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OBJECTIVES: Healthcare worker (HCW) SARS-CoV-2 contacts in England have been required to quarantine, creating staff shortages. We piloted daily contact testing (DCT) to assess its feasibility as an alternative. STUDY DESIGN: Observational service evaluation. METHODS: We conducted an observational service evaluation of 7-day DCT using antigen lateral flow devices (LFDs) at four acute hospital trusts and one ambulance trust in England. Mixed methods were used, using aggregate and individual-level test monitoring data, semi-structured interviews, and a survey of eligible contacts. RESULTS: In total, 138 HCWs were identified as contacts of a confirmed SARS-CoV-2 case. Of these, 111 (80%) consented to daily LFD testing, of whom 82 (74%) completed the required programme without interruption and 12 (11%) completed with interruption. Fifty-eight participants (52%) and two non-participants (7.4%) completed the survey. In total, 28 interviews were conducted with participants, site and infection control leads, and union representatives. One participant tested positive on LFD and polymerase chain reaction (PCR) test. Three participants tested positive on PCR but not LFD. DCT was well-accepted by trusts and staff. Participants reported no relaxation of their infection prevention and control behaviours. No incidents of transmission were detected. An estimated 729 potential days of work absence were averted. CONCLUSIONS: DCT can be acceptably operated in a healthcare setting, averting quarantine-related work absences in HCW SARS-CoV-2 contacts.
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COVID-19 , SARS-CoV-2 , Ambulancias , COVID-19/diagnóstico , Inglaterra , Hospitales , HumanosRESUMEN
BACKGROUND: Bronchiectasis can result from infectious, genetic, immunological and allergic causes. 60-80% of cases are idiopathic, but a well-recognised genetic cause is the motile ciliopathy, primary ciliary dyskinesia (PCD). Diagnosis of PCD has management implications including addressing comorbidities, implementing genetic and fertility counselling and future access to PCD-specific treatments. Diagnostic testing can be complex; however, PCD genetic testing is moving rapidly from research into clinical diagnostics and would confirm the cause of bronchiectasis. METHODS: This observational study used genetic data from severe bronchiectasis patients recruited to the UK 100,000 Genomes Project and patients referred for gene panel testing within a tertiary respiratory hospital. Patients referred for genetic testing due to clinical suspicion of PCD were excluded from both analyses. Data were accessed from the British Thoracic Society audit, to investigate whether motile ciliopathies are underdiagnosed in people with bronchiectasis in the UK. RESULTS: Pathogenic or likely pathogenic variants were identified in motile ciliopathy genes in 17 (12%) out of 142 individuals by whole-genome sequencing. Similarly, in a single centre with access to pathological diagnostic facilities, 5-10% of patients received a PCD diagnosis by gene panel, often linked to normal/inconclusive nasal nitric oxide and cilia functional test results. In 4898 audited patients with bronchiectasis, <2% were tested for PCD and <1% received genetic testing. CONCLUSIONS: PCD is underdiagnosed as a cause of bronchiectasis. Increased uptake of genetic testing may help to identify bronchiectasis due to motile ciliopathies and ensure appropriate management.
