Azathioprine, 6-mercaptopurine and thiopurine s-methyltransferase

Azathioprine, 6-mercaptopurine and thiopurine s-methyltransferase levels in gastroenterology and rheumatology: a comparison of clinical practice in Australia. J Gastroenterol Hepatol 2009;24(s2):222–223. L BESWICK,1 L SOH,2 A MCFARLANE,1 DR VAN LANGENBERG1,2 1Department of Gastroenterology, Eastern Health, Melbourne, Victoria, Australia, 2Eastern Health Clinical School, Monash University, Melbourne, Victoria, Australia Background: Infliximab (IFX) infusion reactions in patients with inflammatory bowel disease

(IBD) vary from minor urticaria to anaphylaxis. Although studies have previously observed infusion reactions in up to 10–50% of patients receiving infliximab infusions, anecdotally the prevalence appears far lower than this. To minimize reactions, standard infliximab infusions run over two hours with Selleckchem Epacadostat two hours of post-infusion monitoring advised, yet many studies have shown more rapid infusion protocols to be safe and cost effective. Hence in a quality improvement initiative, we aimed to evaluate current practice of administering IFX infusions in patients with IBD and assess prevalence of IFX infusion reactions at a large volume, single IBD center, then evaluate predictive factors that are associated with an increased risk of an IFX infusion reaction. Methods: A retrospective audit of all patients with confirmed IBD who received IFX at Eastern Health between 1/1/2005- 1/1/2014 was conducted.

Data encompassing phosphatase inhibitor library demographics, IBD clinical data, the number and time duration of IFX infusions plus the frequency, management and sequelae of infusion 上海皓元 reactions were extracted from hospital records. Results: 2214 IFX infusions were administered to 169 patients throughout the nine-year period. The median number of infusions per patient was 10, with median age 38 (range 19–83) and 94 (56%) males; 126

(75%) patients had Crohn’s disease; 43 (25%) patients had ulcerative colitis. The median duration of IFX infusion was 2 hours 30 minutes (door-door at infusion unit) and 1 hour 25 minutes (start-finish infusion only) for their first documented infusion compared to 2 hours 15 minutes and 1 hour 15 minutes respectively for their most recently documented infusion. The adverse reaction rate per patient was 13.6%; 18 patients classified as having a mild reaction and 5 having a serious reaction (rate per patient 3.6%, per infusion 0.2%) according to the Common Toxicity Criteria. 17/18 (94%) with a mild reaction tolerated subsequent IFX infusions when rechallenged. According to multivariate analysis, predictive factors of an IFX infusion reaction included episodic or gap >3 months in IFX dosing (OR 8.7, 95% CI [1.8, 41.4], concurrent immunomodulator OR 9.4 [1.5, 57.4], smoker at time of reaction OR 3.8 [1.01, 13.9], duration of IBD when IFX started (per year, OR 1.11 [1.04, 1.2]) (each p < 0.05), with a non-significant trend for previous adverse drug reaction(s) OR 3.2 [0.8, 13.3] (p = 0.1).

LY gained were 158 versus 105 for sorafenib and BSC, respective

LY gained were 1.58 versus 1.05 for sorafenib and BSC, respectively. Consistent with a priori expectations, the total costs for sorafenib were higher compared to BSC (Table 2), due to drug costs ($US29 562 vs $US0). Besides drug costs, the other major cost driver was the cost of BSC after progression (Fig. 3). The incremental cost per LY gained was estimated to be $US62 473. At 0% discount rate, the cost per LY gained is $US57 539, and at 5% the cost per LY gained is $US65 719. A tornado diagram illustrates the results of the deterministic one-way sensitivity analysis by depicting the variables to the changes of which the results are most sensitive to (Fig. 4).

