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1.
J Cutan Med Surg ; 25(3): 303-314, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33256431

RESUMO

Squamous cell carcinoma of the nail unit (SCCNU) is a rare neoplastic condition that involves multiple digits (polydactylous SCCNU) in only 3.9% of cases. Here, we report a case of polydactylous SCCNU and perform a comprehensive review of MEDLINE and Embase to collate 44 cases of polydactylous SCCNU reported to date. Polydactylous patients were younger on average (48 to 61-63 years) and had a longer diagnostic delay (44 vs 35.1 months) compared with reported monodactylous cases. Human papillomavirus (HPV) positivity was observed in 49% of cases, and the most common serotypes noted were 16 (25.8%), 73 (16.1%), 58 (9.7%), 18 (6.5%), and 33 (6.5%). Twenty percent of the cases were in immunosuppressed individuals who had a statistically significant lower age at diagnosis (39.33 years vs 51.12 years; P = .01) and diagnostic delay (2.50 months vs 132.46 months, P = .04). Patients with HPV positivity had a lower age at diagnosis (43.74 years vs 53.29 years, P = .04). Environmental exposures noted to be associated with polydactylous disease included X-rays, paint/solvents, soluble oils, and stagnant water. This comprehensive literature review serves to characterize polydactylous SCCNU and distinguish the differences in its characteristics to improve diagnosis and clinical recognition.


Assuntos
Carcinoma de Células Escamosas , Doenças da Unha , Neoplasias Cutâneas , Fatores Etários , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/etiologia , Carcinoma de Células Escamosas/imunologia , Carcinoma de Células Escamosas/virologia , Humanos , Doenças da Unha/diagnóstico , Doenças da Unha/etiologia , Doenças da Unha/imunologia , Doenças da Unha/virologia , Fatores de Risco , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/etiologia , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/virologia
2.
Dermatol Online J ; 26(7)2020 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-32898414

RESUMO

Ingredients found in facial moisturizers can impact a myriad of skin conditions, including sensitive skin syndrome and contact dermatitis. There is a paucity of evidence on the allergenic potential and marketing claims of facial moisturizers, posing challenges to clinician recommendation and consumer selection. In this study, we systematically evaluate the 100 top-selling sun protective facial moisturizers that claim to be natural, fragrance free, expert-approved, age preventing, beneficial for sensitive skin, and sun protective. Allergenic potential of these moisturizers is evaluated based on ingredients used and prices and consumer ratings are compared. Accordingly, 75 of 100 marketed at least one additional benefit. "Anti-aging" products had the highest average price ($14.99/oz) and "expert-approved" had the lowest ($5.91/oz). Consumer rating was highest for facial moisturizers that were "fragrance-free" (4.35/5.00) whereas products that were "natural" received the lowest ratings (3.49/5.00). The most prevalent allergens found in these moisturizers were ethylenediamine tetraacetic acid (EDTA), phenoxyethanol, and cetyl alcohol. "Expert-approved" products had the fewest average allergens in their ingredient lists (P=0.033), whereas products advertising "SPF" had significantly more (P<0.001). Marketing claims play a role in product sales and ratings. When recommending products, physicians should balance allergenic risk with affordability and consumer preferences.


Assuntos
Alérgenos , Cosméticos/efeitos adversos , Marketing , Comportamento do Consumidor , Cosméticos/química , Cosméticos/economia , Custos e Análise de Custo , Face , Humanos , Estados Unidos
3.
Am J Physiol Lung Cell Mol Physiol ; 319(3): L576-L584, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32755324

RESUMO

Prevention of bronchopulmonary dysplasia (BPD) in premature-birth babies continues to be an unmet medical need. Intramuscular vitamin A is currently employed in preterm neonates to prevent BPD but requires intramuscular injections in fragile neonates. We hypothesized that noninvasive inhaled delivery of vitamin A, targeted to lung, would be a more effective and tolerable strategy. We employed our well-established hyperoxia-injury neonatal rat model, exposing newborn rats to 7 days of constant extreme (95% O2) hyperoxia, comparing vitamin A dosed every 48 h via either aerosol inhalation or intramuscular injection with normoxic untreated healthy animals and vehicle-inhalation hyperoxia groups as positive and negative controls, respectively. Separately, similar vitamin A dosing of normoxia-dwelling animals was performed. Analyses after day 7 included characterization of alveolar histomorphology and protein biomarkers of alveolar maturation [surfactant protein C (SP-C), peroxisome proliferator-activated receptor (PPAR) γ, cholinephosphate cytidylyl transferase, vascular endothelial growth factor and its receptor, FLK-1, and retinoid X receptors (RXR-α, -ß, and -γ], apoptosis (Bcl2 and Bax) key injury repair pathway data including protein markers (ALK-5 and ß-catenin) and neutrophil infiltration, and serum vitamin A levels. Compared with intramuscular dosing, inhaled vitamin A significantly enhanced biomarkers of alveolar maturation, mitigated hyperoxia-induced lung damage, and enhanced surfactant protein levels, suggesting that it may be more efficacious in preventing BPD in extremely premature infants than the traditionally used IM dosing regimen. We speculate lung-targeted inhaled vitamin A may also be an effective therapy against other lung damaging conditions leading to BPD or, more generally, to acute lung injury.


