Pediatric Inpatient Headache Therapy: What is Available

Status migrainosus is defined by the international classification of headache disorders (ICHD) criteria as a debilitating migraine lasting more then 72 hours. The epidemiology of status migrainosus is still unknown in adult and children, and frequently underdiagnosed. Children and adolescents often end up in the emergency room with an intractable headache that failed outpatient therapy. Six to seven percent of these children do not respond to acute infusion therapy and require hospitalization. It is imperative that more aggressive therapy is considered when patients are affected by a severe intractable headache to prevent further disability and returning the child to baseline activity. Multiple therapies are available for adults and children. Studies for acute therapy in the emergency room are available in adults and pediatric groups. Small studies are available for inpatient therapy in children and, along with available therapies for children and adolescents, are described in this review. A review of the literature shows growing evidence regarding the use of dihydroergotamine intravenously once patients are hospitalized. Effectiveness and safety have been proven in the last decades in adults and small studies in the pediatric populations.     

Bizepssehnenruptur

Trauma und Berufskrankheit - Zusammenfassung Diese Arbeit beschäftigt sich mit der Häufigkeit, dem Entstehungsmechanismus und der Behandlung von Bizepssehnenrupturen. Veränderte...     

Effect of an education and activation programme on functional limitations and patient-perceived recovery in acute and sub-acute shoulder complaints – a randomised clinical trial

Background  

The education and activation programme (EAP) aims at coping with psychosocial determinants to prevent the development of chronic shoulder complaints (SCs). The effect of the EAP on functional limitations and patient-perceived recovery after 6 and 26 weeks is evaluated in a randomised clinical trial.     

Glucose uptake in human adipose tissue

One hundred grams of glucose with 50 microCi U-14C-glucose were given orally to 17 women with widely varying amounts of body fat. Radioactivity and glucose metabolism in vitro were then measured in adipose tissue obtained by needle biopsies in the abdominal and femoral regions after four hours. Radioactivity in triglycerides was then measured in repeated biopsies 1 day, 1 week, and monthly up to 7 months after glucose administration. Glucose label in triglycerides after four hours was higher in abdominal than femoral adipocytes in obese women. It increased slightly during the following week, and then decreased exponentially with a half-life of 12 months in the abdominal region and 19 months in the femoral region. Uptake of glucose carbon in total body fat was estimated from the triglyceride label measured and determinations of body fat mass, and found to be in the order of less than 4% of given glucose. The studies in vitro suggested that much of the glucose taken up in adipose tissue is converted to lactate. If this is the case in vivo, then glucose uptake in adipose tissue might well be of significance for total body glucose homeostasis, particularly in obese subjects, amounting to maximally perhaps one third to one half of the oral glucose given. The majority of this glucose uptake would then, however, leave adipose tissue again as lactate. The shorter half-life of label in abdominal adipocytes is in agreement with findings of increased lipolysis in these adipocytes in vitro.     

Advancing RAS/RASopathy therapies: An NCI‐sponsored intramural and extramural collaboration for the study of RASopathies

RASopathies caused by germline pathogenic variants in genes that encode RAS pathway proteins. These disorders include neurofibromatosis type 1 (NF1), Noonan syndrome (NS), cardiofaciocutaneous syndrome (CFC), and Costello syndrome (CS), and others. RASopathies are characterized by heterogenous manifestations, including congenital heart disease, failure to thrive, and increased risk of cancers. Previous work led by the NCI Pediatric Oncology Branch has altered the natural course of one of the key manifestations of the RASopathy NF1. Through the conduct of a longitudinal cohort study and early phase clinical trials, the MEK inhibitor selumetinib was identified as the first active therapy for the NF1‐related peripheral nerve sheath tumors called plexiform neurofibromas (PNs). As a result, selumetinib was granted breakthrough therapy designation by the FDA for the treatment of PN. Other RASopathy manifestations may also benefit from RAS targeted therapies. The overall goal of Advancing RAS/RASopathy Therapies (ART), a new NCI initiative, is to develop effective therapies and prevention strategies for the clinical manifestations of the non‐NF1 RASopathies and for tumors characterized by somatic RAS mutations. This report reflects discussions from a February 2019 initiation meeting for this project, which had broad international collaboration from basic and clinical researchers and patient advocates.     

