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1.
Contraception ; 101(5): 309-314, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32014519

RESUMO

OBJECTIVE: To examine the possibility that serum or urine concentrations of pregnancy-associated plasma protein A (PAPP-A), a disintegrin and metalloproteinase 12 (ADAM-12), placental growth factor (PlGF), human placental lactogen (HPL), glypican-3, pregnancy specific beta-1-glycoprotein 1 (PSG-1) or prolactin could predict gestational age (GA) >70 days, the currently recommended limit for medical abortion in the United States. STUDY DESIGN: In this exploratory observational study, we collected serum and urine specimens from 245 healthy individuals with singleton intrauterine pregnancies at GA <40 weeks by ultrasound. We assayed the serum specimens for all seven proteins and the urine specimens for PAPP-A and ADAM-12. We used scatterplots and receiver operating characteristic curves to identify a concentration for each protein that would differentiate GAs above and below 70 days. RESULTS: All seven proteins showed significant ability to distinguish GAs >70 days from earlier gestations. A PAPP-A concentration ≥5.591 ng/ml provided 100% sensitivity and 90% specificity for identifying GAs >70 days. An ADAM-12 concentration of ≥3.11 ng/ml provided 98.5% sensitivity and 77% specificity for identifying GAs >70 days. Serum concentrations of the other compounds showed less diagnostic discrimination. PAPP-A was not detected in urine, and urinary ADAM-12 concentrations were not useful in identifying GAs above 70 days. CONCLUSION: PAPP-A and ADAM-12 showed considerable promise as bases for a sensitive and specific serum test for identifying pregnancies with GA >70 days. If these results are confirmed by future research, such a test could obviate the need for routine ultrasound before medical abortion. IMPLICATIONS: Two placental proteins, PAPP-A and ADAM-12, showed considerable promise as bases for a serum test for identifying pregnancies with gestational age >70 days. Such a test could be highly useful in screening patients for eligibility for medical abortion.

2.
Contraception ; 101(5): 315-320, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32032639

RESUMO

OBJECTIVES: To evaluate the characteristics, clinical information, and storage instructions contained in package inserts from medical abortion commodities collected in low- and middle-income countries. STUDY DESIGN: From November 2017 to February 2018 mifepristone, misoprostol, and combined mifepristone-misoprostol (combipack) products were collected to populate the Medical Abortion Commodities Database. We extracted stated indications for use, storage instructions, and date of last revision from each package insert obtained. For those inserts listing medical abortion as an indication, we also extracted eligibility criteria, recommended regimens, side effects, and contraindications. RESULTS: We identified 41 package inserts from 20 countries; 19 (46%) listed medical abortion as an indication including all 7 combipacks, all 7 mifepristone products, and 5/27 (19%) misoprostol products. Date of last insert revision ranged from 1991 to 2016. Gestational age limits for early medical abortion ranged from 49 days to "first trimester." Three (43%) mifepristone products recommended a 600 mg oral dose and two (29%) recommended regimens with gemeprost. Eighteen (67%) misoprostol and one (14%) combipack inserts recommended protection from moisture. CONCLUSIONS: The characteristics, clinical information, and storage instructions in medical abortion product package inserts from a variety of field settings in low- and middle-income countries included inadequate storage instructions and outdated gestational age limits and regimens. IMPLICATIONS: There is an urgent need to revisit approved inserts for medical abortion products in low- and middle-income countries to ensure information is accurate and reflects the current evidence base. Simultaneously, providing supplemental instructions targeted at users may fill some gaps. People have a right to accurate information to ensure a safe and effective medical abortion experience.

