this study was to describe an outbreak of Shigella sonnei that occurred in the city of Lujan, Buenos Aires, Argentina, in July 2012. Five individuals were affected after eating a hand-made Viennese-style pastry at a family gathering. All of them presented with fever, joint pain, chills and non-bloody diarrhea containing mucus. Stool cultures were performed in all cases and the samples taken from the pastry ingredients were analyzed microbiologically. S.sonnei was isolated and identified in all the patients involved as well as in the almond cream filling. The isolates were analyzed for determining the antimicrobial susceptibility and genetic profiles by pulsed field gel electrophoresis (PFGE). The results showed the genetic relationship among the isolates, confirming that the cases occurred due to the patients' exposure to the same source of infection, i.e., the almond cream. Being the almond cream an industrially-manufactured ingredient, an initial contamination could have been unlikely; however contamination might have occurred as a result of manipulation in the bakery.

Brote de shigelosis en la ciudad de Luján, Argentina / Shigelosis outbreak in the city of Lujan, Argentina

El objetivo del estudio fue describir un brote por Shigella sonnei ocurrido en julio de 2012 en Luján, Buenos Aires, Argentina. Estuvieron afectadas 5 personas que asistieron a una reunión familiar, donde consumieron una rosca vienesa de elaboración artesanal adquirida en un comercio. Todos presentaron fiebre, dolores articulares, escalofríos y diarrea no sanguinolenta con mucus. Se realizaron coprocultivos en los afectados y análisis microbiológicos de los ingredientes. Se aisló y caracterizó S.sonnei de todos los pacientes y de la crema de almendras empleada en la preparación de la rosca vienesa. A los aislamientos se les determinó el perfil de sensibilidad a los antimicrobianos y el genético por electroforesis en campo pulsado. Los resultados demostraron la relación genética de los aislamientos, y esto confirmó la ocurrencia de los casos por exposición a una misma fuente de infección, la crema de almendras. Al ser un ingrediente industrial, de improbable contaminación inicial, la crema de almendras podría haber sufrido una contaminación durante la manipulación en la panadería

The aim of this study was to describe an outbreak of Shigella sonnei that occurred in the city of Lujan, Buenos Aires, Argentina, in July 2012. Five individuals were affected after eating a handmade Viennese-style pastry at a family gathering. All of them presented with fever, joint pain, chills and non-bloody diarrhea containing mucus. Stool cultures were performed in all cases and the samples taken from the pastry ingredients were analyzed microbiologically. S.sonnei was isolated and identified in all the patients involved as well as in the almond cream filling. The isolates were analyzed for determining the antimicrobial susceptibility and genetic profiles by pulsed field gel electrophoresis (PFGE). The results showed the genetic relationship among the isolates, confirming that the cases occurred due to the patients' exposure to the same source of infection, i.e., the almond cream. Being the almond cream an industrially-manufactured ingredient, an initial contamination could have been unlikely; however contamination might have occurred as a result of manipulation in the bakery

Human Plasmacytoid Dendritic Cells Elicited Different Responses after Infection with Pathogenic and Nonpathogenic Junin Virus Strains.

The arenavirus Junin virus (JUNV) is the etiologic agent of Argentine hemorrhagic fever. We characterized the JUNV infection of human peripheral blood-derived plasmacytoid dendritic cells (hpDC), demonstrating that hpDC are susceptible to infection with the C#1 strain (attenuated) and even more susceptible to infection with the P (virulent) JUNV strain. However, hpDC elicited different responses in terms of viability, activation, maturation, and cytokine expression after infection with both JUNV strains.

Acidic preconditioning improves the proangiogenic responses of endothelial colony forming cells.