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Bronquiectasia , Trastornos de la Motilidad Ciliar , Ciliopatías , Síndrome de Kartagener , Humanos , Mutación , Bronquiectasia/diagnóstico , Bronquiectasia/genética , Cilios , Trastornos de la Motilidad Ciliar/diagnóstico , Trastornos de la Motilidad Ciliar/genética , Ciliopatías/complicaciones , Síndrome de Kartagener/diagnóstico , Síndrome de Kartagener/genéticaRESUMEN
OBJECTIVES: To define the incidence of sacral U-type insufficiency fracture and describe management of a consecutive series of patients with this injury. DESIGN: Retrospective analysis. SETTING: Single Level II trauma center. PATIENTS/PARTICIPANTS: Sixteen adult patients with sacral U-type insufficiency fractures treated over a 36-month period. INTERVENTION: Patients were indicated for percutaneous screw fixation of the posterior pelvis if they had posterior pelvic pain that prohibited mobilization. MAIN OUTCOME MEASUREMENTS: Visual analog scale for pain, distance ambulated on postoperative day 1, and change in sacral kyphosis. RESULTS: The sacral U-type insufficiency fracture incidence was 16.7% (19/114); average patient age was 75 years. Delayed surgery was performed after primary nonoperative treatment had failed in 62.5% (10/16) at an average 83 days postinjury. Acute surgery was performed in 37.5% (6/16) at an average 5 days postinjury. Distance ambulated on postoperative day 1 was 114.4 feet [95% confidence interval (CI) (50.6, 178.2)] and 88.7 feet [95% CI (2.8, 174.6)] in the delayed and acute surgery groups, respectively, P = 0.18. Change in visual analog scale for pain was -3.2 [95% CI (-5.0, -1.4)] and -3.7 [95% CI (-7.0, -0.4)] in the delayed and acute surgery groups, respectively, P = 0.15. Change in sacral kyphosis from presentation to surgery was 12.3 degrees [95% CI (6.7, 17.9)] and 0.3 degrees [95% CI (-0.2, 0.9)] in the delayed and acute surgery groups, respectively, P < 0.01. Minimum follow-up was 12 months. CONCLUSIONS: Treatment of sacral U-type insufficiency fractures by percutaneous screw fixation permits early mobilization, provides rapid pain relief, and prevents progressive deformity. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.
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Tornillos Óseos , Fijación Interna de Fracturas/métodos , Fracturas Óseas/cirugía , Fracturas por Estrés/cirugía , Sacro/lesiones , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Intervalos de Confianza , Tratamiento Conservador/efectos adversos , Tratamiento Conservador/métodos , Femenino , Estudios de Seguimiento , Fijación Interna de Fracturas/instrumentación , Curación de Fractura/fisiología , Fracturas Óseas/diagnóstico por imagen , Fracturas por Estrés/diagnóstico por imagen , Evaluación Geriátrica , Humanos , Masculino , Persona de Mediana Edad , Dimensión del Dolor , Estudios Retrospectivos , Medición de Riesgo , Tiempo de TratamientoRESUMEN
BACKGROUND AND PURPOSE: Lithium's antidepressant action may be mediated by inhibition of inositol monophosphatase (IMPase), a key enzyme in Gq -protein coupled receptor signalling. Recently, the antioxidant agent ebselen was identified as an IMPase inhibitor. Here, we investigated both ebselen and lithium in models of the 5-HT2A receptor, a Gq -protein coupled receptor involved in lithium's actions. EXPERIMENTAL APPROACH: 5-HT2A receptor function was assessed in mice by measuring the behavioural (head-twitches, ear scratches) and molecular (cortical immediate early gene [IEG] mRNA; Arc, c-fos, Egr2) responses to 5-HT2A receptor agonists. Ebselen and lithium were administered either acutely or repeatedly prior to assessment of 5-HT2A receptor function. Because lithium and 5-HT2A receptor antagonists augment the action of selective serotonin reuptake inhibitors (SSRIs), ebselen was tested for this activity by co-administration with the SSRI citalopram in microdialysis (extracellular 5-HT) experiments. KEY RESULTS: Acute and repeated administration of ebselen inhibited behavioural and IEG responses to the 5-HT2A receptor agonist DOI. Repeated lithium also inhibited DOI-evoked behavioural and IEG responses. In comparison, a selective IMPase inhibitor (L-690330) attenuated the behavioural response to DOI whereas glycogen synthase kinase inhibitor (AR-A014418) did not. Finally, ebselen enhanced the increase in extracellular 5-HT induced by citalopram, and also increased regional brain 5-HT synthesis. CONCLUSIONS AND IMPLICATIONS: Our data demonstrated lithium-mimetic effects of ebselen in different experimental models of 5-HT2A receptor function, probably mediated by IMPase inhibition. This evidence of lithium-like neuropharmacological effects of ebselen adds further support for the clinical testing of ebselen in mood disorders, including as an antidepressant augmenting agent.