Assuntos
Lesão Pulmonar Aguda/metabolismo , Displasia Broncopulmonar/metabolismo , Hiperóxia/metabolismo , Pulmão/metabolismo , Vitamina A/metabolismo , Animais , Animais Recém-Nascidos , Alvéolos Pulmonares/metabolismo , Surfactantes Pulmonares/metabolismo , Ratos
4.
J Sex Med ; 17(5): 1025-1032, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32199854

RESUMO

BACKGROUND: The definitive treatment for erectile dysfunction is the surgical implantation of a penile prosthesis, of which the most common type is the 3-piece inflatable penile prosthesis (IPP) device. IPP surgery in outpatient freestanding ambulatory surgical centers (ASC) is becoming more prevalent as payers and health systems alike look to reduce healthcare costs. AIM: To evaluate IPP surgical outcomes in an ASC as compared to contemporaneously-performed hospital surgeries. METHODS: A database of all patients undergoing IPP implantation by practitioners in the largest private community urology group practice in the United States, from January 1, 2013 to August 1, 2019, was prospectively compiled and retrospectively reviewed. Cohorts of patients having IPP implantation performed in the hospital vs ASC setting were compared. MAIN OUTCOME MEASURE: The primary outcome measure was to compare surgical data (procedural and surgical times, need for hospital transfer from ASC) and outcomes (risk for device infection, erosion, and need for surgical revision) between ASC and hospital-based surgery groups. RESULTS: A total of 923 patients were included for this analysis, with 674 (73%) having ASC-based surgery and 249 (27%) hospital-based, by a total of 33 surgeons. Median procedural (99.5 vs 120 minutes, P < .001) and surgical (68 vs 75 minutes, P < .001) times were significantly shorter in the ASC. While the risk for device erosion and need for surgical revision were similar between groups, there was no higher risk for prosthetic infection when surgery was performed in the ASC (1.7% vs 4.4% [hospital], P = .02), corroborated by logistic regression analysis (odds ratio 0.39, P = .03). The risk for postoperative transfer of an ASC patient to the hospital was low (0.45%). The primary reason for mandated hospital-based surgery was medical (51.4%), though requirement as a result of insurance directive (39.7%) was substantial. CLINICAL IMPLICATIONS: IPP implantation in the ASC is safe, has similar outcomes compared to hospital-based surgery with a low risk for need for subsequent hospital transfer. STRENGTHS & LIMITATIONS: The strengths of this study include the large patient population in this analysis as well as the real-world nature of our practice. Limitations include the retrospective nature of the review as well as the potential for residual confounding. CONCLUSION: ASC-based IPP implantation is safe, with shorter surgical and procedural times compared to those cases performed in the hospital setting, with similar functional outcomes. These data suggest no added benefit to hospital-based surgery in terms of prosthetic infection risk. Weinberg AC, Siegelbaum MH, Lerner BD, et al. Inflatable Penile Prosthesis in the Ambulatory Surgical Setting: Outcomes From a Large Urological Group Practice. J Sex Med 2020;17:1025-1032.


Assuntos
Disfunção Erétil , Prática de Grupo , Implante Peniano , Prótese de Pênis , Disfunção Erétil/cirurgia , Humanos , Masculino , Estudos Retrospectivos
5.
Eur J Heart Fail ; 22(9): 1684-1693, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-31975496

