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1.
J Vasc Surg ; 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38823529

RESUMO

OBJECTIVE: Occlusive disease of the common femoral artery can generate profound lower extremity ischemia as the normal collateral pathways from the profunda to the superficial femoral artery cannot adequately develop. In patients with lifestyle-limiting claudication, isolated endarterectomy of the common femoral artery (CFE) is highly effective. As CFE does not provide direct, in-line flow to the plantar arch, it has been felt to provide inadequate revascularization to patients with chronic limb-threatening ischemia (CLTI). The purpose of this retrospective clinical study was to report and assess the natural history of selected patients with CLTI treated with isolated CFE (without concomitant infrainguinal revascularization). METHODS: Consecutive CFE performed in a large, urban hospital for CLTI between 2014-2021 were reviewed. Patient characteristics, limb, and anatomic stages using the Wound, Ischemia, foot Infection (WIfI) and Global Anatomic Staging Systems (GLASS) were tabulated. Limb-specific and survival-related endpoints were analyzed. RESULTS: 58 patients presenting with CLTI underwent isolated CFE (mean age 74±10 years; 62% male, 90% current or prior smoker). Comorbidities included diabetes (52%), coronary artery disease (55%), congestive heart failure (22%), and end-stage renal failure on hemodialysis (5%). Patients presented with either rest pain (36%) or tissue loss (64%); the latter group exhibited advanced limb threat (68% in WIfI stage 3 or 4). The majority of patients had associated severe infrainguinal disease (50% GLASS 3). After a median follow-up of 17 months (range 10-29 months), vascular reintervention was required in 7 patients (12%). One patient (2%) required major limb amputation after presentation in WIfI stage 4 (W3I3fI0). Indeed, WIfI stage 4 was a significant univariate predictor of the need for subsequent infrainguinal bypass (p=0.034). CONCLUSIONS: Isolated CFE as primary therapy in highly selected patients with CLTI was safe and effective. Index limb stage is predictive of the need for associated infrainguinal revascularization in this complex population.

2.
J Pharm Bioallied Sci ; 16(Suppl 1): S742-S744, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38595419

RESUMO

Background: Smoking is a well-established risk factor for periodontitis, a chronic inflammatory disease of the oral cavity. While smoking cessation has been linked to improved overall health, its specific impact on periodontal health and gingival inflammation in individuals with periodontitis remains less explored. Materials and Methods: We conducted a prospective cohort study involving 200 smokers diagnosed with periodontitis. Participants were divided into two groups: Group A received comprehensive smoking cessation interventions, including counseling and pharmacotherapy, while group B continued smoking without intervention. Periodontal health was assessed through clinical parameters, including probing depth (PD) and clinical attachment level (CAL), at baseline and 6 months post intervention. Gingival inflammation was evaluated using the Gingival Index (GI). Results: After 6 months, group A exhibited a significant reduction in mean PD (from 4.5 mm to 3.2 mm) and CAL (from 5.0 mm to 3.5 mm) compared to group B. Conversely, group B showed no significant change in these parameters. The GI score significantly decreased in group A (from 2.8 to 1.2) but remained unchanged in group B. Furthermore, group A demonstrated a higher rate of smoking cessation (72%) compared to group B (14%). Conclusion: Smoking cessation interventions play a crucial role in improving periodontal health and reducing gingival inflammation in smokers with periodontitis. The observed reductions in PD, CAL, and gingival inflammation highlight the potential benefits of smoking cessation on oral health outcomes in this high-risk population.

3.
J Am Coll Surg ; 238(2): 157-165, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-37796140

RESUMO

BACKGROUND: In 2006, Cancer Care Ontario created Surgical Oncology Standards for the delivery of hepatopancreatobiliary (HPB) surgery including hepatectomy and pancreaticoduodenectomy (PD). Our objective was to identify the impact of standardization on outcomes after HPB surgery in Ontario, Canada. STUDY DESIGN: This study was a population-level analysis of patients undergoing hepatectomy or PD (2003 to 2019). Logistic regression models were used to compare 30- and 90-day mortality and length of stay (LOS) before (2003 to 2006), during (2007 to 2011), and after (2012 to 2019) standardization. Interrupted time series models were used to co-analyze secular trends. RESULTS: A total of 7,904 hepatectomies and 5,238 PDs were performed. More than 80% of all cases were performed at a designated center (DC) before standardization. This increased to >98% in the poststandardization era. Median volumes at DCs increased from 55 to 67 hepatectomies/year and from 22 to 50 PDs/year over time. In addition, 30-day mortality after hepatectomy was 2.6% before standardization and 2.3% after standardization (p = 0.9); 30-day mortality after PD was 3.6% before standardization and 2.4% after standardization (p = 0.1). Multivariable analyses revealed a significant difference in 90-day mortality following PD poststandardization (4.3% vs 6.3%; adjusted odds ratio, 0.7; p = 0.03). Median LOS was shorter for hepatectomy (6 days vs 8 days) and PD (9 days vs 14 days; p < 0.0001) after standardization. Immediate and late effects on mortality and LOS were likely attributable to secular trends, which predated standardization. CONCLUSIONS: Standardization was associated with a higher volume of hepatectomy and PDs with further concentration of care at DCs. Pre-existing quality initiatives may have attenuated the effect of standardization on quality outcomes. Our data highlight the merits of a multifaceted provincial system for enabling consistent access to high quality HPB care throughout a region of 15 million people over a 16-year period.


