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1.
Children (Basel) ; 8(12)2021 Dec 08.
Artículo en Inglés | MEDLINE | ID: mdl-34943356

RESUMEN

BACKGROUND: Mental imagery (MI) may play a key role in the development of various mental disorders in adolescents. Adolescence is known to be a fragile life period, in which acceptance by one's favored peer group is extremely important, and social rejection is particularly painful. This is the first pilot study investigating MI and its relationship to social pain (SP). METHOD: A sample of 80 adolescents (14-20 years; 75.3% female) completed a web-based quasi-experimental design about the contents and characteristics of their spontaneous positive and negative MI and associated emotions, and were asked to complete the Social Pain Questionnaire, the Becks Depression Inventory and the Social Phobia Inventory. RESULTS: A higher score of SP was significantly associated with increased fear, sadness, and feelings of guilt, and less control over negative MI. Characteristics of negative MI were more precisely predicted by SP scores than depression- and social anxiety scores. Adolescents with higher SP-scores more often reported negative images including social situations and were more likely to perceive negative images in a combination of field-and observer perspectives than adolescents with lower SP scores. CONCLUSION: SP-sensitivity seems to be linked to unique characteristics of negative MI, which reveals the strong emotional impact of social exclusion in youths. The results do not allow causal conclusions to be drawn, but raise questions about previous studies comparing each imagery perspective individually.

2.
World Dev ; 137: 105128, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-32834397

RESUMEN

The COVID-19 pandemic created a critical need for citizen volunteers working with government to protect public health and to augment overwhelmed public services. Our research examines the crucial role of community volunteers and their effective deployment during a crisis. We analyze individual and collaborative service activities based on usage data from 85,699 COVID-19 volunteers gathered through China's leading digital volunteering platform, as well as a survey conducted among a sample of 2,270 of these COVID-19 volunteers using the platform and interviews with 14 civil society leaders in charge of coordinating service activities. Several results emerge: the value of collaboration among local citizens, civil society including community-based groups, and regional government to fill gaps in public services; the key role of experienced local volunteers, who rapidly shifted to COVID-19 from other causes as the pandemic peaked; and an example of state-led coproduction based on long-term relationships. Our analysis provides insight into the role of volunteerism and coproduction in China's response to the pandemic, laying groundwork for future research. The findings can help support the response to COVID-19 and future crises by more effectively leveraging human capital and technology in community service delivery.

3.
Spine (Phila Pa 1976) ; 43(24): 1731-1738, 2018 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-29877995

RESUMEN

STUDY DESIGN: Prospective evaluation of an informational web-based calculator for communicating estimates of personalized treatment outcomes. OBJECTIVE: To evaluate the usability, effectiveness in communicating benefits and risks, and impact on decision quality of a calculator tool for patients with intervertebral disc herniations, spinal stenosis, and degenerative spondylolisthesis who are deciding between surgical and nonsurgical treatments. SUMMARY OF BACKGROUND DATA: The decision to have back surgery is preference-sensitive and warrants shared decision making. However, more patient-specific, individualized tools for presenting clinical evidence on treatment outcomes are needed. METHODS: Using Spine Patient Outcomes Research Trial data, prediction models were designed and integrated into a web-based calculator tool: http://spinesurgerycalc.dartmouth.edu/calc/. Consumer Reports subscribers with back-related pain were invited to use the calculator via email, and patient participants were recruited to use the calculator in a prospective manner following an initial appointment at participating spine centers. Participants completed questionnaires before and after using the calculator. We randomly assigned previously validated questions that tested knowledge about the treatment options to be asked either before or after viewing the calculator. RESULTS: A total of 1256 consumer reports subscribers and 68 patient participants completed the calculator and questionnaires. Knowledge scores were higher in the postcalculator group compared to the precalculator group, indicating that calculator usage successfully informed users. Decisional conflict was lower when measured following calculator use, suggesting the calculator was beneficial in the decision-making process. Participants generally found the tool helpful and easy to use. CONCLUSION: Although the calculator is not a comprehensive decision aid, it does focus on communicating individualized risks and benefits for treatment options. Moreover, it appears to be helpful in achieving the goals of more traditional shared decision-making tools. It not only improved knowledge scores but also improved other aspects of decision quality. LEVEL OF EVIDENCE: 2.


