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1.
ASAIO J ; 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38295395

RESUMO

A 36 year old woman with history of heart failure and left ventricular assist device (LVAD) implantation, with subsequent explantation after myocardial recovery, presented for management of preconception counseling and subsequent pregnancy. To our knowledge, this case represents the first documented successful pregnancy after LVAD explantation. Management details are provided, and relevant literature is reviewed.

2.
Fertil Steril ; 120(5): 957-966, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37532168

RESUMO

OBJECTIVE: To understand the clinical risks associated with the transfer of embryos classified as a mosaic using preimplantation genetic testing for aneuploidy. DESIGN: Analysis of data collected between 2017 and 2023. SETTING: Multicenter. PATIENTS: Patients of infertility treatment. INTERVENTION: Comparison of pregnancies resulting from embryos classified as euploid or mosaic using the 20%-80% interval in chromosomal intermediate copy numbers to define a mosaic result. MAIN OUTCOME MEASURES: Rates of spontaneous abortion, birth weight, length of gestation, incidence of birth defects, and chromosomal status during gestation. RESULTS: Implanted euploid embryos had a significantly lower risk of spontaneous abortion compared with mosaic embryos (8.9% [n = 8,672; 95% confidence interval {CI95} 8.3, 9.5] vs. 22.2% [n = 914; CI95 19.6, 25.0]). Embryos with mosaicism affecting whole chromosomes (not segmental) had the highest risk of spontaneous abortion (27.6% [n = 395; CI95 23.2, 32.3]). Infants born from euploid, mosaic, and whole chromosome mosaic embryos had average birth weights and lengths of gestation that were not statistically different (3,118 g and 267 days [n = 488; CI95 3,067, 3,169, and 266, 268], 3052 g and 265 days [n = 488; CI95 2,993, 3,112, and 264,267], 3,159 g and 268 days [n = 194; CI95 3,070, 3,249, and 266,270], respectively). Out of 488 infants from mosaic embryo transfers (ETs), one had overt gross abnormalities as defined by the Centers for Disease Control and Prevention. Most prenatal tests performed on pregnancies from mosaic ETs had normal results, and only three pregnancies produced prenatal test results reflecting the mosaicism detected at the embryonic stage (3 out of 250, 1.2%; CI95 0.25, 3.5). CONCLUSION: Although embryos classified as mosaic experience higher rates of miscarriage than euploid embryos (with a particularly high frequency shortly after implantation), infants born of mosaic ETs are similar to infants of euploid ETs. Prenatal testing indicates that mosaicism resolves during most pregnancies, although this process is not perfectly efficient. In a small percentage of cases, the mosaicism persists through gestation. These findings can serve as risk-benefit considerations for mosaic ETs in the fertility clinic.


Assuntos
Aborto Espontâneo , Diagnóstico Pré-Implantação , Gravidez , Feminino , Recém-Nascido , Humanos , Aborto Espontâneo/etiologia , Aborto Espontâneo/genética , Diagnóstico Pré-Implantação/métodos , Fertilização in vitro/efeitos adversos , Fertilização in vitro/métodos , Blastocisto , Testes Genéticos/métodos , Aneuploidia , Mosaicismo , Cromossomos
3.
Cureus ; 15(6): e40581, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37469825

RESUMO

Assessing perceptions and attitudes of advocacy in adolescent populations is an important area of research. Previous studies have shown that advocacy programs in high schools are well-received and help promote health advocacy. This pilot study took place at the University of Central Florida College of Medicine Health Leaders Summer Academy hosted by medical students of the Student National Medical Association. A one-hour interactive workshop was administered to high school students interested in the healthcare field. Pre- and post-survey data were collected to assess participants' perceptions, methods, and barriers to engaging in advocacy. A total of 29 students were included in this study. Results indicated that students' definitions of advocacy changed after completing the workshop, as a higher percentage of students indicated that they practiced advocacy (pre-survey, 82.76% versus post-survey, 95.45%). There was a statistically significant difference in perceptions of the importance of advocacy in the student's future career (pre-survey, 3.82 versus post-survey, 4.15, p = .035). Social media was the most effective and common form of advocacy used (post-survey 72.73%). The most common barrier to practicing advocacy was a lack of education on a particular topic (31.82% post-survey). Overall, the workshop increased participants' interest in engaging in advocacy. Future directions include expanding the study to a larger population sample throughout the Orlando community and researching the use of social media as a tool for advocacy.