Assuntos
Neoplasias , Complicações Pós-Operatórias , Humanos , Ontário , Estudos de Coortes , Estudos Retrospectivos , Tempo de Internação , Padrões de Referência
4.
Med ; 4(10): 668-686.e7, 2023 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-37572659

RESUMO

BACKGROUND: RH5 is a leading blood-stage candidate antigen for a Plasmodium falciparum vaccine; however, its safety and immunogenicity in malaria-endemic populations are unknown. METHODS: A phase 1b, single-center, dose-escalation, age-de-escalation, double-blind, randomized, controlled trial was conducted in Bagamoyo, Tanzania (NCT03435874). Between 12th April and 25th October 2018, 63 healthy adults (18-35 years), young children (1-6 years), and infants (6-11 months) received a priming dose of viral-vectored ChAd63 RH5 or rabies control vaccine. Sixty participants were boosted with modified vaccinia virus Ankara (MVA) RH5 or rabies control vaccine 8 weeks later and completed 6 months of follow-up post priming. Primary outcomes were the number of solicited and unsolicited adverse events post vaccination and the number of serious adverse events over the study period. Secondary outcomes included measures of the anti-RH5 immune response. FINDINGS: Vaccinations were well tolerated, with profiles comparable across groups. No serious adverse events were reported. Vaccination induced RH5-specific cellular and humoral responses. Higher anti-RH5 serum immunoglobulin G (IgG) responses were observed post boost in young children and infants compared to adults. Vaccine-induced antibodies showed growth inhibition activity (GIA) in vitro against P. falciparum blood-stage parasites; their highest levels were observed in infants. CONCLUSIONS: The ChAd63-MVA RH5 vaccine shows acceptable safety and reactogenicity and encouraging immunogenicity in children and infants residing in a malaria-endemic area. The levels of functional GIA observed in RH5-vaccinated infants are the highest reported to date following human vaccination. These data support onward clinical development of RH5-based blood-stage vaccines to protect against clinical malaria in young African infants. FUNDING: Medical Research Council, London, UK.


Assuntos
Vacinas Antimaláricas , Malária Falciparum , Adulto , Criança , Pré-Escolar , Humanos , Lactente , Adenovirus dos Símios , Anticorpos Antivirais , Vacinas Antimaláricas/efeitos adversos , Vacinas Antimaláricas/imunologia , Malária Falciparum/prevenção & controle , Raiva , Tanzânia , Adolescente , Adulto Jovem , Método Duplo-Cego
5.
Infect Dis Rep ; 15(4): 417-424, 2023 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-37489396

RESUMO

While the debate on the association between Enterobius vermicularis (E. vermicularis) and acute appendicitis has not been settled, a few case reports of this very rare encounter are beginning to come to light. E. vermicularis is one of the most common parasitic infections around the world, and acute appendicitis, on the other hand, is also a commonly encountered condition in general surgery. However, the association between these two conditions remains controversial. Here we present a case report of a young woman with appendicitis associated with E. vermicularis.

6.
Med Teach ; 45(2): 152-156, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-35944551

RESUMO

PURPOSE: Although health professions education (HPE) scholarship has flourished in recent decades, the influence of HPE journals has received little attention. This study examines the editorial policies and priorities of leading HPE journals. METHODS: Fourteen HPE journals with the highest impact factors were reviewed for their editorial aims, scope, intended readership, and priority topic areas. Text from journal websites was coded using thematic analysis. RESULTS: 10/14 HPE journals included in this study were linked to regional or national education societies. Two focussed predominantly on medicine, one on dentistry, one on nursing, one on nutrition, and the remaining nine on general HPE. Although journals differed in their projected aims and proposed readerships, four overarching editorial themes were identified: (1) methodological and theoretical rigor; (2) impact on practice; (3) global relevance; (4) advancing knowledge. CONCLUSIONS: Leading HPE journals share a number of priority areas and principles, implying some cohesion and consensus amongst the HPE scholarly community. These journals prioritise impact at the level of individual practitioners. Given the importance of policy level change in the development and reform of HPE around the world, the relative lack of focus on policy impact in HPE journals is worthy of further exploration.