The diagram shows OS for sorafenib and BSC to be the most sensitive variables, followed by TTP with sorafenib,

the cost of first-line treatment with sorafenib—no progression, and the cost of first-line treatment Y-27632 nmr with BSC—no progression. The incremental gains in LY were plotted against incremental costs of sorafenib versus BSC on the cost-effectiveness plane (Fig. 5). The cost-effectiveness plane shows that for the cost per LY gained, the BTK inhibitor grouping represents a reasonably tight cluster and thereby provides analytical validity for the base case results. A cost-effectiveness acceptability curve was generated to evaluate the proportion of simulations where sorafenib can be considered cost-effective over a range of the maximum willingness to pay of society for an LY gained. The probability of sorafenib providing a cost-effective alternative to BSC was 68% and 86% at a willingness to pay of $US75 000 and $US100 000, 上海皓元医药股份有限公司 respectively. While the US government has not formally endorsed the use of economic evaluation in coverage and reimbursement decisions, many managed-care organizations have adopted economic evaluations in their formulary decisions.12 Recently, the increasing financial pressure from the health-care sector has formed a renewed interest for a government-funded organization to assess

the cost and cost-effectiveness26 of health-care interventions.27 These suggest an increased role of economic evidence in the future. Sorafenib is a new, novel cancer therapy approved in the USA for the treatment of advanced HCC. It is the first treatment to demonstrate a statistically significant increase in OS compared to BSC, thereby filling a gap in the treatment of advanced HCC. The aim of this analysis was to assess the cost-effectiveness of sorafenib against BSC from the perspective of US third-party payers. To evaluate the cost-effectiveness of sorafenib, a Markov model was built in the treatment of advanced HCC. Prior to the approval of sorafenib, there were no approved treatment options for advanced HCC, and the recommendation of the American Association for the Study of Liver Diseases (AASLD) guidelines was BSC.28 Thus the model evaluated sorafenib in comparison to BSC. The analysis followed the patients over their lifetimes.

LY gained were 158 versus 105 for sorafenib and BSC, respective

LY gained were 1.58 versus 1.05 for sorafenib and BSC, respectively. Consistent with a priori expectations, the total costs for sorafenib were higher compared to BSC (Table 2), due to drug costs ($US29 562 vs $US0). Besides drug costs, the other major cost driver was the cost of BSC after progression (Fig. 3). The incremental cost per LY gained was estimated to be $US62 473. At 0% discount rate, the cost per LY gained is $US57 539, and at 5% the cost per LY gained is $US65 719. A tornado diagram illustrates the results of the deterministic one-way sensitivity analysis by depicting the variables to the changes of which the results are most sensitive to (Fig. 4).

The diagram shows OS for sorafenib and BSC to be the most sensitive variables, followed by TTP with sorafenib,

the cost of first-line treatment with sorafenib—no progression, and the cost of first-line treatment drug discovery with BSC—no progression. The incremental gains in LY were plotted against incremental costs of sorafenib versus BSC on the cost-effectiveness plane (Fig. 5). The cost-effectiveness plane shows that for the cost per LY gained, the Selleck Deforolimus grouping represents a reasonably tight cluster and thereby provides analytical validity for the base case results. A cost-effectiveness acceptability curve was generated to evaluate the proportion of simulations where sorafenib can be considered cost-effective over a range of the maximum willingness to pay of society for an LY gained. The probability of sorafenib providing a cost-effective alternative to BSC was 68% and 86% at a willingness to pay of $US75 000 and $US100 000, MCE respectively. While the US government has not formally endorsed the use of economic evaluation in coverage and reimbursement decisions, many managed-care organizations have adopted economic evaluations in their formulary decisions.12 Recently, the increasing financial pressure from the health-care sector has formed a renewed interest for a government-funded organization to assess

the cost and cost-effectiveness26 of health-care interventions.27 These suggest an increased role of economic evidence in the future. Sorafenib is a new, novel cancer therapy approved in the USA for the treatment of advanced HCC. It is the first treatment to demonstrate a statistically significant increase in OS compared to BSC, thereby filling a gap in the treatment of advanced HCC. The aim of this analysis was to assess the cost-effectiveness of sorafenib against BSC from the perspective of US third-party payers. To evaluate the cost-effectiveness of sorafenib, a Markov model was built in the treatment of advanced HCC. Prior to the approval of sorafenib, there were no approved treatment options for advanced HCC, and the recommendation of the American Association for the Study of Liver Diseases (AASLD) guidelines was BSC.28 Thus the model evaluated sorafenib in comparison to BSC. The analysis followed the patients over their lifetimes.