RESUMO

AIM: Istaroxime is a first-in-class agent which acts through inhibition of the sarcolemmal Na+ /K+ pump and activation of the SERCA2a pump. This study assessed the effects of a 24 h infusion of istaroxime in patients hospitalised for acute heart failure (AHF). METHODS AND RESULTS: We included patients hospitalised for AHF with left ventricular ejection fraction ≤40% and E/e' > 10. Patients were randomised to a 24 h intravenous infusion of placebo or istaroxime at doses of 0.5 µg/kg/min (cohort 1: placebo n = 19; istaroxime n = 41) or 1.0 µg/kg/min (cohort 2: placebo n = 20, istaroxime n = 40). The primary endpoint of change in E/e' ratio from baseline to 24 h decreased with istaroxime vs. placebo (cohort 1: -4.55 ± 4.75 istaroxime 0.5 µg/kg/min vs. -1.55 ± 4.11 placebo, P = 0.029; cohort 2: -3.16 ± 2.59 istaroxime 1.0 µg/kg/min vs. -1.08 ± 2.72 placebo, P = 0.009). Both istaroxime doses significantly increased stroke volume index and decreased heart rate. Systolic blood pressure increased with istaroxime, achieving significance with the high dose. Self-reported dyspnoea and N-terminal pro-brain natriuretic peptide improved in all groups without significant differences between istaroxime and placebo. No significant differences in cardiac troponin absolute values or clinically relevant arrhythmias were observed during or after istaroxime infusion. Serious cardiac adverse events (including arrhythmias and hypotension) did not differ between placebo and istaroxime groups. The most common adverse events were injection site reactions and gastrointestinal events, the latter primarily with istaroxime 1.0 µg/kg/min. CONCLUSIONS: In patients hospitalised for AHF with reduced ejection fraction, a 24 h infusion of istaroxime improved parameters of diastolic and systolic cardiac function without major cardiac adverse effects.


Assuntos
Etiocolanolona/análogos & derivados , Insuficiência Cardíaca , Método Duplo-Cego , Etiocolanolona/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Humanos , Volume Sistólico , Função Ventricular Esquerda
6.
Sex Med Rev ; 8(2): 338-347, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31562047

RESUMO

INTRODUCTION: Erectile dysfunction is a common problem that may be definitively treated with the implantation of an inflatable penile prosthesis (IPP). The preponderance of available data on IPP surgery derives from institutional studies, most notably from academic centers or large single-surgeon series, where the majority of procedures are performed in a hospital setting. Because insurance companies and health systems look to reduce health care costs, IPP surgery in outpatient freestanding ambulatory surgery centers (ASC) is becoming more prevalent. AIM: To review the utility of surgery in an ASC setting and to explore its role in the modern practice of urology, focusing on IPP implantation. METHODS: A critical review was performed of the literature on ambulatory surgery, with specific focus on IPP surgery, using the PubMed database. Key search terms and phrases included erectile dysfunction, penile prosthesis, ambulatory surgery, ambulatory surgery center, outpatient surgery. MAIN OUTCOME MEASURE: The main outcome measure was the use of IPP implantation in an ASC. RESULTS: In contemporary surgical practice, the implementation of ambulatory surgery in free-standing centers is increasing. The principal benefits include reducing cost and improving efficiency. Studies on the modern use of IPPs support the prospect of implantation in an ambulatory setting, which can achieve similar outcomes to surgeries classically performed in the inpatient hospital setting. Novel approaches to anesthesia, surgical, and nursing care have revolutionized IPP surgery so that it can now be safely and effectively performed in the ambulatory setting. CONCLUSION: The role of ambulatory IPP implantation has increased, with the majority of cases being performed outside the hospital. Although there will always be a need for hospital-based surgery, such as significant medical comorbidities, more studies demonstrating the safety and feasibility of ambulatory surgery are needed. For those men who would otherwise be candidates for ambulatory surgery but whose insurance mandates hospital-based treatment, such studies proving utility, safety, and reduced cost could inspire policy change and broaden the ambulatory practice of IPP surgery. Segal RL, Siegelbaum MH, Lerner BD, et al. Inflatable Penile Prosthesis Implantation in the Ambulatory Setting: A Systematic Review. Sex Med Rev 2020;8:338-347.


Assuntos
Assistência Ambulatorial , Disfunção Erétil/cirurgia , Implante Peniano , Humanos , Masculino , Implante Peniano/métodos
7.
BMC Pediatr ; 19(1): 147, 2019 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-31078143