Assuntos
Medicina , Publicações Periódicas como Assunto , Humanos , Políticas Editoriais , Bolsas de Estudo , Ocupações em Saúde/educação
7.
J Maxillofac Oral Surg ; 21(3): 759-764, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36274882

RESUMO

Introduction: Different techniques of the management of sagittal maxillary fractures have been described with different advantages and disadvantages. We herein present our experience and results of managing these cases by reversing pre-activated maxillary expanders and evaluation of its efficacy. Patient and Methods: A prospective study was conducted from April 2016 to February 2020 including all the patients managed for sagittal palatal fractures using the modified technique. The patients were evaluated for healing, occlusion and complications. Results: A total of five patients with sagittal palatal fracture were managed. The mean Glasgow Coma (GCS) score and injury severity score (ISS) of patients were 11.6 ± 2.4 and 15.2 ± 4.3, respectively. Both had a significant strong negative correlation with a correlation coefficient of - 0.889 (p = 0.44). The median duration for initiating the treatment for facial fractures was 2 days (range 2-12 days). All patients achieved satisfactory outcomes and tolerated this technique well. No obvious complications were found. Conclusion: This method could produce enough transversal force to reduce fractured fragments and then serve as an external fixator to maintain stability for bony healing.

8.
Clin Pract ; 12(2): 204-214, 2022 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-35314594

RESUMO

Pulmonary embolism (PE) is the third most common vascular disease in the US, a frequently underdiagnosed and potentially fatal condition where embolic material blocks one or more pulmonary arteries impairing blood flow. In this study, we aim to describe the prevalence, outcomes, and predictors of mortality of PE patients treated with mechanical (MT) and surgical thrombectomy (ST). This is a retrospective study using the Agency for Healthcare Research and Quality's HCUP NIS data from 2010−2018. We used the ninth and tenth revisions of the International Classification of Diseases clinical modification codes (ICD-9-CM and ICD-10-CM) to identify patients admitted with a primary diagnosis of PE (ICD-10-CM codes I26.02, I26.09, I26.92, I26.93, I26.94, and I26.99; ICD-9-CM codes 415.11, 415.13, and 415.19). We extracted demographics, hospital-level, and patient-level characteristics, and defined the severity of comorbid conditions using Deyo modification of the Elixhauser Comorbidity Index. The primary outcomes of interest were the utilization trends of PE (treated with MT and ST); the secondary outcomes were mortality, discharge to facility, peri-procedural complications, and length of hospital (LOS) stay; the tertiary outcome was to identify the predictors of in-hospital mortality. From 2010−2018, there were 1,627,718 hospitalizations for PE, of which 6531 (0.39%) underwent MT and 3465 (0.21%) underwent ST. The utilization trend of MT increased from 336 (0.20%) in 2010 to 1655 (0.87%) in 2018; the utilization trend of ST was 260 (0.15%) in 2010 and 430 (0.23%) in 2018. The unadjusted in-hospital mortality for MT was 9.1% with the mean LOS being 7(±0.3) days; for ST, mortality was 13.9% with a mean LOS of 13(±0.4) days. The occurrences of periprocedural complications for MT and ST were as follows: invasive mechanical ventilation was 13.8% and 32%; cardiopulmonary bypass was 3.3% and 68.3%; pulmonary embolectomy surgery was 1.7%; and bleeding complications were 1.4% and 3.4%. Predictors associated with in-hospital mortality for MT were: increasing age (OR 1.2, 95% CI 1.0−1.3, p < 0.026), female sex (OR 1.9, 95% CI 1.2−2.8, p < 0.004), large hospitals (OR 2.2, 95% 1.4−3.5, p < 0.001), and teaching hospitals (OR 1.8, 95% CI 1.1−3.1, p < 0.023). The predictor of in-hospital mortality for ST was increasing age (OR 1.2, 95% CI 1.0−1.4, p < 0.046). The number of MT procedures performed has rapidly increased over the past decade. Further studies are warranted to determine their rise and therapeutic use.

