177 research outputs found

    Clinical Presentation and Conservative Management of Tympanic Membrane Perforation during Intrapartum Valsalva Maneuver

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    Background. Tympanic membrane perforation may occur when ear pressures are excessive, including valsalva maneuver associated with active labor and vaginal delivery. A pressure differential across the eardrum of about 5 psi can cause rupture; the increased intraabdominal pressure spikes repeatedly manifested by “pushing” during second-stage labor easily approach (and may exceed) this level. Material and Method. We describe a healthy 21-year old nulliparous patient admitted in active labor at 39-weeks' gestational age. Results. Blood appeared asymptomatically in the left ear canal at delivery during active, closed-glottis pushing. Otoscopic examination confirmed perforation of the left tympanic membrane. Complete resolution of the eardrum rupture was noted at postpartum check-up six weeks later. Conclusion. While the precise incidence of intrapartum tympanic membrane rupture is not known, it may be unrecognized without gross blood in the ear canal or subjective hearing loss following delivery. Only one prior published report on tympanic membrane perforation during delivery currently appears in the medical literature; this is the first English language description of the event. Since a vigorous and repetitive valsalva effort is common in normal vaginal delivery, clinicians should be aware of the potential for otic complications associated with the increased intraabdominal pressure characteristic of this technique

    Interleukin-6 Attenuates Insulin-Mediated Increases in Endothelial Cell Signaling but Augments Skeletal Muscle Insulin Action via Differential Effects on Tumor Necrosis Factor-α Expression

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    OBJECTIVE: The cytokine interleukin-6 (IL-6) stimulates AMP-activated protein kinase (AMPK) and insulin signaling in skeletal muscle, both of which result in the activation of endothelial nitric oxide synthase (eNOS). We hypothesized that IL-6 promotes endothelial cell signaling and capillary recruitment in vivo, contributing to increased glucose uptake. RESEARCH DESIGN AND METHODS: The effect of IL-6 with and without insulin on AMPK, insulin, and eNOS signaling in and nitric oxide (NO) release from human aortic endothelial cells (HAECs) was examined. The physiological significance of these in vitro signaling events was assessed by measuring capillary recruitment in rats during control and euglycemic-hyperinsulinemic clamps with or without IL-6 infusion. RESULTS: IL-6 blunted increases in insulin signaling, eNOS phosphorylation (Ser1177), and NO production and reduced phosphorylation of AMPK in HAEC in vitro and capillary recruitment in vivo. In contrast, IL-6 increased Akt phosphorylation (Ser473) in hindlimb skeletal muscle and enhanced whole-body glucose disappearance and glucose uptake during the clamp. The differences in endothelial cell and skeletal muscle signaling were mediated by the cell-specific, additive effects of IL-6 and insulin because this treatment markedly increased tumor necrosis factor (TNF)-alpha protein expression in HAECs without any effect on TNF-alpha in skeletal muscle. When HAECs were incubated with a TNF-alpha-neutralizing antibody, the negative effects of IL-6 on eNOS signaling were abolished. CONCLUSIONS: In the presence of insulin, IL-6 contributes to aberrant endothelial cell signaling because of increased TNF-alpha expression

    Regulation of microvascular flow and metabolism: An overview

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    Skeletal muscle is an important site for insulin to regulate blood glucose levels. It is estimated that skeletal muscle is responsible for ~80% of insulin-mediated glucose disposal in the post-prandial period. The classical action of insulin to increase muscle glucose uptake involves insulin binding to insulin receptors on myocytes to stimulate glucose transporter 4 (GLUT 4) translocation to the cell surface membrane, enhancing glucose uptake. However, an additional role of insulin that is often under-appreciated is its action to increase muscle perfusion thereby improving insulin and glucose delivery to myocytes. Either of these responses (myocyte and/or vascular) may be impaired in insulin resistance, and both impairments are apparent in type 2 diabetes, resulting in diminished glucose disposal by muscle. The aim of this review is to report on the growing body of literature suggesting that insulin-mediated control of skeletal muscle perfusion is an important regulator of muscle glucose uptake and that impairment of microvascular insulin action has important physiological consequences early in the pathogenesis of insulin resistance. This work was discussed at the 2015 Australian Physiological Society Symposium “Physiological mechanisms controlling microvascular flow and muscle metabolism”

    Case Report Clinical Presentation and Conservative Management of Tympanic Membrane Perforation during Intrapartum Valsalva Maneuver

