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  1. Article ; Online: Protein biomarkers GDF15 and FGF21 to differentiate mitochondrial hepatopathies from other pediatric liver diseases.

    Van Hove, Johan L K / Friederich, Marisa W / Strode, Dana K / Van Hove, Roxanne A / Miller, Kristen R / Sharma, Rohit / Shah, Hardik / Estrella, Jane / Gabel, Linda / Horslen, Simon / Kohli, Rohit / Lovell, Mark A / Miethke, Alexander G / Molleston, Jean P / Romero, Rene / Squires, James E / Alonso, Estella M / Guthery, Stephen L / Kamath, Binita M /
    Loomes, Kathleen M / Rosenthal, Philip / Mysore, Krupa R / Cavallo, Laurel A / Valentino, Pamela L / Magee, John C / Sundaram, Shikha S / Sokol, Ronald J

    Hepatology communications

    2024  Volume 8, Issue 1

    Abstract: Background: Mitochondrial hepatopathies (MHs) are primary mitochondrial genetic disorders that can present as childhood liver disease. No recognized biomarkers discriminate MH from other childhood liver diseases. The protein biomarkers growth ... ...

    Abstract Background: Mitochondrial hepatopathies (MHs) are primary mitochondrial genetic disorders that can present as childhood liver disease. No recognized biomarkers discriminate MH from other childhood liver diseases. The protein biomarkers growth differentiation factor 15 (GDF15) and fibroblast growth factor 21 (FGF21) differentiate mitochondrial myopathies from other myopathies. We evaluated these biomarkers to determine if they discriminate MH from other liver diseases in children.
    Methods: Serum biomarkers were measured in 36 children with MH (17 had a genetic diagnosis); 38 each with biliary atresia, α1-antitrypsin deficiency, and Alagille syndrome; 20 with NASH; and 186 controls.
    Results: GDF15 levels compared to controls were mildly elevated in patients with α1-antitrypsin deficiency, Alagille syndrome, and biliary atresia-young subgroup, but markedly elevated in MH (p<0.001). FGF21 levels were mildly elevated in NASH and markedly elevated in MH (p<0.001). Both biomarkers were higher in patients with MH with a known genetic cause but were similar in acute and chronic presentations. Both markers had a strong performance to identify MH with a molecular diagnosis with the AUC for GDF15 0.93±0.04 and for FGF21 0.90±0.06. Simultaneous elevation of both markers >98th percentile of controls identified genetically confirmed MH with a sensitivity of 88% and specificity of 96%. In MH, independent predictors of survival without requiring liver transplantation were international normalized ratio and either GDF15 or FGF21 levels, with levels <2000 ng/L predicting survival without liver transplantation (p<0.01).
    Conclusions: GDF15 and FGF21 are significantly higher in children with MH compared to other childhood liver diseases and controls and, when combined, were predictive of MH and had prognostic implications.
    MeSH term(s) Child ; Humans ; Alagille Syndrome/diagnosis ; Biliary Atresia/diagnosis ; Biomarkers ; Growth Differentiation Factor 15/blood ; Growth Differentiation Factor 15/chemistry ; Non-alcoholic Fatty Liver Disease ; Mitochondrial Diseases/diagnosis
    Chemical Substances Biomarkers ; fibroblast growth factor 21 ; GDF15 protein, human ; Growth Differentiation Factor 15
    Language English
    Publishing date 2024-01-05
    Publishing country United States
    Document type Journal Article
    ISSN 2471-254X
    ISSN (online) 2471-254X
    DOI 10.1097/HC9.0000000000000361
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Modafinil in the treatment of excessive daytime sleepiness.

    Valentino, Roxanne M / Foldvary-Schaefer, Nancy

    Cleveland Clinic journal of medicine

    2007  Volume 74, Issue 8, Page(s) 561–6, 568–71

    Abstract: Modafinil (Provigil) is approved for treating excessive daytime sleepiness associated with narcolepsy, for shift-work sleep disorder, and as an adjunctive treatment in patients with obstructive sleep apnea syndrome who have residual daytime sleepiness ... ...

