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1.
Postgrad Med ; 136(1): 67-77, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38445664

RESUMEN

OBJECTIVES: To understand the role of primary care physicians (PCPs) in the recognition, diagnosis, and management of Crohn's perianal fistulas (CPF) and their referral patterns and treatment expectations. METHODS: This survey-based study was conducted between September 2020 and October 2020. US-based PCPs managing at least one patient with Crohn's disease per week were included. Participants were presented with two case vignettes relevant to primary care practice; Case Vignette 1 comprised three parts and focused on initial CPF presentation and progression to partial response; Case Vignette 2 focused on recurrent CPF. Survey questions elicited the physician's clinical approach to each case. Data were presented as descriptive statistics. RESULTS: Overall, 151 PCPs (median 23 years in practice) who saw about three patients per month with new/existing CPF responded. For Case Vignette 1, upon identification of a fistulous tract, 89% of respondents would refer the patient, mostly to a colorectal surgeon or gastroenterologist. Most PCPs (69%) would begin the patient on medication; 46% would conduct a diagnostic/imaging study. Treatment expectations after referral varied: 55% of respondents believed surgeons would place a seton or use one prior to surgery; 23% expected medical management only; 23% were unsure. Case Vignette 2 revealed that 98% of PCPs preferred to be involved in patient care after referral; however, only 49% were. Of these, 76% considered reinforcing patient treatment adherence as their primary role. While 80% of PCPs were at least moderately satisfied with communication and care coordination with multidisciplinary teams, 52% considered lack of access to specialists as at least a moderate barrier to multidisciplinary team management. CONCLUSION: PCPs want more involvement in multidisciplinary management of patients with CPF. Continuing education providing PCPs with up-to-date information on diagnostic modalities, treatment options, early diagnosis, the role of PCPs within a multidisciplinary team, and effective initial CPF care is required.


What were the study's aims?To understand how primary care physicians recognize, treat, and monitor patients with Crohn's disease-related perianal fistulas (small tunnels between the bowel and skin near the anus).How was the study done?US-based primary care physicians, including internists, were included if they had experience in treating patients with Crohn's disease. Descriptions of the history and symptoms of two hypothetical patients were provided: one patient who may have Crohn's perianal fistulas and another patient whose Crohn's perianal fistulas had returned after being treated. After reading these descriptions, the physicians completed a questionnaire designed to show how they would help each patient.What did the study find out?Not all physicians treat patients with Crohn's perianal fistulas in the same way in terms of diagnostic tests and medical treatments, although most said they would refer them to a specialist if a fistula was identified. Many wanted to be involved in patient care after referral to a specialist but only half were. Of those, most thought their main role was to ensure patients followed the treatments given by specialists. More than half of primary care physicians thought a lack of access to specialists could be a barrier to care.How does this impact care?The physicians surveyed want more involvement in multidisciplinary teams who look after patients with Crohn's perianal fistulas. To do this, they need more education about the diagnosis and treatment of Crohn's perianal fistulas, and clarity around their role within multidisciplinary teams who manage these patients.


Asunto(s)
Enfermedad de Crohn , Gastroenterólogos , Médicos de Atención Primaria , Humanos , Enfermedad de Crohn/diagnóstico , Enfermedad de Crohn/terapia , Comunicación , Cooperación del Paciente
2.
Crohns Colitis 360 ; 6(1): otad081, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38259605

RESUMEN

Background: Little is known about patients' perception of care and management of Crohn's perianal fistulas (CPF). This study was conducted to understand US patient and caregiver attitudes and challenges to CPF care. Methods: Patients with CPF and caregivers of patients with CPF completed a 36-question survey about their perceptions and challenges regarding the diagnosis, treatment, and overall management of CPF. Patients/caregivers were recruited via online Crohn's and fistula support group websites and forums and via their gastroenterologists (GEs) and surgeons from October 2020 through January 2021. Results: The survey was completed by 96 patients and 54 caregivers. Respondents reported over 60% and 14%-23% of CPF were diagnosed and treated by a GE or surgeon, respectively. Nearly all patients/caregivers wanted to be involved in treatment decision-making with their physicians (81%). While the majority of patients/caregivers were satisfied with their quality of care (65%) and access to care (67%), racial disparities exist and there is room for improvement. A smaller proportion of non-White versus White patients/caregivers reported satisfaction with care quality (39% vs 72%, respectively) and access to care (57% vs 69%, respectively). Half of non-White patient/caregivers (50%) versus 69% of White patient/caregivers knew where to access CPF information. Most patients/caregivers (69%) stated that they would benefit from more information on managing day-to-day CPF symptoms. Significant barriers perceived by patients/caregivers to receiving optimal CPF care included lack of effective treatments (69%) and lack of access to specialist care (68%). Conclusions: Improvements in multidisciplinary CPF care are required to optimize treatment.