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Antioxidantes/farmacología , Azoles/farmacología , Litio/farmacología , Compuestos de Organoselenio/farmacología , Receptor de Serotonina 5-HT2A/metabolismo , Animales , Antioxidantes/administración & dosificación , Azoles/administración & dosificación , Relación Dosis-Respuesta a Droga , Isoindoles , Litio/administración & dosificación , Masculino , Ratones , Ratones Endogámicos C57BL , Compuestos de Organoselenio/administración & dosificaciónRESUMEN
Estimates of the incubation period for Q fever vary substantially between different reviews and expert advice documents. We systematically reviewed and quality appraised the literature to provide an evidence-based estimate of the incubation period of the Q fever by the aerosolised infection route. Medline (OVIDSP) and EMBASE were searched with the search limited to human studies and English language. Eligible studies included persons with symptomatic, acute Q fever, and defined exposure to Coxiella burnetti. After review of 7115 titles and abstracts, 320 records were screened at full-text level. Of these, 23 studies contained potentially useful data and were quality assessed, with eight studies (with 403 individual cases where the derivation of incubation period was possible) being of sufficient quality and providing individual-level data to produce a pooled summary. We found a median incubation period of 18 days, with 95% of cases expected to occur between 7 and 32 days after exposure.
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Periodo de Incubación de Enfermedades Infecciosas , Exposición por Inhalación , Fiebre Q/patología , Coxiella burnetii/aislamiento & purificación , HumanosRESUMEN
BACKGROUND: Lake Malawi cichlids represent one of a growing number of vertebrate models used to uncover the genetic and developmental basis of trait diversity. Rapid evolutionary radiation has resulted in species that share similar genomes but differ markedly in phenotypes including brains and behavior, nuptial coloration and the craniofacial skeleton. Research has begun to identify the genes, as well as the molecular and developmental pathways that underlie trait divergence. RESULTS: We assemble a compendium of gene expression for Lake Malawi cichlids, across pharyngula (the phylotypic stage) and larval stages of development, encompassing hundreds of gene transcripts. We chart patterns of expression in Bone morphogenetic protein (BMP), Fibroblast growth factor (FGF), Hedgehog (Hh), Notch and Wingless (Wnt) signaling pathways, as well as genes involved in neurogenesis, calcium and endocrine signaling, stem cell biology, and numerous homeobox (Hox) factors-in three planes using whole-mount in situ hybridization. Because of low sequence divergence across the Malawi cichlid assemblage, the probes we employ are broadly applicable in hundreds of species. We tabulate gene expression across general tissue domains, and highlight examples of unexpected expression patterns. CONCLUSIONS: On the heels of recently published genomes, this compendium of developmental gene expression in Lake Malawi cichlids provides a valuable resource for those interested in the relationship between evolution and development.
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Cíclidos/genética , Proteínas de Peces/genética , Regulación del Desarrollo de la Expresión Génica , Genes del Desarrollo/genética , Animales , Cíclidos/crecimiento & desarrollo , Evolución Molecular , Modelos Animales , FenotipoRESUMEN
BACKGROUND: Lowering the cosyntropin dose needed for ACTH stimulation would make the test more economical. OBJECTIVES: To compare the cortisol response to 1 and 5 µg/kg cosyntropin IV in dogs being screened for hyperadrenocorticism (HAC) and in dogs receiving trilostane or mitotane for pituitary-dependent HAC. ANIMALS: Healthy dogs (n = 10); client-owned dogs suspected of having HAC (n = 39) or being treated for pituitary-dependent HAC with mitotane (n = 12) or trilostane (n = 15). PROCEDURES: In this prospective study, healthy dogs had consecutive ACTH stimulation tests to ensure 2 tests could be performed in sequence. For the first test, cosyntropin (1 µg/kg IV) was administered; the second test was initiated 4 hours after the start of the first (5 µg/kg cosyntropin IV). Dogs suspected of having HAC or being treated with mitotane were tested as the healthy dogs. Dogs receiving trilostane treatment were tested on consecutive days at the same time post pill using the low dose on day 1. RESULTS: In dogs being treated with mitotane or trilostane, the 2 doses were pharmacodynamically equivalent (90% confidence interval, 85.1-108.2%; P = 0.014). However, in dogs suspected of having HAC, the doses were not pharmacodynamically equivalent (90% confidence interval, 73.2-92.8%; P = 0.37); furthermore, in 23% of the dogs, clinical interpretation of test results was different between the doses. CONCLUSIONS AND CLINICAL RELEVANCE: For dogs suspected of having HAC, 5 µg/kg cosyntropin IV is still recommended for ACTH stimulation testing. For dogs receiving mitotane or trilostane treatment, a dose of 1 µg/kg cosyntropin IV can be used.