RESUMO

BACKGROUND: Current guidelines for management of respiratory distress syndrome (RDS) recommend continuous positive airway pressure (CPAP) as the primary mode of respiratory support even in the most premature neonates, reserving endotracheal intubation (ETI) for rescue surfactant or respiratory failure. The incidence and timing of ETI in practice is poorly documented. METHODS: In 27 Level III NICUs in the US (n = 19), Canada (n = 3) and Poland (n = 5), demographics and baseline characteristics, respiratory support modalities including timing of ETI, administration of surfactant and caffeine/other methylxanthines, and neonatal morbidities were prospectively recorded in consecutive preterm neonates following written parental consent. Infants were divided into three groups according to gestational age (GA) at birth, namely 26-28, 29-32 and 33-34 weeks. Statistical comparisons between groups were done using Chi-Square tests. RESULTS: Of 2093 neonates (US = 1507, 254 Canada, 332 Poland), 378 (18%) were 26-28 weeks gestational age (GA), 835 (40%) were 29-32 weeks, and 880 (42%) were 33-34 weeks. Antenatal steroid use was 81% overall, and approximately 89% in neonates ≤32 weeks. RDS incidence and use of ventilatory or supplemental oxygen support were similar across all sites. CPAP was initiated in 43% of all infants, being highest in the 29-32-week group, with a lower proportion in other GA categories (p < 0.001). The overall rate of ETI was 74% for neonates 26-28 weeks (42% within 15 min of birth, 49% within 60 min, and 57% within 3 h), 33% for 29-32 weeks (13 16 and 21%, respectively), and 16% for 33-34 weeks (5, 6 and 8%, respectively). Overall intubation rates and timing were similar between countries in all GAs. Rates within each country varied widely, however. Across US sites, overall ETI rates in 26-28-week neonates were 30-60%, and ETI within 15 min varied from 0 to 83%. Similar within 15-min variability was seen at Polish sites (22-67%) in this GA, and within all countries for 29-32 and 33-34-week neonates. CONCLUSION: Despite published guidelines for management of RDS, rate and timing of ETI varies widely, apparently unrelated to severity of illness. The impact of this variability on outcome is unknown but provides opportunities for further approaches which can avoid the need for ETI.


Assuntos
Pressão Positiva Contínua nas Vias Aéreas/métodos , Idade Gestacional , Recém-Nascido Prematuro , Unidades de Terapia Intensiva Neonatal , Síndrome do Desconforto Respiratório do Recém-Nascido/terapia , Manuseio das Vias Aéreas , Canadá , Distribuição de Qui-Quadrado , Estudos de Coortes , Feminino , Humanos , Recém-Nascido , Internacionalidade , Masculino , Polônia , Gravidez , Prognóstico , Estudos Prospectivos , Surfactantes Pulmonares/administração & dosagem , Síndrome do Desconforto Respiratório do Recém-Nascido/diagnóstico , Síndrome do Desconforto Respiratório do Recém-Nascido/mortalidade , Medição de Risco , Taxa de Sobrevida , Resultado do Tratamento , Estados Unidos
8.
J Clin Aesthet Dermatol ; 12(2): 37-38, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30881582

RESUMO

The practice of adorning the body with permanent ink dates back to the late Neolithic period. Today, a large proportion of the younger generation has at least one tattoo. Despite the recent popularity of tattoos, there are prolific reports within the literature detailing the adverse cutaneous reactions that occur following the intradermal injection of tattoo inks. Such reactions can occur immediately or years later. In addition to these known reactions, consumer preference for "animal-friendly" products has shifted the ingredients used in tattoos and has ushered in the era of "vegan tattoos." Because of its recent emergence and the lack of regulation of intradermal pigment by the United States Food and Drug Administration, we remain unsure of the potential reactions of these new ingredients. Currently, we can only predict complications by extrapolating from the known reactions of the topical administration of these same plant-based ingredients. In this article, we elucidate some potential reactions in an effort to warn the dermatologic community of the need to educate patients and encourage Federal reporting and regulation.

9.
Subst Use Misuse ; 54(2): 177-184, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30422042

RESUMO

BACKGROUND: Recent research indicates that there are widespread differences between men and women's Early Maladaptive Schemas (EMSs) in alcohol dependent populations. This study examined this claim. OBJECTIVE: The purpose of this study was to examine differences between men and women's EMSs in an Australian clinical sample who had sought treatment specifically for alcohol dependence. METHODS: A total of 111 men and 114 women completed the Young Schema Questionnaire-Long Form (YSQ-L3) between 2012 and 2015 in order to assess them on 18 EMSs. RESULTS: Despite previous findings suggesting that women report higher levels across a number of EMSs, the strongest evidence pointed to women scoring significantly higher than men on the EMS of self-sacrifice (the tendency to excessively help others whilst continually sacrificing one's own needs). Smaller differences between men and women were noted for the subjugation and failure EMSs. Conclusions/Importance: With the exception regarding the finding that woman scored higher on the self-sacrifice EMS than men, the homogeneity of the remaining EMS scores across men and women found in this study support the use of inter-gender group Schema Therapy (ST) with alcohol-dependent adults in Australia.