Asunto(s)
Toma de Decisiones , Técnicas de Apoyo para la Decisión , Internet , Degeneración del Disco Intervertebral/terapia , Desplazamiento del Disco Intervertebral/terapia , Estenosis Espinal/terapia , Espondilolistesis/terapia , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Encuestas y Cuestionarios , Resultado del Tratamiento
4.
Am J Perinatol ; 35(9): 858-864, 2018 07.
Artículo en Inglés | MEDLINE | ID: mdl-29365327

RESUMEN

OBJECTIVE: The objective of this study was to ascertain the likelihood of isolated maternal fever and suspected intrauterine inflammation or infection or both (Triple I) among cases of histologic chorioamnionitis with funisitis (HCF) at term. STUDY DESIGN: In this case-control study, placental pathology records were reviewed to identify term singleton laboring patients with HCF. Controls (1:1) were matched for gestational age. RESULTS: During the 6-month period, there were 2,399 term deliveries of laboring women. Of 1,552 (65%) term placentas examined, 4% (n = 60) had HCF.Features of Triple I were significantly more common among cases than controls: (1) isolated maternal fever of ≥100.4°F, twice, at least 30 minutes apart (p = 0.014); (2) fever with fetal tachycardia (p = 0.029); 3) fever with either fetal tachycardia or white blood cell count greater than 15,000 per mm3 (p = 0.034). The feature of Triple I with the highest sensitivity at 10% (95% confidence intervals [CI] 4-21%) was isolated maternal fever using ≥100.4°F on two occasions. The specificity for all features was consistently 100% (95% CI 91-100%). CONCLUSION: To our knowledge, this is the first report on HCF and Triple I features. Though the sensitivity of Triple I to identify HCF is low, specificity is excellent.


Asunto(s)
Corioamnionitis/patología , Corioamnionitis/fisiopatología , Infecciones/etiología , Inflamación/etiología , Complicaciones del Embarazo/diagnóstico , Enfermedades Uterinas/microbiología , Adolescente , Adulto , Líquido Amniótico/microbiología , Estudios de Casos y Controles , Femenino , Edad Gestacional , Humanos , Recién Nacido , Infecciones/diagnóstico , Inflamación/diagnóstico , Trabajo de Parto , Masculino , Embarazo , Resultado del Embarazo , Probabilidad , Sensibilidad y Especificidad , Enfermedades Uterinas/fisiopatología , Adulto Joven
5.
J Clin Oncol ; 29(7): 917-24, 2011 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-21282551

RESUMEN

PURPOSE: Adoptive immunotherapy using tumor-infiltrating lymphocytes represents an effective cancer treatment for patients with metastatic melanoma. The NY-ESO-1 cancer/testis antigen, which is expressed in 80% of patients with synovial cell sarcoma and approximately 25% of patients with melanoma and common epithelial tumors, represents an attractive target for immune-based therapies. The current trial was carried out to evaluate the ability of adoptively transferred autologous T cells transduced with a T-cell receptor (TCR) directed against NY-ESO-1 to mediate tumor regression in patients with metastatic melanoma and synovial cell sarcoma. PATIENTS AND METHODS: A clinical trial was performed in patients with metastatic melanoma or metastatic synovial cell sarcoma refractory to all standard treatments. Patients with NY-ESO-1-positive tumors were treated with autologous TCR-transduced T cells plus 720,000 iU/kg of interleukin-2 to tolerance after preparative chemotherapy. Objective clinical responses were evaluated using Response Evaluation Criteria in Solid Tumors (RECIST). RESULTS: Objective clinical responses were observed in four of six patients with synovial cell sarcoma and five of 11 patients with melanoma bearing tumors expressing NY-ESO-1. Two of 11 patients with melanoma demonstrated complete regressions that persisted after 1 year. A partial response lasting 18 months was observed in one patient with synovial cell sarcoma. CONCLUSION: These observations indicate that TCR-based gene therapies directed against NY-ESO-1 represent a new and effective therapeutic approach for patients with melanoma and synovial cell sarcoma. To our knowledge, this represents the first demonstration of the successful treatment of a nonmelanoma tumor using TCR-transduced T cells.


Asunto(s)
Vacunas contra el Cáncer/administración & dosificación , Inmunoterapia/métodos , Linfocitos Infiltrantes de Tumor/inmunología , Melanoma/terapia , Sarcoma Sinovial/terapia , Neoplasias Cutáneas/terapia , Adulto , Vacunas contra el Cáncer/inmunología , Epigénesis Genética , Femenino , Ingeniería Genética , Humanos , Masculino , Melanoma/inmunología , Melanoma/mortalidad , Melanoma/secundario , Persona de Mediana Edad , Metástasis de la Neoplasia , Estadificación de Neoplasias , Pronóstico , Medición de Riesgo , Sarcoma Sinovial/inmunología , Sarcoma Sinovial/mortalidad , Sarcoma Sinovial/secundario , Neoplasias Cutáneas/inmunología , Neoplasias Cutáneas/mortalidad , Neoplasias Cutáneas/patología , Análisis de Supervivencia , Resultado del Tratamiento , Adulto Joven
6.
Adolesc Med State Art Rev ; 22(3): 367-86, ix, 2011 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-22423456

RESUMEN

Adolescence is a critical period in the human lifecycle, a time of rapid physical and socioemotional growth and a time when individuals establish lifestyle habits and health behaviors that often endure into and have lasting effects in adulthood. Adolescent health promotion programs play a critical role in helping youth establish healthy lifestyles. In this article, we present a socio-ecological model as a framework for identifying effective policy and program areas that have a positive impact on adolescent health behaviors. Our discussion focuses on 4 key areas: reproductive health; obesity prevention; mental health and substance use, including smoking; and injury and violence prevention. We proceed with an overview of the current status of state-led adolescent health promotion policies and programs from a newly created policy database and then examine the evidence on the cost of preventable adolescent health problems and the cost-effectiveness of health promotion programs and policies. We conclude by discussing the threat posed to adolescent health promotion services and state-led policy initiatives by proposed and implemented federal and state-level budget cuts and examine the possible health and economic repercussions of reducing or eliminating these programs.


