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2.
Medicine (Baltimore) ; 103(28): e38839, 2024 Jul 12.
Article de Anglais | MEDLINE | ID: mdl-38996090

RÉSUMÉ

Left ventricular assist devices (LVADs) are widely used as end-stage therapy in patients with advanced heart failure, whereas implantation increases the risks of development of sustained ventricular tachycardia at the later postimplantation stage. Therefore, this study aimed to evaluate the clinical efficacy of orally administered amiodarone and propranolol in 3 patients with ventricular tachycardia (VT) after LVAD implantation who were resistant to initial anti-antiarrhythmic drugs. This retrospective cohort study consisted of the initial evaluation of the clinical data of 14 adult patients who underwent implantation of LVAD between January 2019 and March 2021. A total of 3 patients with resistant VT were finally included. In all cases, the patients were initially administered amiodarone in the different doses intravenously to stabilize the critical condition, whereas its oral form along with that of propranolol was used as maintenance therapy in the first 2 cases. In the third case, amiodarone was withdrawn because of the risk of development of hyperthyroidism, while oral propranolol was used in the treatment. The assessment in the 16-month follow-up period after discharge did not show presence of non-sustained and sustained VT in all 3 cases. In the ventricular arrhythmia-free group, the total mortality rate within the follow-up period was 11.1 ±â€…7.78 months in the 3 patients. We suggest that maintenance oral therapy of propranolol and amiodarone can significantly decrease the risks of complications in patients with VT after implantation of ventricular assist device in the long term.


Sujet(s)
Amiodarone , Antiarythmiques , Propranolol , Tachycardie ventriculaire , Humains , Amiodarone/administration et posologie , Amiodarone/effets indésirables , Propranolol/administration et posologie , Propranolol/usage thérapeutique , Mâle , Antiarythmiques/administration et posologie , Études rétrospectives , Administration par voie orale , Adulte d'âge moyen , Tachycardie ventriculaire/traitement médicamenteux , Femelle , Adulte , Défaillance cardiaque/traitement médicamenteux , Sujet âgé
3.
Vasc Health Risk Manag ; 20: 251-254, 2024.
Article de Anglais | MEDLINE | ID: mdl-38883398

RÉSUMÉ

Kaposiform hemangioendothelioma(KHE) without Kasabach-Merritt phenomenon is a rare tumor primarily observed in pediatric patients; however, its documentation in the literature remains limited. We reported about a 1-year-old boy diagnosed with superficial KHE who received oral propranolol in combination with topical sirolimus and reviewed relevant reports and treatment of superficial KHE.


Sujet(s)
Hémangioendothéliome , Propranolol , Sarcome de Kaposi , Sirolimus , Humains , Nourrisson , Mâle , Administration par voie orale , Biopsie , Hémangioendothéliome/traitement médicamenteux , Hémangioendothéliome/diagnostic , Propranolol/administration et posologie , Propranolol/usage thérapeutique , Sarcome de Kaposi/traitement médicamenteux , Sarcome de Kaposi/anatomopathologie , Sirolimus/administration et posologie , Résultat thérapeutique
5.
J Anxiety Disord ; 104: 102870, 2024 Jun.
Article de Anglais | MEDLINE | ID: mdl-38733644

RÉSUMÉ

Exposure therapy is an evidence-based treatment option for anxiety-related disorders. Many patients also take medication that could, in principle, affect exposure therapy efficacy. Clinical and laboratory evidence indeed suggests that benzodiazepines may have detrimental effects. Large clinical trials with propranolol, a common beta-blocker, are currently lacking, but several preclinical studies do indicate impaired establishment of safety memories. Here, we investigated the effects of propranolol given prior to extinction training in 9 rat studies (N = 215) and one human study (N = 72). A Bayesian meta-analysis of our rat studies provided strong evidence against propranolol-induced extinction memory impairment during a drug-free test, and the human study found no significant difference with placebo. Two of the rat studies actually suggested a small beneficial effect of propranolol. Lastly, two rat studies with a benzodiazepine (midazolam) group provided some evidence for a harmful effect on extinction memory, i.e., impaired extinction retention. In conclusion, our midazolam findings are in line with prior literature (i.e., an extinction retention impairment), but this is not the case for the 10 studies with propranolol. Our data thus support caution regarding the use of benzodiazepines during exposure therapy, but argue against a harmful effect of propranolol on extinction learning.