Reproductive tract immune cells from pregnant women or those using depot medroxyprogesterone acetate show no excess susceptibility to HIV-1: Results of an ex vivo fusion assay

IntroductionEx vivo fusion assays offer an efficient method for studying HIV-1 entry associated with contraceptive use and pregnancy outside of cohort studies of HIV-1 incidence.MethodsWe measured ex vivo HIV-1 fusion to cervical or endometrial immune cells from three groups of women: pregnant, non-pregnant not using hormonal or intrauterine contraception, and using depot medroxyprogesterone acetate (DMPA).Results and conclusionsThere was no excess susceptibility to HIV-1 fusion of cells from pregnant women or DMPA users compared to controls. Although the number of target cells in endometrium was higher in DMPA users compared to controls, HIV-1 fusion was lower.ImplicationsIn ex vivo assays, HIV-1 showed no enhanced fusion to cervical immune cells from pregnant women or DMPA users compared to controls, and lower fusion to endometrial immune cells from DMPA users. This assay is useful for studying hormonal and contraceptive effects on HIV-1 entry into reproductive tract immune cells.     

Effets de l’halothane sur les gaz du sang et l’équilibre acido-basique artériels chez le rat intact et chez le rat chémodénervé

L’halothane diminue la réponse ventilatoire à l’hypoxie et l’activité des chémorécepteurs artériels périphériques, réalisant une «chémodénervation chimique». Afin d’évaluer le rôle de cette «chémodénervation chimique» dans les modifications de l’équilibre acido-basique et des gaz du sang artériel provoquées par l’halothane, ces paramètres ont été mesurés chez des rats intacts éveillés, puis anesthésiés, et chez des rats chémodénervés, éveillés puis anesthésiés. Le niveau de l’anesthésie pouvant être modifié par la chémodénervation anatomique, l’ED₅₀ inspirée d’halothane a été mesurée chez six rats avant et après chémodénervation anatomique. D’éventuelles modifications hémodynamiques dues à l’halothane et /ou à la chémodénervation anatomique pouvant interférer avec les résultats, la pression artérielle systémique et la fréquence cardiaque ont été mesurées chez six rats intacts éveillés, puis anesthésiés, et chez les six mêmes rats chémodénervés, éveillés puis anesthésiés. Chez neuf rats intacts et chez 19 rats chémodénervés, le pH artériel, la concentration artérielle de bicarbonates, et les gaz du sang artériel (PaO₂ et PaCO₂) ont été mesurés avant et après administration d’halothane. La chémodénervation anatomique ne modifia ni l’ED₅₀ inspirée (1,1%), ni la pression artérielle moyenne et la fréquence cardiaque. Les effets hémodynamiques de l’halothane furent comparables chez les rats intacts et chez les rats chémodénervés. Les modifications des gaz du sang et de l’équilibre acido-basique provoquees par l’halothane chez les rats intacts, et par la chémodénervation anatomique chez les rats éveillés, ne furent pas significativement différentes: diminution significative de PaO₂ et de pHa, augmentation significative de PaCO₂ Chez les rats chémodénervés, l’halothane provoqua une diminution supplémental de PaO₂ et une augmentation supplémentaire de PaCO₂. Le fait que l’halothane et que la chémodénervation anatomique modifient de la même manière les gaz du sang et l’équilibre acido-basique est en faveur de l’action «chémodénervatrice chimique» de l’halothane. Mais les effets additionnels de l’halothane chez l’animal chémodénervé anatomiquement confirment que les effets de l’halothane sur les gaz du sang et l’équilibre acido-basique résultent de multiples points d’impact sur le système respiratoire.     

Acute cytomegalovirus infection modulates the intestinal microbiota and targets intestinal epithelial cells

Primary and recurrent cytomegalovirus (CMV) infections frequently cause CMV colitis in immunocompromised as well as inflammatory bowel disease (IBD) patients. Additionally, colitis occasionally occurs upon primary CMV infection in patients who are apparently immunocompetent. In both cases, the underlying pathophysiologic mechanisms are largely elusive - in part due to the lack of adequate access to specimens. We employed the mouse cytomegalovirus (MCMV) model to assess the association between CMV and colitis. During acute primary MCMV infection of immunocompetent mice, the gut microbial composition was affected as manifested by an altered ratio of the Firmicutes to Bacteroidetes phyla. Interestingly, these microbial changes coincided with high-titer MCMV replication in the colon, crypt hyperplasia, increased colonic pro-inflammatory cytokine levels, and a transient increase in the expression of the antimicrobial protein Regenerating islet-derived protein 3 gamma (Reg3γ). Further analyses revealed that murine and human intestinal epithelial cell lines, as well as primary intestinal crypt cells and organoids represent direct targets of CMV infection causing increased cell death. Accordingly, in vivo MCMV infection disrupted the intestinal epithelial barrier and increased apoptosis of intestinal epithelial cells. In summary, our data show that CMV transiently induces colitis in immunocompetent hosts by altering the intestinal homeostasis.