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Hiperfunción de las Glándulas Suprarrenales/veterinaria , Hormona Adrenocorticotrópica/metabolismo , Cosintropina/farmacología , Enfermedades de los Perros/diagnóstico , Hiperfunción de las Glándulas Suprarrenales/diagnóstico , Hiperfunción de las Glándulas Suprarrenales/tratamiento farmacológico , Animales , Antineoplásicos/uso terapéutico , Estudios de Casos y Controles , Cosintropina/administración & dosificación , Dihidrotestosterona/análogos & derivados , Dihidrotestosterona/uso terapéutico , Perros , Relación Dosis-Respuesta a Droga , Femenino , Hormonas/administración & dosificación , Hidrocortisona/sangre , Masculino , Mitotano/uso terapéuticoRESUMEN
INTRODUCTION: Recent reported success in surgical stabilization of flail chest has been described in small series, but scant evidence exists for this procedure in the orthopaedic literature. METHODS: We reviewed 88 consecutive patients who underwent surgical stabilization of flail chest, along with 88 consecutive patients with flail chest who underwent traditional closed management before initiation of our algorithm change to surgical management. RESULTS: Surgical stabilization of flail chest injuries led to statistically significant decreases in hospital length of stay, ventilator-dependency time, pneumonia, tracheostomy, and mortality rate. In addition, the presence of pulmonary contusion did not eliminate the significant improvements in the aforementioned variables. DISCUSSION: Surgical stabilization of flail chest with modern techniques and implants provides significant improvements in both mortality and short-term outcomes. Although pulmonary contusion decreased overall outcomes across both cohorts, this factor did not alter the ability of rib fixation to improve outcomes.
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Tórax Paradójico/cirugía , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Femenino , Tórax Paradójico/mortalidad , Humanos , Tiempo de Internación/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Neumonía/epidemiología , Respiración Artificial/estadística & datos numéricos , Estudios Retrospectivos , Traqueostomía/estadística & datos numéricos , Resultado del Tratamiento , Adulto JovenRESUMEN
Although biomechanical and clinical evidence exists regarding smaller compression screws, biomechanical data regarding the larger headless screws are not currently available. Headed and headless 6.5-mm cannulated compression screws were examined, with analysis of interfragmentary compression, insertion torque, and resistance of the construct to a shear force. No significant differences were seen between the maximum insertion torque of the headless or headed screws. Maximum and steady-state compression forces were also not significantly different between groups. Countersinking the headless model 2 mm led to a 77.01% decrease in steady-state compression levels. Shear testing did not reveal any significant differences in peak load at ultimate failure, specimen stiffness, or final block displacement, although a trend to increased peak load and stiffness was seen with the headless specimens.
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Tornillos Óseos , Ensayo de Materiales , Fenómenos Biomecánicos , Diseño de Equipo , Fijación Interna de Fracturas/instrumentación , Humanos , Resistencia al Corte , TorqueRESUMEN
In November 2013, national public health agencies in England and Scotland identified an increase in laboratory-confirmed Salmonella Mikawasima. The role of proton pump inhibitors (PPIs) as a risk factor for salmonellosis is unclear; we therefore captured information on PPI usage as part of our outbreak investigation. We conducted a case-control study, comparing each case with two controls. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were estimated using multivariable logistic regression. Thirty-nine of 61 eligible cases were included in the study. The median age of cases was 45 years; 56% were female. Of these, 33% were admitted to hospital and 31% reported taking PPIs. We identified an association between PPIs and non-typhoidal salmonellosis (aOR 8·8, 95% CI 2·0-38·3). There is increasing evidence supporting the existence of an association between salmonellosis and PPIs; however, biological studies are needed to understand the effect of PPIs in the pathogenesis of Salmonella. We recommend future outbreak studies investigate PPI usage to strengthen evidence on the relevance of PPIs in Salmonella infection. These findings should be used to support the development of guidelines for patients and prescribers on the risk of gastrointestinal infection and PPI usage.
