RESUMEN
Significance: ALA-PpIX and second-window indocyanine green (ICG) have been studied widely for guiding the resection of high-grade gliomas. These agents have different mechanisms of action and uptake characteristics, which can affect their performance as surgical guidance agents. Elucidating these differences in animal models that approach the size and anatomy of the human brain would help guide the use of these agents. Herein, we report on the use of a new pig glioma model and fluorescence cryotomography to evaluate the 3D distributions of both agents throughout the whole brain. Aim: We aim to assess and compare the 3D spatial distributions of ALA-PpIX and second-window ICG in a glioma-bearing pig brain using fluorescence cryotomography. Approach: A glioma was induced in the brain of a transgenic Oncopig via adeno-associated virus delivery of Cre-recombinase plasmids. After tumor induction, the pro-drug 5-ALA and ICG were administered to the animal 3 and 24 h prior to brain harvest, respectively. The harvested brain was imaged using fluorescence cryotomography. The fluorescence distributions of both agents were evaluated in 3D in the whole brain using various spatial distribution and contrast performance metrics. Results: Significant differences in the spatial distributions of both agents were observed. Indocyanine green accumulated within the tumor core, whereas ALA-PpIX appeared more toward the tumor periphery. Both ALA-PpIX and second-window ICG provided elevated tumor-to-background contrast (13 and 23, respectively). Conclusions: This study is the first to demonstrate the use of a new glioma model and large-specimen fluorescence cryotomography to evaluate and compare imaging agent distribution at high resolution in 3D.
Asunto(s)
Neoplasias Encefálicas , Glioma , Imagenología Tridimensional , Verde de Indocianina , Animales , Verde de Indocianina/farmacocinética , Verde de Indocianina/química , Porcinos , Neoplasias Encefálicas/diagnóstico por imagen , Glioma/diagnóstico por imagen , Glioma/patología , Imagenología Tridimensional/métodos , Ácido Aminolevulínico/farmacocinética , Encéfalo/diagnóstico por imagen , Imagen Óptica/métodos , Modelos Animales de EnfermedadRESUMEN
Excessive exposure to ultraviolet radiation (UVR) causes harmful effects on human skin. Pre-exposure application of sunscreen can be protective, but not after damage already has occurred. There is a need for agents that can be applied post-UVR exposure to repair the damage. We investigated a novel compound, NEO400, that appears to meet this medicinal need. NEO400 was created by conjugating linoleic acid to perillyl alcohol. UVR was repeatedly administered to the skin of mice over several weeks, where it caused the typical signs of UV damage, including scaling of the skin, DNA damage, and elevated levels of inflammatory cytokines. However, when NEO400 was applied immediately post-UVR, it triggered the appearance of markers for dermal stem cell proliferation, and no signs of skin damage emerged. Furthermore, when NEO400 was applied to skin that already had incurred significant damage, it accelerated skin healing. When applied individually, linoleic acid and perillyl alcohol were ineffective, indicating that they had to be conjugated in order to exert therapeutic efficacy. None of these skin-protective effects could be achieved with Aloe vera gel, a popular and widely used post-exposure remedy. Our study suggests that NEO400 holds potential as a regenerative treatment for excessively UVR-exposed skin.