OBJECTIVE: Acidosis is present in several pathological conditions where vasculogenesis takes place including ischemia, tumor growth and wound healing. We have previously demonstrated that acidosis induces human CD34+ cell apoptosis. Considering that endothelial colony-forming cells (ECFC) are a subpopulation of CD34+ cells and key players in vasculogenesis, in the present study we investigated the effect of acidosis on the survival and functionality of ECFC. APPROACH AND RESULTS: Endothelial colony-forming cells obtained by differentiation of human cord blood CD34+ cells in endothelial growth medium-2 for 14-21 days were exposed at pH 7.4, 7.0 or 6.6. We found that acidosis failed to induce ECFC apoptosis and, although an early reduction in proliferation, chemotaxis, wound healing and capillary-like tubule formation was observed, once the medium pH was restored to 7.4, ECFC proliferation and tubulogenesis were augmented. Stromal cell derived factor-1 (SDF1)-driven migration and chemokine receptor type 4 surface expression were also increased. The maximal proangiogenic effect exerted by acidic preconditioning was observed after 6 h at pH 6.6. Furthermore, preconditioned ECFC showed an increased ability to promote tissue revascularization in a murine model of hind limb ischemia. Immunoblotting assays showed that acidosis activated AKT and ERK1/2 and inhibited p38 pathways. Proliferation rises triggered by acidic preconditioning were no longer observed after AKT or ERK1/2 inhibition, whereas p38 suppression not only mimicked but also potentiated the effect of acidosis on ECFC tubule formation abilities. CONCLUSIONS: These results demonstrate that acidic preconditioning greatly increases ECFC-mediated angiogenesis in vitro including ECFC proliferation, tubulogenesis and SDF1-driven chemotaxis and is a positive regulator of microvessel formation in vivo.

Composition and mutagenicity of PAHs associated with urban airborne particles in Córdoba, Argentina.

The comet assay and micronucleous test were used to assess the genotoxicity of organic compounds associated with particulate material collected in the city of Córdoba, Argentina. Samples were collected on fiber glass filters and their organic extracts were analyzed by GC-MS. These extracts were used for the comet assay on human lymphocytes and for the MCN test with Tradescantia pallida. The concentrations of polycyclic aromatic hydrocarbons as well as some of their nitro derivates were higher during winter. Their composition suggested that their main emission sources were gasoline and diesel vehicles. We observed genotoxic effects of these organic extracts due to the presence of both direct and indirect acting mutagens. We found a good agreement between the two test systems employed, which encourages the further use of plant bioassays for air pollution monitoring, especially in developing countries, due to their flexibility, low cost and efficiency.

The effect of airborne particles and weather conditions on pediatric respiratory infections in Cordoba, Argentine.

We studied the effect of estimated PM(10) on respiratory infections in children from Cordoba, Argentine as well as the influence of weather factors, socio-economic conditions and education. We analyzed upper and lower respiratory infections and applied a time-series analysis with a quasi-Poisson distribution link function. To control for seasonally varying factors we fitted cubic smoothing splines of date. We also examined community-specific parameters and differences in susceptibility by sex. We found a significant association between particles and respiratory infections. This relationship was affected by mean temperature, atmospheric pressure and wind speed. These effects were stronger in fall, winter and spring for upper respiratory infections while for lower respiratory infections the association was significant only during spring. Low socio-economic conditions and low education levels increased the risk of respiratory infections. These findings add useful information to understand the influence of airborne particles on children health in developing countries.

Associations of the Emergency Severity Index triage categories with patients' vital signs at triage: a prospective observational study.

STUDY OBJECTIVE: Previous studies on the construct validity of the Emergency Severity Index (ESI) were focused on outcome measures which could not be obtained directly at triage. A study was conducted to the construct validity of the ESI by measuring the association between the ESI triage categories and patients' vital signs at triage. METHODS: A prospective observational study was conducted at an emergency department (ED) in the Netherlands. All patients who entered the ED between 20 July 2009 and 21 August 2009 were eligible for inclusion in the study. Patients' vital signs, triage category, age, gender, referrer and main complaint were registered. Vital signs were scored according to the Worthing Physiological Scoring System (WPSS) and the numerical pain rating scale. The data were analysed using ordinal logistic regression analyses. RESULTS: An association was found between ESI triage categories and patients' vital signs at triage. Patients in WPSS categories 'urgent' and 'alert' were more likely triaged into the urgent triage categories (ESI triage categories 1 and 2) than patients with normal WPSS scores. However, no associations were found between pain scores and ESI triage categories. CONCLUSION: This study supports the validity of the ESI as it showed that patients' vital signs are associated with the ESI triage categories. However, a revision of the ESI guidelines concerning pain assessments is necessary.