Assuntos
Adaptação Psicológica , Alcoolismo/psicologia , Adulto , Idoso , Austrália , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores Sexuais , Inquéritos e Questionários , Adulto Jovem
10.
Am J Clin Dermatol ; 20(1): 97-114, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30361953

RESUMO

Diabetes mellitus is one of the most prevalent chronic diseases in the USA. If uncontrolled, diabetes can lead to devastating complications. Diabetes medications and medical devices largely contribute to the significant financial expense that the disease inflicts on affected individuals and society. Alongside significant economic burden, there are numerous cutaneous adverse effects associated with diabetes medications and medical devices. Despite the large and increasing number of individuals living with diabetes and the wide use of the related medications and medical devices, there is limited literature that comprehensively documents their cutaneous adverse effects. These cutaneous adverse effects are significant as they can worsen glycemic control, increase disease distress, and may increase risk of associated complications. Thus, it is important that providers can recognize these cutaneous adverse effects, identify the culprit agents, and can properly manage them. In this article, we provide a critical review of the cutaneous adverse effects of medications and devices used in the management of diabetes and provide insight into risk factors and prevention and an overview of therapeutic management. An emphasis is placed on clinical recognition and treatment for use of the medical providers who, regardless of practice setting, will treat patients with diabetes.


Assuntos
Automonitorização da Glicemia/efeitos adversos , Diabetes Mellitus/tratamento farmacológico , Toxidermias/etiologia , Hipoglicemiantes/efeitos adversos , Sistemas de Infusão de Insulina/efeitos adversos , Glicemia/análise , Automonitorização da Glicemia/instrumentação , Diabetes Mellitus/sangue , Humanos , Hipoglicemiantes/administração & dosagem , Fatores de Risco
11.
Int J Dermatol ; 58(8): 871-879, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30569580

RESUMO

Extramammary Paget's disease (EMPD) is a rare cutaneous malignancy. The disease typically affects older individuals aged 60-80 years and is seen most frequently in postmenopausal Caucasian women and Asian men. EMPD exhibits a predilection for the genital and perianal regions and may be associated with an underlying carcinoma in adjacent organs. EMPD presents a challenge in both diagnosis and management. Often treated empirically as various dermatitides, the correct diagnosis is frequently delayed by many years. Following diagnosis, an extensive search for an associated malignancy should be initiated. If invasive disease is present on biopsy, a sentinel lymph node biopsy may guide further treatment. Mohs micrographic surgery appears to be superior to wide local excision when considering tissue sparing ability and disease recurrence. Nonsurgical interventions have also been investigated with varied results. Regardless of treatment method, long-term follow-up is recommended to monitor for local disease recurrence, development of internal malignancy, regional lymphadenopathy, or distant metastasis.


Assuntos
Recidiva Local de Neoplasia/prevenção & controle , Doença de Paget Extramamária/diagnóstico , Neoplasias Cutâneas/diagnóstico , Administração Tópica , Assistência ao Convalescente , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/administração & dosagem , Dermatite/diagnóstico , Diagnóstico Diferencial , Feminino , Genitália/patologia , Humanos , Metástase Linfática/diagnóstico , Metástase Linfática/patologia , Pessoa de Meia-Idade , Cirurgia de Mohs , Recidiva Local de Neoplasia/diagnóstico , Doença de Paget Extramamária/patologia , Doença de Paget Extramamária/terapia , Períneo/patologia , Fotoquimioterapia , Biópsia de Linfonodo Sentinela , Pele/patologia , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/terapia , Resultado do Tratamento
13.
Photodiagnosis Photodyn Ther ; 21: 58-62, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29102653

