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1.
Otolaryngol Head Neck Surg ; 169(3): 701-709, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37003297

RESUMO

OBJECTIVE: Evaluate 2-year outcomes after lidocaine/epinephrine iontophoresis and tympanostomy using an automated tube delivery system for pediatric tube placement in-office. STUDY DESIGN: Prospective, single-arm. SETTING: Eighteen otolaryngology practices. METHODS: Children age 6 months to 12 years indicated for tympanostomy were enrolled between October 2017 and February 2019. Local anesthesia of the tympanic membrane was achieved via lidocaine/epinephrine iontophoresis and tympanostomy was completed using an automated tube delivery system (the Tula® System). An additional Lead-In cohort of patients underwent tube placement in the operating room (OR) under general anesthesia using only the tube delivery system. Patients were followed for 2 years or until tube extrusion, whichever occurred first. Otoscopy and tympanometry were performed at 3 weeks, and 6, 12, 18, and 24 months. Tube retention, patency, and safety were evaluated. RESULTS: Tubes were placed in-office for 269 patients (449 ears) and in the OR for 68 patients (131 ears) (mean age, 4.5 years). The median and mean times to tube extrusion for the combined OR and In-Office cohorts were 15.82 (95% confidence interval [CI]: 15.41-19.05) and 16.79 (95% CI: 16.16-17.42) months, respectively. Sequelae included ongoing perforation for 1.9% of ears (11/580) and medial tube displacement for 0.2% (1/580) observed at 18 months. Over a mean follow-up of 14.3 months, 30.3% (176/580) of ears had otorrhea and 14.3% (83/580) had occluded tubes. CONCLUSION: In-office pediatric tympanostomy using lidocaine/epinephrine iontophoresis and automated tube delivery results in tube retention within the ranges described for similar grommet-type tubes and complication rates consistent with traditional tube placement in the OR.


Assuntos
Iontoforese , Otite Média com Derrame , Criança , Humanos , Pré-Escolar , Lidocaína , Ventilação da Orelha Média/métodos , Estudos Prospectivos , Membrana Timpânica , Otite Média com Derrame/cirurgia
2.
Chemistry ; 29(16): e202203672, 2023 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-36562295

RESUMO

Infecting the stomach of almost 50 % of people, Helicobacter pylori is a causative agent of gastritis, peptic ulcers and stomach cancers. Interactions between bacterial membrane-bound lectin, Blood group Antigen Binding Adhesin (BabA), and human blood group antigens are key in the initiation of infection. Herein, the synthesis of a B-antigen hexasaccharide (B6) and a B-Lewis b heptasaccharide (BLeb7) and Bovine Serum Albumin glycoconjugates thereof is reported to assess the binding properties and preferences of BabA from different strains. From a previously reported trisaccharide acceptor a versatile key Lacto-N-tetraose tetrasaccharide intermediate was synthesized, which allowed us to explore various routes to the final targets, either via initial introduction of fucosyl residues followed by introduction of the B-determinant or vice versa. The first approach proved unsuccessful, whereas the second afforded the target structures in good yields. Protein conjugation using isothiocyanate methodology allowed us to reach high glycan loadings (up to 23 per protein) to mimic multivalent displays encountered in Nature. Protein glycoconjugate inhibition binding studies were performed with H. pylori strains displaying high or low affinity for Lewis b hexasaccharide structures showing that the binding to the high affinity strain was reduced due to the presence of the B-determinant in the Bleb7-conjugates and further reduced by the absence of the Lewis fucose residue in the B6-conjugate.


Assuntos
Antígenos de Grupos Sanguíneos , Infecções por Helicobacter , Helicobacter pylori , Humanos , Adesinas Bacterianas/química , Estômago/microbiologia , Antígenos de Grupos Sanguíneos/metabolismo , Glicoconjugados/química , Infecções por Helicobacter/microbiologia
3.
J Foot Ankle Surg ; 60(6): 1179-1183, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34112585

