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INTRODUCTION: We aimed to investigate the impact of reduced contact prenatal care necessitated by the COVID-19 pandemic on meeting standards of care and perinatal outcomes. METHODS: This was a retrospective case-control study of patients in low-risk obstetrics clinic at a tertiary care county facility serving solely publicly insured patients comparing reduced in-person prenatal care (R) over 12 weeks with a control group (C) receiving traditional prenatal care who delivered prior. RESULTS: Total 90 patients in reduced contact (R) cohort were matched with controls (C). There were similar rates of standard prenatal care metrics between groups. Gestational age (GA) of anatomy ultrasound was later in R (p = 0.017). Triage visits and missed appointments were similar, though total number of visits (in-person and telehealth) was higher in R (p = 0.043). R group had higher GA at delivery (p = 0.001). Composite neonatal morbidity and length of stay were lower in R (p = 0.017, p = 0.048). Maternal and neonatal outcomes did not otherwise differ between groups. Using Kotelchuck Adequacy of Prenatal Care Utilization index, R had higher rates of adequate prenatal care (45.6% R vs. 24.4% C, p = 0.005). DISCUSSION: Our study demonstrates the non-inferiority of a hybrid, reduced schedule prenatal schedule to traditional prenatal scheduling. In a reduced contact prenatal care model, more patients met criteria for adequate prenatal care, likely due to higher attendance of telehealth visits. These findings raise the question of revising the prenatal care model to mitigate disparities in disadvantaged populations.
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COVID-19 , Telemedicina , Embarazo , Recién Nacido , Femenino , Humanos , Atención Prenatal , COVID-19/epidemiología , Estudios Retrospectivos , Estudios de Casos y Controles , Pandemias/prevención & control , Nivel de AtenciónRESUMEN
PURPOSE OF REVIEW: A mass cervical cancer screening using World Health Organization-endorsed visual inspection with acetic acid (VIA) and cryotherapy triage was conducted over 5 days at Nansio District Hospital on Ukerewe Island, Tanzania in Lake Victoria. The aim was to evaluate the feasibility of a pilot screen-and-treat on a lower resource island and compare the results to previously held screen-and-treats in higher resource mainland settings. RECENT FINDINGS: Two hundred and eight-two women underwent VIA on Ukerewe Island during July 2017. The frequency of abnormal VIA screens was nearly twice that observed on the mainland in 2016 (18.4% vs 10.7%, respectively; Pâ=â0.0091). Island women had lower rates of grand multiparity (19.8% vs 26.8%, Pâ=â0.02) and more island women did not know their HIV status (80% vs 50%, Pâ<â0.0001). Overall, 31% of abnormal VIA screens occurred among women under 30 years between the two sites. Due to the cost of transporting CO2 tanks, cryotherapy was nearly twice as expensive on the island as compared to the mainland. SUMMARY: Although transfer of an entire pilot screen-and-treat program to Ukerewe Island is feasible and well-received, expenses associated with ferrying equipment may be prohibitive to long-term sustainability. Higher VIA positivity rates were observed on the island.