RESUMO

BACKGROUND: Oral vismodegib therapy and photodynamic therapy (PDT) are non-invasive treatments for basal cell carcinoma (BCC) with overlapping utility in widespread BCCs and patients who are poor surgical candidates. There is no published study to date investigating the combination use of PDT with vismodegib to optimize individual response rates. OBJECTIVE: To evaluate the combination of red light PDT and vismodegib therapy in patients with multiple nodular BCCs. The primary objective was to determine the safety of this combination therapy. Secondary outcomes included evaluation of the overall response rate, treatment-related pain, and cosmesis. METHODS: An open label pilot study of immunocompetent patients with multiple BCCs treated with 3 months of continuous vismodegib therapy (150 mg daily) and 3 consecutive ALA PDT sessions. Outcomes were assessed following each PDT session and 30 days post-treatment. RESULTS: Four patients with multiple nodular BCC (median=5) were enrolled in the trial between January and August of 2016. Three patients completed the full intervention phase trial and a total of 19 lesions were treated. One patient completed 2 months of vismodegib and 2 PDT sessions. One PDT session was sufficient for small lesions, whereas larger lesions required all 3 sessions. The fifteen evaluable lesions at the end of the 3 PDT sessions showed complete responses. At 30-day follow-up, one of the treated lesions was noted to have clinical evidence of disease. Overall response rate showed 90% complete response and 10% partial response for the study. Combination therapy was well tolerated and yielded a similar or superior side effect profile to that of individual therapies with excellent cosmesis. CONCLUSION: Combination PDT-vismodegib is a potential safe & effective therapy for the treatment of multiple BCCs that may enhance efficacy of individual therapies.


Assuntos
Ácido Aminolevulínico/uso terapêutico , Carcinoma Basocelular/tratamento farmacológico , Síndrome do Hamartoma Múltiplo/tratamento farmacológico , Hospedeiro Imunocomprometido , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/uso terapêutico , Neoplasias Cutâneas/tratamento farmacológico , Idoso , Anilidas/uso terapêutico , Antineoplásicos/uso terapêutico , Terapia Combinada , Humanos , Masculino , Pessoa de Meia-Idade , Piridinas/uso terapêutico
14.
Radiat Res ; 188(5): 491-504, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28877030

RESUMO

The threat of exposure to ionizing radiation from a nuclear reactor accident or deliberate terrorist actions is a significant public health concern. The lung is particularly susceptible to radiation-induced injury from external sources or inhalation of radioactive particles from radioactive fallout. Radiation-induced lung disease can manifest with an acute radiation pneumonitis and/or delayed effects leading to pulmonary fibrosis. As prior warning of radiation exposure is unlikely, medical countermeasures (MCMs) to mitigate radiation-induced lung disease that can be given in mass-casualty situations many hours or days postirradiation are needed to prevent both early and late lung damage. In this study, KL4 surfactant (lucinactant) was evaluated as a radiation mitigator in a well-characterized mouse model of targeted thoracic radiation exposure, for its effect on both early (several weeks) and late (18 weeks) lung damage. Here, 120 mg/kg total phospholipid of KL4 surfactant was administered twice daily intranasally, (enabling intrapulmonary inhalation of drug) to C57BL/6 mice 24 h after a single 13.5 Gy dose of thoracic irradiation (LD50 dose). Both early and chronic phase (2 and 4 weeks and 18 weeks postirradiation, respectively) assessments were performed. Mice were evaluated for evidence of reduced arterial blood oxygenation and early and chronic lung and systemic inflammation, lung fibrosis and oxidative stress. Analysis was done by performing lung function/respiration dynamics and measuring cellular protein content of bronchoalveolar lavage fluid (BALF), and levels of cytokines, 8-iso-prostaglandin F2α, hydroxyproline in lung and plasma, along with evaluating lung histology. The results of this study showed that intranasal delivery of KL4 surfactant was able to preserve lung function as evidenced by adequate arterial oxygen saturation and reduced lung inflammation and oxidative stress; total white count and absolute neutrophil count was decreased in BALF, as were plasma pro-inflammatory cytokine levels and biomarker of oxidative stress. KL4 surfactant is a promising MCM for mitigation of lung tissue damage after targeted, thoracic irradiation and has the potential to be developed as a broad-spectrum, multi-use MCM against chemical, biological, radiological or nuclear threat agents with potential to cause lung injury.


Assuntos
Peptídeos/administração & dosagem , Peptídeos/farmacologia , Pneumonite por Radiação/tratamento farmacológico , Administração Intranasal , Animais , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Feminino , Fibrose , Peptídeos e Proteínas de Sinalização Intercelular , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Pulmão/patologia , Pulmão/efeitos da radiação , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/efeitos da radiação , Peptídeos/uso terapêutico , Pneumonite por Radiação/etiologia , Pneumonite por Radiação/metabolismo , Pneumonite por Radiação/patologia
15.
Cutis ; 99(4): 245-249, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28492599