RESUMO

First metatarsophalangeal joint (MTPJ) arthrodesis is currently the gold standard technique for advanced hallux rigidus. This retrospective study aimed to identify the risk factors for nonunion after first MTPJ arthrodesis with a dorsal locking plate and compression screw construct. Between April 2014 and April 2019, 165 consecutive patients (28 men and 137 women; mean age, 60 (range, 28-84) years) who underwent 178 primary first MTPJ arthrodeses were retrospectively reviewed. All arthrodeses were performed using either a dorsal locking plate with an integrated compression screw (Anchorage CP plate, Stryker, n = 97) or a dorsal locking plate (Anchorage V2 plate, Stryker, n = 81) with a separate compression screw (4 mm cannulated ACE screw). Union was defined as bone bridging across the fusion site on at least 2 of the 3 standard foot radiographs (anteroposterior, lateral, oblique) and no MTPJ movement or pain during clinical examination. Potential risk factors for nonunion were analyzed with the use of univariate and multivariate analyses. The overall nonunion rate was 6.2% (11 of 178 cases). The risk factors identified in the univariate analysis included preoperative hallux valgus deformity, postoperative residual hallux valgus deformity, and diabetes (p < .05). Multivariate analysis confirmed that postoperative residual hallux valgus deformity (odds ratio 6.5; p= .015) and diabetes (odds ratio 7.4; p = .019) are independent risk factors for nonunion after first MTPJ arthrodesis. Diabetes is the most important independent risk factor for nonunion after first MTPJ arthrodesis with a dorsal locking plate and compression screw construct. A residual postoperative hallux valgus deformity is associated with a significantly increased risk for nonunion. It is therefore crucial to correct the hallux valgus deformity to a hallux valgus angle of less than 20°.


Assuntos
Hallux Rigidus , Hallux Valgus , Articulação Metatarsofalângica , Artrodese , Placas Ósseas , Parafusos Ósseos , Feminino , Hallux Valgus/diagnóstico por imagem , Hallux Valgus/cirurgia , Humanos , Masculino , Articulação Metatarsofalângica/diagnóstico por imagem , Articulação Metatarsofalângica/cirurgia , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento
6.
Foot Ankle Int ; 41(10): 1212-1218, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32672066

RESUMO

BACKGROUND: Hallux valgus recurrence is an unsatisfactory complication, with many causes postulated. This study investigated the effect of pes planus on recurrence after scarf osteotomy. METHODS: A total of 183 feet were retrospectively reviewed. All patients were treated with a scarf osteotomy and if required Akin osteotomy. We measured preoperative lateral talus first metatarsal angle (T1MA) to study pes planus; an angle of under -4 degrees was considered pes planus. We measured pre and postoperative hallux valgus angle (HVA), intermetatarsal angle (IMA), and sesamoid location. In total 164 feet were suitable for inclusion, with follow-up of at least 6 months (10 males and 154 females, mean age: 52 years). RESULTS: Recurrence frequency (HVA greater than 15 degrees) was 27 feet (16%). Hallux valgus recurrence was not influenced by gender (P value = .66) or preoperative IMA (P value = .48). Preoperative HVA greater than 35 degrees was associated with increased frequency of recurrence (P value = .004). Those with T1MA less than -10 degrees demonstrated progression in HVA and deterioration in sesamoid location up to 6 months postoperatively (P value = .038). HVA did not progress beyond 6 months. The prevalence of recurrent hallux valgus with normal T1MA was 1%, in T1MA -4 to -10 degrees it was 29% and in T1MA less than -10 degrees it was 47% (P value <.001). Breaks in T1MA less than -4 degrees were found at the naviculocuneiform joint in 68% of feet in this series. CONCLUSION: The prevalence of hallux valgus recurrence correlated with the severity of pes planus. LEVEL OF EVIDENCE: Level III, retrospective cohort study.


Assuntos
Joanete/cirurgia , Hallux Valgus/cirurgia , Ossos do Metatarso/cirurgia , Adulto , Idoso , Joanete/fisiopatologia , Feminino , Pé Chato , Humanos , Pessoa de Meia-Idade , Osteotomia , Recidiva , Estudos Retrospectivos , Resultado do Tratamento
7.
Laryngoscope ; 130 Suppl 4: S1-S9, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32160320