9.
BMJ Case Rep ; 15(2)2022 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-35140098

RESUMO

Necrotising scleritis is a rare, inflammatory condition with potentially devastating visual consequences. It can be associated with inflammatory and infectious causes, and has been linked to several different ocular procedures. We present a difficult case of a patient with surgically-induced necrotising scleritis following routine phacoemulsification cataract surgery, who developed a secondary Nocardia bacterial infection. He required a number of surgical interventions and prolonged antibiotic therapy, suffering recurrent scleral abscesses. A literature review accompanies our case report. Prompt recognition and adequate investigation for underlying inflammatory and infective causes are vital to maintain integrity of the globe and ensure suitable treatment of this challenging condition.


Assuntos
Extração de Catarata , Catarata , Nocardiose , Esclerite , Humanos , Masculino , Nocardiose/diagnóstico , Nocardiose/tratamento farmacológico , Esclera , Esclerite/diagnóstico , Esclerite/tratamento farmacológico , Esclerite/etiologia
10.
Cureus ; 13(10): e18432, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34737901

RESUMO

Myxomas, being the most common primary benign tumor among all cardiac tumors, occur rarely with a very low incidence rate. Myxomas can cause various clinical manifestations or can be diagnosed incidentally. Some patients with cardiac myxomas are completely asymptomatic. Cardiac myxomas cause life-threatening complications, thus early diagnosis is imperative. We are reporting a case of atrial myxoma in a 38-year-old female without any significant past medical history, who came to our clinic for cardiology evaluation prior to plastic surgery. The elliptical mobile mass, located in the left atrium with its attachment to the interatrial septum, was diagnosed by transthoracic echocardiography. The patient was referred for surgery and a minimally invasive surgical approach was chosen. A histological report confirmed the diagnosis of myxoma. The patient recovered well. Three years of follow-up did not reveal any signs of recurrence of the tumor. We are also analyzing 20 previously published cases of asymptomatic myxomas and myxomas treated with a minimally invasive surgical approach, reported in the PubMed database for the last 20 years (2001-2021) in the adult patient population (age 19 and over). The aim of this study is to highlight the asymptomatic presentation of cardiac myxomas and to underline the advantages of a minimally invasive surgical approach. In summary, asymptomatic cardiac myxomas are rare incidental findings. Attention to subtle symptoms during a physical exam and scrupulous history-taking can provide a clue to this diagnosis. Early diagnosis of cardiac myxomas is crucial to prevent life-threatening complications. Minimally invasive surgery is a promising alternative approach to standard open-heart surgery for treating cardiac myxomas, providing faster recovery and higher patient satisfaction with surgical care.

11.
Pan Afr Med J ; 38: 10, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33520079

RESUMO

Total abdominal hysterectomy is among the commonest gynaecologic surgeries observed in Africa. However, there exists a gap in published data to support this hypothesis. Information on hysterectomies reported from sub-Saharan Africa reflects mostly obstetric indications. A prospective hospital-based study was conducted in Dar es Salaam, Tanzania from March-October 2017. Women attending the facilities with clinical conditions necessitating abdominal hysterectomies were the target population. Each woman was followed from the time of planning for surgery until at most 72-hours post-surgery or discharge from the wards whichever came first. Continuous variables were summarized using median (with corresponding inter-quartile range). Categorical variables were summarized using frequency (%). Data outputs were created using SAS version 9.4. Verbal informal consent was sought from each individual prior to inclusion to this study. We recruited and prospectively followed-up 107 patients. Median age of participants was 42 (IQR: 37-47) years. Uterine leiomyoma (84.1%) was the leading indication for hysterectomy. Only about a third (30.8%) of followed-up women had provisional diagnoses at the time of surgery. None of the study participants reported receipt for confirmatory histological findings of her uterus up to the hospital discharge time post-surgery.


Assuntos
Histerectomia/estatística & dados numéricos , Leiomioma/cirurgia , Neoplasias Uterinas/cirurgia , Adulto , Feminino , Seguimentos , Hospitais , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Tanzânia
12.
Ann Med Surg (Lond) ; 60: 526-530, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33200030