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Brotes de Enfermedades , Inhibidores de la Bomba de Protones/administración & dosificación , Infecciones por Salmonella/epidemiología , Salmonella enterica/aislamiento & purificación , Adolescente , Adulto , Anciano , Estudios de Casos y Controles , Inglaterra/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Inhibidores de la Bomba de Protones/efectos adversos , Factores de Riesgo , Infecciones por Salmonella/inducido químicamente , Escocia/epidemiología , Gales/epidemiología , Adulto JovenRESUMEN
The direct anterior approach has recently gained popularity for patients undergoing elective total hip arthroplasty. It is unknown whether the reported benefits of the direct anterior approach to elective total hip arthroplasty can be extrapolated to patients undergoing hemiarthroplasty after femoral neck fracture. A retrospective review of 101 patients was performed to compare the outcomes of patients treated with hemiarthroplasty using the direct anterior approach (group 1) with those of patients undergoing the procedure with the posterior, anterolateral, or lateral approach (group 2). No differences in age, American Society of Anesthesiologists classification, and preinjury ambulatory status were identified between treatment groups. No difference in operative time was found between those undergoing the anterior approach (98.7 minutes) and those undergoing other surgical approaches (96.5 minutes) (P=.76). No difference in either the need for transfusion or the number of blood products transfused was seen (P=.21) postoperatively. Patients undergoing the direct anterior approach were more likely to be discharged by postoperative day 3 (P=.004) despite no difference in the recorded number of feet ambulated in the hospital. At a mean clinical follow-up of 16 weeks, there was no difference in the rate of return to baseline ambulatory status between groups (P=.07). The overall rates of major and minor complications for all patients were 23% and 26%, respectively, with no statistically significant differences between groups. The overall dislocation rate of all patients was found to be 3%. All dislocations were observed in group 2. Larger prospective studies are needed to further define the benefits of the direct anterior approach in this patient population.
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Fracturas del Cuello Femoral/cirugía , Hemiartroplastia/métodos , Anciano , Pérdida de Sangre Quirúrgica/estadística & datos numéricos , Femenino , Humanos , Luxaciones Articulares/etiología , Tiempo de Internación , Masculino , Persona de Mediana Edad , Tempo Operativo , Complicaciones Posoperatorias/etiología , Estudios Prospectivos , Estudios RetrospectivosAsunto(s)
2',5'-Oligoadenilato Sintetasa/genética , Cromosomas Humanos Par 12/química , Intrones , Leucemia Linfocítica Crónica de Células B/genética , Polimorfismo de Nucleótido Simple , Alelos , Estudios de Casos y Controles , Mapeo Cromosómico , Frecuencia de los Genes , Sitios Genéticos , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Humanos , Leucemia Linfocítica Crónica de Células B/patología , Oportunidad Relativa , RiesgoRESUMEN
To assess the outcome of routine sexually transmitted infection re-screening after a three-month interval in unselected patients diagnosed with gonorrhoea, we sought to assess whether this active approach would result in an increase in the number of people attending clinic and subsequently diagnosed with gonorrhoea re-infection, compared with normal re-presentation rates. A recall group of patients were invited for re-screening three months after their initial diagnosis of gonorrhoea. Permission was sought to send a reminder two weeks prior to their scheduled recall appointment. Comparisons were made with a historical control group of patients with gonorrhoea in the absence of any formal recall. Of the 242 patients in the intervention arm, 96 (40%) re-attended within six months, and 15 (6%) tested gonorrhoea positive. Two hundred and two patients were assessed in the control group, of whom 45 (22%) re-attended within six months, and 13 (6%) tested gonorrhoea positive. Women were more likely than men to re-attend following active recall, but they were not at higher risk of re-attending while re-infected with gonorrhoea. Active recall following a gonorrhoea diagnosis significantly increases re-attendance rates for repeat screening but did not result in an increased number of subsequent gonorrhoea diagnoses.