Asunto(s)
Servicios de Salud del Adolescente/economía , Planificación en Salud/economía , Política de Salud/economía , Promoción de la Salud/economía , Adolescente , Servicios de Salud del Adolescente/legislación & jurisprudencia , Niño , Análisis Costo-Beneficio , Planificación en Salud/legislación & jurisprudencia , Política de Salud/legislación & jurisprudencia , Promoción de la Salud/legislación & jurisprudencia , Accesibilidad a los Servicios de Salud/economía , Humanos , Estados Unidos , Adulto Joven
7.
J Immunother ; 33(6): 626-9, 2010.
Artículo en Inglés | MEDLINE | ID: mdl-20551834

RESUMEN

Adjuvants are requisite components of many vaccines designed to elicit T-cell immunity although the exact components of commonly used adjuvants are not always fully defined. In 2006, owing to concerns of prion contamination, the formulation of Montanide ISA 51 Incomplete Freund's Adjuvant (IFA) was changed from using oleic acid isolated from beef tallow to that isolated from olives. In sequential clinical trials in the Surgery Branch, NCI patients at high risk for recurrence of melanoma were immunized with the gp100 melanoma/melanocyte antigenic peptide, gp100: 209-217 (210M), emulsified in the beef-derived IFA or the olive-derived IFA. The in vivo generation of gp100 reactive T cells was significantly less in patients receiving the olive compared with the beef IFA as assessed by both ELISPOT (P2=0.0001) and in vitro sensitization assays (P2=0.0001). Local skin reactions to the peptide emulsion were also far less severe using the olive IFA (P2=0.0003). Thus it seems likely that contaminants in the beef-derived IFA played an important role in the increased adjuvanticity of this preparation compared with the olive-derived IFA. These findings raise serious concerns related to the use of the available olive-derived IFA for immunization in clinical trials. A survey of ongoing clinical trials listed in ClinicalTrials.gov revealed 36 trials currently accruing patients that are using the olive-derived Montanide ISA 51 IFA.


Asunto(s)
Vacunas contra el Cáncer , Adyuvante de Freund/administración & dosificación , Manitol/análogos & derivados , Melanoma/terapia , Ácidos Oléicos/administración & dosificación , Neoplasias Cutáneas/terapia , Adyuvantes Inmunológicos/metabolismo , Animales , Bovinos , Línea Celular Transformada , Grasas/metabolismo , Adyuvante de Freund/efectos adversos , Adyuvante de Freund/metabolismo , Humanos , Inmunización , Manitol/administración & dosificación , Manitol/efectos adversos , Manitol/metabolismo , Melanoma/inmunología , Olea/metabolismo , Ácidos Oléicos/efectos adversos , Ácidos Oléicos/metabolismo , Neoplasias Cutáneas/inmunología , Resultado del Tratamiento , Vacunas de Subunidad , Verduras/metabolismo , Antígeno gp100 del Melanoma/administración & dosificación
8.
Blood ; 114(3): 535-46, 2009 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-19451549

RESUMEN

Gene therapy of human cancer using genetically engineered lymphocytes is dependent on the identification of highly reactive T-cell receptors (TCRs) with antitumor activity. We immunized transgenic mice and also conducted high-throughput screening of human lymphocytes to generate TCRs highly reactive to melanoma/melanocyte antigens. Genes encoding these TCRs were engineered into retroviral vectors and used to transduce autologous peripheral lymphocytes administered to 36 patients with metastatic melanoma. Transduced patient lymphocytes were CD45RA(-) and CD45RO(+) after ex vivo expansion. After infusion, the persisting cells displayed a CD45RA(+) and CD45RO(-) phenotype. Gene-engineered cells persisted at high levels in the blood of all patients 1 month after treatment, responding patients with higher ex vivo antitumor reactivity than nonresponders. Objective cancer regressions were seen in 30% and 19% of patients who received the human or mouse TCR, respectively. However, patients exhibited destruction of normal melanocytes in the skin, eye, and ear, and sometimes required local steroid administration to treat uveitis and hearing loss. Thus, T cells expressing highly reactive TCRs mediate cancer regression in humans and target rare cognate-antigen-containing cells throughout the body, a finding with important implications for the gene therapy of cancer. This trial was registered at www.ClinicalTrials.gov as NCI-07-C-0174 and NCI-07-C-0175.