3.
Crohns Colitis 360 ; 5(4): otad073, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-38046445

RESUMEN

Background: Perianal fistulae can undermine physical, emotional, and social well-being in patients with Crohn's disease and are challenging to manage. Social media offers a rich opportunity to gain an in-depth understanding of the impact of perianal fistulae on patients' daily lives outside of controlled environments. In this study, we conducted social media analytics to examine patients' experiences with perianal fistulae and assessed the impact of perianal fistulae on patients' behavior and overall well-being. Methods: We used a mixed-method approach to examine 119 986 publicly available posts collected from 10 Crohn's disease forums in the United States between January 01, 2010 and January 01, 2020. Discussions related to Crohn's perianal fistulae were retrieved. We randomly selected 700 posts and qualitatively analyzed them using an inductive thematic approach. We then applied a latent Dirichlet allocation probabilistic topic model to explore themes in an unsupervised manner on the collection of 119 986 posts. Results: In the qualitative analysis, 5 major themes were identified: (1) burden of perianal fistula; (2) challenges associated with treatment; (3) online information seeking and sharing; (4) patient experiences with treatments; and (5) patients' apprehension about treatments. In the quantitative analysis, the percentages of posts related to the major themes were (1) 20%, (2) 29%, (3) 66%, and (4) 28%, while the topic model did not identify theme 5. Conclusions: Social media reveals a dynamic range of themes governing patients' perspectives and experiences with Crohn's perianal fistulae. In addition to the biopsychosocial burden, patients frequently express dissatisfaction with current treatments and often struggle to navigate among available management options.

4.
Artículo en Inglés | MEDLINE | ID: mdl-37743037

RESUMEN

BACKGROUND & AIMS: Although biologics have revolutionized the treatment of Crohn's disease (CD), an efficacy ceiling has been reached. Combining biologic therapies may improve remission rates. METHODS: EXPLORER, a phase 4, single-arm, open-label study, evaluated triple combination therapy with vedolizumab (300 mg on day 1, weeks 2 and 6, and then every 8 weeks), adalimumab (160 mg on day 2, 80 mg at week 2, then 40 mg every 2 weeks), and methotrexate (15 mg weekly) in biologic-naïve patients with newly diagnosed, moderate- to high-risk CD. Endoscopic remission at week 26 (primary end point; Simple Endoscopic Score for CD ≤2), clinical remission at weeks 10 and 26 (secondary end point; Crohn's Disease Activity Index <150), and incidences of adverse events and serious adverse events were evaluated. RESULTS: Among 55 enrolled patients, the mean CD duration was 0.4 years, the mean baseline Simple Endoscopic Score for CD was 12.6, and the mean baseline Crohn's Disease Activity Index was 265.5. At week 26, 19 patients (34.5%) were in endoscopic remission. At weeks 10 and 26, 34 (61.8%) and 30 patients (54.5%), respectively, were in clinical remission. Post hoc Bayesian analysis showed that the probabilities that triple combination therapy produced a higher endoscopic remission rate (33.5%; 95% credible interval, 22.4-45.7) than placebo (14%), vedolizumab monotherapy (27%), or adalimumab monotherapy (30%) were 99.9% or higher, 86.3%, and 71.4%, respectively. Six patients had serious adverse events. CONCLUSIONS: Combination therapy resulted in endoscopic and clinical remission at week 26 in 34.5% and 54.5% of patients, respectively, with no safety signal related to the treatment regimen. This supports further evaluation of combination therapy in CD. CLINICALTRIALS: gov number: NCT02764762.