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Gonorrea/diagnóstico , Tamizaje Masivo/métodos , Neisseria gonorrhoeae/aislamiento & purificación , Enfermedades de Transmisión Sexual/diagnóstico , Adulto , Femenino , Estudios de Seguimiento , Gonorrea/epidemiología , Gonorrea/microbiología , Humanos , Masculino , Tamizaje Masivo/estadística & datos numéricos , Persona de Mediana Edad , Recurrencia , Factores de TiempoRESUMEN
A controlled, blind research study was conducted to define the innate response of lungs in specific pathogen free (SPF) cats to intravenous (n=10) or subcutaneous (n=4) administration of homogenate of adult Dirofilaria immitis from donor dogs compared with lung response in control cats (n=6). There was no difference in cats that received heartworm homogenate IV for 18 days from donor dogs treated with doxycycline for 1 month compared with cats given heartworm homogenate from untreated donor dogs. Cats did not develop clinical signs, and no radiographic changes were noted. Cats given SC heartworm homogenate at lower concentration than IV groups did not develop histologic changes. Cats that received IV heartworm homogenate for 18 days developed mild interstitial and peribronchial myofibrocyte proliferation and smooth muscle proliferation of the pulmonary arteries. Bronchial ring contractility in vitro was blunted in the IV homogenate cats to the agonists acetylcholine and 5-hydroxytryptamine. Cats in the SC group had increased sensitivity to histamine at high concentrations but normal contractility and relaxation responses to other agonists. No increase in mast cells was noted in lung tissues of cats given homogenate. In the absence of bronchial wall remodeling, cats given IV homogenate had blunted responses to bronchial constriction, but normal relaxation to nitroprusside and substance P and increased sensitivity to histamine. In the absence adult heartworms, the homogenate of adult heartworms in the circulation of SPF cats induced a direct effect on lung parenchyma and altered bronchial ring reactivity.
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Dirofilaria immitis/inmunología , Inmunidad Innata/inmunología , Pulmón/inmunología , Arteria Pulmonar/inmunología , Animales , Gatos , Dirofilariasis/tratamiento farmacológico , Perros , Doxiciclina/uso terapéutico , Arteria Pulmonar/fisiopatología , Organismos Libres de Patógenos EspecíficosRESUMEN
Molecular PorA subtyping provides information that increasingly requires the adaptation of standard public health approaches to outbreak management. We report an outbreak of a rare subtype of meningococcal infection not previously identified in the United Kingdom (UK). The outbreak occurred in the Warwickshire area in England between February and June 2013. Molecular subtyping allowed the identification of additional cases, prompting an enhanced public health response that included efforts to identify potential social networks that might benefit from chemoprophylaxis. It also prompted swabbing to define nasopharyngeal carriage in the focal nursery and helped explain the unusual epidemiological pattern. Without subtyping to identify a link, the additional cases would have been managed as sporadic cases in accordance with current UK guidance.
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Brotes de Enfermedades , Infecciones Meningocócicas/epidemiología , Neisseria meningitidis Serogrupo B/genética , Porinas/genética , Adulto , Niño , Inglaterra/epidemiología , Femenino , Humanos , Masculino , Infecciones Meningocócicas/diagnóstico , Infecciones Meningocócicas/microbiología , Datos de Secuencia Molecular , Neisseria meningitidis Serogrupo B/aislamiento & purificación , Orofaringe/microbiología , Reacción en Cadena de la Polimerasa , Análisis de Secuencia de ADN/métodos , SerotipificaciónRESUMEN
Despite significant advances in critical care management, flail chest remains a clinically significant finding, with a mortality rate of up to 33%. Nonsurgical management is associated with prolonged ventilator support, pneumonia, respiratory difficulties, and lengthy stays in the intensive care unit, as well as chronic pain from nonunion and malunion of the bony thorax. Treatment with aggressive pulmonary toilet, ventilator support, and different modalities of pain control remains the benchmark of care. However, several recent randomized controlled studies of surgical intervention of flail chest have demonstrated an improvement in the number of ventilator days, intensive care unit and hospital stays, incidence of pneumonia, and respiratory function and hospital costs, as well as faster return to work. The success of these surgical constructs compared with those of historical attempts at open fixation is largely the result of modern plating technology and improvement in surgical approaches. Clinical evidence continues to grow regarding proper indications and techniques for surgical stabilization of flail chest.