RESUMO

INTRODUCTION: Involvement of the large vessels is rarely reported and poorly understood in cases of Corona virus disease-19 (COVID-19). The aim of this study is to present a series of cases with large vessel thrombosis (LVT). METHODS: This is a multicenter prospective case series study. The participants were consecutive in order. All the patients were diagnosed as cases of COVID-19 with documented LVT were included in the study. Large vessels were defined as any vessel equal or larger than popliteal artery. The mean duration of follow up was 4 months. RESULTS: The study included 22 cases, 19 (86.4%) cases were male, 3 (13.6%) patients were females. The age ranged from 23 to 76 with a mean of 48.4 years. Four (18.2%) cases had pulmonary embolism confirmed by IV contrast enhanced chest CT scan. All of the cases showed pulmonary parenchymal ground glass opacities (GGO) and high D-Dimers (ranging from 1267 to 6038 ng/ml with a mean of 3601 ng/ml). CONCLUSION: COVID-19 is a hidden risk factor of LVT that may endanger the patient's life and lead to major amputation. Despite therapeutic anticoagulants still all COVID-19 patients are at risk for LVT, a high index of suspicion should be created and with minimal symptoms surgical consultation should be obtained.

13.
Access Microbiol ; 2(6): acmi000124, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32974588

RESUMO

INTRODUCTION: Abiotrophia defectiva is a fastidious organism that has been implicated in severe infections such as endocarditis in immunocompetent patients. Modern tools are available to aid identification, but the main challenge remains clinical suspicion of A. defectiva . CASE PRESENTATION: An otherwise fit and well 65-year-old female presented with reduced vision, red eye and discomfort 2 days following routine left cataract surgery. She had visual acuity of light perception only, significant anterior chamber inflammation (including hypopyon) and limited fundal view. She was diagnosed with post-operative endophthalmitis and 0.1 ml of ceftazidime (2 mg/0.1 ml) and 0.1 ml vancomycin (2 mg/0.1 ml) were injected intravitreally after vitreous aspiration. Subconjunctival cefuroxime was also injected. A repeat injection was performed on day three of admission. Gram staining revealed Gram-positive long-chain cocci, which were identified as A. defectiva . The patient was discharged on oral ciprofloxacin 500 mg twice a day with oral prednisolone 60 mg once a day; this was tapered and stopped at 8 weeks post-discharge. The left eye received dexamethasone 0.1 % 6 times a day (again, tapered over 8 weeks), moxifloxacin 5 % 6 times a day and atropine 1 % twice a day. Vision improved to 6/12 unaided (6/9.5 with pinhole) at 9 weeks post-operatively, with a clear fundal view. CONCLUSION: We present a case of A. defectiva endophthalmitis following routine cataract surgery. To our knowledge, this is the first reported case in the UK and the fourth globally, which with prompt treatment ended with a good visual outcome.

14.
Asian Pac J Cancer Prev ; 20(2): 503-508, 2019 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-30803213

RESUMO

Background: The study aims to analyze Thymidylate Synthase (TS) and Dihydropyrimidine Dehydrogenase (DPD) Expressions on 5-Fluorouracil in Oral Squamous Cell Carcinoma (OSCC). Methods: 50 oral squamous cell carcinoma samples were taken from non-treated cancer patients at Hiroshima University Dental Hospital. The patients were investigated for TS, that included 36 males and 14 females. Additionally, 31 patients were evaluated for DPD that included 22 males and 9 females. Results: The samples had also undergone clinical and pathological evaluation, immunohistochemical staining, evaluation of immune-staining, enzymatic expression, and statistical analyses. Mean age of the population was 62.1 years. Conclusion: Over-expression of TS contributes significantly to the resistance of 5-FU treatment; while inhibition of intra-tumoral DPD increases the sensitivity level. TS levels are not only predictive of 5-FU response, but also prognostic in clinical value of non-treated cancer patients.


Assuntos
Carcinoma de Células Escamosas/enzimologia , Di-Hidrouracila Desidrogenase (NADP)/metabolismo , Resistencia a Medicamentos Antineoplásicos , Fluoruracila/uso terapêutico , Neoplasias Bucais/enzimologia , Recidiva Local de Neoplasia/enzimologia , Timidilato Sintase/metabolismo , Antimetabólitos Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/secundário , Estudos de Casos e Controles , Feminino , Seguimentos , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/tratamento farmacológico , Neoplasias Bucais/patologia , Invasividade Neoplásica , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Prognóstico , Estudos Prospectivos , Taxa de Sobrevida
15.
Int J Infect Dis ; 81: 176-183, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30772468

