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1.
J Obstet Gynaecol ; 39(8): 1117-1122, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31195902

RESUMO

There is conflicting literature on whether the levonorgestrel-releasing intrauterine system (LNG-IUS; Mirena®) induces decidualisation in the tamoxifen-treated endometrium. The expression of the decidualisation marker IGFBP-1 was measured using immunohistochemistry in endometrial biopsies and in serum (using ELISA) of 20 postmenopausal women at the start of tamoxifen-treatment for breast cancer. Ten women were then fitted with LNG-IUS and the other ten received tamoxifen-treatment only and acted as controls. Samples were taken at baseline and after 12 months. At baseline, all endometrial samples were negative for IGFBP-1 and at 12 months, IGFBP-1 was only expressed in the endometria of women fitted with the LNG-IUS, confirming the observed histological features of decidualisation. By contrast, serum IGFBP-1 concentrations were increased by tamoxifen, but not in the group receiving LNG-IUS. In conclusion, tamoxifen induces a rise in serum IGFBP-1 suggesting a systemic, possibly hepatic effect, whilst LNG abrogates this in both the liver and endometrium. Impact statement What is already known on this subject? Previous reports of the use of LNG-IUS in women on tamoxifen have provided conflicting evidence as to whether the endometrium exhibited decidualisation or not. These reports were however based solely on histological examination and lacked supporting biochemical data. What do the results of this study add? After 12 months of treatment with LNG-IUS, the endometria of women on tamoxifen show histological features of decidualisation and the presence of the decidualisation marker IGFBP-1, suggesting that levonorgestrel protects the tamoxifen-treated uterus from additional pathology by causing decidualisation. Serum levels of IGFBP-1 were expected to be a reflection of uterine production, but contrary to expectations, higher levels were identified in women on tamoxifen alone. These data suggest that an inhibition of tamoxifen-induced serum IGFBP-1 production (possibly from a hepatic source) by LNG-IUS occurred and indicates independent systemic effects of both drugs in post menopausal breast cancer patients. What are the implications of these findings for clinical practice and/or further research? This research demonstrated a mechanism for endometrial protection in women on tamoxifen. It also alerts clinicians to the fact that both tamoxifen and LNG-IUS exert systemic effects in this patient group.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Decídua/efeitos dos fármacos , Endométrio/efeitos dos fármacos , Dispositivos Intrauterinos Medicados , Levanogestrel/administração & dosagem , Tamoxifeno/uso terapêutico , Idoso , Biomarcadores/análise , Decídua/química , Decídua/fisiologia , Endométrio/patologia , Endométrio/fisiologia , Feminino , Humanos , Imuno-Histoquímica , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/análise , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Pessoa de Meia-Idade , Pós-Menopausa
2.
PLoS One ; 14(5): e0215825, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31042729

RESUMO

Although mother-to-child transmission of HIV has dramatically declined, the number of in utero HIV-exposed, uninfected infants is on the increase. HIV-exposed infants are at an increased risk of mortality, morbidity and slower early growth than their non-HIV exposed counterparts. Maternal HIV increases the risk of having preterm deliveries, intrauterine growth restriction and low birth weight babies. However, the mechanism underlying dysregulation of fetal growth in HIV-infected pregnant women is unknown. We sought to determine whether maternal HIV is associated with dysregulation of the insulin-like growth factor (IGF) axis, some angiogenic factors or other related biomarkers that regulate fetal growth. A total of 102 normotensive pregnant women were enrolled in a small cross-sectional study. Amongst these were thirty-one HIV-1 positive women receiving combination antiretroviral therapy (cART) (Mean age: 30.0 ± 5.1 years; % on ART: 83.9%; median plasma viral load: 683 copies/ml; median CD4 count: 350 cells/ul) and 71 HIV uninfected women (mean age: 27.3 ± 5.8) recruited at delivery. A panel of biomarkers including IGF1 and IGF binding proteins (IGFBP1, IGFBP3), angiopoietins (ANG) 1 and 2, matrix metalloproteinases (MMP) 2 and 9, and galectin 13, was measured in plasma collected from the placental intervillous space. The levels of IGF1, IGFBP1, ANG1, ANG2, MMP2, MMP9 and Gal-13 were not affected by maternal HIV, even when adjusted for maternal factors in linear regression models (all p>0.05). It was observed that HIV-infection in pregnancy did not significantly affect key markers of the IGF axis and angiogenic factors. If anything, it did not affect women. These findings highlight the importance of the use of ART during pregnancy, which maintains factors necessary for fetal development closer to those of healthy women. However, decrease in IGF1 levels might be exacerbated in women con-infected with HIV and malaria.