5.
Gastro Hep Adv ; 2(8): 1066-1076, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-39131564

RESUMEN

Background and Aims: This study compared disease burden, experiences, and health-related quality of life (HRQoL) between patients with Crohn's perianal fistulas (CPFs) and those with Crohn's disease (CD) without perianal fistulas (PFs; non-PF CD). Methods: This cross-sectional, observational study was conducted in 3 cohorts of US patients aged 18-89 years with self-reported, physician-diagnosed CD: (1) non-PF CD; (2) CPF without PF-related surgery; and (3) CPF with PF-related surgery. Data on medical and surgical interventions, CD-specific symptoms, HRQoL (assessed using the Short Inflammatory Bowel Disease and 5-dimension EuroQol questionnaires), and fecal incontinence (assessed using Revised Faecal Incontinence Scale and Fecal Incontinence Quality of Life questionnaires) were collected via a web-enabled questionnaire. Results: In total, 403 patients with CD completed the questionnaire (non-PF CD, n = 300; CPF without surgery, n = 51; CPF with surgery, n = 52). A high symptom burden was seen across cohorts. More patients with CPF underwent ≥1 CD-related surgery and experienced ≥1 failure of CD-related surgery (79% and 20%) vs non-PF CD (53% and 9%; P < .001). Overall HRQoL outcomes were worse for patients with CPF vs non-PF CD, with significantly worse Short Inflammatory Bowel Disease and 5-dimension EuroQol questionnaire scores for those without PF-related surgery (P < .01). Across all cohorts, 58% of patients reported experiencing fecal incontinence, which had a greater negative impact (higher Revised Faecal Incontinence Scale scores; lower Fecal Incontinence Quality of Life scores) in patients with CPF vs non-PF CD. Conclusion: Patients with CPF experience substantial HRQoL burden, reflecting the impact of symptoms and medical/surgical interventions. These results may help to inform comprehensive care strategies to improve patient HRQoL.

6.
Am J Gastroenterol ; 116(Suppl 1): S9, 2021 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-37461955

RESUMEN

BACKGROUND: Crohn's perianal fistulas (CPF) contribute to lowered quality of life for patients with Crohn's disease. Previous research has indicated potential racial and/or ethnic disparities in diagnosis and management of patients with CPF. This study aimed to expand on previous investigations in the management of patients with CPF to identify educational needs and explore potential disparities in care. METHODS: To understand specific educational needs of US patients and caregivers of patients with CPF, a survey instrument was developed and fielded to patients and caregivers in September/October 2020. Subanalysis and inferential statistics were used to segment the patient/caregiver sample by race/ethnicity and determine potential areas of care disparities. RESULTS: Of 148 patient/caregiver responses analyzed, 28 were non-white (including American/Alaskan Native Indian, Black/African American, Hispanic/Latino, Native Hawaiian/Pacific Islander, and multiethnic); 12/28 were CPF patients and 16/28 were parents or caregivers of CPF patients. The reported mean age of the CPF patient was 32 years for non-whites and 35 for whites. Insurance coverage varied between groups, with non-whites mainly covered by Medicare/Medicaid (68% vs 32% whites), and whites mainly covered by private insurance (64% vs 25% non-whites). Non-white patient/caregivers reported a longer mean time between symptoms and diagnosis (2.08 yr) than white patients/caregivers (less than 1 yr). White patients/caregivers reported more (50%) current use of biologics than non-whites (36%); however, past use of biologics was near equal (51%) for whites and (50%) for non-whites. Of patients who had undergone surgical procedures (86.5%), non-whites had a lower number of different surgery types (1.64) than whites (2.31). The top two reported goals of treatment for both groups were decreasing pain and healing the fistula. Less non-white patients/caregivers agreed or strongly agreed they were satisfied with their current quality of care (39%) and access to care (57%) than white patients/caregivers (72% and 69%, respectively). Non-whites were more likely to disagree or strongly disagree that the main doctor who treats CPF is knowledgeable about their CPF and its treatments (25% vs 3% whites), and that they agree or strongly agree they know more about CPF than their doctor (21% vs 15% whites). Patients/caregivers (non-whites vs whites) perceived somewhat, very or extremely significant barriers to care to be inadequate community social services for CPF care (82% vs 79%), out-of-pocket costs of care (71% vs 84%), limited information to make difficult decisions for their CPF treatment (82% vs 86%), physical/emotional stress of managing their CPF (82% vs 79%), lack of access to specialist care (89% vs 88%) and lack of effective treatments (86% vs 89%). Only 50% of non-white patients/caregivers and 69% of white patients/caregivers agreed or strongly agreed that they know where to go to get CPF information. CONCLUSION: Disparities in diagnosis and management of CPF exist between non-white and white patients/caregivers, including length of time to diagnosis, perceptions of quality of care and barriers to treatment. Further research into disparities in the management of CPF is needed, as is CPF education for patients/caregivers and HCP education on managing CPF in minority populations.

