Improving Temporomandibular Range of Motion in People With Duchenne Muscular Dystrophy and Spinal Muscular Atrophy.

IMPORTANCE: People with Duchenne muscular dystrophy (DMD) and spinal muscular atrophy (SMA) develop impaired oral function because of reduced temporomandibular joint range of motion (ROM), which affects feeding and oral hygiene activities of daily living (ADLs). OBJECTIVE: To assess whether the TheraBite®, an intraoral stretching device, improves ROM. DESIGN: Case series, with intervention duration varying from 7 to 30 mo. Treatment frequency varied from weekly to consultative (several times per year). SETTING: Varied depending on the ease of transportation for the participant and caregivers. Two participants were treated in an outpatient medical clinic. The other was provided consultative care during multidisciplinary medical clinics and completed a home program. PARTICIPANTS: Two adults with DMD and one with SMA. INTERVENTION: Stretching protocol using the TheraBite. OUTCOMES AND MEASURES: Temporomandibular active ROM (AROM) was determined using a disposable TheraBite oral goniometer. Passive ROM (PROM) was determined using the adhesive scale on the TheraBite. Measures were taken at baseline, each intervention or consultation, and the end of care. ADL participation and caregiver burden were measured at the end of intervention. RESULTS: For participants with DMD, AROM remained unchanged, but PROM increased by 40%-65%. The participant with SMA demonstrated 33% and 47% improvements in AROM and PROM, respectively. Participants or caregivers reported improved feeding function, improved oral hygiene, or reduced fatigue. CONCLUSION: TheraBite may improve temporomandibular PROM in people with DMD and temporomandibular AROM and PROM in people with SMA. It may also improve ADL function and consequently reduce caregiver burden. Further investigation is warranted. WHAT THIS ARTICLE ADDS: Temporomandibular contracture in people with DMD and SMA contributes to reduced lifespan and loss of function. Use of the TheraBite with this population may preserve temporomandibular ROM and improve feeding, hygiene, and quality-of-life outcomes.

Cardiac remodelling as a result of pre-term birth: implications for future cardiovascular disease.

AIMS: Pre-term birth affects 10-12% of live births and occurs when the myocardium is still developing; therefore, the final structure of the myocardium could be altered. We hypothesized that, in response to pre-term birth, structural remodelling occurs within the myocardium which enables the immature heart muscle to adapt to the haemodynamic transition at birth but results in persistent alterations in its structure. Our objective was to determine how pre-term birth alters the final structure of the myocardium. METHODS AND RESULTS: Using sheep, pre-term birth was induced at 0.9 of term; hearts were examined at 9 weeks after term-equivalent age, when cardiomyocyte proliferation and maturation have ceased. In pre-term lambs, we found that cardiomyocytes of both ventricles and the interventricular septum were hypertrophied. Cardiomyocyte maturation in pre-term lambs was altered in that there was a greater proportion of mononucleated, polyploid (4n) cardiomyocytes in both ventricles compared with controls; importantly, induction of polyploidy is associated with irreversible stress-related changes in DNA. We also found a six- to seven-fold increase in collagen deposition, usually accompanied by lymphocytic infiltration. CONCLUSION: We conclude that pre-term birth leads to remodelling of the myocardium that alters its final structure. This may programme for long-term cardiac vulnerability.

The influence of naturally occurring differences in birthweight on ventricular cardiomyocyte number in sheep.

In most species including man, cardiomyocytes cease proliferating soon after birth when they become terminally differentiated. A reduced complement of cardiomyocytes in infancy may adversely impact on the function and adaptive capabilities of the heart in later life. Low birthweight is associated with an increased risk of heart disease in adults, but little is known about its effect on the number of cardiomyocytes. Using naturally occurring differences in birthweight, our aim was to determine the effect of birthweight on cardiomyocyte number in postnatal lambs. At 9 weeks after term birth, when the final number of cardiomyocytes is considered to be established, hearts were collected at necropsy from seven singleton and seven twin lambs. Hearts were perfusion-fixed, and tissue samples were systematically taken from the left ventricle plus intraventricular septum (LV+S) and the right ventricle (RV). The number of cardiomyocyte nuclei was estimated using an unbiased optical disector-fractionator stereological technique, and the total number of cardiomyocytes was determined. Weights of the total heart, LV+S and RV were significantly related to both birthweight and necropsy weight. In the LV+S but not the RV, cardiomyocyte number was significantly and directly related to heart tissue weight, birthweight, and necropsy weight. We conclude that the final number of cardiomyocytes in the LV+S is related to prenatal and early postnatal growth, and is proportionate to the weight of heart tissue. A low cardiomyocyte number in the LV+S following restricted fetal growth may contribute to the increased incidence of heart disease in adults born with low birthweight. Anat Rec, 2009. (c) 2008 Wiley-Liss, Inc.

Repeated ethanol exposure during late gestation alters the maturation and innate immune status of the ovine fetal lung.