Assuntos
Angiopoietinas/sangue , Antirretrovirais/uso terapêutico , Infecções por HIV/tratamento farmacológico , Fator de Crescimento Insulin-Like I/metabolismo , Adulto , Biomarcadores/sangue , Camarões , Estudos Transversais , Feminino , Infecções por HIV/complicações , Infecções por HIV/metabolismo , Humanos , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/análise , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Fator de Crescimento Insulin-Like I/análise , Malária/complicações , Malária/diagnóstico , Metaloproteinase 9 da Matriz/sangue , Placenta/metabolismo , Placenta/patologia , Gravidez , Adulto Jovem
3.
Medicina (Kaunas) ; 55(5)2019 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-31100848

RESUMO

Background and Objectives: To investigate if pregnancies conceived using an oocyte donor necessitate an alteration in immune regulation, we compared concentrations of insulin-like growth factor binding protein (IGFBP)-1, insulin-like growth factor (IGF)-1 and T cell immunoglobulin mucin-3 (Tim-3) in women with ongoing successful twin pregnancies conceived spontaneously, using assisted reproductive technologies that utilized homologous oocytes or with donor oocytes. Differences in levels of these immune modulatory proteins may be magnified and easier to detect in twin as compared to singleton pregnancies. Methods: In this prospective study IGFBP-1 and IGF-1 were measured in sera and Tim-3 in lysates of peripheral blood mononuclear cells (PBMCs) by ELISA. Results: Median IGFBP-1 levels were lower in women with donor oocytes (41.4 ng/ml) as compared to those with a spontaneous conception (51.2 ng/mL) or who conceived with various assisted reproduction protocols using homologous oocytes (52.4 ng/mL) (p < 0.001). IGF-1 and Tim-3 levels were comparable in each group. The IGFBP-1 level was inversely correlated to the IGF-1 concentration only in women with donor oocytes (p = 0.032). IGFBP-1 and Tim-3 levels were similarly negatively correlated in the donor oocyte group (p = 0. 012). Women in the assisted reproduction group who conceived following intracytoplasmic sperm injection were the only other group in which IGFBP-1 and Tim-3 were negatively correlated (p = 0.018). Conclusions: Down-regulation of IGFBP-1 production in pregnancies conceived with donor oocytes may reduce the extent of pro-inflammatory immunity and contribute to successful outcome in totally allogeneic pregnancies.


Assuntos
Receptor Celular 2 do Vírus da Hepatite A/análise , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/análise , Fator de Crescimento Insulin-Like I/análise , Oócitos/enzimologia , Adulto , Feminino , Fertilização In Vitro/métodos , Receptor Celular 2 do Vírus da Hepatite A/sangue , Humanos , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Itália , Pessoa de Meia-Idade , Oócitos/patologia , Gravidez , Estudos Prospectivos , Doadores de Tecidos , Gêmeos/genética
4.
J Matern Fetal Neonatal Med ; 32(5): 793-797, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29073805

RESUMO

PURPOSE: The purpose of this study is to first compare the performance of the PAMG-1 biomarker test to that of standard clinical assessment (SCA) for the risk assessment of spontaneous preterm delivery (sPTD) among women with symptoms of preterm labor (PTL) and then calculate the potential impact on unnecessary admission reduction. MATERIALS AND METHODS: Patients of gestational age 240/7-366/7 with PTL symptoms, cervical dilatation ≤3 cm, no intercourse within 24 h, and clinically intact membranes were recruited consecutively into this prospective observational study. Specificity (SP), sensitivity (SN), positive-predictive value (PPV), and negative-predictive value (NPV) for the PAMG-1 test and SCA, for which a positive result was defined as patient admission, for predicting spontaneous delivery ≤7 and ≤14 d of presentation were calculated. RESULTS: One hundred and forty-eight patients were included in the analysis, 132 of which had both SCA and PAMG-1 results available. For the prediction of sPTD ≤7 d for SCA and PAMG-1, the PPV and NPV were 10% and 100%, and 71% and 98%, respectively. For prediction of sPTD ≤14 d for SCA and PAMG-1, the PPV and NPV were 14% and 100%, and 86% and 96%, respectively. Sixty-one per cent (81/132) of patients were admitted for treatment and/or observation. CONCLUSION: Our study reinforces the critical role of the PAMG-1 biomarker test to aid in risk assessment of imminent spontaneous preterm delivery in patients with symptoms of PTL. The PAMG-1 test was found to be statistically superior to standard clinical assessment alone, with respect to specificity. Based on our data, the introduction of a PAMG-1 test result into clinical decision making could reduce up to 91% of unnecessary admissions for women presenting with threatened preterm labor.


