RESUMEN
Large-scale medical sequencing provides a focal point around which to reorganize health care and health care research. Mobile health (mHealth) is also currently undergoing explosive growth and could be another innovation that will change the face of future health care. We are employing primary ovarian insufficiency (POI) as a model rare condition to explore the intersection of these potentials. As both sequencing capabilities and our ability to intepret this information improve, sequencing for medical purposes will play an increasing role in health care beyond basic research: it will help guide the delivery of care to patients. POI is a serious chronic disorder and syndrome characterized by hypergonadotrophic hypogonadism before the age of 40 years and most commonly presents with amenorrhea. It may have adverse health effects that become fully evident years after the initial diagnosis. The condition is most commonly viewed as one of infertility, however, it may also be associated with adverse long-term outcomes related to inadequate bone mineral density, increased risk of cardiovascular disease, adrenal insufficiency, hypothyroidism and, if pregnancy ensues, having a child with Fragile X Syndrome. There may also be adverse outcomes related to increased rates of anxiety and depression. POI is also a rare disease, and accordingly, presents special challenges. Too often advances in research are not effectively integrated into community care at the point of service for those with rare diseases. There is a need to connect community health providers in real time with investigators who have the requisite knowledge and expertise to help manage the rare disease and to conduct ongoing research. Here we review the pathophysiology and management of POI and propose the development of an international Clinical Research Integration Special Program (CRISP) for the condition.
Asunto(s)
Investigación Biomédica/organización & administración , Insuficiencia Ovárica Primaria/terapia , Adulto , Susceptibilidad a Enfermedades/inmunología , Femenino , Predisposición Genética a la Enfermedad , Humanos , Embarazo , Insuficiencia Ovárica Primaria/etiología , Insuficiencia Ovárica Primaria/fisiopatología , Desarrollo de ProgramaRESUMEN
Monoclonal antibodies (Mabs) conjugated to toxins or their subunits (immunotoxins or ITs) are undergoing clinical testing in adults with a variety of malignancies. The potential impact of this form of therapy in pediatric precursor B-lineage acute lymphoblastic leukemia (pre-B ALL) has yet to be determined. Mabs directed against the cell surface antigens, CD19 and CD22 conjugated to deglycosylated ricin A chain (dgRTA) have been tested in patients with non-Hodgkin's lymphoma (NHL), but not in patients with pre-B ALL. Because of the encouraging performance of these ITs in phase I trials, we evaluated the specific cytotoxicity of anti-CD19 (HD37-dgRTA) and anti-CD22 (RFB4-dgRTA) ITs or their combination (Combotox) on patient-derived pre-B ALL cells maintained in vitro on a stromal feeder layer. After 48 h in culture, cytotoxicity to tumor cells was determined by flow cytometry using propidium iodide (PI) and fluorescein isothiocyanate (FITC)-conjugated anti-CD10, 19, and 22. Both RFB4-dgRTA and HD37-dgRTA induced a statistically significant reduction in the number of viable leukemic cells, and Combotox was even more effective. Our results demonstrate that these ITs are specifically cytotoxic to primary pre-B ALL cells and that they should be further evaluated for the therapy of B-lineage ALL.
Asunto(s)
Antígenos CD19/inmunología , Antígenos CD/inmunología , Antígenos de Diferenciación de Linfocitos B/inmunología , Linfoma de Burkitt/inmunología , Linfoma de Burkitt/patología , Moléculas de Adhesión Celular , Inmunotoxinas/toxicidad , Lectinas , Preleucemia/patología , Ricina/toxicidad , Adulto , Especificidad de Anticuerpos , Apoptosis/efectos de los fármacos , Células de la Médula Ósea/patología , Supervivencia Celular/efectos de los fármacos , Niño , Humanos , Linfocitos/efectos de los fármacos , Linfocitos/inmunología , Linfocitos/patología , Preleucemia/inmunología , Lectina 2 Similar a Ig de Unión al Ácido Siálico , Células del Estroma/efectos de los fármacos , Células del Estroma/patología , Células Tumorales CultivadasRESUMEN
PURPOSE: After noticing specific aberrant forms of development in preimplantation embryos from women with endometriosis, we embarked upon this study in order to examine the frequency of these events as compared with controls. METHODS: A total of 235 embryos representing 30 women undergoing 56 cycles of in vitro fertilization were retrospectively analyzed on videotape and placed into categories based upon the incidence of specific morphological criteria found during observations made on the first and second days following oocyte retrieval. RESULTS: Several of the aberrant nuclear and cytoplasmic events were found to be statistically increased in the group of embryos from women with endometriosis. CONCLUSIONS: The incidence of defined aberrant phenotypes in embryos from women with laparoscopically documented endometriosis may allow us to identify specific embryotoxic events with reference to endometriosis and other diagnoses.