Little is known about the effects of fetal ethanol exposure on lung development. Our aim was to determine the effects of repeated ethanol exposure during late gestation on fetal lung growth, maturation, and inflammatory status. Pregnant ewes were chronically catheterized at 91 days of gestational age (DGA; term approximately 147 days). From 95-133 DGA, ewes were given a 1-h daily infusion of either 0.75 g ethanol/kg (n = 9) or saline (n = 8), with tissue collection at 134 DGA. Fetal lungs were examined for changes in tissue growth, structure, maturation, inflammation, and oxidative stress. Between treatment groups, there were no differences in lung weight, DNA and protein contents, percent proliferating and apoptotic cells, tissue and air-space fractions, alveolar number and mean linear intercept, septal thickness, type-II cell number and elastin content. Ethanol exposure caused a 75% increase in pulmonary collagen I alpha1 mRNA levels (P < 0.05) and a significant increase in collagen deposition. Surfactant protein (SP)-A and SP-B mRNA levels were approximately one third of control levels following ethanol exposure (P < 0.05). The mRNA levels of the proinflammatory cytokines interleukin (IL)-1beta and IL-8 were also lower (P < 0.05) in ethanol-exposed fetuses compared with controls. Pulmonary malondialdehyde levels tended to be increased (P = 0.07) in ethanol-exposed fetuses. Daily exposure of the fetus to ethanol during the last third of gestation alters extracellular matrix deposition and surfactant protein gene expression, which could increase the risk of respiratory distress syndrome after birth. Changes to the innate immune status of the fetus could increase the susceptibility of the neonatal lungs to infection.

Does moderate preterm birth lead to altered arterial pressure? Studies in sheep.

1. Low birth weight (LBW) is associated with an increased risk of cardiovascular disease. Preterm birth is a major determinant of LBW and has been shown to result in elevated arterial pressure (AP) in humans, but few studies have investigated the effects of preterm birth in the absence of potentially confounding factors. Our aim was to determine whether moderately preterm birth per se alters the postnatal development of AP in lambs. 2. Preterm lambs were delivered approximately 14 days before term (i.e. approximately 133 days of gestation); controls were born at term (approximately 147 days). Mean arterial pressure (MAP), heart rate (HR), blood composition and indices of growth were measured at 4 and 8 weeks post term-equivalent age (PTEA). We also studied a separate cohort of preterm and term sheep as young adults (approximately 1.1 years). 3. Preterm lambs had significantly lower birth weights than term lambs, but bodyweights were not significantly different by Day 12 PTEA. In addition, MAP, HR and most blood variables did not differ between term and preterm lambs at 4 or 8 weeks PTEA. Preterm birth per se did not alter MAP or HR in young adult sheep. 4. Low birth weight due to preterm birth does not result in an altered AP during early postnatal life or at maturity. Moderate intrauterine growth restriction (IUGR) due to twinning, which further reduces birth weight, does not affect MAP in preterm lambs. Other factors, such as the degree of prematurity or IUGR, exposure to corticosteroids or postnatal nutrition, may be important in the later development of elevated AP.

Spontaneously occurring differences in fetal weight do not affect blood pressure, the hypothalamic-pituitary-adrenal axis or the renin-angiotensin system in the late-gestation ovine fetus.

Fetal growth restriction (FGR) has been associated with an increased incidence of cardiovascular disease in adult life. Animal models of restricted fetal growth often cause FGR over discrete periods of gestation and hence may not be applicable to individuals with low birthweight but who are not clinically growth-restricted. Our aim was to determine whether spontaneously occurring differences in fetal growth influence the functional development of the hypothalamic-pituitary-adrenal (HPA) axis or the renin-angiotensin system (RAS), both of which are involved in arterial pressure regulation. Using sheep, arterial pressure and heart rate were monitored in chronically catheterised singleton and twin fetuses at 130, 134 and 137 days of gestation (term approximately 147 days). Fetuses were challenged, at different times, with exogenous angiotensin (Ang) II, combined administration of arginine vasopressin and corticotrophin releasing hormone (AVP+CRH) and adrenocorticotrophic hormone (ACTH); fetal cardiovascular responses and circulating cortisol concentrations were measured. In all fetuses Ang II and AVP+CRH altered cardiovascular function (increase in mean arterial pressure and decrease in heart rate); both AVP+CRH and ACTH increased circulating cortisol concentrations. Responses were not related to fetal bodyweight. We conclude that naturally occurring differences in growth do not influence the development of the HPA axis or RAS function in fetal sheep.

The perinatal development of arterial pressure in sheep: effects of low birth weight due to twinning.

The aim of this study is to determine the effect of fetal growth restriction due to twinning on the perinatal development of arterial pressure. Arterial pressure was recorded in fetal sheep (5 singletons, 8 twins) during late gestation and at 8 weeks after birth (11 singletons, 18 twins). In fetuses, there were no differences between singletons and twins in arterial pressure or plasma electrolytes. Postnatal twins were 17.3% lighter than singletons at birth, and growth rate was similar to singletons up to 8 weeks. After birth, arterial pressure was not different between groups, except that at 8 weeks, the systolic pressure was lower in twins. After birth, there were no differences between twins and singleton lambs in concentrations of plasma electrolytes, plasma renin, angiotensin II, and cortisol. Taken together with previous findings, the authors conclude that natural twinning in sheep followed by normal postnatal growth does not lead to hypertension.