Assuntos
Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/análise , Trabalho de Parto Prematuro/diagnóstico , Feminino , Humanos , Sobremedicalização/prevenção & controle , Valor Preditivo dos Testes , Gravidez , Estudos Prospectivos , Medição de Risco
5.
Gynecol Obstet Fertil Senol ; 47(1): 18-22, 2019 01.
Artigo em Francês | MEDLINE | ID: mdl-30528545

RESUMO

OBJECTIVES: To assess concordance between double human and automated optical reading (AOR) concerning two biological tests for rupture of membranes (ROM) METHODS: We conducted a monocentric, prospective, observational study comparing Actim Prom® (Alere SAS, Jouy-en Josas, France) and Hiprom Duo® (Fumouze, Levallois-Perret, France). Each test was performed simultaneously in patients with suspected ROM and read independently by 2 biologists and AOR device. ROM was clinically confirmed in case of recurrent leakage or spontaneous labour with no perceived membranes within 48hours. RESULTS: Concerning Actim Prom®, concordance was 100 %, 92.5 % and 91.6 % between biologists, biologists-AOR device and biologists or AOR vs. clinical presentation respectively. Concerning Hiprom Duo®, concordance was 97.2 % between biologists, 97.2 % between biologist 1 and AOR, 95.3 % between biologist 2 and AOR, 63.5 % between clinical presentation and human reading, 62.3 % between clinical presentation and AOR. False positive cases were significantly associated with modified cervix (21 % vs. 46 %, P=0.006). CONCLUSION: We demonstrated excellent correlation between biologists and good or excellent correlation between AOR and human reading supporting the use of AOR in clinical practice.


Assuntos
Ruptura Prematura de Membranas Fetais/diagnóstico , Adulto , Colo do Útero , Feminino , França , Idade Gestacional , Humanos , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/análise , Dispositivos Ópticos , Gravidez , Estudos Prospectivos , Kit de Reagentes para Diagnóstico , alfa-Fetoproteínas/análise
6.
Int J Gynaecol Obstet ; 144(2): 180-186, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30387138

RESUMO

OBJECTIVE: To compare AmnioQuick Duo+ versus the placental α-microglobulin-1 (PAMG-1) test for diagnosis of prolonged premature rupture of membranes (PROM). METHODS: A multicenter prospective cohort study included women with suspected PROM at six tertiary institutions in southern Nigeria between January 1 and December 31, 2015. The inclusion criteria were features of PROM lasting at least 24 hours and a pregnancy duration of more than 24 weeks. AmnioQuick Duo+ (Biosynex, Strasbourg, France) and PAMG-1 (AmniSure International, Boston, USA) tests were used to diagnose PROM, which was confirmed after delivery by any two of the following criteria: delivery within 48 hours to 7 days, chorioamnionitis, membranes perceptibly ruptured at delivery, and adverse perinatal outcomes considerably associated with prolonged PROM. RESULTS: Of 100 women assessed for eligibility, 99 were included. Sensitivity, specificity, and accuracy were, respectively, 97.3%, 100%, and 95.9% for AmnioQuick Duo+, and 93.2%, 100%, and 90.4% for PAMG-1. The differences were not significant and the diagnostic discordant rate between the two tests was 3.1%. In equivocal cases (i.e., negative pooling test result), AmnioQuick Duo+ and PAMG-1 performed equally (diagnostic accuracy, 100% vs 97.7%; P>0.99). CONCLUSION: For diagnosis of PROM, AmnioQuick Duo+ was found to be non-inferior and comparable in accuracy to the PAMG-1 test, with a diagnostic discordance rate of 3.1%.


Assuntos
Ruptura Prematura de Membranas Fetais/diagnóstico , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/análise , alfa-Fetoproteínas/análise , Adolescente , Adulto , Biomarcadores/análise , Feminino , Ruptura Prematura de Membranas Fetais/metabolismo , Humanos , Pessoa de Meia-Idade , Nigéria , Valor Preditivo dos Testes , Gravidez , Estudos Prospectivos , Sensibilidade e Especificidade , Fatores de Tempo , Adulto Jovem
7.
J Matern Fetal Neonatal Med ; 32(23): 3909-3914, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29807458

RESUMO

Objective: The objective of this study is to compare the qualitative fFN test at 50 ng/ml threshold to novel methods for assessing risk of imminent sPTB in women with symptoms of preterm labor (PTL): (1) quantitative fetal fibronectin (qfFN) at four thresholds: 10, 50, 200, and 500 ng/ml; and (2) qualitative PAMG-1 test. Study design: Consecutive patients presenting with singleton pregnancies, signs of PTL, gestational age 23.1-34.6, intact membranes, no coitus within 24 h, and cervical dilation ≤3 cm. fFN was performed as standard of care, while clinicians were blinded to the qfFN and PAMG-1 test results. qfFN accuracy was evaluated at four thresholds of 10, 50, 200, and 500 ng/ml for its ability to predict imminent spontaneous preterm delivery (sPTD) ≤ 7 and ≤14 d from the time of sample collection. The PAMG-1 test was evaluated based on its qualitative result for the same delivery endpoints. Results: Seventy-two patients were analyzed. Fifty-seven percent of patients had an fFN concentration of <10 ng/ml fFN; 75% < 50 ng/ml; 92% < 200 ng/ml; 97% < 500 ng/ml. The SN, SP, PPV, and NPV for fFN at each of the four cutoffs for sPTB ≤7 d: 10 ng/ml: 67%, 58%, 6%, 98%; 50 ng/ml: 67%, 77%, 11%, 98%; 200 ng/ml: 33%, 93%, 17%, 97%; 500 ng/ml: 0%, 97%, 0%, 96%. The PAMG-1 test was positive in 7% of patients. SN, SP, PPV, and NPV for PAMG-1 for sPTD ≤7 d were 67%, 96%, 40%, and 99%, respectively. Conclusion: Compared with qfFN, the PAMG-1 test is a better predictor of spontaneous delivery within 7 d while maintaining a very high negative predictive value. The PAMG-1 test is an easy-to-use bedside test that provides rapid results, does not require a speculum examination, can be used after vaginal exam and coitus and does not require specialized equipment to analyze results. As to be expected, compared with the conventional cutoff of fFN (50 ng/ml), a higher fFN cutoff of 200 ng/ml does seem to increase the PPV of the test, but this comes at a cost to the fFN test's SN and NPV, rendering it of little to no advantage in clinical practice.