4.
Cell Rep ; 28(3): 773-791.e7, 2019 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-31315054

RESUMO

Exquisite regulation of energy homeostasis protects from nutrient deprivation but causes metabolic dysfunction upon nutrient excess. In human and murine adipose tissue, the accumulation of ligands of the receptor for advanced glycation end products (RAGE) accompanies obesity, implicating this receptor in energy metabolism. Here, we demonstrate that mice bearing global- or adipocyte-specific deletion of Ager, the gene encoding RAGE, display superior metabolic recovery after fasting, a cold challenge, or high-fat feeding. The RAGE-dependent mechanisms were traced to suppression of protein kinase A (PKA)-mediated phosphorylation of its key targets, hormone-sensitive lipase and p38 mitogen-activated protein kinase, upon ß-adrenergic receptor stimulation-processes that dampen the expression and activity of uncoupling protein 1 (UCP1) and thermogenic programs. This work identifies the innate role of RAGE as a key node in the immunometabolic networks that control responses to nutrient supply and cold challenges, and it unveils opportunities to harness energy expenditure in environmental and metabolic stress.

6.
PLoS One ; 14(5): e0217306, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31141557

RESUMO

Endobronchial stents are increasingly used to treat airway complications in multiple conditions including lung transplantation but little is known about the biofilms that form on these devices. We applied deep sequencing to profile luminal biofilms of 46 endobronchial stents removed from 20 subjects primarily with lung transplantation-associated airway compromise. Microbial communities were analyzed by bacterial 16S rRNA and fungal ITS marker gene sequencing. Corynebacterium was the most common bacterial taxa across biofilm communities. Clustering analysis revealed three bacterial biofilm types: one low diversity and dominated by Corynebacterium; another was polymicrobial and characterized by Staphylococcus; and the third was polymicrobial and associated with Pseudomonas, Streptococcus, and Prevotella. Biofilm type was significantly correlated with stent material: covered metal with the Staphylococcus-type biofilm, silicone with the Corynebacterium-dominated biofilm, and uncovered metal with the polymicrobial biofilm. Subjects with sequential stents had frequent transitions between community types. Fungal analysis found Candida was most prevalent, Aspergillus was common and highly enriched in two of three stents associated with airway anastomotic dehiscence, and fungal taxa not typically considered pathogens were highly enriched in some stents. Thus, molecular analysis revealed a complex and dynamic endobronchial stent biofilm with three bacterial types that associate with stent material, a central role for Corynebacterium, and that both expected and unexpected fungi inhabit this unique niche. The current work provides a foundation for studies to investigate the relationship between stent biofilm composition and clinical outcomes, mechanisms of biofilm establishment, and strategies for improved stent technology and use in airway compromise.


Assuntos
Stents/efeitos adversos , Stents/microbiologia , Bactérias/genética , Biofilmes/crescimento & desenvolvimento , Brônquios/microbiologia , Brônquios/cirurgia , Feminino , Fungos/genética , Humanos , Masculino , Microbiota , RNA Ribossômico 16S/genética
7.
Diagn Cytopathol ; 47(8): 797-802, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30919592

RESUMO

Dermatofibrosarcoma protuberans (DFSP) is a low-grade spindle cell tumor of the skin commonly arising on the trunk and extremities which tends to be slow growing yet locally aggressive. DFSPs are associated with a good prognosis when surgical excision with negative margins is achieved. Although local recurrences occur up to 50% of incompletely resected cases, distant metastases are very rare. Here, we report a case of DFSP metastasizing to the right hemithorax diagnosed by an endobronchial ultrasound-guided fine-needle aspiration (FNA) 9 years after initial presentation. The aspirate showed a bland spindle cell proliferation that was morphologically similar to the original skin excision; the storiform pattern was particularly prominent in tumor-tissue fragments in the cellblock. Immunostaining showed strong, diffuse positivity for CD34. Molecular studies demonstrated a characteristic COL1A1/PDGFB fusion in both original and metastatic specimens. A review of the literature revealed that metastatic DFSP most often involves the lungs, occurs usually in cases with fibrosarcomatous transformation and after a local recurrence, and presents on average 4.5 years after the original diagnosis. This case did not show fibrosarcomatous transformation or local recurrence prior to metastasis 9 years later. In summary, it is important to consider the potential for metastases years after a nonrecurring primary DFSP, despite its rarity. Cytologic features when complemented by ancillary studies and awareness of the patient's prior clinical history permit a confident diagnosis of metastatic DFSP by FNA. In addition, by confirming the characteristic translocation, tyrosine-kinase inhibitor imatinib can provide additional treatment options for unresectable metastatic DFSP.