RESUMO

OBJECTIVES/HYPOTHESIS: Evaluate technical success, tolerability, and safety of lidocaine iontophoresis and tympanostomy tube placement for children in an office setting. STUDY DESIGN: Prospective individual cohort study. METHODS: This prospective multicenter study evaluated in-office tube placement in children ages 6 months through 12 years of age. Anesthesia was achieved via lidocaine/epinephrine iontophoresis. Tube placement was conducted using an integrated and automated myringotomy and tube delivery system. Anxiolytics, sedation, and papoose board were not used. Technical success and safety were evaluated. Patients 5 to 12 years old self-reported tube placement pain using the Faces Pain Scale-Revised (FPS-R) instrument, which ranges from 0 (no pain) to 10 (very much pain). RESULTS: Children were enrolled into three cohorts with 68, 47, and 222 children in the Operating Room (OR) Lead-In, Office Lead-In, and Pivotal cohorts, respectively. In the Pivotal cohort, there were 120 and 102 children in the <5 and 5- to 12-year-old age groups, respectively, with a mean age of 2.3 and 7.6 years, respectively. Bilateral tube placement was indicated for 94.2% of children <5 and 88.2% of children 5 to 12 years old. Tubes were successfully placed in all indicated ears in 85.8% (103/120) of children <5 and 89.2% (91/102) of children 5 to 12 years old. Mean FPS-R score was 3.30 (standard deviation [SD] = 3.39) for tube placement and 1.69 (SD = 2.43) at 5 minutes postprocedure. There were no serious adverse events. Nonserious adverse events occurred at rates similar to standard tympanostomy procedures. CONCLUSIONS: In-office tube placement in selected patients can be successfully achieved without requiring sedatives, anxiolytics, or papoose restraints via lidocaine iontophoresis local anesthesia and an automated myringotomy and tube delivery system. LEVEL OF EVIDENCE: 2b Laryngoscope, 130:S1-S9, 2020.


Assuntos
Procedimentos Cirúrgicos Ambulatórios/métodos , Iontoforese/métodos , Ventilação da Orelha Média/métodos , Anestesia Local/métodos , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Lidocaína/administração & dosagem , Masculino , Estudos Prospectivos , Resultado do Tratamento
8.
Biotechnol Prog ; 34(6): 1566-1573, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30267619

RESUMO

Process mass intensity (PMI) is a benchmarking metric to evaluate the efficiency of a manufacturing process, which is indicative of the environmental impact of the process. Although this metric is commonly applied for small molecule manufacturing processes, it is less commonly applied to biologics. In this study, an Excel based tool developed by the ACS GCI Pharmaceutical Roundtable was used to calculate PMI of different manufacturing processes for a monoclonal antibody (mAb). For the upstream process, three different versions were compared: fed-batch, fed-batch with N-1 perfusion, and perfusion in the N-stage bioreactor. For each upstream process version, an appropriate downstream operational mode was evaluated from the following: a column chromatography process utilizing Protein A and anion exchange (AEX) resin, a Protein A column and an AEX membrane, and a three-column periodic counter-current (3C PCC) chromatography process for Protein A and an AEX membrane. The impact of these different process variations on PMI was evaluated. Of all the process inputs, water contributes about 92-94% of the overall PMI. Additionally, the upstream processes and the chromatography steps account for 32-47 and 34-54% of the overall PMI, respectively. Sensitivity analysis was performed to identify opportunities for further reducing PMI. These data indicate that a semicontinuous manufacturing process (perfusion, 3C PCC, and AEX membrane) is the most efficient process, resulting in a 23% reduction of PMI when compared with the fed batch and two-column chromatography process. Together, PMI can be used to guide the development of efficient and environmentally sustainable mAb manufacturing processes. © 2018 American Institute of Chemical Engineers Biotechnol. Prog., 34:1566-1573, 2018.


Assuntos
Cromatografia/métodos , Proteína Estafilocócica A/química , Anticorpos Monoclonais/química , Reatores Biológicos
9.
Gut Pathog ; 9: 66, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29201148

RESUMO

The aim of this study was to generate a reference set of Salmonella enterica genomes isolated from wildlife from the United States and to determine the antimicrobial resistance and virulence gene profile of the isolates from the genome sequence data. We sequenced the whole genomes of 103 Salmonella isolates sampled between 1988 and 2003 from wildlife and exotic pet cases that were submitted to the Oklahoma Animal Disease Diagnostic Laboratory, Stillwater, Oklahoma. Among 103 isolates, 50.48% were from wild birds, 0.9% was from fish, 24.27% each were from reptiles and mammals. 50.48% isolates showed resistance to at least one antibiotic. Resistance against the aminoglycoside streptomycin was most common while 9 isolates were found to be multi-drug resistant having resistance against more than three antibiotics. Determination of virulence gene profile revealed that the genes belonging to csg operons, the fim genes that encode for type 1 fimbriae and the genes belonging to type III secretion system were predominant among the isolates. The universal presence of fimbrial genes and the genes encoded by pathogenicity islands 1-2 among the isolates we report here indicates that these isolates could potentially cause disease in humans. Therefore, the genomes we report here could be a valuable reference point for future traceback investigations when wildlife is considered to be the potential source of human Salmonellosis.