4.
Am J Med ; 136(1): 57-59, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36150514
5.
Cardiol Res ; 13(2): 81-87, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35465084

RESUMO

Background: Methamphetamines are a common cause of systolic heart failure (HF). There are limited data on the prognosis associated with hospitalizations for decompensated HF in the setting of methamphetamine use. We aimed to evaluate patient characteristics and outcomes among patients admitted with decompensated HF who had positive drug screens for amphetamines as well as to determine whether any parameters from transthoracic echocardiogram (TTE) can predict outcomes in this population. Methods: This was a retrospective cohort study of consecutive adult patients admitted to the Loma Linda Medical Center who had an active hospital problem of acute on chronic systolic (or systolic and diastolic) HF from 2013 to 2018. Electronic medical records were mined for relevant patient data. Methamphetamine-associated heart failure (MethHF) group was defined as those with an admission urine drug screen (UDS) that was positive for methamphetamines, whereas non-MethHF was defined by patients with negative methamphetamine on UDS or UDS was not done on physician's discretion. The primary outcomes of the study were 30-day composite outcome (defined as combined all-cause readmission and all-cause mortality), 365-day all-cause mortality, and length of stay (LOS). Propensity score weighting for these outcomes was performed using demographics, laboratory and clinical variables, and left ventricular ejection fraction (LVEF) as covariates. TTE parameters from presentation were also evaluated to determine if any had prognostic implications. Results: A total of 1,655 patients were included (101 patients with positive urine methamphetamine and 1,554 patients without). Patients with MethHF were younger, more likely to be male, had fewer comorbidities, had lower LVEF, and were more likely to have right ventricular systolic dysfunction. In propensity-weighted analyses, there were no significant differences in LOS, 30-day composite outcome, or 365-day mortality between the MethHF and non-MethHF group in (P > 0.05 for all). Presence of at least moderate tricuspid valve regurgitation (TR) was the only TTE predictor of 30-day composite outcome (odds ratio (OR) = 4.67, 95% confidence interval (CI): 1.5 - 14.50, P < 0.01) and 365-day mortality (OR = 4.67, 95% CI: 1.5 - 14.50, P < 0.01) in the MethHF group. Conclusion: Patients with MethHF admitted for decompensated HF had similar outcomes compared to non-MethHF after adjusting for baseline characteristics. TR is the only TTE value to predict outcomes in this population.

6.
Chemosphere ; 263: 128307, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33297244

RESUMO

Bisphenol A (BPA) and Diethylhexyl Phthalate (DEHP) are well-studied endocrine disrupting chemicals (EDCs), however, the effects of mixtures of these EDCs are not. To assess the consequences of prenatal exposure to a mixture of these EDCs, dams were orally administered either saline (control), BPA (5 µg/kg BW/day), high dose DEHP (HD-D; 7.5 mg/kg BW/day), or a combination of BPA with HD-D in experiment 1; saline, BPA (5 µg/kg BW/day), low-dose DEHP (LD-D; 5 µg/kg BW/day) or a combination of BPA with LD-D in experiment 2. Gestational weights, number of abortions, litter size and weights, number of live births and stillbirths were recorded. Morphometric measures were obtained at birth and body weight, food and water intake were monitored weekly from postnatal weeks 3-12. Offspring were sacrificed at 16-24 weeks of age and organ weights were measured. The abortion rate of dams exposed to HD-D and the mixtures, BPA + LD-D and BPA + HD-D were higher at 9, 14 and 27% respectively. Prenatal exposure to BPA or HD-D significantly decreased relative thymus weights in male but not female offspring. Apoptotic cells were detected in thymus sections of both male and female offspring prenatally exposed to DEHP. Relative heart weights increased in BPA + HD-D exposed male offspring compared to the other groups. The results indicate that a mixture of BPA and DEHP, produced a pronounced effect on pregnancy outcomes. Male offspring appear to be more susceptible to the programming effects of these EDCs or their mixture suggesting a need to reconsider the possible additive, antagonistic or synergistic effects of EDC mixtures.