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Neoplasias del Cuello Uterino , Detección Precoz del Cáncer/métodos , Estudios de Factibilidad , Femenino , Humanos , Lagos , Masculino , Tamizaje Masivo , Factores de Riesgo , Tanzanía/epidemiología , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/epidemiología , Neoplasias del Cuello Uterino/terapiaRESUMEN
BACKGROUND: Because the global disease burden of cervical cancer is greatest in Africa, the World Health Organization has endorsed visual inspection with acetic acid screening with cryotherapy triage for the screen-and-treat approach. With the lowest doctor-to-patient ratio worldwide (1:50,000), Tanzania has nearly 10,000 new cases of cervical cancer and 7000 deaths annually. OBJECTIVE: We report on the feasibility of visual inspection with acetic acid in the severely resource-limited Mwanza district and on the impact of intervening education on baseline human papillomavirus and cervical cancer knowledge. STUDY DESIGN: Two 5-day free visual inspection with acetic acid (VIA) clinics in urban Buzuruga and rural Sangabuye on the shores of Lake Victoria were approved by our university institutional review board and local Tanzanian health authorities. Participants completed a demographic survey and a 6-question (1 point per question) multiple choice test written in Kiswahili to assess baseline knowledge. A 15-minute educational video in Kiswahili (MedicalAidFilms: Understanding screening, treatment, and prevention of cervical cancer) was followed by repeated assessment using the same test, visual inspection with acetic acid screening, and optional HIV testing. Pre- and postvideo scores and change of score were analyzed via t test, analysis of variance, and multivariate regression. Significance was considered at P<.05. RESULTS: From July 2, 2018 to July 6, 2018, 825 women were screened, and 207 women (25.1%) were VIA positive (VIA+). One hundred forty-seven VIA+ nonpregnant women received same-day cryotherapy. Seven hundred sixty women participated in an educational intervention-61.6% of whom were from an urban site and 38.2% from a rural site. The mean age was 36.4 (standard deviation, 11.1). Primary languages were Kiswahili (62.2%) and Kisukuma (30.6%). Literacy was approximately 73%, and average education level was equivalent to the seventh grade (United States). Less than 20% of urban and rural women reported access to healthcare providers. Mean score of the participants before watching the video was 2.22 (standard deviation, 1.76) and was not different between VIA+ and VIA negative groups. Mean score of the participants after watching the video was 3.86 (standard deviation, 1.78). Postvideo scores significantly improved regardless of age group, clinic site, primary language, education level, literacy, or access to healthcare provider (P<.0001). Change of score after watching the video was significantly greater in participants from urban areas (1.99±2.07) than in those from rural areas (1.07±1.95) (P<.0001). Multivariate analysis identified urban site as an independent factor in change of score (P=.0211). CONCLUSION: Visual inspection with acetic acid screening for cervical cancer is feasible and accepted in northern Tanzania. Short video-based educational intervention improved baseline knowledge on the consequences of human papillomavirus infection in the studied populations. The impact was greater in the urban setting than in the rural setting.
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Papillomaviridae/aislamiento & purificación , Infecciones por Papillomavirus/diagnóstico , Educación del Paciente como Asunto , Participación del Paciente , Displasia del Cuello del Útero/diagnóstico , Neoplasias del Cuello Uterino/diagnóstico , Frotis Vaginal , Adolescente , Adulto , Femenino , Humanos , Persona de Mediana Edad , Infecciones por Papillomavirus/virología , Población Rural , Tanzanía/epidemiología , Población Urbana , Neoplasias del Cuello Uterino/virología , Adulto Joven , Displasia del Cuello del Útero/virologíaRESUMEN
AIM: To evaluate visual inspection with acetic acid (VIA) screening for cervical cancer among human immunodeficiency virus (HIV)-positive patients in an East African community. METHODS: During a July 2018 cervical cancer screen-and-treat in Mwanza, Tanzania, participants were offered free cervical VIA screening, cryotherapy when indicated, and HIV testing. Acetowhite lesions and/or abnormal vascularity were designated VIA positive in accordance with current guidelines. The association between VIA results and HIV status was compared using Chi-square and Fisher exact tests. RESULTS: Eight hundred and twenty-four of 921 consented participants underwent VIA screening and 25.0% (n = 206) were VIA positive. VIA-positive nonpregnant women (n = 147) received cryotherapy and 15 (1.8%) with cancerous-appearing lesions were referred to Bugando Hospital. Sixty-six women were HIV-positive and included 25 diagnosed with HIV at the cervical cancer VIA screening and 41 with a prior diagnosis of HIV who were receiving antiretroviral therapy (ART) at the time of cervical cancer VIA screening. Sixty-four of these 66 patients, were screened with VIA. HIV infection was not associated with VIA findings. Abnormal VIA positive screening was observed in 20.3% (n = 13) of HIV-positive patients and in 24.4% (n = 145) of HIV-negative patients (p = 0.508). A nonsignificant trend of higher VIA positive screens among newly diagnosed HIV patients of 26.1% (n = 6) versus patients with preexisting HIV on ART of 17.1% (n = 7) was observed (p = 0.580). CONCLUSION: The unexpected lack of correlation between HIV infection and VIA positivity in a community with access to ART warrants additional research regarding the previously described role of ART in attenuating HPV-mediated neoplasia.