RESUMEN
BACKGROUND: Glioblastoma is the most common primary malignant and treatment-resistant human brain tumor. Rodent models have played an important role in understanding brain cancer biology and treatment. However, due to their small cranium and tumor volume mismatch, relative to human disease, they have been less useful for translational studies. Therefore, development of a consistent and simple large animal glioma xenograft model would have significant translational benefits. METHODS: Immunosuppression was induced in twelve standard Yucatan minipigs. 3 pigs received cyclosporine only, while 9 pigs received a combined regimen including cyclosporine (55 mg/kg q12 h), prednisone (25 mg, q24 h) and mycophenolate (500 mg q24 h). U87 cells (2 × 106) were stereotactically implanted into the left frontal cortex. The implanted brains were imaged by MRI for monitoring. In a separate study, tumors were grown in 5 additional pigs using the combined regimen, and pigs underwent tumor resection with intra-operative image updating to determine if the xenograft model could accurately capture the spatial tumor resection challenges seen in humans. RESULTS: Tumors were successfully implanted and grown in 11 pigs. One animal in cyclosporine only group failed to show clinical tumor growth. Clinical tumor growth, assessed by MRI, progressed slowly over the first 10 days, then rapidly over the next 10 days. The average tumor growth latency period was 20 days. Animals were monitored twice daily and detailed records were kept throughout the experimental period. Pigs were sacrificed humanely when the tumor reached 1 - 2 cm. Some pigs experienced decreased appetite and activity, however none required premature euthanasia. In the image updating study, all five pigs demonstrated brain shift after craniotomy, consistent with what is observed in humans. Intraoperative image updating was able to accurately capture and correct for this shift in all five pigs. CONCLUSION: This report demonstrates the development and use of a human intracranial glioma model in an immunosuppressed, but nongenetically modified pig. While the immunosuppression of the model may limit its utility in certain studies, the model does overcome several limitations of small animal or genetically modified models. For instance, we demonstrate use of this model for guiding surgical resection with intraoperative image-updating technologies. We further report use of a surrogate extracranial tumor that indicates growth of the intracranial tumor, allowing for relative growth assessment without radiological imaging.
Asunto(s)
Neoplasias Encefálicas , Ciclosporinas , Glioma , Humanos , Porcinos , Animales , Xenoinjertos , Reproducibilidad de los Resultados , Porcinos Enanos , Glioma/tratamiento farmacológico , Glioma/cirugía , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/patología , Terapia de Inmunosupresión , Modelos Animales de EnfermedadRESUMEN
Glucocorticoids (GCs) are among the most widely prescribed medications in dermatologic practice. Although considered generally safe and efficacious, prolonged use and high dosing regimens may precipitate GC-induced osteoporosis, which contributes to an increased risk for fragility fractures. Dermatologists using and prescribing GCs must be aware of the risk for GC-induced osteoporosis. This review details the risks for osteoporosis and osteoporotic (OP) fractures in the setting of topical, intralesional, intramuscular, and systemic GC treatment, as well as nutritional supplementation recommendations that may reduce the risk of these adverse effects.
Asunto(s)
Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Osteoporosis , Fracturas Osteoporóticas , Humanos , Fracturas Osteoporóticas/inducido químicamente , Fracturas Osteoporóticas/prevención & control , Glucocorticoides/efectos adversos , Osteoporosis/inducido químicamente , Osteoporosis/tratamiento farmacológico , Osteoporosis/prevención & control , Suplementos Dietéticos/efectos adversosRESUMEN
BACKGROUND: Antimalarials are first-line systemic therapy for cutaneous lupus erythematosus (CLE). While some patients unresponsive to hydroxychloroquine (HCQ) alone benefit from the addition of quinacrine (QC), a subset of patients is refractory to both antimalarials. METHODS: We classified CLE patients as HCQ-responders, HCQ+QC-responders, or HCQ+QC-nonresponders to compare immune profiles. Immunohistochemistry, immunofluorescence, and qRT-PCR were used to characterize inflammatory cells and cytokines in lesional skin. RESULTS: Immunohistochemistry showed that CD69+ T cells were higher in HCQ+QC-nonresponders compared to HCQ- and HCQ+QC-responders (p < 0.05). Immunofluorescence further identified these cells as CD69+CCR7+ circulating activated T cells. Myeloid dendritic cells were significantly higher in HCQ+QC-responders compared to both HCQ-responders and HCQ+QC-nonresponders. Plasmacytoid dendritic cells were significantly increased in HCQ-responders compared to HCQ- and HCQ+QC-nonresponders. No differences were found in the number of autoreactive T cells, MAC387+ cells, and neutrophils among the groups. CLASI scores of the HCQ+QC-nonresponder group positively correlated with CD69+CCR7+ circulating activated T cells (r = 0.6335, p < 0.05) and MAC387+ cells (r = 0.5726, p < 0.05). IL-17 protein expression was higher in HCQ+QC-responders compared to HCQ-responders or HCQ+QC-nonresponders, while IL-22 protein expression did not differ. mRNA expression demonstrated increased STAT3 expression in a subset of HCQ+QC-nonresponders. CONCLUSION: An increased number of CD69+CCR7+ circulating activated T cells and a strong correlation with CLASI scores in the HCQ+QC-nonresponders suggest these cells are involved in antimalarial-refractory skin disease. STAT3 is also increased in HCQ+QC-nonresponders and may also be a potential target for antimalarial-refractory skin disease.