Use of serum-free conditions was essential to keep the hHpSCs and

Use of serum-free conditions was essential to keep the hHpSCs and their mesenchymal cell partners, the angioblasts, stable and with the requisite paracrine signaling14 enabling them to self-replicate. selleck kinase inhibitor Serum-free KM was changed every 3-4 days. Typical plates have single cells and small clusters of cells that adhere after the initial 24 hours. Colonies began to appear after 1-2 weeks. All hyaluronan materials were obtained from Glycosan Biosciences (Salt Lake City, UT; now a subdivision of BioTime, Alameda, CA),

and consist of thiol-modified carboxymethyl HA, a chemically modified HA derivative with disulfide bridges for cross-linking. The cross-linking is initiated by a PEGDA cross-linker, and the level of cross-linking activity and stiffness can be regulated by the amount of PEGDA added,20, 21, 24, 30-33 proven to be a variable in regulating the stem cell fate. The hydrogel substrata were constructed by dissolving dry reagents in KM to give a 2.0% solution (wt/vol) for the HA gels, and the PEGDA cross-linker was dissolved in KM to give a 4.0% wt/vol solution, and allowed to incubate at 37°C to dissolve. Collagen III and laminin from Sigma (St. Louis, MO) were used at a concentration of 1.0 mg/mL. A ratio of 1:4 was applied to blend the cross-linker and hyaluronans. After 3 weeks in culture, stem cell colonies,

approximating 3,000-5,000 cells/colony, were picked and put into suspension. Cell suspensions of 200,000 cells were then combined with a hyaluronan-matrix mix. PEGDA cross-linker was added, and the cell matrix material was immediately added to wells in a 4-well chamber slide. Once the gel set, an equal Everolimus concentration amount of KM was added to the top of the well. Cultures were then maintained for a period of 21 days, with medium changes MCE every 48 hours. Multiple runs were performed with different liver samples to ensure consistency. Athymic nude, male mice, aged 8-12 weeks, were bred in house at the University of North Carolina Animal Care Facility. Animals

received care according to the Division of Laboratory Animal Medicine, University of North Carolina-Chapel Hill guidelines, approved by the Association for Assessment and Accreditation of Laboratory Animal Care. All protocols regarding animal care and use were approved by the Institutional Animal Care and Use Committee. Freshly isolated hepatic progenitors were infected for 4 hours at 37°C with a luciferase-expressing adenoviral vector at 50 POI (Ad-CMV-Luc; Vector Biolabs, Philadelphia, PA). The vector provides intense expression of luciferase for at least 48 hours and up to 72 hours. By 72 hours or soon thereafter, its expression is terminated by silencing mechanisms involving methylation of the promoter.34 Mice (8-12 weeks) were anesthetized using ketamine (90-120 mg/kg; Bioniche Pharma, Lake Forrest, IL), and Xylazine (10 mg/kg; Akorn, Decatur, IL). Survival surgery was performed, opening the abdomen and slowly injecting 1.

8 years; age range, 23–71), who met the inclusion criteria and ag

8 years; age range, 23–71), who met the inclusion criteria and agreed to take part

in the study, were recruited. The common clinical manifestations BGJ398 solubility dmso included weakness in health or body (n = 70), abdominal distension (n = 52) and dull pain in the liver (n = 40). According to Child–Pugh classifications, the cohort was composed of 68 patients of Child–Pugh A, 32 of Child–Pugh B and 18 of Child–Pugh C. All patients underwent standard upper gastrointestinal endoscopy performed by two gastroenterologists (9th and 10th authors who had more than 10 years of experience in gastroenterology and upper gastrointestinal endoscopy) in consensus. i.v. sedation was not used in any patient. All endoscopic studies were captured as digital imaging and communications in medicine files, and were reviewed in consensus in a picture archiving and communication system by the previous two experienced gastroenterologists who were unaware of knowledge of the patients’ clinical data and MR findings. According to the criteria proposed by the Japanese Research Society for Portal Hypertension (Table 1),[6] patients with the varices were divided into 4 grades based on the severity of the varices as shown on the endoscopic findings. On the basis of their probability for developing an esophageal variceal hemorrhage, the patients were also I-BET-762 purchase divided into two groups with low and high risk. Grade

