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Armstrong M.J.,University of Birmingham | Hazlehurst J.M.,University of Birmingham | Hull D.,University of Birmingham | Guo K.,University of Birmingham | And 5 more authors.
Diabetes, Obesity and Metabolism | Year: 2014

Background: Systemic insulin resistance (IR) is a primary feature in non-alcoholic steatohepatitis (NASH), however, there remain limited data on tissue-specific insulin sensitivity in vivo. Methods: We examined tissue-specific (adipose, muscle and liver) insulin sensitivity and inflammation in 16 European Caucasian patients with biopsy-confirmed NASH and in 15 healthy controls. All underwent a two-step hyperinsulinaemic euglycaemic clamp incorporating stable isotope measurements of carbohydrate and lipid metabolism with concomitant subcutaneous adipose tissue (SAT) microdialysis. Results: Hepatic and muscle insulin sensitivity were decreased in patients with NASH compared with controls, as demonstrated by reduced suppression of hepatic glucose production and glucose disposal (Gd) rates following insulin infusion. In addition, rates of lipolysis were higher in NASH patients with impaired insulin-mediated suppression of free fatty acid levels. At a tissue specific level, abdominal SAT in patients with NASH was severely insulin resistant, requiring >sixfold more insulin to cause 1/2-maximal suppression of glycerol release when compared with healthy controls. Furthermore, patients with NASH had significantly higher circulating levels of pro-inflammatory adipocytokines than controls. Conclusion: NASH patients have profound IR in the liver, muscle and in particular adipose tissues. This study represents the first in vivo description of dysfunctional SAT in patients with NASH. © 2014 The Authors. Diabetes, Obesity and Metabolism published by JohnWiley & Sons Ltd.

Gelfand A.A.,University of California at San Francisco | Goadsby P.J.,University of California at San Francisco | Goadsby P.J.,NIHR Wellcome Trust Clinical Research Facility
Current Pain and Headache Reports | Year: 2014

Medication overuse is not uncommon among children and adolescents with primary headache disorders. Medication overuse in adults is associated with increased headache frequency and reduced effectiveness of acute and preventive medications. These issues probably exist in children. While withdrawal of overused medications is generally recommended, it may not result in improved headache frequency in all patients. This review summarizes what is known about predicting the response to medication withdrawal. Strategies for managing children and adolescents with medication overuse are also offered. © 2014, Springer Science+Business Media New York.

Karsan N.,Institute of Psychiatry | Goadsby P.J.,NIHR Wellcome Trust Clinical Research Facility
Current Neurology and Neuroscience Reports | Year: 2015

Migraine is a complex disorder of the brain that is common and highly disabling. As understanding of the neural pathways has advanced, and it has become clear that the vascular hypothesis does not explain the disorder, new therapeutic avenues have arisen. One such target is calcitonin gene-related peptide (CGRP)-based mechanisms. CGRP is found within the trigeminovascular nociceptive system widely from the trigeminal ganglion to second-order and third-order neurons and in regulatory areas in the brainstem. Studies have shown CGRP is released during severe migraine attacks and the reversal of the attack with effective triptan treatment normalizes those levels. CGRP administration triggers migraine in patients, and CGRP receptor antagonists have been shown to abort migraine. Here, we review the current state of CGRP mechanism antagonist therapy as its research and development is increasing in migraine therapeutics. We discuss several recent trials, highlighting the evidence base behind these novel drugs, and their potential future contribution to migraine management. © 2015, Springer Science+Business Media New York.

Al-Hashel J.Y.,Sina | Al-Hashel J.Y.,Kuwait University | Ahmed S.F.,Sina | Ahmed S.F.,Minia University | And 3 more authors.
Journal of Headache and Pain | Year: 2014

Background: Medical students routinely have triggers, notably stress and irregular sleep, which are typically associated with migraine. We hypothesized that they may be at higher risk to manifest migraine. We aimed to determine the prevalence of migraine among medical students in Kuwait University. Methods: This is cross-sectional, questionnaire-based study. Participants who had two or more headaches in the last 3 months were subjected to two preliminary questions and participants with at least one positive response were asked to perform the validated Identification of Migraine (ID Migraine™) test. Frequency of headache per month and its severity were also reported. Results: Migraine headache was suggested in 27.9% subjects based on ID-Migraine™. Migraine prevalence (35.5% and 44%, versus 31.1%, 25%, 21.1%, 14.8%, 26.5%, p < 0.000), frequency (5.55 + 1.34 and 7.23 + 1.27, versus 3.77 ± 0.99, 2.88 ± 0.85, 3.07 ± 0.96, 2.75 ± 0.75, 4.06 ± 1.66, p < 0.000); and severity of headache (59.1% and 68.2%, versus 28.3%,8.3%, 6.7%,16.7%, p < 0.000; were significantly increased among students in the last 2 years compared to first five years of their study. Stress 43 (24.9%), irregular sleep 36 (20.8%), and substantial reading tasks 32 (18.5%), were the most common triggering factors cited by the students. Conclusion: The prevalence of migraine is higher among medical students in Kuwait University compared to other published studies. The migraine prevalence, frequency and headache severity, all increased in the final two years of education. © 2014, Al-Hashel et al.; licensee Springer.

Bhola R.,eNeura Therapeutics | Kinsella E.,eNeura Therapeutics | Giffin N.,Royal United Hospital | Lipscombe S.,University of Sussex | And 4 more authors.
Journal of Headache and Pain | Year: 2015

Background: Single pulse transcranial magnetic stimulation (sTMS) is a novel treatment for acute migraine. Previous randomised controlled data demonstrated that sTMS is effective and well tolerated in the treatment of migraine with aura. The aim of the programme reported here was to evaluate patient responses in the setting of routine clinical practice. Methods: Migraine patients with and without aura treating with sTMS had an initial review (n = 426) and training call, and then participated in telephone surveys at week six (n = 331) and week 12 during a 3-month treatment period (n = 190). Results: Of patients surveyed with 3 month data (n = 190; episodic, n = 59; chronic, n = 131), 62 % reported pain relief, finding the device effective at reducing or alleviating migraine pain; in addition there was relief reported of associated features: nausea- 52 %; photophobia- 55 %; and phonophobia- 53 %. At 3 months there was a reduction in monthly headache days for episodic migraine, from 12 (median, 8–13 IQ range) to 9 (4–12) and for chronic migraine, a reduction from 24 (median, 16–30 IQ range) to 16 (10–30). There were no serious or unanticipated adverse events. Conclusion: sTMS may be a valuable addition to options for the treatment of both episodic and chronic migraine. © 2015, Bhola et al.

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