RESUMO

Allergy as a cause of adverse outcomes in patients with implanted orthopedic hardware is controversial. Allergy to titanium-based implants has not been well researched, as titanium is traditionally thought to be inert. We highlight the case of a patient who developed systemic dermatitis and implant failure after surgical placement of a titanium alloy (Ti6Al4V) plate in the left foot. The hardware was removed and the eruption cleared in the following weeks. The plate and screws were submitted for metal analysis. The elemental composition of both the plate and screws included 3 major elements-titanium, aluminum, and vanadium-as well as trace elements. Metal analysis revealed that the plate and screws had different microstructures, and electrochemical studies demonstrated that galvanic corrosion could have occurred between the plate and screws due to their different microstructures, contributing to the release of vanadium in vivo. The patient was patch tested with several metals including components of the implant and had a positive patch test reaction only to vanadium trichloride. These findings support a diagnosis of vanadium allergy and suggests that clinicians should consider including vanadium when patch testing patients with a suspected allergic reaction to vanadium-containing implants.


Assuntos
Dermatite Alérgica de Contato/diagnóstico , Fixadores Internos/efeitos adversos , Vanádio/efeitos adversos , Ligas/efeitos adversos , Placas Ósseas/efeitos adversos , Dermatite Alérgica de Contato/etiologia , Diagnóstico Diferencial , Falha de Equipamento , Feminino , Humanos , Pessoa de Meia-Idade , Osteoartrite/cirurgia , Testes do Emplastro , Falanges dos Dedos do Pé
16.
Sex Med ; 5(1): e31-e36, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28190453

RESUMO

INTRODUCTION: Intracavernosal injection (ICI) therapy is widely used for the treatment of erectile dysfunction (ED). Its use in practice is largely empirical and has not been validated with evidence-based approaches. AIM: To compare two strategies for ICI, specifically a risk-based approach and an empiric-based approach, and assess the efficacy, patient satisfaction, and complication rates of the two treatment approaches. METHODS: After obtaining approval from the institutional review board, a prospective database of patients enrolled in the ICI program at the Johns Hopkins Hospital (Baltimore, MD, USA) from May 2012 through May 2014 was amassed. Demographic information, treatment outcomes, and subjective patient evaluations of sexual function (International Index of Erectile Function erectile function domain [IIEF-EF], Quality of Erection Questionnaire [QEQ], Sexual Quality of Life [SQoL], and Erectile Dysfunction Inventory of Treatment Satisfaction [EDITS]) were obtained at baseline and at 3 and 6 months. Two approaches were compared. Group 1 received empiric ICI treatment initially with prostaglandin E1 (PGE1) 10 µg irrespective of ED etiology or severity. After initial dosing with PGE1 in the clinic, adjustments were made to titrate or change formulations pending on patient results. Group 2 received a risk-based approach, in which an algorithm that factored in ED etiology and number of ED risk factors was used for a bimix (papaverine 30 mg/mL, phentolamine 1 mg/mL), a low-dose trimix (papaverine 30 mg/mL, phentolamine 1 mg/mL, PGE1 10 µg/mL), or a high-dose trimix (papaverine 30 mg/mL, phentolamine 2 mg/mL, PGE1 40 µg/mL). Dose titration was permitted in the two groups. Statistical analysis was carried out using t-test and χ2 analysis. MAIN OUTCOME MEASURES: The study design was powered for a non-inferiority comparison of the two approaches, in which the primary end point was a 15-point difference on the EDITS score or a 20% difference in the IIEF-EF score. RESULTS: One hundred seventy-five patients were enrolled (57 in group 1, 118 in group 2) with 3- and 6-month follow-up at 57% and 35%, respectively, and similar between groups. Baseline patient characteristics and sexual function questionnaire responses were similar between groups 1 and 2, although group 1 reported higher-quality erections at baseline (QEQ score = 14.3 vs 7.3, P = .05) and had a smaller proportion of patients with prostatectomy (54.4% vs 74.6%, P = .02). In the two groups, QEQ score (mean = 10.78 vs 56.76, P < .05), SQoL score (mean = 38.41 vs 50.25, P < .05), and IIEF-EF score (mean = 7.51 vs 18.48, P < .05) improved with treatment. However, at 3 and 6 months, there were no statistically significant differences in responses for IIEF, QEQ, SQoL, or EDITS scores and no difference in failure or medication switch rates between groups. There were no significant differences in complication rates, although at 3 months group 2 reported a higher incidence of priapism and pain (23% vs 7.4%, P = .08). CONCLUSION: Empiric and risk-based strategies for ICI therapy resulted in significant improvements across multiple domains of sexual function. Complication rates, satisfaction, and efficacy overall were similar between the two approaches. Clinicians can be reassured that no one approach to ICI therapy for ED management appears inferior to another.