Assuntos
Dietilexilftalato , Disruptores Endócrinos , Efeitos Tardios da Exposição Pré-Natal , Animais , Compostos Benzidrílicos/toxicidade , Dietilexilftalato/toxicidade , Disruptores Endócrinos/toxicidade , Feminino , Humanos , Masculino , Fenóis , Gravidez , Resultado da Gravidez , Ratos , Ratos Sprague-Dawley
7.
Am J Case Rep ; 20: 1120-1123, 2019 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-31353363

RESUMO

BACKGROUND Pericarditis is common in rheumatoid arthritis, mostly occurring as an extra-articular manifestation of the disease. We describe a patient with stable rheumatoid arthritis who presented with a large pericardial effusion and a compressive fibrotic pericardial mass. The patient had recently started treatment with a tumor necrosis factor-alpha (TNF-alpha) antagonist. CASE REPORT The patient was a 58-year-old woman with rheumatoid arthritis who presented with right ventricular compression caused by a pericardial fibrotic mass and a large pericardial effusion. The patient did not have active arthritis at the time of presentation. She had been started on treatment with a tumor necrosis factor-alpha (TNF-alpha) antagonist 4 months prior to this presentation. She was successfully treated with surgical pericardiectomy and resection of the pericardial mass. Pathologic analysis of the pericardial mass demonstrated fibrosis and no evidence of active inflammation, rheumatoid arthritis, opportunistic infection, or malignancy. CONCLUSIONS We describe a patient with stable rheumatoid arthritis who developed subacute right heart compression syndrome secondary to pericardial effusion and fibrous pericardial mass. The exact cause of pericarditis and the pericardial mass remain uncertain. There is a need for increased awareness of the association between use of TNF-alpha antagonists and the possible development of an intrapericardial fibrotic mass and effusion.


Assuntos
Artrite Reumatoide/tratamento farmacológico , Tamponamento Cardíaco/etiologia , Derrame Pericárdico/diagnóstico por imagem , Pericardite/patologia , Pericárdio/patologia , Anticorpos Monoclonais/uso terapêutico , Antirreumáticos/uso terapêutico , Tamponamento Cardíaco/diagnóstico por imagem , Tamponamento Cardíaco/cirurgia , Ecocardiografia , Feminino , Fibrose , Humanos , Imagem Cinética por Ressonância Magnética , Pessoa de Meia-Idade , Derrame Pericárdico/cirurgia , Pericardiectomia , Pericardite/cirurgia , Pericárdio/cirurgia , Fator de Necrose Tumoral alfa/antagonistas & inibidores
8.
J Cutan Pathol ; 46(9): 678-683, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31070801

RESUMO

A 28-year-old woman of Chinese descent, with congenital chronic hepatitis B presented with a 7-year history of erythematous-brown papules and plaques on her groins, axillae, and forehead. A first skin biopsy showed findings consistent with two concomitant, yet highly uncommon cutaneous diseases. The presence of lymphoid nodules with germinal centers and clustered polyclonal plasma cells was consistent with cutaneous plasmocytosis. Second, a diffuse proliferation of non-atypical small vessels (CD31+, CD34+, and HHV8-) in a hypercellular stroma peppered with angulated giant cells (CD163+, CD68-) was suggestive of multinucleate cell angiohistiocytoma (MCAH). Interestingly, the second biopsy of a different plaque on the forehead showed only plasmacytosis and the clinical appearance of both plaques and papules alluded to the distinct presence of both concurrent entities. We speculate the immune modulating effects of chronic hepatitis B may have led to a polyclonal plasmacytic proliferation within the dermis. Furthermore, MCAH has been reported in conjunction with other inflammatory skin diseases such as hidradenitis suppurativa and as such we propose that the MCAH lesion in our case may have arisen as a secondary, reactive process to the cutaneous plasmacytosis.