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Tórax Paradójico/cirugía , Fracturas de las Costillas/cirugía , Humanos , Procedimientos Ortopédicos/métodos , ToracotomíaRESUMEN
A controlled, blind study was conducted to define the initial inflammatory response and lung damage associated with the death of precardiac stages of Dirofilaria immitis in cats as compared to adult heartworm infections and normal cats. Three groups of six cats each were used: UU: uninfected untreated controls; PreS I: infected with 100 D. immitis L3 by subcutaneous injection and treated topically with selamectin 32 and 2 days pre-infection and once monthly for 8 months); IU: infected with 100 D. immitis L3 and left untreated. Peripheral blood, serum, bronchial lavage, and thoracic radiographic images were collected from all cats on Days 0, 70, 110, 168, and 240. CT images were acquired on Days 0, 110, and 240. Cats were euthanized, and necropsies were conducted on Day 240 to determine the presence of heartworms. Bronchial rings were collected for in vitro reactivity. Lung, heart, brain, kidney, and liver tissues were collected for histopathology. Results were compared for changes within each group. Pearson and Spearman correlations were performed for association between histologic, radiographic, serologic, hematologic and bronchoalveolar lavage (BAL) results. Infected cats treated with selamectin did not develop radiographically evident changes throughout the study, were heartworm antibody negative, and were free of adult heartworms and worm fragments at necropsy. Histologic lung scores and CT analysis were not significantly different between PreS I cats and UU controls. Subtle alveolar myofibrosis was noted in isolated areas of several PreS I cats and an eosinophilic BAL cytology was noted on Days 75 and 120. Bronchial ring reactivity was blunted in IU cats but was normal in PreS I and UU cats. The IU cats became antibody positive, and five cats developed adult heartworms. All cats with heartworms were antigen positive at one time point; but one cat was antibody positive, antigen negative, with viable adult females at necropsy. The CT revealed early involvement of all pulmonary arteries and a random pattern of parenchymal disease with severe lesions immediately adjacent to normal areas. Analysis of CT 3D reconstruction and Hounsfield units demonstrated lung disease consistent with restrictive pulmonary fibrosis with an interstitial infiltrate, absence of air trapping, and decrease in total lung volume in Group IU as compared to Groups UU and PreS I. The clinical implications of this study are that cats pretreated with selamectin 1 month before D. immitis L3 infection did not become serologically positive and did not develop pulmonary arterial hypertrophy and myofibrosis.
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Enfermedades de los Gatos/diagnóstico , Enfermedades de los Gatos/patología , Dirofilaria immitis/fisiología , Enfermedades Pulmonares/veterinaria , Animales , Anticuerpos Antihelmínticos/sangre , Antiparasitarios/uso terapéutico , Recuento de Células Sanguíneas , Lavado Broncoalveolar , Estudios de Casos y Controles , Enfermedades de los Gatos/tratamiento farmacológico , Gatos , Ecocardiografía , Ivermectina/análogos & derivados , Ivermectina/uso terapéutico , Pulmón/parasitología , Pulmón/patología , Enfermedades Pulmonares/diagnóstico , Enfermedades Pulmonares/tratamiento farmacológico , Enfermedades Pulmonares/patología , Tomografía Computarizada por Rayos XRESUMEN
Allergic asthma is increasing in industrialized countries, especially in children. Rodent and human studies suggest an opportunity to "prevent" asthma in the perinatal period. The aims of this study were to create a more "natural" model of feline asthma by exposing offspring of asthmatic queens to Bermuda grass allergen (BGA) by inhalation only, and to investigate maternal-fetal-infant interactions in the development of asthma. Kittens from asthmatic queens were divided into four groups: maternal exposure to aerosolized BGA during the third trimester, neonatal exposure to aerosolized BGA in the first three months of life, both maternal and neonatal exposure, or saline control. Kittens failing to achieve an asthmatic phenotype based on bronchoalveolar lavage fluid (BALF) analysis by 6 months underwent traditional sensitization: adjuvanted allergen injection, intranasal allergen, and aerosol challenges. BALF was collected at 3, 4 and 6 months, and after sensitization at 8 months, and analyzed for eosinophil counts and BGA-specific IgG and IgA. Intradermal testing (IDT) was performed at 6 and 7 months. At six months none of the kittens had airway eosinophilia, BGA-specific IgG or IgA, and were non-responsive to IDT. After sensitization, kittens receiving neonatal aerosolization failed to develop airway eosinophilia as seen in the controls. Kittens exposed to BGA aerosols, either in-utero or neonatally, continued to lack IDT response. Chronic exposure to BGA aerosols failed to induce asthma in kittens, and instead tolerized the kittens to BGA. This is the first evidence that neonatal intervention could potentially "prevent" allergic asthma in cats.