Assuntos
Fibronectinas/análise , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/análise , Trabalho de Parto Prematuro/diagnóstico , Nascimento Prematuro/diagnóstico , Diagnóstico Pré-Natal/métodos , Adulto , Líquidos Corporais/química , Líquidos Corporais/metabolismo , Feminino , Feto/metabolismo , Fibronectinas/metabolismo , Humanos , Recém-Nascido , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/metabolismo , Trabalho de Parto Prematuro/metabolismo , Valor Preditivo dos Testes , Gravidez , Nascimento Prematuro/metabolismo , Sensibilidade e Especificidade , Esfregaço Vaginal , Adulto Jovem
8.
Gynecol Obstet Fertil Senol ; 46(12): 1022-1028, 2018 12.
Artigo em Francês | MEDLINE | ID: mdl-30392990

RESUMO

OBJECTIVE: To describe clinical and paraclinical tests diagnosing rupture of fetal membranes (ROM). METHODS: Bibliographic search over the period 1980-2017 considering articles in French and English as well as guidelines from national obstetrical societies. RESULTS: Typical amniotic fluid leakage occurs in ¾ of cases. In this situation, no additional test is required (Professional consensus). For ambiguous cases, a speculum examination can demonstrate pooling of amniotic fluid but suspicion can persist in 50% of cases (evidence level IV). In this context, we recommend to consider performing an IGFBP-1 or PAMG-1 test of vaginal fluid (evidence level III). Ability of these tests to reduce maternal or neonatal morbidity has never been demonstrated (Professional consensus). An isolated positive test should be considered cautiously as false positive does exist (Professional consensus). CONCLUSION: Symptoms suggestive of ROM and speculum examination demonstrating pooling of amniotic fluid are sufficient to diagnose ROM. If pooling is not observed, we recommend to consider performing an IGFBP-1 or PAMG-1 test of vaginal fluid.


Assuntos
Ruptura Prematura de Membranas Fetais/diagnóstico , Líquido Amniótico/química , Biomarcadores/análise , Líquidos Corporais/química , Cristalização , Feminino , França , Idade Gestacional , Humanos , Concentração de Íons de Hidrogênio , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/análise , Gravidez , Nascimento Prematuro , Ultrassonografia Pré-Natal , Vagina
9.
Ultrasound Obstet Gynecol ; 52(4): 442-451, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29920825

RESUMO

OBJECTIVE: To assess the accuracy of placental alpha microglobulin-1 (PAMG-1), fetal fibronectin (fFN) and phosphorylated insulin-like growth factor-binding protein-1 (phIGFBP-1) tests in predicting spontaneous preterm birth (sPTB) within 7 days of testing in women with symptoms of preterm labor, through a systematic review and meta-analysis of the literature. The test performance of each biomarker was also assessed according to pretest probability of sPTB ≤ 7 days. METHODS: The Cochrane, MEDLINE, PubMed and ResearchGate bibliographic databases were searched from inception until October 2017. Cohort studies that reported on the predictive accuracy of PAMG-1, fFN and phIGFBP-1 for the prediction of sPTB within 7 days of testing in women with symptoms of preterm labor were included. Summary receiver-operating characteristics (ROC) curves and sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and positive (LR+) and negative (LR-) likelihood ratios were generated using indirect methods for the calculation of pooled effect sizes with a bivariate linear mixed model for the logit of sensitivity and specificity, with each diagnostic test as a covariate, as described by the Cochrane Handbook for Systematic Reviews of Diagnostic Test Accuracy. RESULTS: Bivariate mixed model pooled sensitivity of PAMG-1, fFN and phIGFBP-1 for the prediction of sPTB ≤ 7 days was 76% (95% CI, 57-89%), 58% (95% CI, 47-68%) and 93% (95% CI, 88-96%), respectively; pooled specificity was 97% (95% CI, 95-98%), 84% (95% CI, 81-87%) and 76% (95% CI, 70-80%) respectively; pooled PPV was 76.3% (95% CI, 69-84%) (P < 0.05), 34.1% (95% CI, 29-39%) and 35.2% (95% CI, 31-40%), respectively; pooled NPV was 96.6% (95% CI, 94-99%), 93.3% (95% CI, 92-95%) and 98.7% (95% CI, 98-99%), respectively; pooled LR+ was 22.51 (95% CI, 15.09-33.60) (P < 0.05), 3.63 (95% CI, 2.93-4.50) and 3.80 (95% CI, 3.11-4.66), respectively; and pooled LR- was 0.24 (95% CI, 0.12-0.48) (P < 0.05), 0.50 (95% CI, 0.39-0.64) and 0.09 (95% CI, 0.05-0.16), respectively. The areas under the ROC curves for PAMG-1, fFN and phIGFBP-1 for sPTB ≤ 7 days were 0.961, 0.874 and 0.801, respectively. CONCLUSIONS: In the prediction of sPTB within 7 days of testing in women with signs and symptoms of preterm labor, the PPV of PAMG-1 was significantly higher than that of phIGFBP-1 or fFN. Other diagnostic accuracy measures did not differ between the three biomarker tests. As prevalence affects the predictive performance of a diagnostic test, use of a highly specific assay for a lower-prevalence syndrome such as sPTB may optimize management. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.