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    Background. Tympanic membrane perforation may occur when ear pressures are excessive, including valsalva maneuver associated with active labor and vaginal delivery. A pressure differential across the eardrum of about 5 psi can cause rupture; the increased intraabdominal pressure spikes repeatedly manifested by "pushing" during second-stage labor easily approach (and may exceed) this level. Material and Method. We describe a healthy 21-year old nulliparous patient admitted in active labor at 39-weeks' gestational age. Results. Blood appeared asymptomatically in the left ear canal at delivery during active, closed-glottis pushing. Otoscopic examination confirmed perforation of the left tympanic membrane. Complete resolution of the eardrum rupture was noted at postpartum check-up six weeks later. Conclusion. While the precise incidence of intrapartum tympanic membrane rupture is not known, it may be unrecognized without gross blood in the ear canal or subjective hearing loss following delivery. Only one prior published report on tympanic membrane perforation during delivery currently appears in the medical literature; this is the first English language description of the event. Since a vigorous and repetitive valsalva effort is common in normal vaginal delivery, clinicians should be aware of the potential for otic complications associated with the increased intraabdominal pressure characteristic of this technique. Background Rupture of the tympanic membrane can result from any pressure or stress exerted on the ear. The vigorous and repetitive valsalva efforts of active labor can yield internal ear pressures that exceed the safe threshold for tympanic membrane integrity, causing intrapartum injury to the eardrum. Intrapartum tympanic membrane rupture appears to be encountered with low frequency, although underreporting could be a result of inadequate clinical familiarity and minimal awareness of the condition. Clinical Presentation A 21-year-old nonsmoking nullipara presented at 39-weeks' gestation in active labor. Her prenatal course was unremarkable; results from all routine prenatal laboratory tests were normal. The patient had no prior ear infections, tympanoplasty or other surgery, and her baseline evaluation identified no deficit in hearing acuity. With the exception of prenatal vitamins, she took no regular medications. Social history was negative for diving, mountainclimbing, skydiving or other activities at barometric pressure extremes. Intravenous oxytocin was not indicated for labor augmentation. Fetal status remained reassuring and the patient achieved full cervical dilation and effacement within 90 min of admission. Neither neuraxial anaesthesia nor intravenous narcotics were required for pain management. Upon confirmation of full cervical dilation, the patient began closed-glottis pushing simultaneous with uterine contractions. Following a 32-minute second stage of labor, she delivered a viable male infant over a mediolateral episiotomy. Five and ten minute Apgar scores were 9 and 9; birth weight was 3291 g. The placenta was delivered spontaneously and intact. The episiotomy was repaired routinely. Intrapartum blood loss was approximately 300 mL. Case Reports in Medicine Mother and baby did well following delivery. While the mother had no complaints in the postpartum period, she was noted to have several new small petechiae on her face and blood in her left ear about one hour after delivery. The right ear appeared grossly normal and the patient denied placing anything in the ear. However, otoscopic examination of the left external auditory canal revealed minimal dark blood and 1 cm superficial thrombus blocked a clear view of the eardrum. No active bleeding was observed and the patient remained afebrile. The patient reported no ear pain and denied any reduction in hearing sensitivity from either ear. Gentle extraction resulted in removal of the clot, revealing a 2-3 mm perforation in the inferior aspect of the left tympanic membrane. Otic lavage with bulb-syringe was not performed. Consultation with an ophthalmologist confirmed left tympanic membrane perforation. The contralateral tympanic membrane was intact. Cotton packing was placed in the ear canal and the left tympanic membrane was allowed to heal; antibiotics were not prescribed. At the postpartum follow-up exam six weeks later, the patient had no complaint and no additional ear bleeding was reported. She had no ear pain or hearing deficit, and the left eardrum appeared grossly normal. The patient was counseled to treat future ear infections promptly, to seek treatment immediately should any ear discharge be noted, and to avoid insertion of any object into the ear to clean it

    Impaired postprandial skeletal muscle vascular responses to a mixed meal challenge in normoglycaemic people with a parent with type 2 diabetes

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    Aims/hypothesis: Microvascular blood flow (MBF) increases in skeletal muscle postprandially to aid in glucose delivery and uptake in muscle. This vascular action is impaired in individuals who are obese or have type 2 diabetes. Whether MBF is impaired in normoglycaemic people at risk of type 2 diabetes is unknown. We aimed to determine whether apparently healthy people at risk of type 2 diabetes display impaired skeletal muscle microvascular responses to a mixed-nutrient meal. Methods: In this cross-sectional study, participants with no family history of type 2 diabetes (FH-) for two generations (n = 18), participants with a positive family history of type 2 diabetes (FH+; i.e. a parent with type 2 diabetes; n = 16) and those with type 2 diabetes (n = 12) underwent a mixed meal challenge (MMC). Metabolic responses (blood glucose, plasma insulin and indirect calorimetry) were measured before and during the MMC. Skeletal muscle large artery haemodynamics (2D and Doppler ultrasound, and Mobil-O-graph) and microvascular responses (contrast-enhanced ultrasound) were measured at baseline and 1 h post MMC. Results: Despite normal blood glucose concentrations, FH+ individuals displayed impaired metabolic flexibility (reduced ability to switch from fat to carbohydrate oxidation vs FH-; p \u3c 0.05) during the MMC. The MMC increased forearm muscle microvascular blood volume in both the FH- (1.3-fold, p \u3c 0.01) and FH+ (1.3-fold, p \u3c 0.05) groups but not in participants with type 2 diabetes. However, the MMC increased MBF (1.9-fold, p \u3c 0.01), brachial artery diameter (1.1-fold, p \u3c 0.01) and brachial artery blood flow (1.7-fold, p \u3c 0.001) and reduced vascular resistance (0.7-fold, p \u3c 0.001) only in FH- participants, with these changes being absent in FH+ and type 2 diabetes. Participants with type 2 diabetes displayed significantly higher vascular stiffness (p \u3c 0.001) compared with those in the FH- and FH+ groups; however, vascular stiffness did not change during the MMC in any participant group. Conclusions/interpretation: Normoglycaemic FH+ participants display impaired postprandial skeletal muscle macro- and microvascular responses, suggesting that poor vascular responses to a meal may contribute to their increased risk of type 2 diabetes. We conclude that vascular insulin resistance may be an early precursor to type 2 diabetes in humans, which can be revealed using an MMC