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Infecciones por VIH , Infecciones por Papillomavirus , Neoplasias del Cuello Uterino , Ácido Acético , Detección Precoz del Cáncer , Femenino , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Humanos , Tamizaje Masivo , Tanzanía/epidemiología , Neoplasias del Cuello Uterino/diagnósticoRESUMEN
A 24-year-old woman, G6P2032, initially presented with a right-sided ruptured tubal ectopic pregnancy. Salpingectomy was performed with care to completely remove the fallopian tube. The patient then presented with ipsilateral interstitial pregnancy 11 weeks later and initially underwent systemic methotrexate injection, which failed to resolve the pregnancy. She then underwent laparoscopic cornuostomy and dilation and curettage. Cornuostomy was performed with injection of dilute vasopressin around the gestational sac to help minimize blood loss, followed by hydrodissection and sharp dissection to remove the pregnancy. Judicial electrocautery was used and the myometrium and serosa were closed in layers. Attention was given to preserve uterine myometrial tissue integrity at the cornua. The patient recovered and was discharged. Her beta-hCG level trended from 11,902 mIU/mL pre-surgery to 7726 on postoperative day 0, and 289 on postoperative day 7. Pathology from the interstitial region showed fragments of chorionic villi, and the dilation and curettage pathology demonstrated decidualized secretory endometrium. Short-interval interstitial ectopic pregnancies after prior salpingectomy for tubal ectopic pregnancy are extremely rare. This case demonstrated successful management with a minimally invasive laparoscopic cornuostomy. This case also displays that ipsilateral interstitial pregnancy can occur after salpingectomy even after care is taken to remove all visible portions of the fallopian tube. Thus, patients should be counseled carefully about the risks of short-interval pregnancy after a recent tubal ectopic pregnancy.
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Objective American College of Obstetricians and Gynecologists (ACOG) recently published the California (CA) cardiovascular disease (CVD) screening algorithm for pregnant and postpartum women. We aim to prospectively determine screen-positive and true-positive rates of CVD among women across two populations. Study Design This is a prospective cohort study of obstetrical patients from April 2018 to July 2019 at academic medical centers in CA and New York (NY). We attempted to screen all patients at least once during their pregnancy care (prenatal or postpartum). Women who screened positive ("Red Flags," >3-4 moderate risk factors, abnormal physical examination, and persistent symptoms) underwent further testing. The primary outcome was the screen-positive rate. Secondary outcomes included the true-positive rate and the strength of each moderate factor in predicting a positive CVD screen. Results We screened 846 women. The overall screen-positive rate was 8% (5% in CA vs. 19% in NY). The sites differed in ethnicity, that is, African American women (2.7% in CA vs. 35% in NY, p < 0.01) and substance use (2.7 vs. 5.6%, p < 0.04). The true-positive rate was 1.5% at both sites. The percentage of screen-positive patients who did not complete follow-up studies was higher in NY (70%) than in CA (27%). CVD was confirmed in 30% with positive screens with complete follow-up. Combinations of moderate factors were the main driver of screen-positive rates in both populations. Conclusion This is the first data describing the performance of the CVD screening algorithm in a general obstetric population. Factors, such as proportion of African American women affect the likelihood of a positive screen. The screening algorithm highlights patients at higher lifetime risk of CVD and may identify a group that could be targeted for more direct care transitions postpartum. Data may be used to design a larger validation study.
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Cervical cancer is the most common cancer in Tanzania. After excluding human immunodeficiency virus, lower respiratory infections, malaria, diarrheal diseases, and tuberculosis, cervical cancer kills more women than any other form of illness in the country. Unfortunately, Tanzania has a low doctor-to-patient ratio (1:50,000) and nearly 7000 women die each year from this disease. The clinical problem is further magnified by the country's lack of resources and prevailing poverty, sporadic cervical cancer screening, prevalence of high-risk oncogenic human papillomavirus subtypes, and relatively high rates of human immunodeficiency virus co-infection. In recent years, addressing the cervical cancer problem has become a priority for the Tanzanian government. In this systematic review of 39 peer-reviewed publications that appeared in the PubMed/MEDLINE (NCBI) database from 2013 to 2018, we synthesize the growing body of literature to capture current trends in Tanzania's evolving cervical cancer landscape. Six domains were identified, including risk factors, primary prevention, barriers to screening, treatment, healthcare worker education, and sustainability. In addition to traditional risk factors associated with sexual behavior, acetowhite changes observed during visual inspection of the cervix with acetic acid, lower education, rural setting, and HIV positivity also have a noteworthy clinical impact.