Asunto(s)
Antígenos de Neoplasias/inmunología , Terapia Genética/métodos , Melanoma/terapia , Receptores de Antígenos de Linfocitos T/administración & dosificación , Traslado Adoptivo/efectos adversos , Traslado Adoptivo/métodos , Adulto , Animales , Autoantígenos/inmunología , Femenino , Vectores Genéticos , Pérdida Auditiva/etiología , Humanos , Transfusión de Linfocitos/efectos adversos , Transfusión de Linfocitos/métodos , Linfocitos/metabolismo , Masculino , Melanocitos/inmunología , Melanoma/complicaciones , Ratones , Ratones Transgénicos , Persona de Mediana Edad , Receptores de Antígenos de Linfocitos T/genética , Receptores de Antígenos de Linfocitos T/inmunología , Especificidad del Receptor de Antígeno de Linfocitos T , Transducción Genética , Trasplante Autólogo , Resultado del Tratamiento , Uveítis/etiología
9.
Am J Obstet Gynecol ; 197(3): 319.e1-6, 2007 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-17826437

RESUMEN

OBJECTIVE: The objective of the study was to determine whether placental abruption is associated with an increased incidence of histologic chorioamnionitis among singleton gestations and whether this association is dependent on its severity. STUDY DESIGN: Data were derived from the New Jersey-Placental Abruption Study, an ongoing, multicenter, case-control study conducted in New Jersey since August 2002. Subjects were women with a clinical diagnosis of abruption, and controls were matched to cases based on parity and maternal race/ethnicity. Two perinatal pathologists, blinded to the case-control status, performed all histologic examination based on standardized protocol. The association between chorioamnionitis and abruption was quantified based on odds ratio (OR) with 95% confidence interval (CI), after adjustment for potential confounders, and all analyses were stratified based on preterm birth (less than 37 weeks) status. RESULTS: At preterm gestations (n = 141), chorioamnionitis was present in 30.8% and 12.5% of abruption cases and controls, respectively (OR 3.6, 95% CI 1.7 to 10.5). At term gestations (n = 205), the corresponding rates were 34.6% and 20.4%, respectively (OR 2.8, 95% CI 1.3 to 6.1). Severe chorioamnionitis was 7.2 (95% CI 1.6 to 20.1) and 18.3 (95% CI 2.2 to 150.4) times more common in abruption patients at preterm and term gestations, respectively. CONCLUSION: Histologic chorioamnionitis is associated with placental abruption. The association was strongest in the presence of severe chorioamnionitis at term and, to a lesser extent, at preterm gestations. These observations suggest that the histologic findings in abruption are accompanied by severe inflammation, in both preterm and term gestations.


Asunto(s)
Desprendimiento Prematuro de la Placenta/inmunología , Corioamnionitis/patología , Rotura Prematura de Membranas Fetales/inmunología , Infiltración Neutrófila , Desprendimiento Prematuro de la Placenta/etiología , Adulto , Estudios de Casos y Controles , Corioamnionitis/inmunología , Femenino , Humanos , Placenta/patología , Enfermedades Placentarias/inmunología , Embarazo , Nacimiento Prematuro/inmunología , Estudios Prospectivos , Factores de Riesgo
10.
Urology ; 70(1): 178.e13-5, 2007 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-17656235

RESUMEN

We report a case of renal cell carcinoma (RCC) with extensive oncocytoid features developing in a 12-year-old African-American boy after chemotherapy for cardiac leiomyosarcoma at 3 months of age. The tumor showed histopathologic features similar to those previously reported in RCC after chemotherapy for neuroblastoma and now considered a specific entity in the World Health Organization classification of renal tumors as "RCC associated with neuroblastoma." Our report expands the spectrum of tumors (beyond neuroblastoma) in which RCCs with such an appearance can arise in the pediatric age group after chemotherapy.


Asunto(s)
Carcinoma de Células Renales/patología , Neoplasias Cardíacas/tratamiento farmacológico , Neoplasias Renales/patología , Leiomiosarcoma/tratamiento farmacológico , Neoplasias Primarias Secundarias/patología , Niño , Humanos , Masculino
11.
J Immunother ; 29(3): 313-9, 2006.
Artículo en Inglés | MEDLINE | ID: mdl-16699374

RESUMEN

Lymphopenia is a serious consequence of HIV infection and the administration of cancer chemotherapeutic agents. Although growth factors can be administered to patients to increase circulating neutrophils, there is no effective method to stimulate CD8+ lymphocyte production in humans, in vivo. This report is the first to describe the administration of recombinant interleukin-7 to humans and demonstrates the ability of this cytokine to mediate selective increases in CD4+ and CD8+ lymphocytes along with a decrease in the percentage of CD4+ T-regulatory cells. These studies suggest an important role for interleukin-7 in the treatment of patients with lymphopenia.