RESUMO

OBJECTIVES: Acute Respiratory Infection (ARI) is the most common cause of childhood morbidity and mortality in developing countries, including Haiti. Our objective was to detect pathogens found in children with ARI in rural Haiti to help develop evidence-based guidelines for treatment and prevention. METHODS: Retrospective study of students with ARI at four schools in rural Haiti. Viral and/or bacterial pathogens were identified by qPCR in 177 nasal swabs collected from April 2013 through November 2015. RESULTS: Most common viruses detected were Rhinovirus (36%), Influenza A (16%) and Adenovirus (7%), and bacteria were Streptococcus pneumoniae (58%) and Staphylococcus aureus (28%). Compared to older children, children aged 3-5 years had more Influenza A (28% vs. 9%, p=0.002) and Adenovirus detected (14% vs. 3%, p=0.01). Similarly, S. pneumoniae was greatest in children 3-5 years old (71% 3-5yrs; 58% 6-15 years; 25% 16-20 years; p=0.008). Children 3-10 years old presented with fever more than children 11-20 years old (22% vs 7%; p=0.02) and were more often diagnosed with pneumonia (28% vs 4%, p<0.001). CONCLUSIONS: Younger children had increased fever, pneumonia, and detection of Influenza A and S. pneumoniae. These data support the need for influenza and pneumococcus vaccination in early childhood in Haiti.


Assuntos
Infecções Respiratórias/epidemiologia , Infecções Estafilocócicas/epidemiologia , Viroses/epidemiologia , Vírus/isolamento & purificação , Doença Aguda/epidemiologia , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Haiti/epidemiologia , Humanos , Lactente , Masculino , Reação em Cadeia da Polimerase em Tempo Real , Infecções Respiratórias/microbiologia , Infecções Respiratórias/virologia , Estudos Retrospectivos , População Rural/estatística & dados numéricos , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/classificação , Staphylococcus aureus/genética , Staphylococcus aureus/isolamento & purificação , Streptococcus pneumoniae/genética , Streptococcus pneumoniae/isolamento & purificação , Streptococcus pneumoniae/fisiologia , Viroses/virologia , Vírus/classificação , Vírus/genética , Adulto Jovem
16.
Oncotarget ; 8(15): 25080-25096, 2017 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-28212575

RESUMO

BACKGROUND: Mucin glycoprotein 1 (MUC1) is a glycosylated transmembrane protein on epithelial cells. We investigate MUC1 as a therapeutic target in Barrett's epithelium (BE) and esophageal adenocarcinoma (EA) and provide proof of concept for a light based therapy targeting MUC1. RESULTS: MUC1 was present in 21% and 30% of significantly enriched pathways comparing BE and EA to squamous epithelium respectively. MUC1 gene expression was x2.3 and x2.2 higher in BE (p=<0.001) and EA (p=0.03). MUC1 immunohistochemical expression increased during progression to EA and followed tumor invasion. HuHMFG1 based photosensitive antibody drug conjugates (ADC) showed cell internalization, MUC1 selective and light-dependent cytotoxicity (p=0.0006) and superior toxicity over photosensitizer alone (p=0.0022). METHODS: Gene set enrichment analysis (GSEA) evaluated pathways during BE and EA development and quantified MUC1 gene expression. Immunohistochemistry and flow cytometry evaluated the anti-MUC1 antibody HuHMFG1 in esophageal cells of varying pathological grade. Confocal microscopy examined HuHMFG1 internalization and HuHMFG1 ADCs were created to deliver a MUC1 targeted phototoxic payload. CONCLUSIONS: MUC1 is a promising target in EA. Molecular and light based targeting of MUC1 with a photosensitive ADC is effective in vitro and after development may enable treatment of locoregional tumors endoscopically.


Assuntos
Adenocarcinoma/genética , Antineoplásicos Imunológicos/farmacologia , Neoplasias Esofágicas/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Imunoconjugados/farmacologia , Luz , Mucina-1/genética , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Biomarcadores , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Biologia Computacional , Progressão da Doença , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patologia , Perfilação da Expressão Gênica , Glicoproteínas/genética , Glicoproteínas/metabolismo , Humanos , Imuno-Histoquímica , Mucina-1/metabolismo , Gradação de Tumores , Metástase Neoplásica
17.
Eur J Nucl Med Mol Imaging ; 42(2): 288-301, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25391547