Assuntos
Células Gigantes , Neoplasias de Cabeça e Pescoço , Histiocitoma , Plasmócitos , Neoplasias Cutâneas , Adulto , Derme/metabolismo , Derme/patologia , Feminino , Testa/patologia , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/patologia , Hepatite B Crônica/metabolismo , Hepatite B Crônica/patologia , Histiocitoma/metabolismo , Histiocitoma/patologia , Humanos , Plasmócitos/metabolismo , Plasmócitos/patologia , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/patologia
9.
Clin Transpl ; 31: 151-161, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-28514577

RESUMO

Success and advances in the management of all aspects of heart disease and heart transplantation have allowed for normalcy in life, including the question as to the possibility of pregnancy in transplantation. With the growing young adult population undergoing heart transplant, pregnancy and transplantation have become an issue of importance. Despite the fact that nearly 50 years have passed since the first heart transplant, there remains to be little evidence in regard to management of pregnant heart transplant recipients. Thus, this review will address issues related to pregnancy in this patient population, such as preconception counseling, timing and optimization for pregnancy post transplant, immunosuppression, cardiac assessment, and management of pregnant heart transplant recipients, as well as hemodynamic effects of pregnancy on the transplanted heart. Based on the available literature from registrar data, case reports and series, with careful planning, monitoring, and appropriate therapies, pregnancy in heart transplantation is a viable option in select patients. To optimize maternal and fetal outcomes, recommendations are included in this review to minimize complications including rejection, graft dysfunction, maternal diabetes and hypertension, as well as appropriate changes in immunosuppression.

10.
Br J Neurosurg ; 28(5): 616-21, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24377670

RESUMO

OBJECT: With an increasingly ageing population, the number of elderly people diagnosed with pituitary tumours continues to rise. There is a concern that with increasing age and comorbidities, there is higher anaesthetic risk, as well as peri-operative morbidity and mortality from pituitary surgery. This study aimed to audit the benefits and complications of transsphenoidal surgery performed in a large pituitary centre in elderly patients. METHODS: Data on all elderly patients (age: ≥ 70 years) undergoing transsphenoidal surgery at a large tertiary referral centre between November 2003 and August 2012 were collected retrospectively. RESULTS: A total of 104 operations were performed on 102 patients during 106 months. Median age was 75.2 years (range: 70-94) and 63 (61%) of the patients were male. Median follow-up was 15.2 months (range: 2.3-84.4). The majority presented with either peripheral visual field defects (26.4%) or pituitary hormone deficits (17.9%). A significant number (21.7%) of tumours were incidental radiological findings while investigating other diagnoses like stroke and dementia. 48.1% of operations were undertaken microscopically and the remaining 51.9% were endoscopic. Median hospital stay was 4 days (range: 3-18). Intra-operative complications included hypotension (1.9%) and blood loss requiring transfusion (2.9%). The 30-day complications included transient diabetes insipidus (9.6%), syndrome of inappropriate anti-diuretic hormone secretion (8.7%), delayed cerebrospinal fluid leak requiring lumbar drainage (0.9%) with no patient requiring formal repair. There were no peri-operative deaths. Long-term assessment suggested 79% had improved or stable endocrine function with 7% achieving biochemical cure and 91% showed improved or stable visual fields. CONCLUSIONS: Pituitary surgery in the elderly, whether microscopic or endoscopic, has low morbidity and mortality and is a safe and effective intervention for both symptom control and functional outcomes.