10.
Sci Rep ; 7(1): 12257, 2017 09 25.
Artigo em Inglês | MEDLINE | ID: mdl-28947833

RESUMO

In North America, antibiotic feed additives such as monensin and tylosin are added to the finishing diets of feedlot cattle to counter the ill-effects of feeding diets with rapidly digestible carbohydrates. While these feed additives have been proven to improve feed efficiency and reduce liver abscess incidence, how these products impact the gastrointestinal microbiota is not completely understood. In this study, we analyzed the impact of providing antibiotic feed additives to feedlot cattle using metagenome sequencing of treated and control animals. Our results indicate that use of antibiotic feed additives does not produce discernable changes at the phylum level. However, treated cattle had reduced abundance of gram-positive bacteria at the genus level. The abundance of Ruminococcus, Erysipelotrichaceae and Lachnospiraceae in the gut of treated steers was reduced. Functional analysis of the data indicates that there was only minimal impact due to the treatment in the rumen. Genes involved in detoxification were significantly increased in the rumen of AB steers. But the relative abundance of these genes was < 0.3%. However, our results did not show any correlation between the presence of antimicrobial resistance genes in the gut microbiota and the administration of antibiotic feed additives.


Assuntos
Ração Animal , Antibacterianos/administração & dosagem , Suplementos Nutricionais , Farmacorresistência Bacteriana/efeitos dos fármacos , Microbioma Gastrointestinal/efeitos dos fármacos , Animais , Bactérias/classificação , Bactérias/genética , Bovinos , Genes Bacterianos , Metagenômica , América do Norte
11.
Biotechnol Prog ; 33(4): 867-878, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27977910

RESUMO

Process intensification in biomanufacturing has attracted a great deal of interest in recent years. Manufacturing platform improvements leading to higher cell density and bioreactor productivity have been pursued. Here we evaluated a variety of intensified mammalian cell culture processes for producing monoclonal antibodies. Cell culture operational modes including fed-batch (normal seeding density or high seeding density with N-1 perfusion), perfusion, and concentrated fed-batch (CFB) were assessed using the same media set with the same Chinese Hamster Ovary (CHO) cell line. Limited media modification was done to quickly fit the media set to different operational modes. Perfusion and CFB processes were developed using an alternating tangential flow filtration device. Independent of the operational modes, comparable cell specific productivity (fed-batch: 29.4 pg/cell/day; fed-batch with N-1 perfusion: 32.0 pg/cell/day; perfusion: 31.0 pg/cell/day; CFB: 20.1 - 45.1 pg/cell/day) was reached with similar media conditions. Continuous media exchange enabled much higher bioreactor productivity in the perfusion (up to 2.29 g/L/day) and CFB processes (up to 2.04 g/L/day), compared with that in the fed-batch processes (ranging from 0.39 to 0.49 g/L/day), largely due to the higher cell density maintained. Furthermore, media cost per gram of antibody produced from perfusion was found to be highly comparable with that from fed-batch; and the media cost for CFB was the highest due to the short batch duration. Our experimental data supports the argument that media cost for perfusion process could be even lower than that in a fed-batch process, as long as sufficient bioreactor productivity is achieved. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 33:867-878, 2017.


Assuntos
Técnicas de Cultura Celular por Lotes/economia , Técnicas de Cultura Celular por Lotes/métodos , Reatores Biológicos/economia , Meios de Cultura/economia , Animais , Células CHO , Contagem de Células , Cricetulus
12.
J Int Adv Otol ; 12(3): 332-336, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27897130