Asunto(s)
Linfocitos T CD4-Positivos/metabolismo , Linfocitos T CD8-positivos/metabolismo , Interleucina-7/metabolismo , Linfocitos T Reguladores/metabolismo , Adulto , Anciano , Médula Ósea/metabolismo , Células de la Médula Ósea/metabolismo , Linfocitos T CD4-Positivos/efectos de los fármacos , Linfocitos T CD8-positivos/efectos de los fármacos , Proliferación Celular , Femenino , Factores de Transcripción Forkhead/metabolismo , Humanos , Linfopoyesis/efectos de los fármacos , Masculino , Persona de Mediana Edad , Linfocitos T Reguladores/efectos de los fármacos
12.
J Immunother ; 29(2): 224-31, 2006.
Artículo en Inglés | MEDLINE | ID: mdl-16531823

RESUMEN

Efforts to develop effective cancer vaccines often use combinations of immunogenic peptides to increase the applicability and effectiveness of the immunizations. The immunologic consequences of combining more than 1 self/tumor antigen in a single vaccine emulsion remain unclear, however. We performed 2 sequential clinical trials in patients at high risk for melanoma recurrence. Patients were given the highly immunogenic gp100:209-217(210M) peptide and the less immunogenic tyrosinase:368-376(370D) peptide once every 3 weeks for 4 weeks. This vaccination course was 12 weeks long, and patients were vaccinated for up to 4 courses (16 total vaccinations). In the first trial in 31 patients, the peptides were emulsified separately in incomplete Freund adjuvant and injected at 2 different sites. In the second trial in 33 patients, the peptides were emulsified together and injected at the same site. Cryopreserved lymphocytes were obtained by apheresis after each course and were evaluated for antipeptide activity using tetramer, enzyme-linked immunospot, and in vitro sensitization boost assays. When the peptides were injected at separate sites, robust specific reactivity to the native gp100:209-217 peptide was measured by each of the assays, whereas immunization with the tyrosinase:368-376(370D) peptide was far less effective. When the peptides were emulsified and injected together at the same site, immunization to the gp100:209-217(210M) epitope dropped precipitously, whereas reactivity to the tyrosinase:368-376(370D) peptide was enhanced. These cautionary data indicate that mixing peptides in the same emulsion can alter reactivity compared with peptides injected separately by mechanisms that may include the induction of localized nonspecific inflammation or competitive binding of peptides to major histocompatibility complex molecules.


Asunto(s)
Vacunas contra el Cáncer/inmunología , Melanoma/inmunología , Melanoma/terapia , Glicoproteínas de Membrana/inmunología , Adulto , Anciano , Antígenos de Neoplasias/administración & dosificación , Antígenos de Neoplasias/inmunología , Vacunas contra el Cáncer/administración & dosificación , Interacciones Farmacológicas/inmunología , Femenino , Humanos , Masculino , Melanoma/patología , Glicoproteínas de Membrana/administración & dosificación , Persona de Mediana Edad , Monofenol Monooxigenasa/administración & dosificación , Monofenol Monooxigenasa/química , Monofenol Monooxigenasa/inmunología , Prevención Secundaria , Resultado del Tratamiento , Antígeno gp100 del Melanoma
13.
Indian J Pediatr ; 73(1): 25-8, 2006 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-16444056

RESUMEN

OBJECTIVE: To investigate the association between gestational age, placental pathology and outcome among preterm births. METHODS: Medical records and placental pathology results of 165 preterm infants (gestational age pound 34 weeks) were used to analyze the development of intraventricular hemorrhage (IVH), bronchopulmonary dysplasia (BPD), retinopathy of prematurity (ROP), patent ductus arteriosus (PDA) and sepsis, in association with placental findings in the gestational age categories of 22-27 (n=71) and 28-33 (n=93) weeks. RESULTS: Significant differences were found in placental findings based on gestational age and neonatal morbidity. Lower gestational age was associated with increased infection-related lesions such as chorionic vasculitis (47.9%, P< 0.001) and acute chorioamnionitis (67.6%, P< 0.001). Placental lesions reflecting disturbances of fetal-placental blood flow (infarction, chorionic plate thrombi and basal perivillous fibrin) were predominantly seen in the 28-33 week gestational age category (P< 0.05-0.01). Despite the high prevalence of chorioamnionitis (38.8%), no significant association was found between this lesion and the tested preterm morbidity after controlling for gestational age. Only, villous edema and chorionic vasculitis were identified as independent predictors for the development of IVH (49.2%, ORA 2.57, 95% CI 1.01, 6.58 and 39.3%, ORA1.95, 95% CI 1.01, 4.21, respectively). CONCLUSION: Villous edema and chorionic vasculitis are significant risk factors for the development of the IVH among neonates born at gestational age pound 34 weeks.