Sujet(s)
Antagonistes bêta-adrénergiques , Extinction (psychologie) , Peur , Mémoire , Midazolam , Propranolol , Propranolol/pharmacologie , Propranolol/administration et posologie , Animaux , Peur/effets des médicaments et des substances chimiques , Extinction (psychologie)/effets des médicaments et des substances chimiques , Rats , Humains , Antagonistes bêta-adrénergiques/pharmacologie , Antagonistes bêta-adrénergiques/administration et posologie , Mâle , Mémoire/effets des médicaments et des substances chimiques , Midazolam/pharmacologie , Midazolam/administration et posologie , Midazolam/effets indésirables , Adulte , Théorème de Bayes , Femelle , Conditionnement classique/effets des médicaments et des substances chimiques , Jeune adulte
7.
Eur J Clin Pharmacol ; 80(6): 901-910, 2024 Jun.
Article de Anglais | MEDLINE | ID: mdl-38436704

RÉSUMÉ

PURPOSE: To systematically review the impact of propranolol combined with oxytocin on the process and outcomes of labor. METHODS: A comprehensive literature search was performed across multiple databases, including China National Knowledge Infrastructure (CNKI), VIP, Wanfang, China Biomedical Literature Database, PubMed, Embase, and the Cochrane Library. All publicly published randomized controlled trials (RCTs) of propranolol combined with oxytocin compared to the use of oxytocin alone in labor were collected. After screening the literature and extracting data, the Cochrane Handbook for Systematic Reviews of Interventions 5.1.0 recommended bias risk assessment tool was used to assess the quality of the included studies. A meta-analysis was conducted using RevMan 5.3 software, and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was used to rate the quality of evidence for outcome measures. RESULTS: Meta-analysis results showed that the group receiving propranolol combined with oxytocin was more capable of reducing the cesarean section rate (eight studies, 815 women, RR = 0.67, 95% CI (0.53, 0.86), P = 0.001) and shortening the duration of the latent phase (two studies, 206 women, MD = - 1.20, 95% CI (- 1.97, - 0.43), P = 0.002) and the duration of the active phase on day 1 (two studies, 296 women, MD = - 0.69, 95% CI (- 0.83, - 0.54), P < 0.00001), compared to the oxytocin monotherapy group. No significant difference was found between the two groups in terms of the 5-min Apgar score (five studies, 609 women, MD = - 0.05, 95% CI (- 0.14, 0.04), P = 0.32) and the rate of admissions to the Neonatal Intensive Care Unit (NICU) (three studies, 359 women, RR = 0.82, 95% CI (0.38, 1.79), P = 0.62). CONCLUSION: The combined use of propranolol and oxytocin can significantly reduce the cesarean section rate, shorten the duration of the latent phase and the duration of the active phase on day 1, and is safe. However, due to the limitations, the conclusions of this article still need to be verified by large-sample, multicenter, rigorously designed high-quality clinical RCTs. TRIAL REGISTRATION: Registration number is INPLASY202390107.


Sujet(s)
Césarienne , Association de médicaments , Ocytocine , Propranolol , Essais contrôlés randomisés comme sujet , Humains , Propranolol/administration et posologie , Ocytocine/administration et posologie , Grossesse , Femelle , Travail obstétrical/effets des médicaments et des substances chimiques , Ocytociques/administration et posologie , Ocytociques/usage thérapeutique
8.
Actas dermo-sifiliogr. (Ed. impr.) ; 114(7): 631-635, jul.- ago. 2023. tab
Article de Espagnol | IBECS | ID: ibc-223011

RÉSUMÉ

El diagnóstico diferencial clínico entre los hemangiomas congénitos (HC) y los infantiles (HI) es complicado pero esencial para el tratamiento. El marcador inmunohistoquímico GLUT-1 ayuda a distinguirlos, sin embargo, la biopsia no es habitual. Se diseñó un estudio retrospectivo incluyendo los HI y a los HC diagnosticados en un hospital terciario en un periodo de 3 años, con el objetivo de describir y comparar los principales aspectos clínicos, epidemiológicos y terapéuticos. Se incluyeron un total de 107 hemangiomas, 34 HC (NICH/PICH/RICH), 70 HI y 3 pendientes de clasificar. El HI superficial de cabeza y cuello fue el tumor más frecuente. El tronco fue la localización más frecuente de los HC. Los factores de riesgo estudiados fueron más frecuentes en el grupo de los HI. Para los HI, el tipo de respuesta obtenida fue independiente de las variables (sexo, fecundación in vitro, profundidad, localización y tipo de tratamiento) (AU)