RESUMO

PURPOSE: Human epidermal growth factor receptor-2 (HER2) overexpression is a predictor of response to anti-HER2 therapy in breast and gastric cancer. Currently, HER2 status is assessed by tumour biopsy, but this may not be representative of the larger tumour mass or other metastatic sites, risking misclassification and selection of suboptimal therapy. The designed ankyrin repeat protein (DARPin) G3 binds HER2 with high affinity at an epitope that does not overlap with trastuzumab and is biologically inert. We hypothesized that radiolabelled DARPin G3 would be capable of selectively imaging HER2-positive tumours, and aimed to identify a suitable format for clinical application. METHODS: G3 DARPins tagged with hexahistidine (His6) or with histidine glutamate (HE)3 and untagged G3 DARPins were manufactured using a GMP-compatible Pichia pastoris protocol and radiolabelled with (125)I, or with (111)In via DOTA linked to a C-terminal cysteine. BALB/c mice were injected with radiolabelled G3 and tissue biodistribution was evaluated by gamma counting. The lead construct ((HE)3-G3) was assessed in mice bearing HER2-positive human breast tumour (BT474) xenografts. RESULTS: For both isotopes, (HE)3-G3 had significantly lower liver uptake than His6-G3 and untagged G3 counterparts in non-tumour-bearing mice, and there was no significantly different liver uptake between His6-G3 and untagged G3. (HE)3-G3 was taken forward for evaluation in mice bearing HER2-positive tumour xenografts. The results demonstrated that radioactivity from (111)In-(HE)3-G3 was better maintained in tumours and cleared faster from serum than radioactivity from (125)I-(HE)3-G3, achieving superior tumour-to-blood ratios (343.7 ± 161.3 vs. 22.0 ± 11.3 at 24 h, respectively). On microSPECT/CT, (111)In-labelled and (125)I-labelled (HE)3-G3 could image HER2-positive tumours at 4 h after administration, but there was less normal tissue uptake of radioactivity with (111)In-(HE)3-G3. Preadministration of trastuzumab did not affect the uptake of (HE)3-G3 by HER2-positive tumours. CONCLUSION: Radiolabelled DARPin (HE)3-G3 is a versatile radioligand with potential to allow the acquisition of whole-body HER2 scans on the day of administration.


Assuntos
Repetição de Anquirina , Complexos de Coordenação/farmacocinética , Compostos Radiofarmacêuticos/farmacocinética , Receptor ErbB-2/metabolismo , Tomografia Computadorizada de Emissão de Fóton Único , Animais , Linhagem Celular Tumoral , Feminino , Humanos , Radioisótopos de Índio/farmacocinética , Neoplasias Mamárias Experimentais/diagnóstico por imagem , Camundongos , Camundongos Endogâmicos BALB C , Ligação Proteica , Proteínas Recombinantes de Fusão/farmacocinética , Distribuição Tecidual
18.
Environ Monit Assess ; 186(12): 8509-16, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25182685

RESUMO

In 2010, a magnitude 7.0 earthquake struck Haiti, severely damaging the drinking and wastewater infrastructure and leaving millions homeless. Compounding this problem, the introduction of Vibrio cholerae resulted in a massive cholera outbreak that infected over 700,000 people and threatened the safety of Haiti's drinking water. To mitigate this public health crisis, non-government organizations installed thousands of wells to provide communities with safe drinking water. However, despite increased access, Haiti currently lacks the monitoring capacity to assure the microbial safety of any of its water resources. For these reasons, this study was designed to assess the feasibility of using a simple, low-cost method to detect indicators of fecal contamination of drinking water that could be implemented at the community level. Water samples from 358 sources of drinking water in the Léogâne flood basin were screened with a commercially available hydrogen sulfide test and a standard membrane method for the enumeration of thermotolerant coliforms. When compared with the gold standard method, the hydrogen sulfide test had a sensitivity of 65 % and a specificity of 93 %. While the sensitivity of the assay increased at higher fecal coliform concentrations, it never exceeded 88 %, even with fecal coliform concentrations greater than 100 colony-forming units per 100 ml. While its simplicity makes the hydrogen sulfide test attractive for assessing water quality in low-resource settings, the low sensitivity raises concerns about its use as the sole indicator of the presence or absence of fecal coliforms in individual or community water sources.


Assuntos
Água Potável/química , Monitoramento Ambiental/métodos , Sulfeto de Hidrogênio/análise , Terremotos , Haiti , Humanos , Microbiologia da Água , Qualidade da Água/normas , Abastecimento de Água/estatística & dados numéricos
19.
Sex Transm Dis ; 41(8): 486-92, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25013976