Assuntos
alfa-Globulinas/análise , Fibronectinas/análise , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/análise , Trabalho de Parto Prematuro/diagnóstico , Nascimento Prematuro/diagnóstico , Biomarcadores/análise , Muco do Colo Uterino/química , Feminino , Idade Gestacional , Humanos , Valor Preditivo dos Testes , Gravidez , Sensibilidade e Especificidade
10.
J Histochem Cytochem ; 66(9): 617-630, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29718759

RESUMO

Intrauterine growth restriction (IUGR) is often caused by placental insufficiency, which is believed to be associated with decreased delivery of oxygen and nutrients to the placental barrier. We recently reported that hypoxia and/or leucine deprivation triggered hyperphosphorylation of insulin-like growth factor binding protein-1 (IGFBP-1) in decidualized human immortalized endometrial stromal cells (HIESCs), resulting in decreased insulin-like growth factor-1 (IGF-1) bioactivity. To test the hypothesis that human IUGR is associated with increased decidual IGFBP-1 phosphorylation at discrete sites, we used IUGR and gestational age matched appropriate for gestational age (AGA) placentas ( n=5 each). We performed dual immunofluorescence immunohistochemistry (IHC) using IGFBP-1 and vimentin as decidual and mesenchymal markers, respectively. Employing a unique strategy with imaging software, we extracted signal intensity of IGFBP-1 expressed specifically from truly decidualized cells of the placenta. Relative IGFBP-1 was increased (85%; p=0.0001) and using custom phospho-site-specific antibodies, we found that IGFBP-1 phosphorylation (pSer101; +40%, p=0.0677/pSer119; +60%, p=0.0064/pSer169; +100%, p=0.0021) was markedly enhanced in IUGR. Together, our data links for the first time, increased decidual IGFBP-1 phosphorylation at discrete sites with human IUGR. These novel findings suggest that hyperphosphorylation of IGFBP-1 in decidualized stromal mesenchymal decidua basalis contributes to potentially elevated levels of phosphorylated IGFBP-1 in maternal circulation in IUGR pregnancies.


Assuntos
Decídua/patologia , Retardo do Crescimento Fetal/patologia , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/análise , Células-Tronco Mesenquimais/patologia , Adulto , Feminino , Imunofluorescência/métodos , Humanos , Microscopia de Fluorescência , Fosforilação , Gravidez
11.
Mil Med ; 182(7): e1957-e1962, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28810998