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Cystic fibrosis is an autosomal recessive disease reported in 1 in 2500 live births in Northern American and Northern European Caucasian populations. Classic disease findings include chronic bacterial infection of airways and sinuses, malabsorption of fat, infertility in men, and elevated concentrations of chloride in sweat. Less well-recognized findings associated with cystic fibrosis include cutaneous findings, which can be primary or secondary manifestations of the disease process. Patients demonstrate more atopic and drug hypersensitivity reactions than the general population, but have similar rates of urticaria compared with the general population. In atypical presentations of cystic fibrosis, the nutrient deficiency dermatitis of the disease may aid with diagnosis, and notably can be the presenting sign. Other dermatologic manifestations of cystic fibrosis include early aquagenic skin wrinkling and cutaneous vasculitis, which can be associated with arthralgias. Familiarity with the nutrient deficiency dermatitis of this entity may play a role in the timely diagnosis of the disease, and the other cutaneous findings add to our understanding of the protean nature of its manifestations.
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Fibrosis Quística/diagnóstico , Dermatitis/diagnóstico , Vasculitis/diagnóstico , Fibrosis Quística/complicaciones , Fibrosis Quística/metabolismo , Dermatitis/clasificación , Dermatitis/etiología , Diagnóstico Diferencial , Ácidos Grasos/metabolismo , Femenino , Humanos , Masculino , Vasculitis/etiología , Zinc/deficienciaRESUMEN
Background: The purpose of this study is to evaluate the development of a 1-wk screening campaign and efforts towards the implementation of a sustainable system that addresses cervical cancer in Mwanza, Tanzania with a screen-and-treat model utilizing visual inspection of the cervix with acetic acid (VIA) and cryotherapy. Methods: In partnership with CureCervicalCancer (CCC), a non-profit organization based in Los Angeles, CA, USA, 11 medical students at the University of California, Irvine School of Medicine established a model for sustainable human papillomavirus screening practices in Mwanza, Tanzania. This study both quantitatively and qualitatively assesses the successes and limitations of the program model. Results: During the 5-day training, a total of 614 women attended the screenings and 556 women were screened with VIA, of whom 10.6% (n=59) were VIA positive and 89.4% (n=499) were VIA negative. Of those who were VIA positive, 83.1% (n=49) received cryotherapy while 16.9% (n=10) did not due to suspicion of advanced cancer (n=7), refusal to receive cryotherapy (n=2) or pregnancy (n=1). Conclusions: The screen-and-treat model for the identification and treatment of precancerous cervical lesions is an effective public health intervention with the potential to impact women by providing the tools and education needed by local healthcare professionals. However, limitations common to resource-poor settings, such as continuity of funding, loss to follow-up and transportation costs, remain barriers to sustainability.
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Personal de Salud/educación , Tamizaje Masivo/organización & administración , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/terapia , Adolescente , Adulto , Niño , Crioterapia , Femenino , Humanos , Persona de Mediana Edad , Modelos Organizacionales , Evaluación de Programas y Proyectos de Salud , Tanzanía , Neoplasias del Cuello Uterino/prevención & control , Adulto JovenRESUMEN
BACKGROUND: Diagnostic imaging is an integral aspect of care that is often insufficient, if not altogether absent, in rural and remote regions of low to middle income countries (LMICs) such as Tanzania. The introduction of ultrasound can significantly impact treatment in these countries due to its portability, low cost, safety, and usefulness in various medical assessments. This study reviews the implementation of a four-week ultrasound course administered annually from 2013-2016 in a healthcare professional school in Mwanza, Tanzania by first-year allopathic US medical students. METHODS: Participants (n=582, over 4 years) were recruited from the Tandabui Institute of Health Sciences and Technology to take the ultrasound course. Subjects were predominantly clinical officer students, but other participants included other healthcare professional students, practicing healthcare professionals, and school employees. Data collected includes pre-course examination scores, post-course examination scores, course quiz scores, demographic surveys, and post-course feedback surveys. Data was analyzed using two-tailed t-tests and the single factor analysis of variance (ANOVA). RESULTS: For all participants who completed both the pre- and post-course examinations (n=229, 39.1% of the total recruited), there was a significant mean improvement in their ultrasound knowledge of 42.5%, P<0.01. CONCLUSION: Our data suggests that trained first-year medical students can effectively teach a point of care ultrasound course to healthcare professional students within four weeks in Tanzania. Future investigation into the level of long-term knowledge retention, impact of ultrasound training on knowledge of human anatomy and diagnostic capabilities, and how expansion of an ultrasound curriculum has impacted access to care in rural Tanzania is warranted.