Assuntos
Dermatofibrossarcoma/patologia , Neoplasias Cutâneas/patologia , Neoplasias Torácicas/secundário , Veia Cava Superior/patologia , Biópsia por Agulha Fina , Feminino , Humanos , Proteínas de Fusão Oncogênica/metabolismo , Radiografia Torácica , Neoplasias Torácicas/diagnóstico por imagem , Ultrassonografia
8.
Nat Commun ; 9(1): 658, 2018 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-29440643

RESUMO

Enhancers regulate gene expression and have been linked with disease pathogenesis. Little is known about enhancers that regulate human disease-associated genes in primary cells relevant for pathogenesis. Here we use BAC transgenics and genome editing to dissect, in vivo and in primary immune cells, enhancers that regulate human TNFAIP3, which encodes A20 and is linked with autoimmune diseases. A20 expression is dependent on a topologically associating subdomain (sub-TAD) that harbors four enhancers, while another >20 enhancers in the A20 locus are redundant. This sub-TAD contains cell- and activation-specific enhancers, including an enhancer (termed TT>A) harboring a proposed causal SLE-associated SNV. Deletion of the sub-TAD or the TT>A enhancer results in enhanced inflammatory responses, autoantibody production, and inflammatory arthritis, thus establishing functional importance in vivo and linking enhancers with a specific disease phenotype. These findings provide insights into enhancers that regulate human A20 expression to prevent inflammatory pathology and autoimmunity.


Assuntos
Doenças Autoimunes/genética , Elementos Facilitadores Genéticos/genética , Predisposição Genética para Doença/genética , Proteína 3 Induzida por Fator de Necrose Tumoral alfa/genética , Animais , Artrite Reumatoide/genética , Artrite Reumatoide/metabolismo , Doenças Autoimunes/metabolismo , Autoimunidade/genética , Sequência de Bases , Células Cultivadas , Feminino , Regulação da Expressão Gênica , Células HEK293 , Humanos , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Polimorfismo de Nucleotídeo Único , Proteína 3 Induzida por Fator de Necrose Tumoral alfa/metabolismo
9.
Clin Chest Med ; 38(4): 693-706, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-29128019

RESUMO

Airway complications remain a significant source of morbidity and mortality after lung transplantation. The incidence of complications is wide-ranging depending on the definition of the event, and there is still no universally accepted grading system for airway findings after transplantation. Additionally, although surgical technique and organ preservation have improved, other modifiable risk factors remain unclear. The management is as wide-ranging as the definitions. A multimodality approach is often needed with airway stenting reserved for refractory cases and stent management by a transplant team with expertise in placement and management of long-term complications."


Assuntos
Broncopatias/etiologia , Broncoscopia/métodos , Transplante de Pulmão/efeitos adversos , Broncopatias/patologia , Humanos , Transplante de Pulmão/métodos , Complicações Pós-Operatórias , Fatores de Risco
10.
BMC Res Notes ; 10(1): 516, 2017 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-29073923