17.
BMJ Case Rep ; 20162016 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-27194675

RESUMO

Interstitial granulomatous dermatitis (IGD), a rare disease, is well known to be associated with connective tissue disorders, malignancies and several drugs. We describe this first case of IGD in association with chronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL/SLL). A 66-year-old woman with a 6-year history of untreated CLL/SLL, presented with a 2-month history of progressively worsening eruption of the left thigh, along with fatigue, lymphadenopathy and night sweats. Skin biopsy showed findings consistent with IGD and infiltration of CLL. The eruption was non-responsive to treatment with antibiotics and local steroids. There was a significant improvement in the rash after an initial cycle of chemotherapy (combination therapy with bendamustine and rituximab) and complete resolution by the third cycle, for the treatment of her CLL. We suggest that the possibility of an underlying haematological malignancy should be investigated in patients with a skin rash non-responsive to conventional therapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Dermatite/tratamento farmacológico , Leucemia Linfocítica Crônica de Células B/complicações , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cloridrato de Bendamustina/administração & dosagem , Cloridrato de Bendamustina/uso terapêutico , Dermatite/diagnóstico , Feminino , Humanos , Rituximab/administração & dosagem , Rituximab/uso terapêutico , Resultado do Tratamento
18.
Inhal Toxicol ; 27(14): 832-40, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26671199

RESUMO

CONTEXT: Phosgene's primary mode of action is as a pulmonary irritant characterized by its early latent phase where life-threatening, non-cardiogenic pulmonary edema is typically observed 6-24 h post-exposure. OBJECTIVE: To develop an inhaled phosgene acute lung injury (ALI) model in C57BL/6 mice that can be used to screen potential medical countermeasures. METHODS: A Cannon style nose-only inhalation exposure tower was used to expose mice to phosgene (8 ppm) or air (sham). An inhalation lethality study was conducted to determine the 8 ppm median lethal exposure (LCt50) at 24 and 48 h post-exposure. The model was then developed at 1.2 times the 24 h LCt50. At predetermined serial sacrifice time points, survivors were euthanized, body and lung weights collected, and lung tissues processed for histopathology. Additionally, post-exposure clinical observations were used to assess quality of life. RESULTS AND DISCUSSION: The 24-hour LCt50 was 226 ppm*min (8 ppm for 28.2 min) and the 48-hour LCt50 was 215 ppm*min (8 ppm for 26.9 min). The phosgene exposed animals had a distinct progression of clinical signs, histopathological changes and increased lung/body weight ratios. Early indicators of a 1.2 times the 24-hour LCt50 phosgene exposure were significant changes in the lung-to-body weight ratios by 4 h post-exposure. The progression of clinical signs and histopathological changes were important endpoints for characterizing phosgene-induced ALI for future countermeasure studies. CONCLUSION: An 8 ppm phosgene exposure for 34 min (1.2 × LCt50) is the minimum challenge recommended for evaluating therapeutic interventions. The predicted higher mortality in the phosgene-only controls will help demonstrate efficacy of candidate treatments and increase the probability that a change in survival rate is statistically significant.


Assuntos
Lesão Pulmonar Aguda/induzido quimicamente , Fosgênio/toxicidade , Lesão Pulmonar Aguda/patologia , Administração Intranasal , Animais , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fosgênio/administração & dosagem
19.
Endocr Pract ; 21(5): 482-7, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25667366

RESUMO

OBJECTIVE: We report on the unique occurrence of Graves disease (thyrotoxicosis) in 7 male endocrinologists at the Mount Sinai Hospital (MSH) in New York City, New York between 1954 and 2011. METHODS: We followed the endocrinologists and fellows assigned to the division over a period of 57 years by survey and personal contact. In the statistical studies, we assumed that the number of cases had a Poisson distribution and computed the exact probability based on the expected values. RESULTS: Seven male endocrinologists had proven thyrotoxicosis during or following their service in the Endocrine Division at MSH. Six had a family history of thyrotoxicosis. None had known iodine 131 (131-I) thyroid contamination. CONCLUSION: The incidence of thyrotoxicosis greatly exceeds the rate predicted. Postulated factors in the causation of this unique occurrence are discussed.


Assuntos
Endocrinologia , Doença de Graves/epidemiologia , Médicos , Adulto , Idoso , Feminino , Hospitais , Humanos , Masculino , Pessoa de Meia-Idade , Cidade de Nova Iorque/epidemiologia , Distribuição de Poisson , Fatores de Risco , Tireotoxicose/epidemiologia
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