Distinguishing between congenital and infantile hemangiomas is challenging, but essential for appropriate treatment. The immunohistochemical marker glucose transporter type 1 is helpful, but biopsies are uncommon in this setting. The aim of this retrospective study was to describe and compare epidemiological, clinical, and treatment characteristics of congenital and infantile hemangiomas diagnosed at a tertiary care hospital over 3 years. We studied 107 hemangiomas: 34 congenital hemangiomas (rapidly involuting, partially involuting, and noninvoluting), 70 infantile hemangiomas, and 3 hemangiomas pending classification. Superficial infantile hemangiomas of the head and neck were the most prevalent tumors. Congenital hemangiomas were most often located on the trunk. Studied risk factors were more common in patients with infantile hemangiomas. In this group of patients, treatment response was independent of sex, in vitro fertilization, lesion depth and location, and type of treatment (AU)


Sujet(s)
Humains , Mâle , Femelle , Hémangiome/congénital , Hémangiome/diagnostic , Tumeurs cutanées/congénital , Tumeurs cutanées/diagnostic , Propranolol/administration et posologie , Timolol/administration et posologie , Études rétrospectives , Diagnostic différentiel , Facteurs de risque , Hémangiome/traitement médicamenteux , Tumeurs cutanées/traitement médicamenteux
9.
Actas dermo-sifiliogr. (Ed. impr.) ; 114(7): t631-t635, jul.- ago. 2023. tab
Article de Anglais | IBECS | ID: ibc-223012

RÉSUMÉ

Distinguishing between congenital and infantile hemangiomas is challenging, but essential for appropriate treatment. The immunohistochemical marker glucose transporter type 1 is helpful, but biopsies are uncommon in this setting. The aim of this retrospective study was to describe and compare epidemiological, clinical, and treatment characteristics of congenital and infantile hemangiomas diagnosed at a tertiary care hospital over 3 years. We studied 107 hemangiomas: 34 congenital hemangiomas (rapidly involuting, partially involuting, and noninvoluting), 70 infantile hemangiomas, and 3 hemangiomas pending classification. Superficial infantile hemangiomas of the head and neck were the most prevalent tumors. Congenital hemangiomas were most often located on the trunk. Studied risk factors were more common in patients with infantile hemangiomas. In this group of patients, treatment response was independent of sex, in vitro fertilization, lesion depth and location, and type of treatment (AU)


El diagnóstico diferencial clínico entre los hemangiomas congénitos (HC) y los infantiles (HI) es complicado pero esencial para el tratamiento. El marcador inmunohistoquímico GLUT-1 ayuda a distinguirlos, sin embargo, la biopsia no es habitual. Se diseñó un estudio retrospectivo incluyendo los HI y a los HC diagnosticados en un hospital terciario en un periodo de 3 años, con el objetivo de describir y comparar los principales aspectos clínicos, epidemiológicos y terapéuticos. Se incluyeron un total de 107 hemangiomas, 34 HC (NICH/PICH/RICH), 70 HI y 3 pendientes de clasificar. El HI superficial de cabeza y cuello fue el tumor más frecuente. El tronco fue la localización más frecuente de los HC. Los factores de riesgo estudiados fueron más frecuentes en el grupo de los HI. Para los HI, el tipo de respuesta obtenida fue independiente de las variables (sexo, fecundación in vitro, profundidad, localización y tipo de tratamiento) (AU)


Sujet(s)
Humains , Mâle , Femelle , Hémangiome/congénital , Hémangiome/diagnostic , Tumeurs cutanées/congénital , Tumeurs cutanées/diagnostic , Propranolol/administration et posologie , Timolol/administration et posologie , Études rétrospectives , Diagnostic différentiel , Facteurs de risque , Hémangiome/traitement médicamenteux , Tumeurs cutanées/traitement médicamenteux
10.
Rev. Hosp. Ital. B. Aires (2004) ; 43(2): 98-101, jun. 2023. ilus
Article de Espagnol | LILACS, UNISALUD, BINACIS | ID: biblio-1510712

RÉSUMÉ

Los hemangiomas infantiles son el resultado de la proliferación de células del endotelio vascular y representan los tumores benignos más frecuentes en la infancia, con una incidencia estimada del 4-10% en bebés caucásicos. Se clasifican según el número, la profundidad y la distribución. Dentro de esta última clasificación se encuentran aquellos denominados segmentarios, que se caracterizan por su distribución extensa en áreas de prolongaciones mesodérmicas embrionarias. Se comunica el caso de una paciente evaluada al mes y medio de vida, con un hemangioma extenso del área mandibular y cuello anterior (hemangioma segmentario de la barba). Se describe la importancia de los estudios complementarios para evaluar el compromiso de órganos subyacentes, para detectar síndromes asociados y definir el tratamiento sobre la base de estos resultados. (AU)