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HIV-related stigma remains a persistent global health concern among people living with HIV/AIDS (PLWA) in developing nations. The literature is lacking in studies about healthcare students' perceptions of PLWA. This study is the first effort to understand stigmatizing attitudes toward HIV-positive patients by healthcare students in Mwanza, Tanzania, not just those who will be directly treating patients but also those who will be indirectly involved through nonclinical roles, such as handling patient specimens and private health information. A total of 208 students were drawn from Clinical Medicine, Laboratory Sciences, Health Records and Information Management, and Community Health classes at the Tandabui Institute of Health Sciences and Technology for a voluntary survey that assessed stigmatizing beliefs toward PLWA. Students generally obtained high scores on the overall survey instrument, pointing to low stigmatizing beliefs toward PLWA and an overall willingness to treat PLWA with the same standard of care as other patients. However, there are gaps in knowledge that exist among students, such as a comprehensive understanding of all routes of HIV infection. The study also suggests that students who interact with patients as part of their training are less likely to exhibit stigmatizing beliefs toward PLWA. A comprehensive course in HIV infection, one that includes classroom sessions focused on the epidemiology and routes of transmission as well as clinical opportunities to directly interact with PLWA-perhaps through teaching sessions led by PLWA-may allow for significant reductions in stigma toward such patients and improve clinical outcomes for PLWA around the world.
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Infecciones por VIH/diagnóstico , Conocimientos, Actitudes y Práctica en Salud , Estigma Social , Estereotipo , Estudiantes del Área de la Salud/psicología , Adulto , Estudios Transversales , Femenino , Infecciones por VIH/epidemiología , Infecciones por VIH/psicología , Humanos , Percepción , Estudiantes del Área de la Salud/estadística & datos numéricos , Estudiantes de Medicina/psicología , Estudiantes de Medicina/estadística & datos numéricos , Encuestas y Cuestionarios , Tanzanía/epidemiologíaRESUMEN
Skin and joint involvements are the most commonly occurring manifestations of systemic lupus erythematosus. There are 3 forms of cutaneous lupus: chronic cutaneous (discoid) lupus, subacute cutaneous lupus, and acute cutaneous lupus. Joint manifestations are usually not associated with warmth of the joints and may be only associated with pain and swelling. Painful or swollen joints respond rapidly to small or moderate doses of corticosteroids, whereas cutaneous manifestations usually respond to antimalarial drugs. Anti-Ro is associated closely with a photosensitive rash and with subacute lupus.
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Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/patología , Enfermedades Musculoesqueléticas/patología , Enfermedades de la Piel/patología , Sistema Cardiovascular/patología , Sistema Cardiovascular/fisiopatología , Tracto Gastrointestinal/patología , Tracto Gastrointestinal/fisiopatología , Humanos , Lupus Eritematoso Sistémico/fisiopatología , Lupus Eritematoso Sistémico/terapia , Enfermedades Musculoesqueléticas/etiología , Enfermedades Musculoesqueléticas/fisiopatología , Enfermedades Musculoesqueléticas/terapia , Sistema Musculoesquelético/patología , Sistema Musculoesquelético/fisiopatología , Sistema Nervioso/patología , Sistema Nervioso/fisiopatología , Sistema Respiratorio/patología , Sistema Respiratorio/fisiopatología , Piel/patología , Piel/fisiopatología , Enfermedades de la Piel/etiología , Enfermedades de la Piel/fisiopatología , Enfermedades de la Piel/terapiaRESUMEN
Most patients with erythema migrans, the pathognomonic rash of Lyme disease, do not recall a deer tick bite. The rash is classically 5 to 68 cm of annular homogenous erythema (59%), central erythema (30%), central clearing (9%), or central purpura (2%). Serologic testing is not indicated for patients with erythema migrans, because initially, the result is usually negative. Successful treatment of a patient with erythema migrans can be accomplished with 20 days of oral doxycycline, amoxicillin, or cefuroxime axetil. Patients with Lyme arthritis usually present with a mildly painful swollen knee. Patients with Lyme arthritis have markedly positive serology and can usually be successfully treated with 28 days of oral doxycycline or amoxicillin. Some patients may have persistent effusion despite 4 to 8 weeks of antibiotics and may need synovectomy. Persistent effusion is not due to persistent infection. Antibiotic therapy for more than 8 weeks for patients with Lyme disease is not indicated. Chronic Lyme disease due to antibiotic resistant infection has not been demonstrated.