RESUMO

BACKGROUND: Advance provision of misoprostol to women during antenatal care aims to achieve broader access to uterotonics for the prevention of postpartum hemorrhage. Studies of this community-based approach usually involve antenatal education as well as timely postpartum follow-up visits to confirm maternal and neonatal outcomes. The MamaMiso study in Mbale, Uganda sought to assess the feasibility of conducting follow-up visits in the postpartum period following advance provision of misoprostol for postpartum hemorrhage prevention. MamaMiso recruited women during antenatal care visits. Participants were asked to contact the research team within 48 h of giving birth so that postpartum follow-up visits could be carried out at their homes. Women's baseline and delivery characteristics were collected and analyzed with respect to follow-up time ('on time' ≤ 7 days, 'late' > 7 days, and 'lost to follow up'). Every woman who was followed up late due to a failure to report the delivery was asked for the underlying reasons for the delay. When attempts at following up participants were unsuccessful, a file note was generated explaining the details of the failure. We abstracted data and identified themes from these notes. RESULTS: Of 748 recruited women, 700 (94%) were successfully followed up during the study period, 465 (62%) within the first week postpartum. The median time to follow up was 4 days and was similar for women who delivered at home or in facilities and for women who had attended or unattended births. Women recruited at the urban hospital site (as opposed to rural health clinics) were more likely to be lost to follow up or followed up late. Of the women followed up late, 202 provided a reason. File notes explaining failed attempts at follow up were generated for 164 participants. Several themes emerged from qualitative analysis of these notes including phone difficulties, inaccurate baseline information, misperceptions, postpartum travel, and the condition of the mother and neonate. CONCLUSIONS: Keeping women connected to the health system in the postpartum period is feasible, though reaching them within the first week of their delivery is challenging. Understanding characteristics of women who are harder to reach can help tailor follow-up efforts and elucidate possible biases in postpartum study data. Trial Registration Number ISRCTN70408620 December 28, 2011.


Assuntos
Assistência ao Convalescente/estatística & dados numéricos , Serviços de Saúde Comunitária/estatística & dados numéricos , Parto Domiciliar/estatística & dados numéricos , Misoprostol/administração & dosagem , Ocitócicos/administração & dosagem , Assistência Perinatal/estatística & dados numéricos , Hemorragia Pós-Parto/prevenção & controle , Cuidado Pré-Natal/estatística & dados numéricos , Adulto , Assistência ao Convalescente/normas , Serviços de Saúde Comunitária/normas , Feminino , Humanos , Assistência Perinatal/normas , Período Pós-Parto , Uganda , Adulto Jovem
11.
Oxf Med Case Reports ; 2016(12): omw090, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28031854

RESUMO

Pleomorphic adenomas are the most common tumors of the salivary glands. Rarely, they occur as benign lesions in the lungs in both the central airways and the lung parenchyma. Herein, we present a case of a 60-year-old smoker who was incidentally found to have an endobronchial mass while undergoing evaluation for a lung nodule. During bronchoscopy, a smooth globular nodule was identified at the main carina and removed using electrocautery snare. Histopathology examination revealed this to be a pleomorphic adenoma.

13.
Eur J Contracept Reprod Health Care ; 21(4): 265-8, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27102981

RESUMO

OBJECTIVES: The aim of the study was to compare the pharmacokinetic parameters of 800 µg oral, sublingual and buccal misoprostol in healthy non-pregnant women. METHODS: This was an open-label, randomised study with a three-way crossover design. Eighteen participants were randomly assigned to treatment sequences of 800 µg oral, sublingual and buccal misoprostol administered under fasting conditions, with a 7-day washout period. Ten participants completed all routes. The primary pharmacokinetic parameters measured were the area under the plasma misoprostol acid concentration-time curve (AUC) from dosing to last quantifiable concentration (AUC0-t), the AUC from 0 to infinity (AUC0-∞) and the maximum plasma concentration (Cmax). Secondary parameters included the plasma elimination rate constant (ke), the half-life and the mean residence time (MRT). RESULTS: There were statistically significant differences in AUC0-∞, AUC0-t and Cmax at the p < 0.05 level for the three routes of administration. The sublingual route achieved the highest bioavailability, and the buccal route achieved the lowest peak concentration. The oral and buccal routes had a similar AUC0-∞ and the buccal route had the highest MRT and ke. There were no differences in half-lives, and no serious adverse events were reported. CONCLUSIONS: This study shows variability in Cmax and AUC by three by-mouth routes of misoprostol administration. The dose in this study was 800 µg, which is among the highest doses seen in current guidelines. These data contribute to the understanding of efficacy and safety of different routes and could provide a basis for deciding whether certain routes are preferable for particular indications.