Infantile hemangiomas arise from the proliferation of vascular endothelial cells and represent the most common benign tumors in infancy, with an estimated incidence of 4-10% in Caucasian infants. They vary according to their number, depth, and distribution. Within the latter classification are the so-called segmental ones, which feature an extensive distribution in areas of embryonic mesodermal extensions. We report the case of a patient evaluated at one and a half months of life with an extensive hemangioma of the mandibular area and anterior neck (segmental hemangioma of the beard). We describe the importance of complementary studies for evaluating the involvement of underlying organs, detecting associated syndromes, and defining the treatment based on these findings. (AU)


Sujet(s)
Humains , Femelle , Nourrisson , Tumeurs de la face/diagnostic , Hémangiome/diagnostic , Propranolol/administration et posologie , Tumeurs de la face/traitement médicamenteux , Résultat thérapeutique , Hémangiome/traitement médicamenteux
11.
BMC Pregnancy Childbirth ; 23(1): 226, 2023 Apr 04.
Article de Anglais | MEDLINE | ID: mdl-37016326

RÉSUMÉ

BACKGROUND: The Induction of labor is the most common obstetric procedure in daily practice. Introducing propranolol as a new drug to augment the action of prostaglandins will help in the induction process and decrease CS rates. Several researchers have used propranolol in the augmentation of labor. AIM: This pilot study compares propranolol and misoprostol versus misoprostol alone for labor induction in primigravids. METHODS: This is a Randomized clinical trial, single-blinded, placebo-controlled trial at Ain Shams University Maternity hospital. This study included 128 pregnant full-term primigravid women candidates for labor induction, randomized into two groups. All candidates underwent labor induction with 25 µg of vaginal misoprostol. Group I received 20 mg of oral propranolol tablets, while group II received sugary pills as a placebo. Candidates who responded successfully to induction were assessed for possible augmentation of labor by amniotomy or oxytocin infusion. The Primary outcome was induction to delivery interval, while the secondary outcomes were the duration of the latent phase, mode of delivery, and APGAR score of the neonate. RESULTS: The induction-delivery time was (11.8 ± 8.1 h. vs. 12.6 ± 8.9 h., P value = 0.027) and the duration of the latent phase of labor (7.9 ± 5.6 h. vs. 9.2 ± 6.03 h., P value = 0.017) were significantly shorter in the group of misoprostol and propranolol compared to the group of misoprostol and placebo. There was no statistically significant difference between both groups' mode of delivery, indications for cesarean section, misoprostol, and oxytocin doses, or neonatal outcome. (P value > 0.05). CONCLUSION: Propranolol, when used with misoprostol for induction of labor, results in augmentation of action of misoprostol and a significantly shorter induction-delivery interval. TRIAL REGISTRATION: We retrospectively registered this trial in clinicaltrial.gov on 01/09/2020 (NCT04533841). https://clinicaltrials.gov/ct2/show/NCT04533841.


Sujet(s)
Misoprostol , Ocytociques , Propranolol , Femelle , Humains , Nouveau-né , Grossesse , Administration par voie vaginale , Césarienne , Accouchement provoqué/méthodes , Misoprostol/administration et posologie , Ocytociques/administration et posologie , Ocytocine , Projets pilotes , Propranolol/administration et posologie
13.
PLoS One ; 16(11): e0259446, 2021.
Article de Anglais | MEDLINE | ID: mdl-34784367

RÉSUMÉ

Combination antiretroviral therapy (cART) targets viral replication, but early viral protein production by astrocytes may still occur and contribute to the progression of HIV-1 associated neurocognitive disorders and secondary complications seen in patients receiving cART. In prior work with our model, astrocytic HIV-1 Nef expression exhibits neurotoxic effects leading to neurological damage, learning impairment, and immune upregulation that induces inflammation in the lungs and small intestine (SI). In this follow-up study, we focus on the sympathetic nervous system (SNS) as the important branch for peripheral inflammation resulting from astrocytic Nef expression. Male and female Sprague Dawley rats were infused with transfected astrocytes to produce Nef. The rats were divided in four groups: Nef, Nef + propranolol, propranolol and naïve. The beta-adrenergic blocker, propranolol, was administered for 3 consecutive days, starting one day prior to surgery. Two days after the surgery, the rats were sacrificed, and then blood, brain, small intestine (SI), and lung tissues were collected. Levels of IL-1ß were higher in both male and female rats, and treatment with propranolol restored IL-1ß to basal levels. We observed that Nef expression decreased staining of the tight junction protein claudin-5 in brain tissue while animals co-treated with propranolol restored claudin-5 expression. Lungs and SI of rats in the Nef group showed histological signs of damage including larger Peyer's Patches, increased tissue thickness, and infiltration of immune cells; these findings were abrogated by propranolol co-treatment. Results suggest that interruption of the beta adrenergic signaling reduces the peripheral organ inflammation caused after Nef expression in astrocytes of the brain.