Asunto(s)
Lupus Eritematoso Cutáneo/tratamiento farmacológico , Receptores CCR7 , Factor de Transcripción STAT3 , Antígenos CD , Antígenos de Diferenciación de Linfocitos T , Antimaláricos/farmacología , Antimaláricos/uso terapéutico , Femenino , Técnica del Anticuerpo Fluorescente , Humanos , Hidroxicloroquina/uso terapéutico , Inmunohistoquímica , Lectinas Tipo C , Lupus Eritematoso Cutáneo/inmunología , Masculino , Persona de Mediana Edad , Quinacrina/uso terapéutico , Receptores CCR7/uso terapéutico , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factor de Transcripción STAT3/genética , Factor de Transcripción STAT3/metabolismo , Linfocitos T , Resultado del TratamientoRESUMEN
BACKGROUND: Lenabasum is a cannabinoid type 2 receptor (CB2R) reverse agonist that demonstrates anti-inflammatory effects in vivo and in vitro in dermatomyositis (DM) and is currently being investigated for therapeutic potential. The purpose of our study is to investigate CB2R distribution as well as the effects of lenabasum in DM. METHODS: Immunohistochemistry staining (IHC) was utilized to examine immune cell and cytokine production changes in lesional DM skin biopsies from lenabasum and placebo-treated patients. CB2R expression in various immune cell populations within DM skin was investigated with image mass cytometry (IMC), whereas flow cytometry elucidated CB2R expression in DM peripheral blood mononuclear cells (PBMCs) as well as cytokine production by CB2R-expressing cell populations. RESULTS: After 12 weeks of lenabasum treatment, IHC staining showed that CD4+ T cells, CB2R, IL-31, IFN-γ, and IFN-ß cytokines were downregulated. IFN-γ and IFN-ß mRNA decreased in lesional DM skin but not in PBMCs. IMC findings revealed that CB2R was upregulated in DM lesional skin compared to HC skin and DM PBMCs (p<0.05). In DM skin, CB2R was upregulated on dendritic cells, B cells, T cells, and macrophages while dendritic cells had the greatest expression in both DM skin and PBMCs (p<0.05). These CB2R+ cells in the skin produce IL-31, IL-4, IFN-γ, and IFN-ß. CONCLUSION: Our findings of differential CB2R expression based on location and cell type suggest modes by which lenabasum may exert anti-inflammatory effects in DM and highlights dendritic cells as potential therapeutic targets.
Asunto(s)
Dermatomiositis , Leucocitos Mononucleares , Dermatomiositis/patología , Dronabinol/análogos & derivados , Dronabinol/metabolismo , Dronabinol/farmacología , Dronabinol/uso terapéutico , Humanos , Leucocitos Mononucleares/metabolismo , Receptores de Cannabinoides/metabolismo , Receptores de Cannabinoides/uso terapéuticoRESUMEN
Dermatomyositis pathogenesis remains incompletely understood; however, recent work suggests a predominant IFN-1 response. We explored dermatomyositis pathogenesis by quantifying the inflammatory cells in the skin, comparing myeloid with plasmacytoid dendritic cell release of IFN-ß, and assessing myeloid dendritic cell (mDC) contribution to hydroxychloroquine refractoriness. Immunohistochemistry was performed to assess cell-type expression in lesional skin biopsies from 12 patients with moderate-to-severe cutaneous dermatomyositis. Immunofluorescence, laser-capture microdissection, and flow cytometry were used to assess mDC release of IFN-ß in lesional skin biopsies and blood of patients with dermatomyositis. Immunohistochemistry was utilized to determine whether myeloid or plasmacytoid dendritic cells were increased in hydroxychloroquine nonresponders. CD4+, CD11c+, and CD69+ cells were more populous in lesional skin of patients with dermatomyositis. mDCs colocalized with IFN-ß by immunofluorescence and laser-capture microdissection revealed increased IFN-ß mRNA expression by mDCs in lesional skin of patients with dermatomyositis. In blood, both mDCs and plasmacytoid dendritic cells were major producers of IFN-ß in patients with dermatomyositis, whereas plasmacytoid dendritic cells predominately released IFN-ß in healthy controls (P < 0.01). mDCs were significantly increased in the skin of hydroxychloroquine nonresponders compared with that in the skin of responders (P < 0.05). mDCs cells appear to play an important role in dermatomyositis pathogenesis and IFN-ß production.