Suppression of cancer growth by nonviral gene therapy based on a novel reactive oxygen species-responsive promoter.

Increased reactive oxygen species (ROS) production has been reported as a distinctive feature of different pathologies including cancer. Therefore, we assessed whether increased ROS production in the cancer microenvironment could be selectively exploited to develop a selective anticancer therapy. For this purpose, we constructed a novel chimeric promoter, based on a ROS-response motif located in the VEGF gene promoter placed, in turn, downstream of a second ROS-response motif obtained from the early growth response 1 (Egr-1) gene promoter. The activity of the chimeric promoter was largely dependent on variations in intracellular ROS levels and showed a high inducible response to exogenous H(2)O(2). Transient expression of the thymidine kinase (TK) gene driven by the chimeric promoter, followed by gancyclovir (GCV) administration, inhibited human colorectal cancer and melanoma cell growth in vitro and in vivo. Moreover, electrotransfer of the TK gene followed by GCV administration exerted a potent therapeutic effect on established tumors. This response was improved when combined with chemotherapeutic drugs. Thus, we show for the first time that a distinctive pro-oxidant state can be used to develop new selective gene therapeutics for cancer.

Assessment of human health risk related to metals by the use of biomonitors in the province of Córdoba, Argentina.

The evaluation of metal contents in the environment is of vital importance for the assessment of human exposure. Thus the species Usnea amblyoclada, Ramalina celastri and Tillandsia capillaris were tested as bioaccumulators of transition metals in the urban area of Córdoba city, Argentina. The level of metals on biomonitors was compared to that of total deposition samples. All three species discriminated zones within the urban area of Córdoba city with different pollution levels; they revealed high levels of Zn in the downtown area and confirmed high levels of some transition metals in an industrial area. The correlation analysis revealed that the lichen R. celastri had the highest correlation rates with total deposition samples, suggesting it is a valuable biomonitor of atmospheric pollution. A significant relationship was also observed between respiratory diseases in children and the contents of metal accumulated in R. celastri and T. capillaris, indicating their usefulness when assessing human exposure to metals.

Estudio de la relación entre los niveles de deposición atmosférica total y algunos indicadores de salud respiratoria en la ciudad de Córdoba / Relationship between atmospheric deposition levels and some respiratory health indicators in the city of Córdoba

Antecedentes: si bien existe numerosa información sobre los efectos de material particulado en la salud humano, son muy escasos los estudios realizados en países en desarrollo, donde las condiciones socioeconómicas así como el tipo y niveles de contaminantes son muy diferentes de los países desarrollados. Objetivo. Evaluar la relación entre los niveles de deposición atmosférica total (húmeda y seca), los cuales estuvieron expuestos durante 6 meses. El número total de pacientes que fueron atendidos por afecciones respiratorias en los centros de salud localizados cerca de los puntos de muestreo se obtuvo de las bases de datos de la Municipalidad de Córdoba. Con todas las afecciones respiratorias estudiadas, se creó una nueva variable a partir de la suma de sus registros y se calculó su frecuencia. Ésta fue luego relacionada con los valores de deposición total correspondientes a cada sitio de muestreo. Resultados y conclusiones. Se observó una relación significativa entre ambas variables, lo cual sugiere que esta metodología sencilla y de bajo costo podría ser de utilidad para estimar el riesgo de exposición del hombre a material particulado atmosférico.

Effects of the heavy metals Cu2+, Ni2+, Pb2+, and Zn2+ on some physiological parameters of the lichen Usnea amblyoclada.