Sujet(s)
Antagonistes bêta-adrénergiques/pharmacologie , Barrière hémato-encéphalique/effets des médicaments et des substances chimiques , Produits du gène nef du virus de l'immunodéficience humaine/métabolisme , Antagonistes bêta-adrénergiques/administration et posologie , Animaux , Astrocytes/cytologie , Astrocytes/métabolisme , Barrière hémato-encéphalique/métabolisme , Encéphale/cytologie , Encéphale/métabolisme , Encéphale/anatomopathologie , Cellules cultivées , Claudine-5/génétique , Claudine-5/métabolisme , Régulation négative/effets des médicaments et des substances chimiques , Femelle , VIH-1 (Virus de l'Immunodéficience Humaine de type 1)/métabolisme , Interleukine-1 bêta/sang , Intestin grêle/métabolisme , Intestin grêle/anatomopathologie , Poumon/métabolisme , Poumon/anatomopathologie , Mâle , Propranolol/administration et posologie , Propranolol/pharmacologie , Rats , Rat Sprague-Dawley , Produits du gène nef du virus de l'immunodéficience humaine/génétique
14.
Am Surg ; 87(10): 1556-1560, 2021 Dec.
Article de Anglais | MEDLINE | ID: mdl-34704840

RÉSUMÉ

BACKGROUND: Traumatic brain injury (TBI) results in an elaborate systemic cascade of secondary injury elicited in part by an intrinsic catecholamine response, which ultimately leads to changes in inflammation and coagulopathy. Attenuation of this catecholamine response with agents such as propranolol confers a survival advantage. The related impact of propranolol on venous thromboembolism (VTE) after TBI is largely unknown. STUDY DESIGN: A single institution retrospective review was conducted of all TBI patients requiring intensive care unit (ICU) admission with an injury severity scale (ISS) ≥ 25 from January 2013 to May 2015. Patients who received at least one dose of propranolol within 24 hours of admission (PROP) were compared to patients who did not receive any doses of propranolol (NPROP) during their hospitalization. RESULTS: Of the 131 patients analyzed, 31 (23.7%) patients received propranolol. The PROP cohort was more severely injured overall (ISS 29 vs 26.5, P = .02). While unadjusted VTE rates were similar (16.1% vs 19.0%, P = .72), the adjusted VTE rate was lower in the PROP cohort (AOR 0.20 (95% CI 0.04-0.97), adjusted P-value < .05). CONCLUSION: Propranolol use in TBI patients who have sustained critical injuries may mitigate the risk of VTE. The mechanism by which this outcome is achieved requires further investigation.


Sujet(s)
Lésions traumatiques de l'encéphale/complications , Propranolol/administration et posologie , Vasodilatateurs/administration et posologie , Thromboembolisme veineux/étiologie , Thromboembolisme veineux/prévention et contrôle , Adulte , Sujet âgé , Femelle , Humains , Score de gravité des lésions traumatiques , Unités de soins intensifs , Mâle , Adulte d'âge moyen , Études rétrospectives
15.
Retina ; 41(10): 2163-2171, 2021 Oct 01.
Article de Anglais | MEDLINE | ID: mdl-34543245

RÉSUMÉ

PURPOSE: To quantitatively analyze and compare the novice vitreoretinal surgeons' performance after various types of external exposures. METHODS: This prospective, self-controlled, cross-sectional study included 15 vitreoretinal fellows with less than 2 years of experience. Surgical performance was assessed using the Eyesi simulator after each exposure: Day 1, placebo, 2.5, and 5 mg/kg caffeine; Day 2, placebo, 0.2, and 0.6 mg/kg propranolol; Day 3, baseline simulation, breathalyzer reading of 0.06% to 0.10% and 0.11% to 0.15% blood alcohol concentration; Day 4, baseline simulation, push-up sets with 50% and 85% repetition maximum; Day 5, 3-hour sleep deprivation. Eyesi-generated total scores were the main outcome measured (0-700, worst to best). RESULTS: Performances worsened after increasing alcohol exposure based on the total score (χ2 = 7; degrees of freedom = 2; P = 0.03). Blood alcohol concentration 0.06% to 0.10% and 0.11% to 0.15% was associated with diminished performance compared with improvements after propranolol 0.6 and 0.2 mg/kg, respectively (∆1 = -22 vs. ∆2 = +13; P = 0.02; ∆1 = -43 vs. ∆2 = +23; P = 0.01). Propranolol 0.6 mg/kg was positively associated with the total score, compared with deterioration after 2.5 mg/kg caffeine (∆1 = +7 vs. ∆2 = -13; P = 0.03). CONCLUSION: Surgical performance diminished dose dependently after alcohol. Caffeine 2.5 mg/kg was negatively associated with dexterity, and performance improved after 0.2 mg/kg propranolol. No changes occurred after short-term exercise or acute 3-hour sleep deprivation.