RESUMO

Potassium-titanyl-phosphage (KTP) lasers possess many characteristics suitable for otologic surgery. The objective of this report is to provide recommendations on the use of KTP laser for cholesteatoma surgery based on a narrative review of currently available evidence. PubMed and the Cochrane Review of randomized control trials were searched for relevant publications on efficacy and adverse effects and relevant articles appraised by the authors using Oxford Centre for Evidence-based Medicine criteria for recommendations. The potential benefits of KTP laser in cholesteatoma surgery include reduced rates of residual cholesteatoma and improved hearing outcomes. Cholesteatoma may be more effectively removed using KTP laser than using mechanical dissection alone. Reduced rates of residual cholesteatoma have been reported with KTP laser with level 2 evidence. In addition, KTP laser may facilitate the removal of cholesteatoma without the risk of mechanical trauma. This potentially allows for improved postoperative hearing outcomes through a) minimizing cochlear trauma and reducing sensorineural hearing loss and b) reducing the need for disruption of an intact ossicular chain. Currently, level 4 evidence exists to support improved postoperative hearing outcomes with the use of KTP laser. KTP laser use appears to be safe in otologic surgery if appropriate guidelines are followed. Current evidence is sufficient to strongly recommend KTP laser use for the prevention of residual cholesteatoma (Grade B recommendation) and an option for KTP laser use for optimizing hearing outcomes (Grade C recommendation).


Assuntos
Colesteatoma da Orelha Média/cirurgia , Lasers de Estado Sólido/uso terapêutico , Humanos , Seleção de Pacientes , Resultado do Tratamento
13.
Acta Orthop Traumatol Turc ; 50(3): 309-14, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27130387

RESUMO

OBJECTIVE: The aim of this study was to assess the effect of education and use of a referral protocol on fracture clinic referral pathways, function, and patient care in the emergency department. METHODS: At Craigavon Area Hospital, a district general hospital, 58 new patient referrals were reviewed by the attending orthopedic surgeon at the fracture clinic. Each case was reviewed with regards to diagnosis, appropriateness of review time, and actual review time. Following this, the senior author performed a 1-hour teaching program in the ED utilizing a referral protocol. The study was then repeated in 63 patients to evaluate any improvement in patient treatment. RESULTS: Following the teaching program, a statistically significant improvement was found in interpretation of protocol (p=0.02), review time suggested (<0.00), and proportion of patients that actually receive an appropriate review time (p=0.004). No significant change was found with regards to grade of ED clinician referring the patient. CONCLUSION: The use of a simple education program and referral protocol may provide a significant improvement in appropriateness of patient referrals in the emergency department. This leads to a significant increase in patients referred with correct diagnoses, timeliness of review times, and subsequently improved patient care.


Assuntos
Protocolos Clínicos , Serviço Hospitalar de Emergência/organização & administração , Corpo Clínico/educação , Assistência ao Paciente/normas , Encaminhamento e Consulta/normas , Hospitais Gerais , Humanos , Irlanda do Norte
14.
Adv Exp Med Biol ; 875: 391-8, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26610983

RESUMO

We experimentally played back tones and sweeps to captive herring (Clupea harengus) in a net pen and measured the collective response of a large and a small group of fish using a camera, echo sounder, and multibeam sonar. The playbacks ranged in frequency from 160 to 500 Hz and 131 to 147 dB re 1 µPa in received sound pressure level. Herring behavior was scored by a team that blindly evaluated the observations. Overall, the responses were modest. Stronger reactions were observed at higher source levels, lower frequencies, and smaller school sizes, but there was no effect on signal rise time.


Assuntos
Comportamento Animal/fisiologia , Peixes/fisiologia , Som , Animais
15.
Arch Trauma Res ; 4(2): e27123, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26101764

RESUMO

BACKGROUND: At Altnagelvin, a district general hospital in Northern Ireland, we have observed that a significant number of hip fracture admissions are later readmitted for treatment of other medical conditions. These readmissions place increasing stress on the already significant burden that orthopedic trauma poses on national health services. OBJECTIVES: The aim of this study was to review a series of consecutive patients managed at our unit at least 1 year prior to the onset of the study. Also, we aimed to identify predictors for raised admission rates following treatment for hip fracture. PATIENTS AND METHODS: We reviewed a prospective fracture database and online patient note system for patient details, past medical history, discharge destination and routine blood tests for any factors that may influence readmission rates up to 1 year. Data were analyzed using SPSS software. RESULTS: Over 2 years, 451 patients were reviewed and 23 were managed conservatively. There was a 1-year readmission rate of 21%. Most readmission diagnoses were medical including bronchopneumonia, falls, urosepsis, cardiac exacerbations and stroke. Prolonged length of stay and discharge to a residential, fold or nursing home were found to increase readmission rate. Readmission diagnoses closely reflected the perioperative diagnoses that prolonged length of stay. Increased odds radio and risk of readmission were also found with female gender, surgery with a cephalomedullary nail, hip hemiarthroplasty or total hip replacement, time to surgery < 36 hours, alcohol consumption, smoking status, Hb drop > 2 g/dL and also if a blood transfusion was received. CONCLUSIONS: Our results indicate that hip fracture treatment begins at acute fracture clerk in, with consideration of comorbid status and ultimate discharge planning remaining significant predictors for morbidity and subsequent readmission.