RESUMO

BACKGROUND: Acromegaly is caused by elevated secretion of human growth hormone, which is frequently because of intracranial tumors. This diagnosis is fairly uncommon with an incidence of 3 to 4 cases per million patients per year. We are presenting a case of acromegaly diagnosed in an active duty Chief Petty Officer. MATERIALS AND METHODS: A 38-year-old male Chief Petty Officer with no previous mental health diagnosis experienced post-traumatic stress disorder (PTSD)-like symptoms in early 2012 after deploying to Iraq and Afghanistan from 2010 to 2011. Initially he self-managed his symptoms, but in July 2012 he required a reduction mammoplasty because of gynecomastia. The metabolic workup revealed elevated prolactin, but this was not further investigated. His recovery from anesthesia was complicated by intensified PTSD-like symptoms, which continued to worsen after the surgery. On self-referral to mental health, he was diagnosed with PTSD and managed for 6 months with cognitive behavioral therapy. Because of persistent and worsening symptoms, his therapy was augmented to include continued cognitive behavioral therapy, alpha-blockers, antidepressants, antihistamines, and sleep aids. Because of night sweats, the selective serotonin reuptake inhibitors doses were modified. Night sweats persisted, and the patient was re-evaluated for other potential etiologies. On evaluation, the patient endorsed a history of obstructive sleep apnea, cervicalgia, visual changes, depressed mood, as well as multiple physical symptoms including coarsened facial features, large hands/feet, and increased interdental distance. On laboratory analysis, insulin-like growth factor 1 was noted to be 3 times the upper limit of normal, and a prolactin level was five times the upper limit of normal. A brain magnetic resonance imaging revealed a cystic pituitary lesion with suprasellar extension, compression of the infundibulum without invasion of the cavernous sinus, or displacement of the optic chiasm. Based on clinical history, physical examination, laboratory data, and the pituitary lesion, this patient was diagnosed with acromegaly. He was referred to neurosurgery for further evaluation and management. RESULTS AND CONCLUSION: This case shows that side effects of medications can easily mimic some medical conditions. The possibility of unrecognized disease should not be overlooked simply because a patient's symptoms that develop after starting a medication correspond well the side effect profile of the prescribed medications. This is especially true if side effects do not stop with alteration of medication dose, cessation of the medication, or changing to another medication. Pituitary adenomas are rare in patients treated for PTSD. However, attribution of PTSD patient's symptoms to the side effects of selective serotonin reuptake inhibitors therapy without considering a broader differential may lead to a missed diagnosis of an endocrine disease. In this case, the presence of an undiagnosed pituitary lesion resulted in ineffective medical management of PTSD in the patient. Mental health providers should remain allied with their primary care counterparts and consider directing patients to primary care for periodic physical re-evaluation to provide the most effective approach to symptom evaluation and management.


Assuntos
Acromegalia/complicações , Acromegalia/diagnóstico , Psicotrópicos/efeitos adversos , Transtornos de Estresse Pós-Traumáticos/complicações , Adulto , Diagnóstico Tardio/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/diagnóstico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/psicologia , Humanos , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/análise , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Masculino , Prolactina/análise , Prolactina/sangue , Prolactinoma/complicações , Prolactinoma/diagnóstico , Transtornos de Estresse Pós-Traumáticos/diagnóstico , Transtornos de Estresse Pós-Traumáticos/psicologia
12.
BMC Pregnancy Childbirth ; 17(1): 246, 2017 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-28747164

RESUMO

BACKGROUND: To investigate the utility of vaginal placental alpha microglobulin-1 (PAMG-1) protein as a predictor of preterm delivery within 7 days in pregnancies at risk of premature birth. METHODS: This prospective study was performed in women at risk of premature birth. The levels of vaginal PAMG-1 and foetal fibronectin (fFN) and the transvaginal cervical length measurement (CLM) were investigated and compared. RESULTS: Seventy-two pregnant women were included in this study. The sensitivities of PAMG-1, fFN and CLM were 73.3, 73.6%, and 52.9%, respectively, while the specificities of PAMG-1, fFN and CLM were 92.9%, 94.3%, and 90.9%, respectively. The positive predictive values of PAMG-1, fFN and CLM were 73.3%, 82.3%, and 64.2%, respectively, and the negative predictive values of PAMG-1, fFN and CLM were 92.9%, 90.9%, and 86.2%, respectively. CONCLUSION: The diagnostic accuracy of PAMG-1 is similar to that of fFN in terms of preterm labour detection within 7 days.


Assuntos
Medida do Comprimento Cervical/enfermagem , Colo do Útero/metabolismo , Fibronectinas/análise , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/análise , Trabalho de Parto Prematuro/diagnóstico , Biomarcadores/análise , Feminino , Humanos , Trabalho de Parto Prematuro/metabolismo , Gravidez , Cuidado Pré-Natal/métodos , Estudos Prospectivos , Fatores de Risco
13.
J Obstet Gynaecol Res ; 43(8): 1263-1269, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28613021

RESUMO

AIM: We aimed to evaluate the combined value of placental alpha microglobulin-1 (PAMG-1) and cervical length (CL) via transvaginal ultrasound for assessing risk of imminent spontaneous preterm delivery in patients presenting with threatened preterm labor (PTL). METHODS: Clinical exam, PAMG-1 test, cardiotocography, and CL measurement via transvaginal ultrasound were performed on all patients meeting inclusion criteria. Ninety-nine patients at 22+0 -36+6 gestational weeks with the symptoms of PTL were included. The interval between sample collection and delivery was measured for each method. RESULTS: Performance metrics were calculated for PAMG-1 test, CL < 25 mm, and contractions ≥ 8/h. The sensitivity, specificity, positive predictive value, and negative predictive value for the PAMG-1 test were 100%, 95%, 75%, 100% and 100%, 98%, 88%, 100% for 7 and 14 days, respectively; the respective values for CL < 25 mm were 83%, 59%, 22%, 96% and 79%, 59%, 24%, 94% for 7 and 14 days; and those for contractions ≥ 8/h were 42%, 38%, 8%, 83% and 43%, 38%, 10%, 80% for 7 and 14 days. Specificity for the PAMG-1 test was statistically significant (P < 0.001) in pairwise comparisons for all other methods. Patients were divided into four groups for analysis of PAMG-1 test performance as follows: CL < 15 mm (100%, 100%, 100%, 100% and 100%, 100%, 100%, 100% for 7 and 14 days, respectively); CL < 25 mm (100%, 94%, 83%, 100% and 100%, 97%, 92%, 100% for 7 and 14 days, respectively); CL of 15-30 mm (100%, 95%, 64%, 100% and 100%, 97%, 82%, 100% for 7 and 14 days, respectively); and CL ≥ 30 mm (100%, 100%, 100%, 100% and 100%, 100%, 100%, 100% for 7 and 14 days, respectively). CONCLUSION: The use of the PAMG-1 test in patients with a CL of 15-30 mm is highly predictive of imminent spontaneous preterm delivery in women presenting with threatened PTL and could save hospital resources.