Sujet(s)
Consommation d'alcool/physiopathologie , Caféine/administration et posologie , Propranolol/administration et posologie , Performance psychomotrice/physiologie , Privation de sommeil/physiopathologie , Chirurgie vitréorétinienne , Antagonistes bêta-adrénergiques/administration et posologie , Adulte , Alcoolémie , Stimulants du système nerveux central/administration et posologie , Compétence clinique , Simulation numérique , Études transversales , Évaluation des acquis scolaires , Humains , Études prospectives
16.
Dermatol Surg ; 47(8): 1052-1057, 2021 08 01.
Article de Anglais | MEDLINE | ID: mdl-34397540

RÉSUMÉ

BACKGROUND: Oral propranolol is the first-line therapy for infantile hemangioma. Combining it with pulse dye laser (PDL) (595nm-long PDL) could reduce treatment duration and sequelae incidence and severity. OBJECTIVE: To determine the effect of PDL-propranolol treatment on duration to cure and sequelae. METHODS: All consecutive patients with infantile hemangioma who were cured by PDL-propranolol treatment were identified. RESULTS: In the 27 cases, average age at treatment start was 4.3 ± 3.8 months, mean tumor diameter was 11.1 ± 14.0 cm2, and tumor-type was most common (72.4% of lesions). The patients received 9.8 ± 10.5 PDL sessions. After ensuring patients had no physical contraindications, including heart disease, oral propranolol was started at 1 mg/kg/d, increased up to 3 mg/kg/d as a maintenance dose. Mean propranolol treatment duration was 11.1 ± 4.9 months. Total treatment duration was 15.3 ± 10.8 months. CONCLUSION: Our data in the context of recent literature suggest combining propranolol with PDL may reduce propranolol duration without increasing harms.


Sujet(s)
Cicatrice/épidémiologie , Hémangiome capillaire/thérapie , Lasers à colorant/usage thérapeutique , Propranolol/administration et posologie , Tumeurs cutanées/thérapie , Administration par voie orale , Cicatrice/étiologie , Cicatrice/prévention et contrôle , Études de cohortes , Association thérapeutique , Relation dose-effet des médicaments , Calendrier d'administration des médicaments , Femelle , Hémangiome capillaire/complications , Humains , Nourrisson , Nouveau-né , Mâle , Études rétrospectives , Tumeurs cutanées/complications , Facteurs temps , Résultat thérapeutique
17.
Reprod Biomed Online ; 43(3): 379-393, 2021 Sep.
Article de Anglais | MEDLINE | ID: mdl-34330642

RÉSUMÉ

RESEARCH QUESTION: Can preoperative or perioperative intervention reduce the risk of recurrence of endometriosis caused by either incomplete excision or spillage and dissemination? DESIGN: A mouse model of endometriosis recurrence caused by spillage and dissemination was first established using 24 female Balb/c mice. The spillage and dissemination model was used to test the efficacy of preoperative use of ketorolac, perioperative use of aprepitant and combined use of propranolol and andrographolide in a prospective, randomized mouse experiment involving 75 mice. The efficacy of these preoperative and perioperative interventions in a mouse recurrence model caused by incomplete excision was also tested using 72 mice. In all experiments, the baseline body weight and hotplate latency of all mice were measured and recorded before the induction of endometriosis, before the primary surgery and before sacrifice. In addition, all lesions were excised, weighed and processed for quantification and immunohistochemistry analysis of E-cadherin, α-SMA, VEGF, ADRB2 and putative markers of recurrence PR-B, p-p65, as well as Masson trichrome staining. RESULTS: All interventions substantially and significantly suppressed the outgrowth of endometriotic lesions and reduced the risk of recurrence caused by either spillage and dissemination or incomplete excision (P = 0.0007 to 0.042). These interventions also significantly attenuated the generalized hyperalgesia, inhibited the staining of α-SMA, p-p65, VEGF and ADRB2 but increased staining of E-cadherin and PR-B, resulting in reduced fibrosis. CONCLUSION: Given the excellent safety profiles of these drugs, these data strongly suggest that preoperative and perioperative intervention may potentially reduce the risk of endometriosis recurrence effectively.