    Abstract Modafinil (Provigil) is approved for treating excessive daytime sleepiness associated with narcolepsy, for shift-work sleep disorder, and as an adjunctive treatment in patients with obstructive sleep apnea syndrome who have residual daytime sleepiness despite optimal treatment with continuous positive airway pressure. Although modafinil improves measures of sleepiness, it does not generally normalize them, and it may be less effective than other stimulants for some narcoleptic patients. We need head-to-head comparisons of modafinil with traditional stimulants in humans to better define its role. We review the current approved and off-label uses of this drug and the evidence behind them.
    MeSH term(s) Attention Deficit Disorder with Hyperactivity/drug therapy ; Benzhydryl Compounds/adverse effects ; Benzhydryl Compounds/pharmacology ; Benzhydryl Compounds/therapeutic use ; Central Nervous System Stimulants/adverse effects ; Central Nervous System Stimulants/pharmacology ; Central Nervous System Stimulants/therapeutic use ; Continuous Positive Airway Pressure ; Disorders of Excessive Somnolence ; Drug Interactions ; Humans ; Modafinil ; Multiple Sclerosis/drug therapy ; Narcolepsy/drug therapy ; Parkinson Disease/drug therapy ; Sleep Apnea, Obstructive/drug therapy
    Chemical Substances Benzhydryl Compounds ; Central Nervous System Stimulants ; Modafinil (R3UK8X3U3D)
    Language English
    Publishing date 2007-08-10
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 639116-3
    ISSN 0891-1150
    ISSN 0891-1150
    DOI 10.3949/ccjm.74.8.561
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Acute effects of MK63 stun device discharges in miniature swine.

    Valentino, Daniel J / Walter, Robert J / Dennis, Andrew J / Nagy, Kimberly / Loor, Michele M / Winners, Jerry / Bokhari, Faran / Wiley, Dorion / Merchant, Azher / Joseph, Kimberly / Roberts, Roxanne

    Military medicine

    2008  Volume 173, Issue 2, Page(s) 167–173

    Abstract: Objective: Electromuscular incapacitation (EMI) devices are being used and evaluated by both military and law enforcement agencies. Although the gross muscular response is obvious, physiological responses to these devices are poorly understood. We ... ...

    Abstract Objective: Electromuscular incapacitation (EMI) devices are being used and evaluated by both military and law enforcement agencies. Although the gross muscular response is obvious, physiological responses to these devices are poorly understood. We hypothesized that the intense, repetitive, muscle contractions evoked by EMI devices would cause dose-dependent metabolic acidosis, accompanied by neuromuscular or cardiac injury.
    Methods: Using an approved protocol, 26 Yucatan mini-pigs (22 experimental animals and 4 control animals) were anesthetized with ketamine and xylazine. Experimental animals were exposed to MK63 (Aegis Industries, Bellevue, Idaho) discharges over the left anterior hind limb for 10, 20, 40, or 80 seconds. Electrocardiograms, electromyograms, troponin I levels, blood gas values, and electrolyte levels were recorded before and 5, 15, 30, and 60 minutes and 24, 48, and 72 hours after discharge. Skin, muscle, and nerve biopsies were taken from the shocked and contralateral sides.
    Results: Core body temperature significantly decreased (1.0-1.5 degrees C) in all shocked animals but not in sham-treated control animals. No cardiac dysrhythmias or deaths were seen, and heart rate was unaffected. No clinically significant changes were seen in troponin I, myoglobin, or creatine kinase-MB levels. Central venous blood pH decreased, whereas carbon dioxide pressure and lactate levels increased for 60 minutes after discharge. All values returned to normal by 24 hours after discharge, and no significant histological or electromyographic changes were found.
    Conclusions: Changes in blood chemistry were observed but were of little clinical significance, and no neuromuscular damage was detected. Therefore, within the limitations of this model, it appears that EMI can safely be achieved by using this device, even for lengthy periods, without causing significant injury.
    MeSH term(s) Acidosis/etiology ; Animals ; Electroshock/adverse effects ; Electroshock/instrumentation ; Heart Injuries/etiology ; Models, Animal ; Monitoring, Physiologic/methods ; Muscle, Skeletal/innervation ; Muscle, Skeletal/physiopathology ; Swine ; Swine, Miniature
    Language English
    Publishing date 2008-02-29
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 391061-1
    ISSN 1930-613X ; 0026-4075
    ISSN (online) 1930-613X
    ISSN 0026-4075
    DOI 10.7205/milmed.173.2.167
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Un I Zs.546: Show issues Location:
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  4. Article: Neuromuscular effects of stun device discharges.

