ABSTRACT
OBJECTIVES: The use of simulation-based education to train surgeons is widely accepted. Although many authors describe the use of an Objective Skills Assessment Test (OSAT) to assess performance of various surgical procedures, there is a paucity of research on use of this modality to evaluate vaginal surgery skills. We created a vaginal hysterectomy procedure-specific checklist (PSC) to complete the OSAT (which is composed of a PSC and a global rating scale [GRS]). The primary objective of this study is to evaluate the performance of a novel evaluation strategy for vaginal hysterectomy using an OSAT combining PSC and GRS. METHODS: This is a descriptive prospective study from a single institution. After orientation to the model, participants were filmed performing vaginal hysterectomy. A blinded grader scored each subject using the PSC and GRS. RESULTS: Medical students, residents, fellows, and attendings performed vaginal hysterectomy on a simulated model. Mean PSC and GRS scores increased significantly with surgeon level of experience (P < 0.001). Procedure-specific checklist scores significantly correlated with GRS scores (P < 0.001). CONCLUSIONS: The vaginal hysterectomy model and PSC have been studied across different surgeon levels using OSATs. Training programs should consider using this low-cost task trainer as a teaching tool.
Subject(s)
Clinical Competence , Hysterectomy, Vaginal/education , Simulation Training/methods , Checklist , Female , Gynecology/education , Humans , Internship and Residency/standards , Obstetrics/education , Physicians/standards , Prospective Studies , Single-Blind Method , Students, MedicalABSTRACT
An open-label dose-escalation trial was performed to assess the safety and tolerability of high doses of coenzyme Q10 (CoQ10) in ALS. CoQ10, a cofactor in mitochondrial electron transfer, may improve the mitochondrial dysfunction in ALS. In this study, CoQ10 was safe and well tolerated in 31 subjects treated with doses as high as 3,000 mg/day for 8 months.
Subject(s)
Amyotrophic Lateral Sclerosis/drug therapy , Central Nervous System/drug effects , Nerve Degeneration/prevention & control , Neurons/drug effects , Neuroprotective Agents/administration & dosage , Ubiquinone/analogs & derivatives , Amyotrophic Lateral Sclerosis/metabolism , Amyotrophic Lateral Sclerosis/physiopathology , Central Nervous System/metabolism , Central Nervous System/physiopathology , Coenzymes , Dose-Response Relationship, Drug , Drug Tolerance/physiology , Energy Metabolism/drug effects , Energy Metabolism/physiology , Female , Free Radical Scavengers/administration & dosage , Free Radical Scavengers/adverse effects , Humans , Male , Maximum Tolerated Dose , Middle Aged , Mitochondria/drug effects , Mitochondria/metabolism , Nerve Degeneration/drug therapy , Nerve Degeneration/metabolism , Neurons/metabolism , Neuroprotective Agents/adverse effects , Neuroprotective Agents/blood , Ubiquinone/administration & dosage , Ubiquinone/adverse effects , Ubiquinone/bloodABSTRACT
There is substantial evidence for bioenergetic defects in Huntington's disease (HD). Creatine administration increases brain phosphocreatine levels and it stabilizes the mitochondrial permeability transition. We examined the effects of creatine administration in a transgenic mouse model of HD produced by 82 polyglutamine repeats in a 171 amino acid N-terminal fragment of huntingtin (N171-82Q). Dietary supplementation of 2% creatine significantly improved survival, slowed the development of motor symptoms, and delayed the onset of weight loss. Creatine lessened brain atrophy and the formation of intranuclear inclusions, attenuated reductions in striatal N-acetylaspartate as assessed by NMR spectroscopy, and delayed the development of hyperglycemia. These results are similar to those observed using dietary creatine supplementation in the R6/2 transgenic mouse model of HD and provide further evidence that creatine may exert therapeutic effects in HD.