Asunto(s)
Células Dendríticas/inmunología , Dermatomiositis/inmunología , Hidroxicloroquina/farmacología , Interferón beta/metabolismo , Anciano , Biopsia , Células Dendríticas/metabolismo , Dermatomiositis/sangre , Dermatomiositis/diagnóstico , Dermatomiositis/tratamiento farmacológico , Femenino , Humanos , Hidroxicloroquina/uso terapéutico , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Piel/inmunología , Piel/patologíaRESUMEN
BACKGROUND: Dermatomyositis (DM) is conventionally characterized by interface dermatitis (ID) on skin histopathology. A subset of DM patients has skin biopsies showing spongiotic dermatitis (SD), a histopathology more commonly seen in eczema. In this study, we aimed to (a) identify the percentage of clinically diagnosed DM patients with SD skin biopsies, (b) identify cytokine and cell markers that can help determine if a SD skin biopsy is consistent with DM. METHODS: In this case-control study, biopsy specimens from ten DM patients with SD (DM-SD) were compared to specimens from ten healthy controls, ten patients with eczema, and 12 patients with DM with ID (DM-ID). Specimens were stained by immunohistochemistry for MxA, IFN-ß, CD11c, and BDCA2. One-way ANOVA with Bonferroni's multiple comparison test was used to compare protein expression between groups. RESULTS: Eleven of 164 (6.7%) patients with a clinical diagnosis of DM at our tertiary care center were identified as having SD. MxA, IFN-ß, CD11c, and BDCA2 protein expression was significantly higher in DM-SD compared to eczema and healthy controls. Expressions of MxA, IFN-ß, and BDCA2 were not significantly different between DM-SD and DM-ID. CONCLUSION: Increased MxA, IFN-ß, CD11c, and BDCA2 protein expression may aid in distinguishing between DM-SD and eczema and warrants further investigation.
Asunto(s)
Células Dendríticas/patología , Dermatomiositis/metabolismo , Dermatomiositis/patología , Eccema/patología , Proteínas de Resistencia a Mixovirus/metabolismo , Biomarcadores/metabolismo , Biopsia , Antígeno CD11c/metabolismo , Estudios de Casos y Controles , Dermatomiositis/diagnóstico , Dermatomiositis/etnología , Diagnóstico Diferencial , Eccema/metabolismo , Femenino , Humanos , Inmunohistoquímica/métodos , Interferón beta/metabolismo , Lectinas Tipo C/metabolismo , Masculino , Glicoproteínas de Membrana/metabolismo , Persona de Mediana Edad , Proteómica/métodos , Receptores Inmunológicos/metabolismo , Piel/patologíaRESUMEN
Placenta-mediated pregnancy complications are a major challenge in the management of maternal-fetal health. Maternal thrombophilia is a suspected risk factor, but the role of thrombotic processes in these complications has remained unclear. Endothelial protein C receptor (EPCR) is an anticoagulant protein highly expressed in the placenta. EPCR autoantibodies and gene variants are associated with poor pregnancy outcomes. In mice, fetal EPCR deficiency results in placental failure and in utero death. We show that inhibition of molecules involved in thrombin generation or in the activation of maternal platelets allows placental development and embryonic survival. Nonetheless, placentae exhibit venous thrombosis in uteroplacental circulation associated with neonatal death. In contrast, maternal EPCR deficiency results in clinical and histological features of placental abruption and is ameliorated with concomitant Par4 deficiency. Our findings unveil a causal link between maternal thrombophilia, uterine hemorrhage, and placental abruption and identify Par4 as a potential target of therapeutic intervention.