The effect of Cu2+, Ni2+, Pb2+, and Zn2+ on some physiological parameters of the lichen Usnea amblyoclada and the selective uptake of Cu2+ and Pb2+ was assessed. Fresh thalli were soaked in single or mixed metallic solutions. The concentration of chlorophylls and malondialdehyde; the dry weight/fresh weight ratio as well as the water content and the concentration of Cu, Ni, Pb, and Zn were measured in the treated and control thalli. The exposure to Cu, Ni, and Pb solutions caused several changes on the parameters measured; no differences were found with Zn. A stronger ability for binding Pb2+ was also observed. The results suggest that Cu2+ was the most harmful cation followed by Pb and Ni. Consequently, the damage observed in U. amblyoclada thalli when it is used as a biomonitor in polluted areas is possibly due to the presence of these heavy metals, masking the effect of other gaseous pollutants.

Assessment of heavy metal accumulation in two species of Tillandsia in relation to atmospheric emission sources in Argentina.

The ability of Tillandsia capillaris Ruiz and Pav. f. capillaris and Tillandsia permutata A. Cast. to accumulate heavy metals was evaluated in relation to potential atmospheric emission sources in Argentina. The sampling areas (n=38) were chosen in the province of Córdoba, located in the center of Argentina, and categorized according to land use, anthropogenic activities and/or distance to potential heavy metal emission sources. In each sampling site, pools of 40-50 individuals of each species were made from plants collected along the four cardinal directions. The concentrations of V, Mn, Fe, Co, Ni, Cu, Zn, Pb and Br of these samples were measured by Total Reflection X-Ray Fluorescence (TXRF) analysis with Synchrotron Radiation. Each species was submitted to a cluster analysis in order to discriminate different groups of heavy metals as tracers of natural or anthropogenic sources. A Contamination Factor (CF) was calculated using the concentrations of the elements in each sample compared to their concentrations in the control samples. Finally, the rank coefficients of correlation between the CFs and the categorical variables characteristic of each site (land use and anthropogenic load) were analyzed. A positive correlation was found for T. capillaris between the CFs of V, Mn, Co, Ni, Cu and Zn and the urban-industrial category, whereas the CF values for Zn and Pb were positively correlated with the road category. In T. permutata there was a positive correlation between the CF of Zn and the urban-industrial category and the CF of Pb with the road category. We therefore conclude that T. capillaris is a more efficient metal accumulator in passive biomonitoring studies.

The role of urban air pollutants on the performance of heavy metal accumulation in Usnea amblyoclada.

Lichens incorporate heavy metals according to a selectivity sequence; therefore, their uptake rate can be affected when elements with a high affinity for cell wall exchange sites or that provoke harmful alterations to the metabolism of lichen thalli are present in the environment. The aim of this study was to examine the effect of urban pollutants on the accumulation of some heavy metals in Usnea amblyoclada. Lichen samples were transplanted for 1 month to both a polluted and a nonpolluted area in Cordoba, Argentina. They were then collected and soaked in tridistilled water or in solutions containing different concentrations of Cu, Ni, Pb, and Zn salts. The uptake of Cu2+, Ni2+, Zn2+, and Pb2+, and other parameters indicative of lichen damage were measured in all the lichen samples. The thalli retrieved from the polluted area showed significant increases in both the malonaldehyde content and the electrical conductivity of the water in which they had been immersed. These results indicate that the atmospheric pollutants could be responsible for the significant damage to the lichen's cellular membranes, thus altering several mechanisms related to the uptake of heavy metals. Both the area of transplantation and the concentration of the metallic solutions had significant effects on the levels of Cu, Ni, and Pb measured in lichen thalli; however, no significant differences were observed in Zn concentrations. The highest uptakes corresponded to Pb and Cu, suggesting that they probably have a higher affinity with the lichen cell wall exchange sites. This study confirms the fact that, although lichens can be useful biological indicators, the physiological mechanisms involved in metal uptake should be carefully analyzed. Therefore, when estimating the heavy metal content of an environment, the competitive mechanism for cation uptake should be considered especially in areas where the presence of high levels of metals with a strong binding affinity is suspected. The presence of secondary products in the lichens could be responsible for the selective uptake of cations and for a possible tolerance to their presence.