7.
Am J Emerg Med ; 37(3): 439-443, 2019 03.
Artículo en Inglés | MEDLINE | ID: mdl-29884589

RESUMEN

PURPOSE: In 2015, approximately 13,436 snowboarding or skiing injuries occurred in children younger than 15. We describe injury patterns of pediatric snow sport participants based on age, activity at the time of injury, and use of protective equipment. METHODS: A retrospective analysis was performed of 10-17 year old patients with snow-sport related injuries at a Level-1 trauma center from 2005 to 2015. Participants were divided into groups, 10-13 (middle-school, MS) and 14-17 years (high-school, HS) and compared using chi-square, Student's t-tests, and multivariable logistic regression. RESULTS: We identified 235 patients. The HS group had a higher proportion of females than MS (17.5% vs. 7.4%, p = 0.03) but groups were otherwise similar. Helmet use was significantly lower in the HS group (51.6% vs. 76.5%, p < 0.01). MS students were more likely to suffer any head injury (aOR 4.66, 95% CI: 1.70-12.8), closed head injury (aOR 3.69 95% CI: 1.37-9.99), or loss of consciousness (aOR 5.56 95% CI 1.76-17.6) after 4 pm. HS students engaging in jumps or tricks had 2.79 times the risk of any head injury (aOR 2.79 95% CI: 1.18-6.57) compared to peers that did not. HS students had increased risk of solid organ injury when helmeted (aOR 4.86 95% CI: 1.30-18.2). CONCLUSIONS: Injured high-school snow sports participants were less likely to wear helmets and more likely to have solid organ injuries when helmeted than middle-schoolers. Additionally, high-schoolers with head injuries were more like to sustain these injures while engaging in jumps or tricks. Injury prevention in this vulnerable population deserves further study. LEVEL OF EVIDENCE: Level III (Retrospective Comparative Study).


Asunto(s)
Traumatismos en Atletas/epidemiología , Traumatismos Craneocerebrales/epidemiología , Dispositivos de Protección de la Cabeza/estadística & datos numéricos , Esquí/lesiones , Adolescente , Traumatismos en Atletas/prevención & control , Niño , Traumatismos Craneocerebrales/prevención & control , Femenino , Humanos , Puntaje de Gravedad del Traumatismo , Modelos Logísticos , Masculino , Massachusetts/epidemiología , Análisis Multivariante , Sistema de Registros , Estudios Retrospectivos
8.
J Trauma Acute Care Surg ; 83(2): 284-288, 2017 08.
Artículo en Inglés | MEDLINE | ID: mdl-28452897

RESUMEN

BACKGROUND: Gun violence remains a leading cause of death in the United States. Community gun buyback programs provide an opportunity to dispose of extraneous firearms. The purpose of this study was to understand the demographics, motivation, child access to firearms, and household mental illness of buyback participants in hopes of improving the program's effectiveness. METHODS: A 2015 Injury Free Coalition for Kids gun buyback program which collaborated with local police departments was studied. We administered a 23-item questionnaire survey to gun buyback participants assessing demographic characteristics, motivation for relinquishing firearms, child firearm accessibility, and mental illness/domestic violence history. RESULTS: A total of 186 individuals from Central/Western Massachusetts turned in 339 weapons. Participants received between US $25 and US $75 in gift cards dependent on what type of gun was turned in, with an average cost of $41/gun. A total of 109 (59%) participants completed the survey. Respondents were mostly white (99%), men (90%) and first-time participants in the program (85.2%). Among survey respondents, 54% turned in firearms "for safety reasons." Respondents reported no longer needing/wanting their weapons (47%) and approximately one in eight participants were concerned the firearm(s) were accessible to children. Most respondents (87%) felt the program encouraged neighborhood awareness of firearm safety. Three of every five participants reported that guns still remained in their homes; additionally, 21% where children could potentially access them and 14% with a history of mental illness/suicide/domestic violence in the home. CONCLUSION: Gun buybacks can provide a low-cost means of removing unwanted firearms from the community. Most participants felt their homes were safer after turning in the firearm(s). In homes still possessing guns, emphasis on secure gun storage should continue, increasing the safety of children and families. The results of this survey also provided new insights into the association between mental illness/suicide and gun ownership. LEVEL OF EVIDENCE: Epidemiological, level III.