Asunto(s)
Desprendimiento Prematuro de la Placenta , Receptor de Proteína C Endotelial , Trombofilia , Trombosis , Desprendimiento Prematuro de la Placenta/etiología , Desprendimiento Prematuro de la Placenta/patología , Animales , Receptor de Proteína C Endotelial/fisiología , Femenino , Ratones , Placenta/patología , Embarazo , Trombofilia/complicaciones , Trombofilia/patología , Trombosis/patologíaRESUMEN
Orofacial granulomatosis (OFG) is an uncommon chronic granulomatous condition presenting as perioral inflammation in the absence of systemic disease. There is continued debate regarding whether OFG is a distinct clinical disorder or a manifestation of orofacial Crohn's disease. Our retrospective review identified 7 patients diagnosed with OFG between 2000 and 2018 at a tertiary pediatric hospital. Four of the 7 patients subsequently developed Crohn's disease with a median delay of 3.1 years (range 0.4-6.9 years). This indicates that gastroenterology evaluation with long-term monitoring for intestinal Crohn's disease is warranted.
Asunto(s)
Enfermedad de Crohn , Granulomatosis Orofacial , Niño , Enfermedad de Crohn/complicaciones , Enfermedad de Crohn/diagnóstico , Granulomatosis Orofacial/diagnóstico , Granulomatosis Orofacial/tratamiento farmacológico , Granulomatosis Orofacial/etiología , Humanos , Inflamación , Estudios Retrospectivos , Centros de Atención TerciariaAsunto(s)
Vesícula/diagnóstico , Ferroquelatasa/genética , Predisposición Genética a la Enfermedad , Hipertricosis/complicaciones , Porfiria Eritropoyética/diagnóstico , Porfiria Eritropoyética/genética , Vesícula/complicaciones , Diagnóstico Diferencial , Progresión de la Enfermedad , Femenino , Dermatosis de la Mano/diagnóstico , Humanos , Hipertricosis/diagnóstico , Lactante , Índice de Severidad de la EnfermedadRESUMEN
PURPOSE OF THE REVIEW: Dermatomyositis (DM) is an uncommon autoimmune disease that primarily affects the skin, muscle, and/or lungs, and remains a therapeutic challenge. We discuss recent studies evaluating efficacy of conventional treatments for clinically amyopathic DM (CADM), DM-associated interstitial lung (ILD) disease, and classic DM (CDM). We highlight several emerging new therapies with a focus on clinical trials, systematic reviews, and case series in the last 5 years. RECENT FINDINGS: Recent studies report a significant number of patients remain refractory to antimalarials and require second- and third-line agents. Effective treatment for DM-associated ILD can vary based on patient specific antibodies. CDM requires oral glucocorticoids; recent studies have evaluated the benefits of adjunctive therapies including methotrexate and calcineurin inhibitors. New therapies target cell populations or cytokines thought to drive disease pathogenesis. Dermatomyositis is an autoimmune disease that remains challenging to treat. Many patients are refractory to conventional therapies, warranting the development and evaluation of new treatments.