Assuntos
Abortivos não Esteroides/administração & dosagem , Abortivos não Esteroides/farmacocinética , Misoprostol/administração & dosagem , Misoprostol/farmacocinética , Administração Bucal , Administração Oral , Administração Sublingual , Adulto , Área Sob a Curva , Disponibilidade Biológica , Estudos Cross-Over , Feminino , Meia-Vida , Humanos , Taxa de Depuração Metabólica
15.
BMC Pregnancy Childbirth ; 15: 219, 2015 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-26370443

RESUMO

BACKGROUND: 600 mcg of oral misoprostol reduces the incidence of postpartum haemorrhage (PPH), but in previous research this medication has been administered by health workers. It is unclear whether it is also safe and effective when self-administered by women. METHODS: This placebo-controlled, double-blind randomised trial enrolled consenting women of at least 34 weeks gestation, recruited over a 2-month period in Mbale District, Eastern Uganda. Participants had their haemoglobin measured antenatally and were given either 600 mcg misoprostol or placebo to take home and use immediately after birth in the event of delivery at home. The primary clinical outcome was the incidence of fall in haemoglobin of over 20% in home births followed-up within 5 days. RESULTS: 748 women were randomised to either misoprostol (374) or placebo (374). Of those enrolled, 57% delivered at a health facility and 43% delivered at home. 82% of all medicine packs were retrieved at postnatal follow-up and 97% of women delivering at home reported self-administration of the medicine. Two women in the misoprostol group took the study medication antenatally without adverse effects. There was no significant difference between the study groups in the drop of maternal haemoglobin by >20% (misoprostol 9.4% vs placebo 7.5%, risk ratio 1.11, 95% confidence interval 0.717 to 1.719). There was significantly more fever and shivering in the misoprostol group, but women found the medication highly acceptable. CONCLUSIONS: This study has shown that antenatally distributed, self-administered misoprostol can be appropriately taken by study participants. The rarity of the primary outcome means that a very large sample size would be required to demonstrate clinical effectiveness. TRIAL REGISTRATION: This study was registered with the ISRCTN Register (ISRCTN70408620).


Assuntos
Parto Domiciliar/estatística & dados numéricos , Misoprostol/administração & dosagem , Ocitócicos/administração & dosagem , Hemorragia Pós-Parto/prevenção & controle , Adulto , Parto Obstétrico/métodos , Método Duplo-Cego , Feminino , Idade Gestacional , Hemoglobinas/análise , Humanos , Incidência , Hemorragia Pós-Parto/epidemiologia , Gravidez , População Rural , Autoadministração , Uganda/epidemiologia
16.
Contraception ; 92(3): 215-9, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26142620

RESUMO

OBJECTIVE: To determine the acceptability of taking mifepristone at home for early medical abortion in the United States. STUDY DESIGN: This prospective, non-randomized, open-label study at six Planned Parenthood centers gave women with pregnancies up to 63 days' gestation seeking medical abortion the choice of taking mifepristone in the center or at home. Participants were interviewed at a follow-up visit 1-2 weeks after mifepristone administration to assess their experience with the option they selected. RESULTS: Four-hundred women were enrolled between April 2013 and June 2014 of which 32% (n=128) chose to take mifepristone at home. Abortion success rates did not differ between home and center users (96% and 97%). Among home users, 82% reported taking the mifepristone at the time they planned with their provider and no participant took it after 63 days' gestation. The most common reason cited for selecting home use was scheduling flexibility and significantly more home users took misoprostol on the weekend (50% vs. 36%, p=.02). Home users were more likely than center users to report missing no days of work due to the abortion (47% vs. 28%, p=.08). Ninety-nine percent of home users reported that they would take mifepristone at home again and 96% would recommend home use to a friend. Offering this option did not increase the service delivery burden on study providers, who would recommend home use in the future for most participants. CONCLUSIONS: Home use of mifepristone is a highly acceptable practice for which there is current demand, and it should be offered as part of routine medical abortion services. IMPLICATIONS: Offering the option of home use of mifepristone to medical abortion patients can provide women and clinics with more flexibility while maintaining a safe, effective and acceptable service. These results provide support for telemedicine or pharmacy distribution.