Asunto(s)
Comercio/métodos , Armas de Fuego , Características de la Residencia , Seguridad , Heridas por Arma de Fuego/prevención & control , Adulto , Causas de Muerte , Niño , Femenino , Humanos , Masculino , Massachusetts , Enfermos Mentales/estadística & datos numéricos , Policia , Factores de Riesgo , Encuestas y Cuestionarios , Violencia/prevención & control , Heridas por Arma de Fuego/mortalidad , Prevención del Suicidio
9.
J Pediatr Surg ; 52(2): 354-359, 2017 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-27616616

RESUMEN

BACKGROUND: Gun buyback programs represent one arm of a multipronged approach to raise awareness and education about gun safety. METHODS: The city of Worcester, MA has conducted an annual gun buyback at the Police Department Headquarters since 2002. We analyzed survey responses from a voluntary, 18-question, face-to-face structured interview from December 2009 to June 2015 using descriptive statistics to determine participant demographics and motivations for participation. RESULTS: A total of 943 guns were collected, and 273 individuals completed surveys. The majority of participants were white males older than 55years (42.4%). Participants represented 61 zip codes across Worcester County, with 68% having prior gun safety training and 61% with weapons remaining in the home (27% of which children could potentially access). The top reasons for turning in guns were "no longer needed" (48%) and "fear of children accessing the gun" (14%). About 1 in 3 respondents knew someone injured/killed by gun violence. Almost all (96%) respondents claimed the program raised community awareness of firearm risk. CONCLUSION: The Worcester Goods for Guns Buyback has collected more than 900 guns between 2009 and 2015. The buyback removes unwanted guns from homes and raises community awareness about firearm safety.


Asunto(s)
Armas de Fuego , Conocimientos, Actitudes y Práctica en Salud , Promoción de la Salud/métodos , Homicidio/prevención & control , Motivación , Seguridad , Heridas por Arma de Fuego/prevención & control , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Femenino , Armas de Fuego/economía , Promoción de la Salud/economía , Homicidio/economía , Homicidio/psicología , Humanos , Entrevistas como Asunto , Masculino , Massachusetts , Persona de Mediana Edad , Policia , Características de la Residencia , Riesgo , Seguridad/economía , Encuestas y Cuestionarios , Heridas por Arma de Fuego/economía , Heridas por Arma de Fuego/psicología
10.
J Pediatr Surg ; 49(3): 447-50, 2014 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-24650475

RESUMEN

BACKGROUND: Initial antibiotics with planned interval appendectomy (interval AP) have been used to treat patients with complicated perforated appendicitis; however, little experience exists with this approach in children with suspected acute perforated appendicitis (SAPA). We sought to determine the outcome of initial antibiotics and interval AP in children with SAPA. METHODS: Over an 18-month period, 751 consecutive patients underwent appendectomy including 105 patients with SAPA who were treated with initial intravenous antibiotics and planned interval AP ≥ 8 weeks after presentation. All SAPA patients had symptoms for ≤ 96 hours. Primary outcome variables were rates of readmission, abscess formation, and need for interval AP prior to the planned ≥ 8 weeks. RESULTS: Intraabdominal abscess rate was 27%. Appendectomy prior to planned interval AP was 11% and readmission occurred in 34%. All patients underwent eventual appendectomy with pathologic confirmation confirming the previous appendiceal inflammation. White blood cell (WBC) count >15,000, WBC >15,000 plus fecalith on imaging, and WBC >15,000 plus duration of symptoms >48 hours were all significantly associated with higher rates of readmission (p=0.01, p=0.04, p=0.02) and need for interval AP prior to the planned ≥ 8 weeks (p=0.003, p=0.05, p=0.03). CONCLUSIONS: Treatment of SAPA with antibiotics and planned interval AP is successful in the majority of patients; however, complications such as abscess formation and/or readmission prior to planned interval AP occur in up to one-third of patients. Certain clinical variables are associated with increased treatment complications.


Asunto(s)
Antibacterianos/uso terapéutico , Apendicectomía/métodos , Apendicitis/tratamiento farmacológico , Apendicitis/cirugía , Peritonitis/tratamiento farmacológico , Absceso Abdominal/etiología , Absceso Abdominal/cirugía , Dolor Abdominal/etiología , Apendicitis/complicaciones , Niño , Vías Clínicas , Esquema de Medicación , Combinación de Medicamentos , Fiebre/etiología , Humanos , Perforación Intestinal/etiología , Perforación Intestinal/cirugía , Readmisión del Paciente , Ácido Penicilánico/análogos & derivados , Ácido Penicilánico/uso terapéutico , Peritonitis/etiología , Piperacilina/uso terapéutico , Combinación Piperacilina y Tazobactam , Estudios Prospectivos , Succión , Factores de Tiempo , Resultado del Tratamiento
11.
J Pediatr Surg ; 47(2): 313-6, 2012 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-22325382