Assuntos
Medida do Comprimento Cervical , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/análise , Trabalho de Parto Prematuro/diagnóstico por imagem , Adulto , Feminino , Humanos , Valor Preditivo dos Testes , Gravidez , Estudos Prospectivos , Adulto Jovem
16.
J Perinat Med ; 45(8): 915-924, 2017 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-28236632

RESUMO

PURPOSE: To determine values of combinations of interleukin-6 (IL-6)/cervical native insulin-like growth factor-binding protein-1 (IGFBP-1)/total IGFBP-1 (Premaquick©) in predicting spontaneous deliveries and spontaneous exclusive preterm deliveries in women with threatened preterm labor. METHODS: Women with singleton pregnancies between gestation age (GA) of 24 weeks and 36 weeks and 6 days with preterm labor were recruited during a prospective multicenter study. Premaquick© was positive when at least two of three biomarkers were positive. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy were estimated for both prediction of spontaneous deliveries and spontaneous exclusive preterm deliveries. RESULTS: Ninety-seven (99.0%) out of 98 women enrolled were analyzed. Based on delivery status 7/14 days post-enrollment of general study population, Premaquick© had a sensitivity of 87.1/85.7%, a specificity of 92.4/96.8%, a PPV of 84.4/93.8% and a NPV of 93.9/92.3% for prediction of spontaneous delivery. Predictive accuracy of Premaquick© test in relation to days of enrollment were: 90.7% (≤7 days) and 92.8% (≤14 days). For women enrolled at GA <35 weeks, Premaquick© had a sensitivity of 100.0/87.5%, a specificity of 94.1/96.9%, a PPV of 70.5/87.5%, a NPV of 100.0/96.9% and an accuracy of 95.0/95.0% for prediction of preterm delivery within 7/14 days of enrollment, respectively. PPV was most significantly different in both groups when outcomes were compared between 2 days and 14 days post-enrollment (P<0.001). CONCLUSION: This novel triple biomarker model of native and total IGFBP-1 and IL-6 appears to be an accurate test in predicting spontaneous deliveries and spontaneous exclusive preterm deliveries in threatened preterm labor in singleton pregnancies.


Assuntos
Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/análise , Interleucina-6/análise , Trabalho de Parto Prematuro/diagnóstico , Feminino , Humanos , Valor Preditivo dos Testes , Gravidez , Estudos Prospectivos , Esfregaço Vaginal
17.
BJOG ; 124(8): 1274-1283, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27348806

RESUMO

OBJECTIVE: To evaluate the tolerability of cervical insulin-like growth factor binding protein 1 (IGFBP-1) and its value as a predictor of successful labour induction, compared with Bishop score and transvaginal ultrasound (TVUS) cervical length. DESIGN: A prospective study. SETTING: A tertiary hospital in Malaysia. POPULATION: A cohort of 193 term nulliparous women with intact membranes. METHODS: Prior to labour induction, cervical fluid was obtained via a vaginal speculum and tested for IGFBP-1, followed by TVUS and finally Bishop score. After each assessment the procedure-related pain was scored from 0 to 10. Cut-off values for Bishop score and cervical length were obtained from the receiver operating characteristic (ROC) curve. Multivariable logistic regression analysis was performed. MAIN OUTCOMES MEASURES: Vaginal delivery and vaginal delivery within 24 hours of starting induction. RESULTS: Bedside IGFBP-1 testing is better tolerated than Bishop score, but is less well tolerated than TVUS [median (interquartile range) of pain scores: 5 (4-5) versus 6 (5-7) versus 3 (2-3), respectively; P < 0.001]. IGFBP-1 independently predicted vaginal delivery (adjusted odds ratio, AOR 5.5; 95% confidence interval, 95% CI 2.3-12.9) and vaginal delivery within 24 hours of induction (AOR 4.9; 95% CI 2.1-11.6) after controlling for Bishop score (≥4 or ≥5), cervical length (≤29 or ≤27 mm), and other significant characteristics for which the Bishop score and TVUS were not predictive of vaginal delivery after adjustment. IGFBP-1 has 81% sensitivity, 59% specificity, positive and negative predictive values of 82 and 58%, respectively, and positive and negative likelihood ratios of 2.0 and 0.3 for vaginal delivery, respectively. CONCLUSION: IGFBP-1 better predicted vaginal delivery than BS or TVUS, and may help guide decision making regarding labour induction in nulliparous women. TWEETABLE ABSTRACT: IGFBP-1: a stronger independent predictor of labour induction success than Bishop score or cervical sonography.