Sujet(s)
Endométriose/chirurgie , Procédures de chirurgie gynécologique/effets indésirables , Maladies du péritoine/chirurgie , Complications postopératoires/prévention et contrôle , Prévention secondaire/méthodes , Animaux , Aprépitant/usage thérapeutique , Prolifération cellulaire/effets des médicaments et des substances chimiques , Association thérapeutique , Modèles animaux de maladie humaine , Diterpènes/administration et posologie , Association de médicaments , Endométriose/traitement médicamenteux , Endométriose/anatomopathologie , Femelle , Procédures de chirurgie gynécologique/méthodes , Kétorolac/pharmacologie , Kétorolac/usage thérapeutique , Marges d'exérèse , Souris , Souris de lignée BALB C , Soins périopératoires/méthodes , Maladies du péritoine/traitement médicamenteux , Maladies du péritoine/anatomopathologie , Soins préopératoires/méthodes , Propranolol/administration et posologie , Récidive
18.
Pediatrics ; 148(1)2021 07.
Article de Anglais | MEDLINE | ID: mdl-34187907

RÉSUMÉ

Chylothorax and chyloperitoneum are rare in infants and challenging to definitively diagnose by using current criteria extrapolated from the adult population. They can be of primary or secondary etiologies, including congenital lymphatic malformations and postoperatively, after cardiothoracic or abdominal surgery. Current first-line management consists of bowel rest, parenteral nutrition, and a modified diet of medium-chain triglycerides but can often take weeks to be effective. Off-label use of octreotide has been reported in numerous case studies for the management of chylous effusions. However, there are no definitive neonatal data available regarding dosing, safety, and efficacy; moreover, octreotide has a side effect profile that been linked to serious morbidities, such as pulmonary hypertension and necrotizing enterocolitis. Propranolol, commonly used for the treatment of infantile hemangiomas, is currently gaining interest as a novel therapy for chylous effusions. In this case series review, we describe the use of propranolol in 4 infants with presumed chylous effusions: 1 with congenital pleural effusions and 3 infants who developed postoperative chylothorax and/or chylous ascites. Clinical improvement was noted within a few days of initiating oral propranolol, and the maximum dose used in our cases was 6 mg/kg per day. In previous case reports, researchers describe the use of oral propranolol in infants with chylous effusions, with the dose used ranging from 0.5 to 4 mg/kg per day. However, this is the first case series in which researchers report its use exclusively in infants with chylothorax and chyloperitoneum. Although further research is needed to establish safety and efficacy, our experiences suggest that propranolol could be an acceptable treatment option for chylous effusions in infants.


Sujet(s)
Antagonistes bêta-adrénergiques/usage thérapeutique , Chylothorax/traitement médicamenteux , Ascite chyleuse/traitement médicamenteux , Agents gastro-intestinaux/usage thérapeutique , Épanchement pleural/traitement médicamenteux , Propranolol/usage thérapeutique , Antagonistes bêta-adrénergiques/administration et posologie , Chylothorax/imagerie diagnostique , Chylothorax/étiologie , Ascite chyleuse/imagerie diagnostique , Ascite chyleuse/étiologie , Femelle , Agents gastro-intestinaux/administration et posologie , Âge gestationnel , Humains , Nouveau-né , Prématuré , Mâle , Octréotide/usage thérapeutique , Épanchement pleural/imagerie diagnostique , Épanchement pleural/étiologie , Propranolol/administration et posologie , Résultat thérapeutique
19.
Drug Metab Dispos ; 49(7): 521-529, 2021 07.
Article de Anglais | MEDLINE | ID: mdl-33941544