Asunto(s)
Enfermedades del Prematuro/etiología , Enfermedades Placentarias , Corioamnionitis/etiología , Vellosidades Coriónicas/irrigación sanguínea , Edema/complicaciones , Femenino , Edad Gestacional , Humanos , Recién Nacido , Hemorragias Intracraneales/etiología , Embarazo , Resultado del Embarazo , Nacimiento Prematuro , Factores de Riesgo , Vasculitis/complicaciones
14.
Arch Pediatr Adolesc Med ; 159(11): 1032-5, 2005 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-16275792

RESUMEN

OBJECTIVE: To assess the association of neurodevelopmental outcome with the placental diagnosis of chorioamnionitis in very low-birth-weight infants. METHODS: One hundred seventy-seven surviving very low-birth-weight infants, 22 to 29 weeks' gestational age, born after varying severity of chorioamnionitis, were evaluated at a mean +/- SD age of 19 +/- 6 months' corrected age with Bayley Scales of Infant Development II and neurologic examination. Select maternal and infant variables were abstracted from the medical records. Neonatal morbidities, Mental Developmental Index (MDI) score, Psychomotor Developmental Index (PDI) score, probability of normal MDI and PDI scores (>84), and cerebral palsy between the chorioamnionitis and the control groups were assessed, controlling for gestational age, sex, and the maternal use of steroids and antibiotics. RESULTS: The chorioamnionitis group of 102 infants was compared with 75 control infants (mean +/- SD birth weight, 947 +/- 236 g and 966 +/- 219 g, respectively; mean +/- SD gestational age, 26.1 +/- 2.8 weeks and 27.1 +/- 1.5 weeks, respectively). Infants with chorioamnionitis, compared with controls, had a significantly higher incidence of intraventricular hemorrhage (30% vs 13%) and retinopathy of prematurity (68% vs 42%). Cerebral palsy was diagnosed in 8.6% of the infants with chorioamnionitis and 6.6% of the controls. The MDI and PDI scores were similar between the chorioamnionitis and control groups (mean +/- SD MDI score, 96 +/- 16 vs 97 +/- 18 and mean +/- SD PDI score, 94 +/- 19 vs 92 +/- 19, respectively). CONCLUSIONS: In very low-birth-weight infants we found a higher incidence of intraventricular hemorrhage and retinopathy of prematurity but similar MDI and PDI scores and risk of cerebral palsy associated with chorioamnionitis.


Asunto(s)
Corioamnionitis , Enfermedades del Prematuro/etiología , Recién Nacido de muy Bajo Peso/crecimiento & desarrollo , Enfermedades del Sistema Nervioso/diagnóstico , Sistema Nervioso/crecimiento & desarrollo , Resultado del Embarazo , Femenino , Estudios de Seguimiento , Edad Gestacional , Humanos , Incidencia , Lactante , Recién Nacido , Enfermedades del Prematuro/epidemiología , Masculino , Enfermedades del Sistema Nervioso/epidemiología , Embarazo , Estudios Retrospectivos , Factores de Riesgo
15.
J Immunol ; 175(9): 6169-76, 2005 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-16237114

RESUMEN

The identification of many tumor-associated epitopes as nonmutated "self" Ags led to the hypothesis that the induction of large numbers of self/tumor Ag-specific T cells would be prevented because of central and peripheral tolerance. We report in this study on vaccination efforts in 95 HLA-A*0201 patients at high risk for recurrence of malignant melanoma who received prolonged immunization with the "anchor-modified" synthetic peptide, gp100209-217(210M). Vaccination using this altered peptide immunogen was highly effective at inducing large numbers of self/tumor-Ag reactive T cells in virtually every patient tested, with levels as high as 42% of all CD8+ T cells assessed by tetramer analysis. From 1 to 10% of all CD8+ cells were tumor-Ag reactive in 44% of patients and levels >10% were generated in 17% of patients. These studies were substantiated using the ELISPOT assay and a bulk cytokine release assay. Although our data regarding "tumor escape" were inconclusive, some patients had growing tumors that expressed Ag and HLA-A*0201 in the presence of high levels of antitumor T cells. There was no difference in the levels of antitumor Ag-specific T cells in patients who recurred compared with those that remained disease-free. Thus, the mere presence of profoundly expanded numbers of vaccine-induced, self/tumor Ag-specific T cells cannot by themselves be used as a "surrogate marker" for vaccine efficacy. Further, the induction of even high levels of antitumor T cells may be insufficient to alter tumor progression.


Asunto(s)
Antígenos de Neoplasias/inmunología , Autoantígenos/inmunología , Linfocitos T CD8-positivos/inmunología , Vacunas contra el Cáncer/inmunología , Melanoma/inmunología , Glicoproteínas de Membrana/inmunología , Fragmentos de Péptidos/inmunología , Neoplasias Cutáneas/inmunología , Adulto , Anciano , Progresión de la Enfermedad , Femenino , Humanos , Inmunización , Masculino , Melanoma/mortalidad , Melanoma/terapia , Persona de Mediana Edad , Neoplasias Cutáneas/mortalidad , Neoplasias Cutáneas/terapia , Antígeno gp100 del Melanoma
16.
J Matern Fetal Neonatal Med ; 16(5): 287-93, 2004 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-15621545