The role of topically administered FK506 (tacrolimus) at the time of facial nerve repair using entubulation neurorrhaphy in a rabbit model.

Peripheral facial nerve palsy is a common sequela of traumatic craniofacial injury, often resulting in dramatic and sometimes permanent functional deficits. Exogenous agents and methods of repair that accelerate axonal regeneration would be of great benefit to the multitude of patients with facial nerve injuries. The objective of this study was to evaluate the effect of FK506 at the time of facial nerve repair using entubulation neurorrhaphy, and to compare entubulation neurorrhaphy versus interposition autograft in critical facial nerve gap defects. The study design was a prospective, randomized, blinded animal study with a control group. Twenty-five New Zealand White rabbits were assigned to 4 experimental groups and a control group. The buccal branch of the facial nerve was used in all procedures. Group 1 was the control group. Rabbits in group 2 underwent sham surgery. Group 3 was an interposition autograft group in which a 6-mm segment of nerve was transacted, flipped, and followed by epineural repair. Groups 4 and 5 underwent transection followed by entubulation neurorrhaphy with topical administration of either a carrier molecule (group 4) or an FK506 carrier molecule (group 5). Outcome measures included daily subjective assessment of upper lip movement; electromyographic studies at weeks 3, 5, and 8 postoperatively; and blinded quantitative histomorphometric evaluation after 8 weeks. All rabbits in all groups were noted to have spontaneous movement after 8 weeks, with 1 rabbit in group 5 obtaining the highest functional score among all study groups. Electrophysiologic studies showed polyphasic potentials, indicating reinnervation in 1 rabbit in group 5. Histomorphometric examination of group 5 rabbits revealed a similar cross-sectional area distal to transection and remyelination. Other groups showed decreased cross-sectional area and/or incomplete remyelination distal to the transection. FK506 applied topically at the time of facial nerve repair using entubulation neurorrhaphy demonstrated superior results in nerve regeneration versus entubulation neurorrhaphy carrier protein alone, and interposition autograft.

Gender-related changes in the practice and outcomes of percutaneous coronary interventions in Northern New England from 1994 to 1999.

OBJECTIVES: We sought to determine whether the changing practice of interventional cardiology has been associated with improved outcomes for women, and how these outcomes compare with those for men. BACKGROUND: Previous work from the early 1990s suggested women are at a higher risk than men for adverse outcomes after percutaneous coronary interventions (PCIs). From 1994 to 1999 data were collected on 33,666 consecutive hospital admissions for a PCI in Northern New England. Multivariate models were used to adjust for differences in case-mix across year of procedure when comparing outcomes. Direct standardization was used to calculate adjusted rates. RESULTS: From 1994 to 1999, the case-mix worsened for both women and men, although women had more co-morbidities than did men throughout the period. Stent use increased over time (>75% in 1999). Concomitantly, the need for emergency coronary artery bypass graft surgery (CABG) decreased significantly (p(trend) < or = 0.001; in 1999: 0.06% for women, 0.05% for men). Although the emergency CABG rates were higher for women at the beginning of the study, by the end, they were comparable (adjusted odds ratio 1.34, 95% confidence interval 0.76 to 2.38, p = 0.315). The myocardial infarction (MI) rates decreased over time for both women (by 29.7%, p(trend) = 0.378) and men (by 37.6%, p(trend) = 0.009) and did not differ by gender. The mortality rates did not decrease significantly over time and were not significantly different between the genders (mean 1.21% for women, 1.06% for men; p = 0.096). CONCLUSIONS: Concurrent with the changing practice of PCI, and despite treating sicker patients, there have been important improvements in post-PCI CABG and MI rates for women, as well as for men. Unlike in earlier years, there are no longer significant differences in outcomes by gender.