16.
Psychiatry Res ; 228(3): 626-32, 2015 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-26099655

RESUMO

Childhood trauma (CT) and psychosis may be associated. Drawing on the dissociation and social psychological literature, the current study examined the mediating role of structural aspects of self in explaining the relationship between childhood trauma and psychosis. Twenty-nine individuals with psychosis were compared with 31 healthy volunteers regarding childhood trauma, dissociation and self-concept clarity (SCC). High rates of maltreatment were found in the psychosis sample. Additionally, clinical participants reported more dissociation and less self-concept clarity. Mediational analyses were carried out on pooled data from across both clinical and non-clinical samples. These suggested that the influence of physical neglect in increasing the likelihood of experiencing psychosis was explicable through the effects of increased dissociation. Self-concept clarity mediated the relationship between psychosis and total childhood trauma, emotional abuse, physical abuse, emotional and physical neglect. Furthermore, dissociation and self-concept clarity were strongly correlated providing evidence that they may form a unitary underlying concept of 'self-concept integration'. The study provides further evidence of the link between childhood trauma and psychosis. Self-concept integration may be adversely affected by negative childhood experiences, which increases psychosis risk. Methodological limitations, clinical implications and suggestions for future research are considered.


Assuntos
Transtornos Dissociativos/psicologia , Transtornos Psicóticos/psicologia , Autoimagem , Transtornos de Estresse Pós-Traumáticos/psicologia , Adolescente , Adulto , Criança , Maus-Tratos Infantis/psicologia , Feminino , Humanos , Masculino , Fatores de Risco , Estatística como Assunto , Inquéritos e Questionários , Adulto Jovem
17.
Vaccine ; 33(15): 1890-6, 2015 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-25698492

RESUMO

BACKGROUND: The safety and immunogenicity of a replication deficient adenovirus serotype 35 tuberculosis (TB) vaccine containing gene inserts for Antigens (Ag) 85A, Ag85B and TB10.4 (AERAS-402/AD35.TB-S) was evaluated in previously BCG vaccinated, HIV-infected South African adults with baseline CD4 counts >350 cells/mm(3). METHODS: Subjects were randomized (1:1) to receive two doses of either intramuscular AERAS-402/AD35.TB-S or placebo at month 0 and at month 1. Participants were monitored for adverse events 28 days after each vaccination and for serious adverse events over 12 months. CD4(+) and CD8(+) T-cell and antibody responses to vaccine antigens were evaluated post first and second vaccination. RESULTS: 26 subjects were randomly assigned to receive AERAS-402/AD35.TB-S (N=13) or placebo (N=13). The mean age was 29.0 years, all were Black-African, 88.5% were female, 46.2% were QuantiFERON Test (QFT) positive at baseline, and the median CD4 count was 559.5 cells/mm(3), all similar by treatment group. All subjects received their first vaccination and 24 subjects received their second vaccination. Injection site reactions and some systemic reactions were reported more commonly in the AERAS-402/AD35.TB-S versus placebo recipients. AERAS-402/AD35.TB-S did not appear to influence CD4 counts and HIV-1 viral load over the course of study follow-up. AERAS-402/AD35.TB-S induced a mixed CD4(+) T-cell and CD8(+) T-cell responses to Ag85B. The CD4(+) T-cell responses peaked to Ag85A and Ag85B 14 days after the second vaccination and had declined by Day 182. AERAS-402/AD35.TB-S predominantly induced CD4(+) T-cells expressing three (IFN-γ, TNF, IL-2) or two (IL-2 and TNF) cytokines, two weeks after the last vaccination, which did not differ by baseline Quantiferon test status. AERAS-402/AD35.TB-S induced strong Ag85A and Ag85B specific antibody responses, particularly after the second vaccination. CONCLUSION: AERAS-402/AD35.TB-S was well tolerated, safe and induced predominantly polyfunctional CD4(+) and CD8(+) T-cell responses to vaccine.