RESUMEN

OBJECTIVE: To determine whether differences in the clinical entities of HELLP syndrome and severe preeclampsia are associated with different placental lesions. STUDY DESIGN: This was a case control study of singleton pregnancies with HELLP syndrome or severe preeclampsia. Archived pathology slides were retrieved and reviewed. Clinical and histopathological features were compared between the two groups. RESULTS: There were 31 women with HELLP syndrome and 56 with severe preeclampsia. HELLP syndrome was associated with epigastric pain and higher levels of LDH, bilirubin, liver enzymes and fibrin degradation products. Hemoglobin, hematocrit and platelet counts were lower. Abruption lesions of the placenta were less common with HELLP syndrome (Odds Ratio 0.1 95% Confidence Interval 0.01,0.8). None of the other 22 placental features examined were different between the two conditions. CONCLUSION: The significant overlap between HELLP syndrome and severe preeclampsia for both clinical and placental features suggests that the two conditions represent a spectrum of essentially the same pathophysiologic process.


Asunto(s)
Síndrome HELLP/diagnóstico , Complicaciones del Embarazo/diagnóstico , Adulto , Biomarcadores/sangre , Estudios de Casos y Controles , Femenino , Síndrome HELLP/patología , Humanos , Hígado/patología , Placenta/patología , Preeclampsia/diagnóstico , Preeclampsia/patología , Embarazo , Complicaciones del Embarazo/patología , Estadísticas no Paramétricas
17.
Am J Obstet Gynecol ; 188(1): 269-74, 2003 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-12548228

RESUMEN

OBJECTIVE: This study was undertaken to determine whether intrapartum fevers at term are associated with markers of acute inflammation in maternal, fetal, and placental compartments. STUDY DESIGN: Term cases with intrapartum fever (temperature >/=100.4 degrees F) were recruited with gestational age-matched controls. Maternal serum and umbilical vein blood were collected and assayed for interleukin-6 (IL-6) levels. Placentas were examined for histologic chorioamnionitis. Demographic and clinical data were collected and compared between cases and controls. RESULTS: Forty-seven case-control pairs were analyzed. Maternal IL-6 levels were higher in cases than in controls (median of 145 pg/mL vs 42 pg/mL, P <.0001). Umbilical vein IL-6 levels also were higher in cases than controls (median 9 pg/mL vs 3.5 pg/mL, P =.01), but more than half of levels in cases were below 11 pg/mL. Only 31.1% of febrile cases had moderate or severe histologic chorioamnionitis. Multivariable logistic regression identified maternal serum IL-6 levels, nulliparity, and number of vaginal examinations as the major predictors of intrapartum fever at term. CONCLUSION: The maternal inflammatory response as measured by maternal serum IL-6 levels is a strong marker for term intrapartum fever. The much weaker association of fetal and placental inflammatory responses suggest a smaller than expected contribution of intra-amniotic inflammation to term intrapartum fevers.


Asunto(s)
Fiebre , Inflamación/diagnóstico , Trabajo de Parto , Adulto , Estudios de Casos y Controles , Corioamnionitis/sangre , Corioamnionitis/patología , Femenino , Sangre Fetal/química , Enfermedades Fetales , Edad Gestacional , Humanos , Inflamación/sangre , Inflamación/patología , Interleucina-6/sangre , Paridad , Examen Físico , Placenta/patología , Embarazo , Estudios Prospectivos , Grupos Raciales , Análisis de Regresión , Factores de Riesgo , Taquicardia , Venas Umbilicales , Vagina
18.
Am J Obstet Gynecol ; 187(6): 1679-85, 2002 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-12501083

RESUMEN

OBJECTIVE: It has been suggested that there is a decrease in the collagen content of the fetal membranes when there is premature rupture of the membranes before the onset of labor. This study was designed to determine whether decreased amniochorion collagen production (as measured by reduced amounts of messenger RNA) or alterations in relative production of different fibrillar and nonfibrillar collagens are associated with premature rupture of the membranes. STUDY DESIGN: Fetal membranes were collected after preterm (24-36 weeks of gestation) and term (> or =37 weeks of gestation) deliveries both with and without premature rupture of the membranes. Specimens with evidence of histologic chorioamnionitis were excluded. The messenger RNA levels for fibrillar collagen types I, III, and V and fibril-associated collagens with interrupted triple-helices types XII and XIV were measured with relative quantitative reverse transcriptase-polymerase chain reaction. RESULTS: The messenger RNA levels for fibrillar collagens decreased with advancing gestational age. Preterm premature rupture of membranes was associated with increased messenger RNA levels for fibrillar collagens and fibril-associated collagens with interrupted triple-helices collagen XII, but not type XIV. The greatest change in relative amounts of collagen messsenger RNA was demonstrated by an increased type I/XIV ratio, which was due to the up-regulation of type I levels, but not type XIV levels. CONCLUSION: A rise in fibrillar collagen production (messenger RNA) for types I, III, and V and fibril-associated collagens with interrupted triple-helices collagen type XII is observed with preterm premature rupture of the membranes. There is no evidence for a similar up-regulation of messenger RNA for fibril-associated collagens with interrupted triple-helices collagen type XIV. The rise in the collagen I/XIV messenger RNA ratio in preterm premature rupture of the membranes may result in collagen fibrils without enough stabilizing fibril-associated collagens with interrupted triple-helices type XIV on the fibril surface to maintain structural integrity.