    Imagination and narrative : young people's experiences

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    Imagery generation in dramatized audio drama is still poorly understood with the majority of work having been done from a radio advertising perspective. This study sought to understand audio drama imagery generation by using teenage listeners. The study demonstrated that teenagers can follow purely auditory narrative with ease and can generate unique and vivid imagery through aural dramatic stimulation. The study also showed that listening in the dark and as a group are appealing for audiences

    Oncogenic Kras Activates a Hematopoietic-to-Epithelial IL-17 Signaling Axis in Preinvasive Pancreatic Neoplasia

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    SummaryMany human cancers are dramatically accelerated by chronic inflammation. However, the specific cellular and molecular elements mediating this effect remain largely unknown. Using a murine model of pancreatic intraepithelial neoplasia (PanIN), we found that KrasG12D induces expression of functional IL-17 receptors on PanIN epithelial cells and also stimulates infiltration of the pancreatic stroma by IL-17-producing immune cells. Both effects are augmented by associated chronic pancreatitis, resulting in functional in vivo changes in PanIN epithelial gene expression. Forced IL-17 overexpression dramatically accelerates PanIN initiation and progression, while inhibition of IL-17 signaling using genetic or pharmacologic techniques effectively prevents PanIN formation. Together, these studies suggest that a hematopoietic-to-epithelial IL-17 signaling axis is a potent and requisite driver of PanIN formation

    War Memorial: the Calling Blighty films and remembrance

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    The Calling Blighty series of nearly 400 films were messages from servicemen in India and Burma to be shown to families in local cinemas at the end of the Second World War. They are remarkable because of their cinematic quality and the men’s direct address to camera, and the 64 remaining films reveal much about family memories, public remembrance and representation of the Northern voice on screen. Along with Marion Hewitt of the North West Film Archive, the author has been engaged in an ongoing project to find the relatives of the men of the ‘Forgotten Army’ in the films and recreate the screenings. These ritual ceremonies of remembrance have been augmented by a media memorial, a Channel 4 TV documentary about the project and creative critical reflection through an experimental artist’s film, drawing on the archive material. This analysis of the project looks at the relationship of the Blighty films to wartime film and documentary, in particular, as well as soldier self-representation, and their implications for both family and communal remembrance

    Association of circulating angiotensin converting enzyme activity with respiratory muscle function in infants

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    <p>Abstract</p> <p>Background</p> <p>Angiotensin converting enzyme (ACE) gene contains a polymorphism, consisting of either the presence (I) or absence (D) of a 287 base pair fragment. Deletion (D) is associated with increased circulating ACE (cACE) activity. It has been suggested that the D-allele of ACE genotype is associated with power-oriented performance and that cACE activity is correlated with muscle strength. Respiratory muscle function may be similarly influenced. Respiratory muscle strength in infants can be assessed specifically by measurement of the maximum inspiratory pressure during crying (Pi<sub>max</sub>). Pressure-time index of the respiratory muscles (PTImus) is a non-invasive method, which assesses the load to capacity ratio of the respiratory muscles.</p> <p>The objective of this study was to determine whether increased cACE activity in infants could be related to greater respiratory muscle strength and to investigate the potential association of cACE with PTImus measurements as well as the association of ACE genotypes with cACE activity and respiratory muscle strength in this population.</p> <p>Methods</p> <p>Serum ACE activity was assayed by using a UV-kinetic method. ACE genotyping was performed by polymerase chain reaction amplification, using DNA from peripheral blood. PTImus was calculated as (Pi<sub>mean</sub>/Pi<sub>max</sub>) × (Ti/Ttot), where Pi<sub>mean </sub>was the mean inspiratory pressure estimated from airway pressure, generated 100 milliseconds after an occlusion (P<sub>0.1</sub>), Pi<sub>max </sub>was the maximum inspiratory pressure and Ti/Ttot was the ratio of the inspiratory time to the total respiratory cycle time. Pi<sub>max </sub>was the largest pressure generated during brief airway occlusions performed at the end of a spontaneous crying effort.</p> <p>Results</p> <p>A hundred and ten infants were studied. Infants with D/D genotype had significantly higher serum ACE activity than infants with I/I or I/D genotypes. cACE activity was significantly related to Pi<sub>max </sub>and inversely related to PTImus. No association between ACE genotypes and Pdi<sub>max </sub>measurements was found.</p> <p>Conclusions</p> <p>These results suggest that a relation in cACE activity and respiratory muscle function may exist in infants. In addition, an association between ACE genotypes and cACE activity, but not respiratory muscle strength, was demonstrated.</p
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