Assuntos
Antígenos de Bactérias/imunologia , Vacina BCG/imunologia , Infecções por HIV/imunologia , Vacinas contra a Tuberculose/efeitos adversos , Vacinas contra a Tuberculose/imunologia , Tuberculose/prevenção & controle , Adulto , Anticorpos Antibacterianos/sangue , Contagem de Linfócito CD4 , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos , Método Duplo-Cego , Feminino , Humanos , Injeções Intramusculares , Interferon gama/imunologia , Interleucina-2/imunologia , Masculino , Pessoa de Meia-Idade , Mycobacterium tuberculosis/imunologia , África do Sul , Vacinas contra a Tuberculose/administração & dosagem , Fator de Necrose Tumoral alfa/imunologia , Vacinação , Vacinas de DNA , Carga Viral , Adulto Jovem
18.
Front Neurol ; 5: 258, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25538677

RESUMO

Interventions to treat cerebral palsy should be initiated as soon as possible in order to restore the nervous system to the correct developmental trajectory. One drawback to this approach is that interventions have to undergo exceptionally rigorous assessment for both safety and efficacy prior to use in infants. Part of this process should involve research using animals but how good are our animal models? Part of the problem is that cerebral palsy is an umbrella term that covers a number of conditions. There are also many causal pathways to cerebral palsy, such as periventricular white matter injury in premature babies, perinatal infarcts of the middle cerebral artery, or generalized anoxia at the time of birth, indeed multiple causes, including intra-uterine infection or a genetic predisposition to infarction, may need to interact to produce a clinically significant injury. In this review, we consider which animal models best reproduce certain aspects of the condition, and the extent to which the multifactorial nature of cerebral palsy has been modeled. The degree to which the corticospinal system of various animal models human corticospinal system function and development is also explored. Where attempts have already been made to test early intervention in animal models, the outcomes are evaluated in light of the suitability of the model.

19.
J Urol ; 184(6): 2527-31, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21030049

RESUMO

PURPOSE: Sleep disordered breathing caused by tonsillar hypertrophy has been implicated as a cause of primary and secondary nocturnal enuresis in children. We prospectively studied the preoperative and postoperative rates of nocturnal and daytime incontinence in a group of children with tonsillar hypertrophy undergoing tonsillectomy compared to a matched control group undergoing surgery unrelated to the airway or urinary tract. MATERIALS AND METHODS: A total of 326 toilet trained children 3 to 15 years old were included, with 257 in the tonsillectomy group and 69 in the control group. Severity of tonsillar hypertrophy was graded preoperatively on a scale of 1 to 4. A voiding questionnaire regarding number of bedwetting and daytime incontinence episodes per week, voids per day, bowel movements per week, secondary or primary enuresis and family history was completed by parents preoperatively, and at 3 and 6 months postoperatively. RESULTS: Preoperatively the respective rates of nocturnal enuresis and daytime incontinence were 33% and 17% in the tonsillectomy group (p=0.89), and 35% and 14% in the control group (p=0.3). The respective cure rates for bedwetting at 3 and 6 months postoperatively were 40% and 50% in the tonsillectomy group (p=0.60), and 35% and 48% in the control group (p=0.61). Similarly no difference was seen in improvement or cure of daytime incontinence at 3 and 6 months postoperatively. CONCLUSIONS: We found no association between tonsillar hypertrophy and urinary incontinence before or after tonsillectomy.


Assuntos
Tonsila Faríngea/patologia , Enurese Noturna/terapia , Tonsilectomia , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Hipertrofia/complicações , Masculino , Enurese Noturna/etiologia , Estudos Prospectivos
20.
Open Nurs J ; 4: 1-8, 2010 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-20305746

RESUMO

Whilst the experience of a patient suicide is likely to have a significant impact upon the nurses who had been providing care, little work has actually explored this experience in any depth. In this article we explore how two psychiatric nurses construct and orient to accountability when talking of their experiences of a patient suicide. Discourse analysis was used to explore particular phases that the nurses oriented to in their accounts: scene setting; risk assessment; attributing for the suicide. Findings highlight the different, sometimes contradictory, ways the nurses attended to interactional concerns relating to implicit accountability and potential inferences of blame. Analysis of the nurses' talk can make a valuable contribution to understanding the nature and the impact of 'accountability' in a mental health setting and so help nurses and other professionals gain an insight into their practice. The results from this study suggest that as a consequence of internalising fundamentally unrealisable expectations regarding suicide prevention, nurses can hold themselves to blame raising significant concerns around their needs in terms of support, which may not be recognised. This paper also makes a valuable contribution to our methodological understanding and the value of using discourse analysis in this setting.

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