Assuntos
Adenoma/cirurgia , Procedimentos Neurocirúrgicos , Neoplasias Hipofisárias/cirurgia , Idoso , Idoso de 80 Anos ou mais , Endoscopia/métodos , Feminino , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Procedimentos Neurocirúrgicos/efeitos adversos , Hormônios Hipofisários/metabolismo , Complicações Pós-Operatórias/prevenção & controle , Estudos Retrospectivos , Resultado do Tratamento
11.
Expert Opin Biol Ther ; 14(1): 51-61, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24219367

RESUMO

INTRODUCTION: Erythropoiesis-stimulating agents (ESAs) are widely used in treating anemia associated with renal failure. They are also now used perioperatively to reduce the use of allogeneic blood transfusions (ABTs) in patients undergoing surgery with anticipated high blood loss. Although they can reduce the risks associated with ABT and improve quality of life, the use of ESAs is still associated with adverse effects. AREAS COVERED: A narrative review is provided on ESAs and a systematic review has been conducted to examine the current evidence for the efficacy and safety of perioperative ESAs use. A search of PubMed and Medline databases has been performed using a combination of search terms including erythropoietin, perioperative, surgical, safety and efficacy. EXPERT OPINION: Current evidence supports the use of perioperative ESAs to reduce the need for ABT. However, large studies assessing safety in anemic patients with chronic renal disease have found adverse effects including cardiovascular, stroke and thromboembolic events. However, whether these concerns can be conferred onto the surgical population remains to be seen as the perioperative dosing strategies have been more variable in timing, dose and duration in comparison with those used for chronic diseases. Future research needs to address the questions of optimal dosing strategies in order to maximize the positive effects and minimize adverse events.


Assuntos
Anemia/tratamento farmacológico , Eritropoese/efeitos dos fármacos , Eritropoetina/administração & dosagem , Hematínicos/administração & dosagem , Anemia/sangue , Anemia/complicações , Animais , Perda Sanguínea Cirúrgica/prevenção & controle , Transfusão de Sangue , Esquema de Medicação , Eritropoetina/efeitos adversos , Hematínicos/efeitos adversos , Humanos , Assistência Perioperatória , Hemorragia Pós-Operatória/sangue , Hemorragia Pós-Operatória/prevenção & controle , Proteínas Recombinantes/administração & dosagem , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
12.
Orthop J Sports Med ; 2(8): 2325967114541237, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26535350

RESUMO

BACKGROUND: Lateral meniscal tears are often seen with acute anterior cruciate ligament (ACL) injury and may be left in situ, repaired, or treated with meniscectomy. Clinical studies have shown good outcomes with vertical tears left in situ and poor outcomes following meniscectomy. However, clinically relevant studies are needed to establish a biomechanical foundation for treatment of these tears, particularly regarding the effects of meniscectomy. PURPOSE: To compare tibiofemoral joint mechanics following vertical lateral meniscal tears and meniscectomies. We hypothesized that a peripheral vertical tear of the lateral meniscus would alter joint mechanics, increasing contact pressure and area, and that more drastic effects would be seen following meniscectomy, at higher knee flexion angles, and with increased loads. STUDY DESIGN: Controlled laboratory study. METHODS: Ten fresh-frozen cadaveric knees (average age, 55 ± 12 years) were tested with 5 lateral meniscus states: intact, short vertical tear, extended vertical tear, posterior horn partial meniscectomy (rim intact), and posterior horn subtotal meniscectomy (rim excised). The specimens were loaded axially at knee flexion angles of 0°, 30°, and 60°, and musculotendinous forces were applied, simulating a 2-legged squat. Intra-articular contact pressures were measured using pressure-sensitive Fuji film. Kinematic data were acquired through digitization of fiducial markers. RESULTS: Vertical tears did not cause a significant change in contact pressure or area. Partial meniscectomy increased maximum contact pressures in the lateral compartment at 30° and 60° from 5.3 MPa to 7.2 MPa and 7.6 MPa, respectively (P = .02, P = .007). Subtotal meniscectomy (8.4 MPa) significantly increased contact pressure compared with partial meniscectomy (7.6 MPa) at 60° (P = .04). Both meniscectomy states significantly increased contact pressures with increasing flexion from 0° to 60° (P < .001, P < .001). CONCLUSION: Vertical tears of the lateral meniscus during a simulated 2-legged squat did not significantly change contact pressures and areas compared with an intact meniscus. However, treating these tears with partial and complete meniscectomy significantly increased maximum contact pressures. CLINICAL RELEVANCE: Biomechanical evidence supports treating vertical lateral meniscus tears with meniscal-sparing techniques as opposed to meniscectomy, which may lead to progressive degenerative joint disease from altered joint biomechanics.