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Antibacterianos/uso terapéutico , Borrelia burgdorferi/patogenicidad , Doxiciclina/uso terapéutico , Enfermedad de Lyme , Adolescente , Adulto , Animales , Eritema Crónico Migrans/diagnóstico , Eritema Crónico Migrans/tratamiento farmacológico , Eritema Crónico Migrans/inmunología , Eritema Crónico Migrans/patología , Femenino , Humanos , Mordeduras y Picaduras de Insectos/microbiología , Ixodidae/microbiología , Enfermedad de Lyme/diagnóstico , Enfermedad de Lyme/tratamiento farmacológico , Enfermedad de Lyme/inmunología , Enfermedad de Lyme/fisiopatología , Masculino , Persona de Mediana EdadRESUMEN
Exfoliative erythroderma, or diffuse erythema and scaling of the skin, may be the morphologic presentation of a variety of cutaneous and systemic diseases. Establishing the diagnosis of the underlying disease is often difficult and, not uncommonly, erythroderma is classified as idiopathic. Several cases are presented to demonstrate the diversity of presentation of this disease. Laboratory findings are typically unhelpful in establishing the etiology of erythroderma. Clinical data combined with multiple skin biopsies over time are necessary. Systemic complications of erythroderma include infection, fluid and electrolyte imbalances, thermoregulatory disturbance, high output cardiac failure, and acute respiratory distress syndrome. The initial approach to the management of erythroderma of any etiology includes attention to nutrition, fluid and electrolyte replacement, and the institution of gentle local skin care measures. Oatmeal baths and wet dressings to weeping or crusted sites should be followed by application of bland emollients and low-potency topical corticosteroids. Systemic dermatologic therapy may be required to maintain improvement achieved with local measures or to control erythroderma refractory to local measures. The prognosis of erythroderma is dependent on the underlying etiology.
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Dermatitis Exfoliativa , Adulto , Anciano , Anciano de 80 o más Años , Algoritmos , Dermatitis Exfoliativa/diagnóstico , Dermatitis Exfoliativa/mortalidad , Dermatitis Exfoliativa/terapia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Índice de Severidad de la EnfermedadRESUMEN
Based upon molecular allelotyping and comparative genomic hybridization studies, chromosome 15q is the likely location of a tumor suppressor gene important in the pathogeneses of sporadic enteropancreatic endocrine tumors and parathyroid adenomas. Interest has focused on Smad3 as a candidate endocrine tumor suppressor gene because 1) it is localized to 15q and 2) it encodes a TGF beta signaling molecule that has been identified as a binding partner of the multiple endocrine neoplasm type 1 gene product menin, itself involved in enteropancreatic and parathyroid neoplasia. To determine whether Smad3 plays a primary role in development of these tumors, 20 enteropancreatic tumors and 67 parathyroid adenomas were investigated for loss of heterozygosity at DNA markers surrounding Smad3. Twenty percent of enteropancreatic tumors and 24% of parathyroid adenomas showed loss. All 9 coding exons and intron-exon boundaries of the Smad3 gene were then sequenced in genomic DNA from all 20 enteropancreatic and 25 parathyroid tumors, including every case with loss of heterozygosity. No acquired clonal mutations, insertions, or microdeletions in Smad3 were detected in any tumors. Because inactivating somatic mutation is the hallmark of an authentic tumor suppressor, Smad3 is unlikely to function as a classical tumor suppressor gene in the pathogenesis of sporadic parathyroid or enteropancreatic endocrine tumors.