Asunto(s)
Dermatomiositis/tratamiento farmacológico , Glucocorticoides/uso terapéutico , Inmunosupresores/uso terapéutico , Metotrexato/uso terapéutico , Humanos , Resultado del TratamientoRESUMEN
The management of autoimmune blistering diseases (AIBD) is therapeutically challenging, particularly in patients who plan to conceive, or are pregnant or breastfeeding. Not only is a patient's immune system altered by pregnancy-associated hormonal changes, but several medications used for AIBD treatment are not recommended for use in pregnancy or lactation. The data acquired regarding the safety and efficacy of these therapeutic interventions are gathered from studies or case reports from other diseases, as the treatment modalities are similar and randomized controlled trials are typically not performed in the setting of pregnancy. Although some medications for AIBD treatment are considered unsafe for use in pregnancy, many effective and tolerable therapies are able to provide benefit to these patients. In fact, most first-line agents may be used in pregnancy, to a given extent. This article discusses the medications used to treat AIBD prior to conception, during pregnancy, and while breastfeeding, as well as highlights those that are contraindicated. The preferred approach to management in these patients is also discussed. Additionally, we present the available information regarding neonates of mothers with a diagnosis of AIBD, including the likelihood, identification, and management of neonatal blistering and the effects from medication exposure in utero.
Asunto(s)
Enfermedades Autoinmunes/terapia , Complicaciones del Embarazo/terapia , Enfermedades Cutáneas Vesiculoampollosas/terapia , Enfermedades Autoinmunes/inmunología , Lactancia Materna , Femenino , Humanos , Recién Nacido , Enfermedades del Recién Nacido/inmunología , Enfermedades del Recién Nacido/terapia , Embarazo , Complicaciones del Embarazo/inmunología , Enfermedades Cutáneas Vesiculoampollosas/inmunologíaRESUMEN
Cutaneous lupus erythematosus (CLE) is an autoimmune disease that can be associated with systemic lupus erythematosus (SLE) symptoms. The pathogenesis of both CLE and SLE is multifactorial, involving genetic susceptibility, environmental factors, and innate and adaptive immune responses. Despite the efficacy of current medications, many patients remain refractory, highlighting the necessity for new treatment options. Unfortunately, owing to challenges related in part to trial design and disease heterogeneity, only one new biologic in the last 50 years has been approved by the US Food and Drug Administration for the treatment of SLE. Thus, although SLE and CLE have a similar pathogenesis, patients with CLE who do not meet criteria for SLE cannot benefit from this advancement. This article discusses the recent trials and emphasizes the need to include patients with single-organ lupus, such as CLE, in SLE trials.
Asunto(s)
Lupus Eritematoso Cutáneo/diagnóstico , Lupus Eritematoso Cutáneo/terapia , Lupus Eritematoso Sistémico , Predisposición Genética a la Enfermedad , Humanos , Estados UnidosRESUMEN
Despite new treatments introduced over the past several years, metastatic melanoma remains difficult to cure. Although melanoma in situ (MIS) has better prognosis, it relies heavily on thorough surgical excision, where ill-defined margins can pose a challenge to successful removal, potentially leading to invasive melanoma. As well, MIS in the head and neck area can create serious aesthetic concerns with regard to the surgical defect and substantial scar formation. Toward improved treatment of localized melanoma, including the targeting of unrecognized invasive components, we have been studying a novel agent, NEO412, designed for transdermal application. NEO412 is a tripartite agent that was created by covalent conjugation of three bioactive agents: temozolomide (TMZ, an alkylating agent), perillyl alcohol (POH, a naturally occurring monoterpene with anticancer properties), and linoleic acid (LA, an omega-6 essential fatty acid). We investigated the anti-melanoma potency of NEO412 in vitro and in mouse models in vivo. The in vitro results showed that NEO412 effectively killed melanoma cells, including TMZ-resistant and BRAF mutant ones, through DNA alkylation and subsequent apoptosis. in vivo, NEO412 inhibited tumor growth when applied topically to the skin of tumor-bearing animals, and this effect involved a combination of increased tumor cell death with decreased blood vessel development. At the same time, drug-treated mice continued to thrive, and there was no apparent damage to normal skin in response to daily drug applications. Combined, our results present NEO412 as a potentially promising new treatment for cutaneous melanoma, in particular MIS, deserving of further study.