13.
Health Hum Rights ; 13(2): E17-35, 2011 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-22773029

RESUMO

Systematic violations of migrant workers' human rights and striking health disparities among these populations in the United Arab Emirates (UAE) are the norm in member countries of the Gulf Cooperation Council (GCC). Migrant laborers comprise about 90 percent of the UAE workforce and include approximately 500,000 construction workers and 450,000 domestic workers. Like many other GCC members countries, the UAE witnessed an unprecedented construction boom during the early 2000s, attracting large numbers of Western expatriates and increasing demand for cheap migrant labor. Elite Emiratis' and Western expatriates' dependence on household staff further promoted labor migration. This paper offers a summary of existing literature on migrant workers and human rights in the UAE, focusing on their impact on related health ramifications and disparities, with specific attention to construction workers, domestic workers, and trafficked women and children. Construction workers and domestic laborers are victims of debt bondage and face severe wage exploitation, and experience serious health and safety problems resulting from inhumane work and living conditions. High rates of physical, sexual, and psychological abuse impact the health of domestic workers. Through a review of available literature, including official reports, scientific papers, and media reports, the paper discusses the responsibility of employers, governments, and the global community in mitigating these problems and reveals the paucity of systematic data on the health of migrant workers in the Gulf.


Assuntos
Emigrantes e Imigrantes , Disparidades nos Níveis de Saúde , Direitos Humanos , Acessibilidade aos Serviços de Saúde , Nível de Saúde , Humanos , Ocupações , Delitos Sexuais , Problemas Sociais , Emirados Árabes Unidos
14.
J Virol ; 80(17): 8820-3, 2006 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16912328

RESUMO

We mapped 226 unique integration sites in human hepatoma cells following gene transfer with a feline immunodeficiency virus (FIV)-based lentivirus vector. FIV integrated across the entire length of the transcriptional units. Microarray data indicated that FIV integration favored actively transcribed genes. Approximately 21% of FIV integrations within transcriptional units occurred in genes regulated by the LEDGF/p75 transcriptional coactivator. DNA in regions of FIV insertion sites exhibited a "bendable" structure and a pattern of duplex destabilization favoring strand separation. FIV integration preferences are more similar to those of primate lentiviruses and distinct from those of Moloney murine leukemia virus, avian sarcoma leukosis virus, and foamy virus.


Assuntos
Vetores Genéticos , Vírus da Imunodeficiência Felina/genética , Vírus da Imunodeficiência Felina/patogenicidade , Integração Viral , Animais , Gatos , Linhagem Celular Tumoral , Mapeamento Cromossômico , Perfilação da Expressão Gênica , Humanos , Análise de Sequência com Séries de Oligonucleotídeos , Proteínas/genética , Proteínas/metabolismo
15.
Blood ; 106(5): 1552-8, 2005 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-15886327

RESUMO

Hemophilia A is a clinically important coagulation disorder caused by the lack or abnormality of plasma coagulation factor VIII (FVIII). Gene transfer of the FVIII cDNA to hepatocytes using lentiviral vectors is a potential therapeutic approach. We investigated the efficacy of feline immunodeficiency virus (FIV)-based vectors in targeting hepatocytes and correcting FVIII deficiency in a hemophilia A mouse model. Several viral envelope glycoproteins were screened for efficient FIV vector pseudotyping and hepatocyte transduction. The GP64 glycoprotein from baculovirus Autographa californica multinuclear polyhedrosis virus pseudo-typed FIV efficiently and showed excellent hepatocyte tropism. The GP64-pseudotyped vector was stable in the presence of human or mouse complement. Inclusion of a hybrid liver-specific promoter (murine albumin enhancer/human alpha1-antitrypsin promoter) further enhanced transgene expression in hepatocytes. We generated a GP64-pseudotyped FIV vector encoding the B domain-deleted human FVIII coding region driven by the liver-specific promoter, with 2 beneficial point mutations in the A1 domain. Intravenous vector administration conferred sustained FVIII expression in hemophilia A mice for several months without the generation of anti-human FVIII antibodies and resulted in partial phenotypic correction. These findings demonstrate the utility of GP64-pseudotyped FIV lentiviral vectors for targeting hepatocytes to correct disorders associated with deficiencies of secreted proteins.


