The effect of morbid obesity or advanced maternal age on oxytocin-induced myometrial contractions: an in vitro study.

Purpose: The purpose of this study was to investigate myometrial contractility induced by oxytocin in women with advanced maternal age (AMA) and morbid obesity (MO). We hypothesized that both oxytocin-pretreated and oxytocin-naïve myometrial tissues from women of AMA and women who are MO would exhibit poor myometrial contractility compared with women that are younger and of normal body mass index (BMI).

Methods: This prospective in vitro study was conducted using myometrial samples obtained from women undergoing elective Cesarean deliveries.

Outpatient High-dose Methotrexate for Osteosarcoma: It's Safe and Feasible, If You Want It.

Background: High-dose methotrexate (HD MTX) is usually administered as an inpatient to those with osteosarcoma. We prospectively tested the safety and feasibility of administering HD MTX in the ambulatory setting.

Materials And Methods: In this single arm prospective observational study, eligible patients had previously completed 2 courses of HD MTX as an inpatient.

Pediatric oncology clinical trial participation where the geography is vast: Development of a clinical research system for tertiary and satellite centers in Ontario, Canada.

Opportunities for participation in clinical trials are a core component of the care of children with cancer. In Ontario, many pediatric patients live long distances from their cancer center. This paper describes the work that was done in order to allow patients participating in Children's Oncology Group trials to receive care, including research protocol related care, jointly between the tertiary pediatric cancer center and the closer-to-home satellite center.

The Effect of Extracellular Calcium on Oxytocin-Induced Contractility in Naive and Oxytocin-Pretreated Human Myometrium In Vitro.

Background: Prolonged exposure to oxytocin during augmentation of labor is a significant risk factor for uterine atony, resulting in the desensitization phenomenon, a decrease in the responsiveness of myometrium to further oxytocin. The importance of extracellular calcium is well established in spontaneous myometrial contractility; however, its significance is unknown in the context of desensitized myometrium. We aimed to investigate the effect of low, normal, and high extracellular calcium concentration on oxytocin-induced contractility in oxytocin-pretreated human myometrium in vitro.

The Recovery Time of Myometrial Responsiveness After Oxytocin-Induced Desensitization in Human Myometrium In Vitro.

Background: Postpartum hemorrhage secondary to uterine atony is a leading cause of maternal morbidity. Prolonged exposure to oxytocin for labor augmentation can result in the desensitization phenomenon, a decrease in the responsiveness of myometrium to further oxytocin. It is currently not known whether waiting for a specific time interval after the cessation of oxytocin allows the oxytocin receptors to resensitize and recover, thereby improving subsequent oxytocin-induced myometrial contractility.

In Vitro Comparative Effect of Carbetocin and Oxytocin in Pregnant Human Myometrium with and without Oxytocin Pretreatment.

Background: The purpose of this study was to compare in vitro contractile effects of oxytocin and carbetocin on human term pregnant myometrium with and without oxytocin pretreatment.

Methods: This laboratory investigation was conducted on myometrial samples from women undergoing elective cesarean deliveries. The samples were dissected into four strips and suspended in individual organ bath chambers containing physiologic salt solution.

No cardiomyopathy in X-linked myopathy with excessive autophagy.

In X-linked myopathy with excessive autophagy (XMEA) progressive sarcoplasmic accumulation of autolysosomes filled with undegraded debris leads to atrophy and weakness of skeletal muscles. XMEA is caused by compromised acidification of lysosomes resulting from hypofunction of the proton pump vacuolar ATPase (V-ATPase), due to hypomorphic mutations in VMA21, whose protein product assembles V-ATPase. To what extent the cardiac muscle is affected is unknown.

The Contractile Effects of Oxytocin, Ergonovine, and Carboprost and Their Combinations: an In Vitro Study on Human Myometrial Strips.

Background: The objective of this study was to compare the in vitro contractile effects of the combination of oxytocin (low dose and high dose) with either ergonovine or carboprost in myometrial strips from women undergoing cesarean delivery (CD), and to study the effect of oxytocin pretreatment on these contractions. We hypothesized that the use of ergonovine or carboprost in combination with oxytocin would improve contractility compared with oxytocin alone.

Methods: Myometrial samples obtained from women undergoing elective CD were pretreated in organ bath chambers with either oxytocin 10 M (experimental) or physiological salt solution (control) for 2 hours.

Late adult-onset of X-linked myopathy with excessive autophagy.

Introduction: X-linked myopathy with excessive autophagy (XMEA) is characterized by autophagic vacuoles with sarcolemmal features. Mutations in VMA21 result in insufficient lysosome acidification, causing progressive proximal weakness with onset before age 20 years and loss of ambulation by middle age.

Methods: We describe a patient with onset of slowly progressive proximal weakness of the lower limbs after age 50, who maintains ambulation with the assistance of a cane at age 71.

Progressive myoclonus epilepsy.

The progressive myoclonus epilepsies (PMEs) consist of a group of diseases with myoclonic seizures and progressive neurodegeneration, with onset in childhood and/or adolescence. Lafora disease is a neuronal glycogenosis in which normal glycogen is transformed into starch-like polyglucosans that accumulate in the neuronal somatodendritic compartment. It is caused by defects of two genes of yet unknown function, one encoding a glycogen phosphatase (laforin) and the other an ubiquitin E3 ligase (malin).

VMA21 deficiency prevents vacuolar ATPase assembly and causes autophagic vacuolar myopathy.

X-linked Myopathy with Excessive Autophagy (XMEA) is a childhood onset disease characterized by progressive vacuolation and atrophy of skeletal muscle. We show that XMEA is caused by hypomorphic alleles of the VMA21 gene, that VMA21 is the diverged human ortholog of the yeast Vma21p protein, and that like Vma21p, VMA21 is an essential assembly chaperone of the vacuolar ATPase (V-ATPase), the principal mammalian proton pump complex. Decreased VMA21 raises lysosomal pH which reduces lysosomal degradative ability and blocks autophagy.

The autosomal recessively inherited progressive myoclonus epilepsies and their genes.

Autosomal recessively inherited progressive myoclonus epilepsies (PMEs) include Lafora disease, Unverricht-Lundborg disease, the neuronal ceroid lipofuscinoses, type I sialidosis (cherry-red spot myoclonus), action myoclonus-renal failure syndrome, and type III Gaucher disease. Almost all the autosomal recessively inherited PMEs are lysosomal diseases, with the exception of Lafora disease in which neither the accumulating material nor the gene products are in lysosomes. Progress in identifying the causative defects of PME is near-complete.

VMA21 deficiency causes an autophagic myopathy by compromising V-ATPase activity and lysosomal acidification.

X-linked myopathy with excessive autophagy (XMEA) is a childhood-onset disease characterized by progressive vacuolation and atrophy of skeletal muscle. We show that XMEA is caused by hypomorphic alleles of the VMA21 gene, that VMA21 is the diverged human ortholog of the yeast Vma21p protein, and that like Vma21p it is an essential assembly chaperone of the V-ATPase, the principal mammalian proton pump complex. Decreased VMA21 raises lysosomal pH, which reduces lysosomal degradative ability and blocks autophagy.