RESUMEN
BACKGROUND: Mitral annuloplasty with either a partial band or complete ring is an integral part of mitral valve repair for degenerative disease. The affect of annuloplasty type on outcomes has not been well described. The objective of our study was to compare echocardiographic and functional characteristics of patients who underwent mitral repair with either a complete ring or a partial band. METHODS: We evaluated 107 patients who underwent mitral repair of myxomatous degeneration at our institution by stress echocardiography, 6-minute walk testing, and short form-36 questionnaire. These assessments were performed 4.3 ± 2.2 years following mitral repair by a single surgeon. A band was used in 65 patients (61%) and a ring in 42 patients (39%). Parametric and nonparametric tests were used in the analyses. RESULTS: The labeled band and ring size used for repair were 30.7 ± 2.8 mm and 30.4 ± 2.1 mm, respectively (P = .6). The resting mean mitral gradient and valve area were 3.7 ± 1.9 mm Hg and 2.3 ± 0.6 cm(2) for patients who received a band and 5.8 ± 2.6 mm Hg and 1.8 ± 0.5 cm(2) for patients who received a ring (both P < .001). Distance traversed on 6-minute walk testing was 471 ± 77 m in the band group and 443 ± 107 m in the ring group (P = .1). At peak exercise, the mean mitral gradient (15.3 ± 8.2 mm Hg vs 10.6 ± 4.8 mm Hg; P < .001) and right ventricular systolic pressure (52.6 ± 14.2 mm Hg vs 45.8 ± 9.5 mm Hg; P = .004) were higher for patients who received a ring versus a band. Ring patients reported lower levels of energy (P = .02) and general health (P = .007) on short form-36 assessment. CONCLUSIONS: Annuloplasty using a complete ring may be associated with a higher mitral valve gradient at rest and at peak exercise in certain patients. These patients may also have worse quality of life. In view of these findings, we recommend careful consideration of annuloplasty type and size at the time of mitral repair of organic disease.
Asunto(s)
Implantación de Prótesis de Válvulas Cardíacas/efectos adversos , Anuloplastia de la Válvula Mitral/efectos adversos , Insuficiencia de la Válvula Mitral/cirugía , Estenosis de la Válvula Mitral/diagnóstico , Válvula Mitral/cirugía , Anciano , Biomarcadores/sangre , Distribución de Chi-Cuadrado , Estudios Transversales , Ecocardiografía de Estrés , Prueba de Esfuerzo , Tolerancia al Ejercicio , Femenino , Prótesis Valvulares Cardíacas , Implantación de Prótesis de Válvulas Cardíacas/instrumentación , Humanos , Masculino , Persona de Mediana Edad , Válvula Mitral/diagnóstico por imagen , Válvula Mitral/fisiopatología , Anuloplastia de la Válvula Mitral/instrumentación , Insuficiencia de la Válvula Mitral/diagnóstico , Insuficiencia de la Válvula Mitral/fisiopatología , Estenosis de la Válvula Mitral/sangre , Estenosis de la Válvula Mitral/etiología , Estenosis de la Válvula Mitral/fisiopatología , Péptido Natriurético Encefálico/sangre , Selección de Paciente , Valor Predictivo de las Pruebas , Estudios Prospectivos , Diseño de Prótesis , Calidad de Vida , Factores de Riesgo , Encuestas y Cuestionarios , Sístole , Resultado del Tratamiento , Función Ventricular Derecha , Presión VentricularRESUMEN
Chimerism occurs when an organism contains cells derived from more than one distinct zygote. We focus on monochorionic dizygotic twin blood chimerism, and particularly twin-twin transfusion syndrome in such pregnancies. For years, researchers have understood chimerism to be a common phenomenon in cattle. Although, this review will not delve deeply into animal chimerism, an understanding of chimerism in the animal world can provide clues regarding health implications for human chimeras. This report serves two purposes: an update and assessment of the twins we reported previously in 2010 [Assaf et al., 2010] and a review on dizygotic monochorionic chimeric twins. First, our updated assessment of the twins shows no identifiable regression of Müllerian sex derivatives in the female, and normal neurodevelopment was documented in both. Our research has suggested several key points; one that blood chimerism persists from fetal life to at least age two years. Second, chimerism in humans is not as rare as previously thought, although it has been studied only recently. Third, assisted reproductive technologies appear to increase the risk of monochorionic dizygotic twin pregnancies.