RESUMO

BACKGROUND: Oral human papillomavirus (HPV) is associated with a rising incidence of certain head and neck cancers, and oral sex has been associated with oral HPV. This study sought to identify more specific patterns of oral sexual activity, including self-inoculation, that are associated with oral HPV infections in young women. METHODS: A total of 1010 women attending a large university completed a computer-based questionnaire and provided oral specimens that were tested for any oral HPV using a Linear Array assay that detects any HPV as well as 37 HPV genotypes. Twenty-seven women provided additional samples up to 12 months after enrollment. Bivariable and multivariable analyses were conducted to identify oral sexual patterns and other risk factors associated with prevalent oral HPV. RESULTS: Nineteen women had prevalent oral HPV (1.9%), with 10 women (1%) having a type-specific infection. Oral HPV was significantly associated with lifetime coital sex partnership numbers (P = 0.03), lifetime and yearly oral sex partnership numbers (P < 0.01), and hand and/or sex toy transfer from genitals to mouth (P < 0.001). Oral HPV was also associated with greater use of alcohol, cigarettes, marijuana, and sharing of smoking devices, lipstick, or toothbrushes (P < 0.05 for each), with an apparent dose-response for alcohol use and smoking behavior, stratified by number of sexual partners. Of 7 women with prevalent HPV who provided follow-up samples, none had evidence of a persistent type-specific infection. CONCLUSIONS: These data provide additional evidence of transmission of oral HPV from oral sexual activity and also suggest possible transmission from self-inoculation or sharing of oral products.


Assuntos
Papillomavirus Humano 16/isolamento & purificação , Mucosa Bucal/patologia , Infecções por Papillomavirus/transmissão , Comportamento Sexual , Parceiros Sexuais , Consumo de Bebidas Alcoólicas/efeitos adversos , Carcinoma de Células Escamosas/prevenção & controle , Carcinoma de Células Escamosas/virologia , Feminino , Neoplasias de Cabeça e Pescoço/prevenção & controle , Neoplasias de Cabeça e Pescoço/virologia , Humanos , Fumar Maconha/efeitos adversos , Programas de Rastreamento , Mucosa Bucal/virologia , Higiene Bucal , Prevalência , Medição de Risco , Fatores de Risco , Fumar/efeitos adversos , Inquéritos e Questionários , Carga Viral , Adulto Jovem
20.
Radiother Oncol ; 111(2): 206-11, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24746564

RESUMO

BACKGROUND AND PURPOSE: Mast cells are involved in the pathogenesis of radiation fibrosis and may be a therapeutic target. The mechanism of increased mast cell number in relation to acute and late tissue responses in human skin was investigated. MATERIALS AND METHODS: Punch biopsies of skin 1 and 15-18 months after breast radiotherapy and a contralateral control biopsy were collected. Mast cells were quantified by immunohistochemistry using the markers c-Kit and tryptase. Stem cell factor (SCF) and collagen-1 expression was analysed by qRT-PCR. Clinical photographic scores were performed at post-surgical baseline and 18 months and 5 years post-radiotherapy. Primary human dermal microvascular endothelial cell (HDMEC) cultures were exposed to 2Gy ionising radiation and p53 and SCF expression was analysed by Western blotting and ELISA. RESULTS: Dermal mast cell numbers were increased at 1 (p=0.047) and 18 months (p=0.040) using c-Kit, and at 18 months (p=0.024) using tryptase immunostaining. Collagen-1 mRNA in skin was increased at 1 month (p=0.047) and 18 months (p=0.032) and SCF mRNA increased at 1 month (p=0.003). None of 16 cases scored had a change in photographic appearance at 5 years, compared to baseline. SCF expression was not increased in HDMECs irradiated in vitro. CONCLUSIONS: Increased mast cell number was associated with up-regulated collagen-1 expression in human skin at early and late time points. This increase could be secondary to elevated SCF expression at 1 month after radiotherapy. Although mast cells accumulate around blood vessels, no endothelial cell secretion of SCF was seen after in vitro irradiation. Modification of mast cell number and collagen-1 expression may be observed in skin at 1 and 18 months after radiotherapy in breast cancer patients with no change in photographic breast appearance at 5 years.


Assuntos
Neoplasias da Mama/radioterapia , Mastócitos , Lesões por Radiação , Pele/efeitos da radiação , Fator de Células-Tronco/metabolismo , Adulto , Idoso , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Contagem de Células , Células Cultivadas , Colágeno Tipo I/genética , Colágeno Tipo I/metabolismo , Células Endoteliais/efeitos da radiação , Feminino , Fibrose/etiologia , Fibrose/metabolismo , Fibrose/patologia , Humanos , Imuno-Histoquímica , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Proteínas Proto-Oncogênicas c-kit/metabolismo , RNA Mensageiro/metabolismo , Lesões por Radiação/metabolismo , Lesões por Radiação/patologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Pele/metabolismo , Pele/patologia , Fator de Células-Tronco/genética , Fatores de Tempo , Regulação para Cima
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