Assuntos
Fator VIII/biossíntese , Fator VIII/genética , Vetores Genéticos/uso terapêutico , Hemofilia A/terapia , Vírus da Imunodeficiência Felina/genética , Glicoproteínas de Membrana/uso terapêutico , Animais , DNA Complementar/genética , Modelos Animais de Doenças , Fator VIII/efeitos dos fármacos , Feminino , Terapia Genética/métodos , Vetores Genéticos/sangue , Vetores Genéticos/genética , Hemofilia A/genética , Hemofilia A/metabolismo , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Hepatócitos/virologia , Humanos , Vírus da Imunodeficiência Felina/metabolismo , Masculino , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Distribuição Tecidual
16.
Drug Saf ; 26(7): 453-60, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-12735784

RESUMO

Initial reports of myocardial infarction and sudden death in men with erectile dysfunction who had taken sildenafil (sometimes in conjunction with nitrates) raised concerns that sildenafil may increase the risk of cardiovascular events in men with erectile dysfunction and vascular disease. A significant body of evidence now indicates that sildenafil generally has a good safety profile in men with erectile dysfunction and cardiovascular disease. Sildenafil therapy does not appear to be associated with ischaemic events either at the time of introduction of therapy or during longer-term use. Rates of discontinuation from sildenafil therapy due to adverse events are similar to placebo in men with cardiovascular disease. Sildenafil does not interact in a potentially hazardous way with antihypertensive or antianginal therapy, with the exception of nitrates. Nitrates should not be administered within 24 hours of sildenafil therapy, and care should be taken to determine whether sildenafil may have been used before nitrates are administered to patients. Sildenafil appears to be generally well tolerated in most patients with chronic, stable cardiovascular disease.


Assuntos
Doenças Cardiovasculares/induzido quimicamente , Disfunção Erétil/tratamento farmacológico , Piperazinas/efeitos adversos , Segurança , Vasodilatadores/efeitos adversos , Anti-Hipertensivos/uso terapêutico , Doenças Cardiovasculares/fisiopatologia , Ensaios Clínicos como Assunto , Interações Medicamentosas , Hemodinâmica , Humanos , Masculino , Doadores de Óxido Nítrico/uso terapêutico , Piperazinas/uso terapêutico , Purinas , Citrato de Sildenafila , Sulfonas , Vasodilatadores/uso terapêutico
17.
Drug Saf ; 25(2): 73-6, 2002.
Artigo em Inglês | MEDLINE | ID: mdl-11888349

RESUMO

Angioedema is an uncommon but potentially life-threatening adverse event associated with ACE inhibitor therapy which is believed to be due to potentiation of the vascular effects of bradykinin. Angiotensin receptor antagonists were not expected to produce angioedema, as they do not inhibit the catabolism of bradykinin. However, it is now apparent that angioedema is occasionally associated with angiotensin receptor antagonist therapy and may be more likely to occur in patients who have previously experienced angioedema while receiving ACE inhibitors. Angiotensin receptor antagonists cannot be considered to be a safe alternative therapy in patients who have previously experienced ACE inhibitor-associated angioedema.


Assuntos
Angioedema/induzido quimicamente , Antagonistas de Receptores de Angiotensina , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Anti-Hipertensivos/efeitos adversos , Benzimidazóis/efeitos adversos , Benzimidazóis/uso terapêutico , Benzoatos/efeitos adversos , Benzoatos/uso terapêutico , Compostos de Bifenilo/efeitos adversos , Compostos de Bifenilo/uso terapêutico , Humanos , Irbesartana , Losartan/efeitos adversos , Losartan/uso terapêutico , Telmisartan , Tetrazóis/efeitos adversos , Tetrazóis/uso terapêutico
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