Asunto(s)
Amnios/química , Corion/química , Colágeno/genética , Rotura Prematura de Membranas Fetales/metabolismo , Expresión Génica , ARN Mensajero/análisis , Colágeno/metabolismo , Colágeno Tipo I/genética , Colágeno Tipo III/genética , Colágeno Tipo V/genética , Colágeno Tipo XII/análisis , Colágeno Tipo XII/genética , Femenino , Colágenos Asociados a Fibrillas/genética , Técnica del Anticuerpo Fluorescente , Edad Gestacional , Glicoproteínas/genética , Glicoproteínas/metabolismo , Humanos , Inmunohistoquímica , Embarazo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa
19.
J Ultrasound Med ; 21(5): 501-10, 2002 May.
Artículo en Inglés | MEDLINE | ID: mdl-12008812

RESUMEN

OBJECTIVE: To determine the sensitivity of using a complete anatomic sonographic survey in detecting fetal abnormalities via correlation with perinatal autopsy results. METHODS: All perinatal autopsies (1994-2001) with positive findings for at least 1 fetal abnormality and performed by a single perinatal pathologist at our institution were retrospectively reviewed. From these cases, singleton fetuses who received prenatal sonography solely in our unit were identified. The sensitivity of sonography in detecting anomalous fetuses as well as fetal abnormalities and abnormalities by organ system was determined. Abnormalities were classified as major or minor In addition, findings from sonography and autopsy were compared, and their correlation was assigned to 1 of 3 categories. RESULTS: Of 88 fetuses identified, 85 had 1 or more abnormal structural sonographic findings (sensitivity for fetuses with anomalies, 97%). A total of 372 separate abnormalities were found on autopsy; of the 299 major and 73 minor abnormalities, prenatal sonography showed 224 (75%) and 13 (18%), respectively. There was either complete agreement or only minor differences between sonographic and autopsy findings in 57 (65%) of 88. The sensitivity of sonography in identifying abnormalities was greater than 70% in these systems: central nervous system, cardiac system, urinary system, extremities, genitalia, ribs, and hydrops. CONCLUSIONS: In experienced hands, sonography has 97% sensitivity in detecting anomalous fetuses when compared with perinatal autopsy results. Although the sensitivity of sonography in detecting major fetal abnormalities is 75%, the sensitivity for minor abnormalities is poor, even when using a complete anatomic sonographic survey. Although it has limitations, this type of survey is invaluable for both patients and physicians in diagnosing fetal abnormalities.


Asunto(s)
Feto/anomalías , Ultrasonografía Prenatal , Anomalías Múltiples/diagnóstico por imagen , Adolescente , Adulto , Autopsia , Reacciones Falso Negativas , Reacciones Falso Positivas , Femenino , Muerte Fetal/patología , Feto/patología , Humanos , Embarazo , Estudios Retrospectivos , Sensibilidad y Especificidad
20.
Obstet Gynecol ; 99(3): 477-82, 2002 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-11864677

RESUMEN

OBJECTIVE: To evaluate whether abnormal umbilical cord insertion (UCI) into the placenta is a risk factor for birth weight discordancy in twin gestations. METHODS: Pathology records of all liveborn twins delivered between January 1993 and June 1996 were reviewed. The information collected included gestational age at delivery, birth weight, gross placental pathology, and placental UCI-velamentous, marginal, or disc. Discordancy in birth weight was defined as an intrapair difference of at least 20%. Analyses were stratified on placental chorionicity. Odds ratios and 95% confidence intervals for birth weight discordancy were calculated based on the presence of an abnormal (velamentous or marginal) placental UCI relative to normal (disc) UCI on both placentae, after adjusting for potential confounders. RESULTS: There were 447 twin pairs identified. Dichorionic diamniotic placentation was present in 358 pairs (80.1%), monochorionic diamniotic in 84 (18.8%), and monochorionic monoamniotic in five (1.1%). There was a 13-fold increase in the risk of birth weight discordancy in monochorionic diamniotic twins in the presence of a velamentous UCI (odds ratio 13.5, 95% confidence interval 1.4, 138.4), with a rate of birth weight discordancy of 46%. This relationship was not demonstrated in dichorionic diamniotic twins (odds ratio 1.0, 95% confidence interval 0.3, 3.5). CONCLUSION: Birth weight discordancy in twins is a different entity depending on chorionicity. The substantial increase in birth weight discordancy in monochorionic diamniotic twins that accompanies velamentous UCI underscores the need for prenatal detection and increased surveillance in these twins.


Asunto(s)
Peso al Nacer , Placenta , Embarazo Múltiple , Gemelos , Cordón Umbilical , Adulto , Corion , Femenino , Humanos , Recién Nacido , Embarazo , Factores de Riesgo , Ultrasonografía Prenatal
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