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Alérgenos/inmunología , Asma/veterinaria , Enfermedades de los Gatos/prevención & control , Cynodon/inmunología , Aerosoles , Animales , Animales Recién Nacidos , Asma/inmunología , Asma/prevención & control , Gatos , Ensayo de Inmunoadsorción Enzimática/veterinaria , Inmunoglobulina A/sangre , Inmunoglobulina G/sangre , Pruebas IntradérmicasRESUMEN
Surgical techniques and fixation strategies for the treatment of unstable posterior pelvic ring injuries continue to evolve. The safety of the posterior surgical approach in particular has been questioned due to historically high rates of wound related complications. More contemporary studies have shown lower infection rates, however concern still persists. These concerns for infection and wound necrosis have led, in part, to increased interest in closed reduction and percutaneous fixation for treatment of these injuries but an open posterior approach remains the optimal strategy in some injury patterns. We describe herein a modified posterior approach to the pelvis designed to minimize wound related complications and present our clinical results demonstrating wound complication rates consistent with contemporary publications.
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Fijación Interna de Fracturas/métodos , Fracturas Óseas/cirugía , Procedimientos Ortopédicos/métodos , Huesos Pélvicos/lesiones , Traumatismos de los Tejidos Blandos/prevención & control , Adolescente , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Adulto JovenRESUMEN
BACKGROUND: There is a need for biomarkers for diagnosis, therapeutic monitoring, and prognosis for asthma in cats. Endothelin-1 (ET-1) is implicated in the pathogenesis of inflammatory airway diseases in other species but not the cat. OBJECTIVE: To conduct a prospective experimental study to show that experimentally asthmatic cats, but not control cats without airway inflammation, would have increased concentrations of ET in BALF. ANIMALS: Eleven healthy, adult research cats. METHODS: Prospective experimental study. Six healthy cats without airway inflammation were used as controls. Asthma was induced using Bermuda grass allergen (BGA) in 5 cats. Collection of BALF for total nucleated cell and differential counts was performed. The concentration of ET-1 in cell-free BALF samples was determined. Data were analyzed using a Mann-Whitney U-test with P < .05 considered significant. RESULTS: The median [range] BALF total cell numbers, eosinophil numbers, and eosinophil percentages were significantly higher in the cats following experimental induction of asthma (1,870 cells/µL [1,450-3,440], 711 cells/µL [356-1,686] and 38% [20-49]) compared to baseline control parameters (462 cells/µL [239-780], 18 cells/µL [18-62] and 3.5% [0-8]) (P < .01). The median [range] BALF ET concentration was also significantly higher after induction of asthma (1.393 fmol/mL[0.977-2.247]) compared to healthy control cats (0.83250 fmol/mL [0.625-1.038]) (P = .012). CONCLUSIONS AND CLINICAL IMPORTANCE: This study suggests that BAL ET-1 concentration can be used to differentiate normal cats from those with experimentally induced asthma. If the same holds true for cats with naturally developing asthma, BAL ET-1 may prove a useful diagnostic biomarker for asthma.