RÉSUMÉ

In traditional pharmacokinetic models, blood flow or liquid transit is often expressed as first-order kinetics. When the flow expression by first-order kinetics is used for dynamic simulation, the flow velocity illogically depends on the step size of a solver of ordinary differential equations. In this study, we propose flow modeling using hybrid automata that combine ordinary differential equations and recursive equations, and we have preliminarily applied the constructed models to several examples. The blood concentration-time profiles of p-aminohippurate and propranolol after intravenous administration were successfully reproduced by simple hybrid automata. The simulation results of one-dimensional tube flow have demonstrated that the fluid velocity in the hybrid automata was independent of the step size of the ordinary differential equation solver. A body fluid model coordinated various flows in a human body with scheduled daily activities and could be used as a drug container to describe formulation-dependent disposition of 5-aminosalicylic acid and enterohepatic circulation of a virtual drug. These findings suggested that flow modeling using hybrid automata could avoid the logical inconsistency in the traditional pharmacokinetic modeling and that the hybrid automata have high versatility and a wide range of applicability to pharmacokinetic analysis. Because our method can define various intervals for multiple recursive equations, the resolution of a specific part of a model can be adjusted relatively freely while the whole body is being roughly modeled, which would be beneficial to refine a coarse model into a fine model in future. SIGNIFICANCE STATEMENT: There is a logical inconsistency in flow expression by first-order kinetics in ordinary differential equations used in traditional pharmacokinetic modeling. It is difficult to model a whole human body using flow models in partial differential equations because of the excessive calculation costs. Our simulations on tube flow and body fluids have demonstrated that the flow modeling using hybrid automata could avoid the problems. The preliminary applications of hybrid automata to several examples highlighted its high versatility in pharmacokinetic analysis.


Sujet(s)
Modèles cardiovasculaires , Administration par voie intraveineuse , Vitesse du flux sanguin , Simulation numérique , Humains , Propranolol/administration et posologie , Propranolol/pharmacocinétique , Acide 4-amino-hippurique/administration et posologie , Acide 4-amino-hippurique/pharmacocinétique
20.
JAMA Otolaryngol Head Neck Surg ; 147(7): 599-607, 2021 07 01.
Article de Anglais | MEDLINE | ID: mdl-33856430

RÉSUMÉ

Importance: Propranolol has become the first-line therapy for problematic infantile hemangiomas (IHs) that require systemic therapy. However, different adverse events have been reported during propranolol treatment. The positive efficacy and safety of atenolol raise the question of whether it could be used as a promising therapy for IH. Objective: To compare the efficacy and safety of propranolol vs atenolol in infants (between age 5 and 20 weeks) with problematic IHs who required systemic therapy. Design, Setting, and Participants: This was a prospective, multicenter, randomized, controlled, open-label clinical trial conducted in collaboration among 6 separate investigation sites in China from February 1, 2015, to December 31, 2018. A total of 377 patients met the criteria for inclusion and were randomized to the propranolol (190 [50.4%]) and atenolol (187 [49.6%]) groups. Data were analyzed in June 2020. Interventions: Participants were randomized to receive either propranolol or atenolol for at least 6 months. They completed efficacy assessments at 2 years after the initial treatment. Main Outcomes and Measures: The primary outcome was any response or nonresponse at 6 months. The key secondary outcome was changes in the hemangioma activity score. Results: Of 377 participants, 287 (76.1%) were female, and the mean (SD) age was 10.2 (4.0) weeks in the propranolol group and 9.8 (4.1) weeks in the atenolol group. After 6 months of treatment, in the propranolol and atenolol groups, the overall response rates were 93.7% and 92.5%, respectively (difference, 1.2%; 95% CI, -4.1% to 6.6%). At 1 and 4 weeks after treatment, and thereafter, the hemangioma activity score in the atenolol group aligned with the propranolol group (odds ratio, 1.034; 95% CI, 0.886-1.206). No differences between the propranolol group and atenolol group were observed in successful initial responses, quality of life scores, complete ulceration healing times, or the rebound rate. Both groups presented a similar percentage of complete/nearly complete responses at 2 years (82.1% vs 79.7%; difference, 2.4%; 95% CI, -5.9% to 10.7%). Adverse events were more common in the propranolol group (70.0% vs 44.4%; difference, 25.6%; 95% CI, 15.7%-34.8%), but the frequency of severe adverse events did not differ meaningfully between the groups. Conclusions and Relevance: In this randomized clinical trial, when compared with propranolol, atenolol had similar efficacy and fewer adverse events in the treatment of infants with problematic IHs. The results suggest that oral atenolol can be used as an alternative treatment option for patients with IH who require systemic therapy. Trial Registration: ClinicalTrial.gov Identifier: NCT02342275.


Sujet(s)
Antagonistes des récepteurs bêta-1 adrénergiques/usage thérapeutique , Antagonistes bêta-adrénergiques/usage thérapeutique , Aténolol/usage thérapeutique , Hémangiome capillaire/traitement médicamenteux , Propranolol/usage thérapeutique , Antagonistes des récepteurs bêta-1 adrénergiques/administration et posologie , Antagonistes bêta-adrénergiques/administration et posologie , Aténolol/administration et posologie , Chine , Femelle , Humains , Nourrisson , Mâle , Propranolol/administration et posologie , Études prospectives
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