Assuntos
Medida do Comprimento Cervical/estatística & dados numéricos , Tomada de Decisão Clínica/métodos , Parto Obstétrico/métodos , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/análise , Trabalho de Parto Induzido/métodos , Adulto , Colo do Útero/diagnóstico por imagem , Colo do Útero/metabolismo , Feminino , Humanos , Modelos Logísticos , Malásia , Paridade , Valor Preditivo dos Testes , Gravidez , Estudos Prospectivos , Curva ROC , Nascimento a Termo/metabolismo , Fatores de Tempo , Vagina
18.
J Perinat Med ; 45(1): 105-112, 2017 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-27855117

RESUMO

PURPOSE: To determine the diagnostic accuracy of insulin-like growth factor binding protein-1/alpha fetoprotein (Amnioquick duo+®) compared with traditional clinical assessment (TCA) of nitrazine, ferning and pooling for the diagnosis of prelabor rupture of membranes (PROM). METHODS: A double-blinded, multicenter clinical study was conducted between February 2015 and August 2015 among pregnant women presenting with symptoms or features suggestive of PROM between 24 and 42 weeks gestation. Confirmation of PROM was done after delivery based on the presence of any two of these criteria: delivery within 48 h to 7 days, evidence of chorioamnionitis, membranes explicitly ruptured at delivery and adverse perinatal outcomes strongly correlated with prolonged PROM. Sensitivity, specificity and accuracy were outcome measures assessed. RESULTS: Two hundred and thirty-six women were recruited. Three women were excluded from the final analysis due to lack of follow-up data and failure to meet inclusion criteria. Two hundred and thirty-three women had complete data for analysis. The specificity and sensitivity values for TCA were 76.2% and 85.2%, which were lower than those of Amnioquick duo+, which were 97.6% and 97.9%, respectively. The accuracy of Amnioquick duo+ was statistically higher (97.9% vs. 83.7%; RR=1.17; 95%CI=1.10-1.24; P<0.001). In equivocal cases (pooling=negative), the accuracy of Amnioquick duo+ vs. TCA was 98.4% vs. 69.4% (RR=1.42; 95%CI=1.20-1.68; P<0.001) at ≥34 weeks gestation and 100.0% vs. 71.4% (RR=1.40; 95%CI=1.07-1.83; P=0.021) at <34 weeks gestation. CONCLUSION: The performance matrix of Amnioquick duo+® was superior to that of TCA for diagnosing PROM even in equivocal cases.


Assuntos
Ruptura Prematura de Membranas Fetais/diagnóstico , Imunoensaio/estatística & dados numéricos , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/análise , alfa-Fetoproteínas/análise , Adolescente , Adulto , Método Duplo-Cego , Feminino , Humanos , Imunoensaio/métodos , Valor Preditivo dos Testes , Gravidez , Adulto Jovem
20.
Int J Gynaecol Obstet ; 134(2): 165-8, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27233814

RESUMO

OBJECTIVE: To evaluate the utility of measuring phosphorylated insulin-like growth factor-binding protein 1 (phIGFBP-1) in cervical secretions to predict preterm birth among women with premature uterine contractions. METHODS: A prospective study was conducted between September 27, 2013, and February 28, 2014, at a tertiary center in India. Participants with symptoms of preterm labor at 24-36weeks underwent testing for phIGFBP-1 in cervical secretions. Cervical length was measured by ultrasonography. RESULTS: Cervical swab samples tested positive for phIGFBP-1 among 34 (57%) of the 60 participants. Mean cervical length was 2.15±0.63cm among the 46 (77%) women who delivered preterm and 2.54±0.47cm among the 14 (23%) women who delivered at term. Of the 46 preterm deliveries, 29 (63%) women tested positive for phIGFBP-1 and 17 (37%) tested negative. Mean length of pregnancy at delivery was 32.11±4.09weeks and 35.77±1.68weeks among women who tested positive and negative for phIGFBP-1, respectively. The sensitivity, specificity, positive predictive value, and negative predictive value of phIGFBP-1 to predict preterm birth were 86.96%, 35.29%, 64.52%, and 66.67%, respectively. CONCLUSION: A rapid bedside test measuring phIGFBP-1 identified women at high risk of preterm delivery.


Assuntos
Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/análise , Testes Imediatos , Nascimento Prematuro/diagnóstico , Adulto , Medida do Comprimento Cervical , Feminino , Idade Gestacional , Humanos , Índia , Recém-Nascido , Valor Preditivo dos Testes , Gravidez , Estudos Prospectivos , Medição de Risco , Centros de Atenção Terciária , Ultrassonografia , Adulto Jovem
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