Assuntos
Abortivos/administração & dosagem , Mifepristona/administração & dosagem , Misoprostol/administração & dosagem , Aceitação pelo Paciente de Cuidados de Saúde , Autoadministração , Aborto Induzido , Adolescente , Adulto , Comportamento de Escolha , Feminino , Humanos , Gravidez , Estudos Prospectivos , Estados Unidos , Adulto Jovem
17.
Contraception ; 91(1): 19-24, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25444253

RESUMO

OBJECTIVES: Routine provision of antibiotics following medical abortion is common yet practitioners and professional societies differ on its utility. Our study compares the side effects experienced by women who were prescribed doxycycline following medical abortion to those who were not and assesses the adherence to one prescribed regimen. STUDY DESIGN: This was a prospective, observational, open-label study from a convenience sample. Women seeking medical abortion were enrolled in nine study sites, including four clinics that routinely prescribe a seven-day course of doxycycline (Doxycycline arm) and five clinics that do not routinely prescribe any antibiotics (No Doxycycline arm). Seven to fourteen days following the administration of mifepristone, women were asked to self-administer a computer-based survey. The survey asked about side effects experienced (both arms) and adherence to the regimen (Doxycycline arm only). RESULTS: Five hundred eighty-one women were enrolled (278 in the Doxycycline arm and 303 in the No Doxycycline arm). There was a trend toward increased nausea in the Doxycycline arm (47.8% vs. 40.9%; p=.056) and a statistically significant difference in vomiting (25.2% vs. 18.5%; p=.032). Almost all women in the Doxycycline arm reported taking at least one pill, however only 28.3% reported "perfect adherence." The most common reasons reported for taking fewer pills than instructed were that participants were still taking them (beyond 7 days) or that they forgot to take them. CONCLUSION: Women who were prescribed doxycycline following medical abortion reported moderate adherence and experienced significantly more vomiting than their counterparts. IMPLICATIONS: In the absence of robust evidence that prescribing 7 days of doxycycline following medical abortion is effective at reducing serious infections, these data can assist the public health community with deciding whether routine provision is the most appropriate strategy.


Assuntos
Aborto Induzido/efeitos adversos , Antibacterianos/efeitos adversos , Antibioticoprofilaxia/efeitos adversos , Doxiciclina/efeitos adversos , Adesão à Medicação , Vômito/induzido quimicamente , Abortivos Esteroides , Adulto , Instituições de Assistência Ambulatorial , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Doxiciclina/administração & dosagem , Doxiciclina/uso terapêutico , Feminino , Seguimentos , Humanos , Internet , Mifepristona , Náusea/induzido quimicamente , Padrões de Prática Médica , Gravidez , Inquéritos e Questionários , Estados Unidos , Adulto Jovem
18.
Int J Gynaecol Obstet ; 127(2): 125-6, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25220862

RESUMO

Efforts to prosecute women for induced abortion have included allegations that misoprostol was found in body fluids. These claims, however, are questionable owing to the timing of specimen collection for accurate results, the scarcity and expense of validated assays, and the onerous lab procedures required to determine the presence of the substance. Adequate scrutiny should be applied each time such a claim is made.


Assuntos
Abortivos não Esteroides/análise , Aborto Induzido , Testes de Química Clínica , Misoprostol/análise , Aborto Induzido/legislação & jurisprudência , Aborto Induzido/métodos , Adolescente , Adulto , Feminino , Humanos , México , Gravidez , Estados Unidos
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