Subject(s)
Creatinine/pharmacology , Huntington Disease/drug therapy , Huntington Disease/metabolism , Motor Activity/drug effects , Neurons/pathology , Animals , Aspartic Acid/analogs & derivatives , Aspartic Acid/metabolism , Blood Glucose , Brain Chemistry/drug effects , Cell Survival/drug effects , Disease Models, Animal , Energy Metabolism/drug effects , Energy Metabolism/physiology , Female , Huntingtin Protein , Huntington Disease/mortality , Hyperglycemia/metabolism , Insulin/blood , Magnetic Resonance Spectroscopy , Male , Mice , Mice, Transgenic , Neostriatum/drug effects , Neostriatum/pathology , Nerve Tissue Proteins/genetics , Neurons/drug effects , Nuclear Proteins/genetics , Organ Size , Survival RateABSTRACT
Dichloroacetate (DCA) stimulates pyruvate dehydrogenase complex (PDHC) activity and lowers cerebral lactate concentrations. In the R6/2 and N171-82Q transgenic mouse models of Huntington's disease (HD), DCA significantly increased survival, improved motor function, delayed loss of body weight, attenuated the development of striatal neuron atrophy, and prevented diabetes. The percentage of PDHC in the active form was significantly reduced in R6/2 mice at 12 weeks of age, and DCA ameliorated the deficit. These results provide further evidence for a role of energy dysfunction in HD pathogenesis and suggest that DCA may exert therapeutic benefits in HD.
Subject(s)
Dichloroacetic Acid/therapeutic use , Huntington Disease/drug therapy , Animals , Behavior, Animal/drug effects , Disease Models, Animal , Male , Mice , Mice, Transgenic , Time FactorsABSTRACT
Several lines of evidence implicate excitotoxic mechanisms in the pathogenesis of amyotrophic lateral sclerosis (ALS). Transgenic mice with a superoxide dismutase mutation (G93A) have been utilized as an animal model of familial ALS (FALS). We examined the cortical concentrations of glutamate using in vivo microdialysis and in vivo nuclear magnetic resonance (NMR) spectroscopy, and the effect of long-term creatine supplementation. NMDA-stimulated and Ltrans-pyrrolidine-2,4-dicarboxylate (LTPD)-induced increases in glutamate were significantly higher in G93A mice compared with littermate wild-type mice at 115 days of age. At this age, the tissue concentrations of glutamate were also significantly increased as measured with NMR spectroscopy. Creatine significantly increased longevity and motor performance of the G93A mice, and significantly attenuated the increases in glutamate measured with spectroscopy at 75 days of age, but had no effect at 115 days of age. These results are consistent with impaired glutamate transport in G93A transgenic mice. The beneficial effect of creatine may be partially mediated by improved function of the glutamate transporter, which has a high demand for energy and is susceptible to oxidative stress.
Subject(s)
Brain Chemistry/drug effects , Creatine/therapeutic use , Glutamic Acid/metabolism , Motor Neuron Disease/drug therapy , ATP-Binding Cassette Transporters/metabolism , Amino Acid Transport System X-AG , Animals , Biological Transport/drug effects , Body Weight/drug effects , Creatine/pharmacology , Dicarboxylic Acids/pharmacology , Dicarboxylic Acids/toxicity , Disease Models, Animal , Excitatory Amino Acid Agonists/pharmacology , Excitatory Amino Acid Agonists/toxicity , Glutamine/metabolism , Magnetic Resonance Spectroscopy , Male , Mice , Mice, Transgenic , Microdialysis , Motor Activity/drug effects , Motor Neuron Disease/genetics , Motor Neuron Disease/metabolism , N-Methylaspartate/pharmacology , N-Methylaspartate/toxicity , Neurotransmitter Uptake Inhibitors/pharmacology , Neurotransmitter Uptake Inhibitors/toxicity , Oxidative Stress , Psychomotor Performance/drug effects , Pyrrolidines/pharmacology , Pyrrolidines/toxicity , Superoxide Dismutase/deficiency , Superoxide Dismutase/geneticsABSTRACT
The development of transgenic mouse models of amyotrophic lateral sclerosis (ALS) allows the testing of neuroprotective agents. We evaluated the effects of five agents in transgenic mice with the G93A Cu,Zn superoxide dismutase mutation. A novel inhibitor of poly(ADP-ribose) polymerase showed no effects on survival. Desmethylselegiline and CGP3466 are agents that exert antiapoptotic effects in vitro by preventing nuclear translocation of glyceraldehyde-3-phosphate dehydrogenase. They had no significant effects on survival in the G93A mice. Trientine, a copper chelator, produced a modest significant increase in survival. Similarly administration of lipoic acid in the diet produced a significant improvement in survival. These results therefore provide evidence for potential therapeutic effects of copper chelators and lipoic acid in the treatment of ALS.