RESUMEN

BACKGROUND/PURPOSE: This study examines the safety and patient satisfaction in discharging children undergoing laparoscopic appendectomy (LapAppy) for acute appendicitis on the day of surgery. METHODS: After institutional review board approval, data were collected prospectively for 158 consecutive patients undergoing LapAppy for simple appendicitis. Time from operation to discharge and complications were analyzed. At follow-up, parents completed a satisfaction survey. The Student t test was used for statistical analysis. RESULTS: Laparoscopic appendectomy was performed in 158 children ranging from age 2 to 19 years (mean, 12 years) over a 6-month period. Single-port, single-instrument LapAppy was possible in 152 patients (96%). Eighty percent of patients (n = 126) were discharged on the day of surgery, a mean of 4.8 hours postoperatively (range, 1-12 hours). Of the remaining 32, 24 (75%) were admitted because the operation ended too late for postoperative discharge; 3 (9%), for medical reasons; and 5 (16%), when the families declined to leave. One hundred nine parents (87%) whose children went home postoperatively stated that they were happy with the expeditious discharge, whereas 17 (13%) felt nervous. In addition, 116 parents (92%) stated that, in retrospect, same-day discharge was preferable, whereas 10 parents (8%) were not sure that it was the best decision. None, however, would insist on admission if faced with the situation again. There were no major complications and no significant difference in the rate of umbilical wound infections for same-day discharge patients (2%) and admitted patients (3%). CONCLUSION: Routine same-day discharge after pediatric LapAppy for acute appendicitis is safe, with good parent satisfaction.


Asunto(s)
Procedimientos Quirúrgicos Ambulatorios/estadística & datos numéricos , Apendicectomía/estadística & datos numéricos , Apendicitis/cirugía , Laparoscopía/estadística & datos numéricos , Padres/psicología , Satisfacción Personal , Adolescente , Procedimientos Quirúrgicos Ambulatorios/efectos adversos , Procedimientos Quirúrgicos Ambulatorios/psicología , Apendicectomía/efectos adversos , Apendicectomía/métodos , Apendicectomía/psicología , Niño , Preescolar , Servicio de Urgencia en Hospital/estadística & datos numéricos , Femenino , Humanos , Laparoscopía/efectos adversos , Laparoscopía/métodos , Laparoscopía/psicología , Tiempo de Internación/estadística & datos numéricos , Masculino , Readmisión del Paciente/estadística & datos numéricos , Complicaciones Posoperatorias/epidemiología , Estudios Prospectivos , Infección de la Herida Quirúrgica/epidemiología , Encuestas y Cuestionarios , Adulto Joven
13.
Birth Defects Res B Dev Reprod Toxicol ; 80(5): 406-16, 2007 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-17896343

RESUMEN

BACKGROUND: Nitrofen is a diphenyl ether that induces a spectrum of birth defects subsequent to administration to pregnant rodents, in which the molecular etiology of these defects are poorly characterized. Because previous reports showed that nitrofen induced apoptosis in undifferentiated P19 teratocarcinoma cells, we hypothesized that undifferentiated fetal cells have greater susceptibility to nitrofen-induced apoptosis than their differentiated derivatives. METHODS: To investigate this hypothesis, cell lines including P19 and F9 were differentiated with retinoic acid into neuronal and endodermal derivatives respectively. Apoptosis was characterized by caspase-3 cleavage and Terminal transferase dUTP nick end labeling (TUNEL) assays. RESULTS: Both differentiated cell-types had reduced nitrofen-induced caspase-3 cleavage and DNA fragmentation compared with the naive controls, strongly suggesting that differentiation of these cells protects against nitrofen-induced apoptosis. In addition, resistance to apoptotic induction was proportional to the expression levels of the differentiation marker, p27 (kip1) while direct proportionality was not observed for the antiapoptotic protein Bcl-2. CONCLUSIONS: These studies show that nitrofen may induce its associated birth defects via a mechanism involving apoptosis of undifferentiated fetal cells.


Asunto(s)
Apoptosis/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Éteres Fenílicos/toxicidad , Tretinoina/farmacología , Anomalías Inducidas por Medicamentos/etiología , Anomalías Inducidas por Medicamentos/patología , Animales , Caspasa 3/metabolismo , Línea Celular , Herbicidas/toxicidad , Ratones , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo
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