    Valentino, Daniel J / Walter, Robert J / Dennis, Andrew J / Nagy, Kimberly / Loor, Michele M / Winners, Jerry / Bokhari, Faran / Wiley, Dorion / Merchant, Azher / Joseph, Kimberly / Roberts, Roxanne

    The Journal of surgical research

    2007  Volume 143, Issue 1, Page(s) 78–87

    Abstract: ... slowing, or axonal loss were detected on EMG. M-wave latency (M(lat), ms), amplitude (M(amp), mV), area (M ... area), mV-ms), and duration (M(dur), ms) were not significantly affected by MK63 discharge compared ...

    Abstract Background: Stun guns or electromuscular incapacitation devices (EMIs) generate between 25,000 and 250,000 V and can be discharged continuously for as long as 5 to 10 min. In the United States, over 200,000 individuals have been exposed to discharges from the most common type of device used. EMI devices are being used increasingly despite a lack of objective laboratory data describing the physiological effects and safety of these devices. An increasing amount of morbidity, and even death, is associated with EMI device use. To examine this type of electrical injury, we hypothesized that EMI discharges will induce acute or delayed cardiac arrhythmia and neuromuscular injury in an animal model.
    Methods: Using an IACUC approved protocol, from May 2005 through June 2006 in a teaching hospital research setting, 30 Yucatan mini-pigs (24 experimentals and 6 sham controls) were deeply anesthetized with ketamine and xylazine without paralytics. Experimentals were exposed to discharges from an EID (MK63; Aegis Industries, Bellevue, ID) over the femoral nerve on the anterior left hind limb for an 80 s exposure delivered as two 40 s discharges. EKGs, EMGs, troponin I, CK-MB, potassium, and myoglobin levels were obtained pre-discharge and post-discharge at 5, 15, 30, and 60 min, 24, 48, and 72 h (n = 6 animals) and 5, 15, and 30 d post-discharge (n = 6 animals at each time point). Skin, skeletal muscle, and peripheral nerve biopsies were studied bilaterally. Data were compared using one-way analysis of variance and paired t-tests. P-values <0.05 were considered significant.
    Results: No cardiac arrhythmias or sudden deaths were seen in any animals at any time point. No evidence of skeletal muscle damage was detected. No significant changes were seen in troponin I, myoglobin, CK-MB, potassium, or creatinine levels. There were no significant changes in compound muscle action potentials (CMAP). No evidence of conduction block, conduction slowing, or axonal loss were detected on EMG. M-wave latency (M(lat), ms), amplitude (M(amp), mV), area (M(area), mV-ms), and duration (M(dur), ms) were not significantly affected by MK63 discharge compared with contralateral or sham controls. F-wave latency (F(lat), ms), a sensitive indicator of retrograde nerve conduction and function, was not significantly affected by MK63 discharge compared with contralateral or sham controls. No significant histological changes were seen at any time point in skeletal muscle or peripheral nerve biopsies although mild skin inflammation was evident.
    Conclusions: There was no evidence of acute arrhythmia from MK63 discharges. No clinically significant changes were seen in any of the physiological parameters measured here at any time point. Neuromuscular function was not significantly altered by the MK63 discharge. In this animal model, even lengthy MK63 discharges did not induce muscle or nerve injury as seen using EMG, blood chemistry, or histology.
    MeSH term(s) Animals ; Arrhythmias, Cardiac/etiology ; Biopsy ; Creatine Kinase, MB Form/metabolism ; Electromyography ; Electroshock/adverse effects ; Heart Rate/physiology ; Models, Animal ; Muscle, Skeletal/innervation ; Muscle, Skeletal/pathology ; Muscle, Skeletal/physiopathology ; Myoglobin/blood ; Peripheral Nerves/pathology ; Potassium/metabolism ; Skin/pathology ; Swine ; Swine, Miniature ; Weapons
    Chemical Substances Myoglobin ; Creatine Kinase, MB Form (EC 2.7.3.2) ; Potassium (RWP5GA015D)
    Language English
    Publishing date 2007-11
    Publishing country United States
    Document type Journal Article
    ZDB-ID 80170-7
    ISSN 1095-8673 ; 0022-4804
    ISSN (online) 1095-8673
    ISSN 0022-4804
    DOI 10.1016/j.jss.2007.03.049
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 178: Show issues Location:
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    Jg. 1995 - 2021: Lesesall (1.OG)
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