2 and 3 varices were defined as high-risk varices, and grade 0 and 1 varices were defined as low-risk varices.[6] All scans were conducted with a 1.5-T MR scanner (Signa Excite; medchemexpress GE Medical Systems, Milwaukee, WI, USA) with 38-mT/M gradients and a 120-T/M/s slew rate using a phased-array torso coil. The sequences were T2-weighted axial fast recovery fast spin-echo (FRFSE) fat-suppressed sequence and dynamic 3-D contrast enhanced imaging. The scan range

was from the level of the left atrium to that of the iliac crests. Each sequence acquisition was performed within a breath-hold. Scanning parameters for the T2-weighted axial FRFSE fat-suppressed sequence were: repetition time (TR)/echo time (TE), 3000/121.5 msec; bandwidth, 62.5 kHz; section thickness, 5.0 mm; overlap, 2.0 mm; field of view (FOV), 24 cm × 32 cm; and matrix, 256 mm × 192 mm. Subsequently, dynamic 3-D contrast enhanced imaging was performed with a bolus injection of gadolinium chelate (Magnevist; Berlex Laboratories, Wayne, NJ, USA) via an automated pump injector (Spectris MR Injection System; Medrad, Indianola, PA, USA) into an antecubital vein according to 0.2 mmol/L per kilogram of bodyweight at the rate of 3.5 mL/s followed by a 20-mL saline solution flush. The scanning delays for triphasic MR imaging were 14 s, 1 min and 3 min after initiation of the contrast injection, representing the arterial, portal and delayed phases, respectively.

8 years; age range, 23–71), who met the inclusion criteria and ag

8 years; age range, 23–71), who met the inclusion criteria and agreed to take part

in the study, were recruited. The common clinical manifestations Inhibitor Library manufacturer included weakness in health or body (n = 70), abdominal distension (n = 52) and dull pain in the liver (n = 40). According to Child–Pugh classifications, the cohort was composed of 68 patients of Child–Pugh A, 32 of Child–Pugh B and 18 of Child–Pugh C. All patients underwent standard upper gastrointestinal endoscopy performed by two gastroenterologists (9th and 10th authors who had more than 10 years of experience in gastroenterology and upper gastrointestinal endoscopy) in consensus. i.v. sedation was not used in any patient. All endoscopic studies were captured as digital imaging and communications in medicine files, and were reviewed in consensus in a picture archiving and communication system by the previous two experienced gastroenterologists who were unaware of knowledge of the patients’ clinical data and MR findings. According to the criteria proposed by the Japanese Research Society for Portal Hypertension (Table 1),[6] patients with the varices were divided into 4 grades based on the severity of the varices as shown on the endoscopic findings. On the basis of their probability for developing an esophageal variceal hemorrhage, the patients were also BVD-523 mw divided into two groups with low and high risk. Grade

2 and 3 varices were defined as high-risk varices, and grade 0 and 1 varices were defined as low-risk varices.[6] All scans were conducted with a 1.5-T MR scanner (Signa Excite; MCE GE Medical Systems, Milwaukee, WI, USA) with 38-mT/M gradients and a 120-T/M/s slew rate using a phased-array torso coil. The sequences were T2-weighted axial fast recovery fast spin-echo (FRFSE) fat-suppressed sequence and dynamic 3-D contrast enhanced imaging. The scan range

was from the level of the left atrium to that of the iliac crests. Each sequence acquisition was performed within a breath-hold. Scanning parameters for the T2-weighted axial FRFSE fat-suppressed sequence were: repetition time (TR)/echo time (TE), 3000/121.5 msec; bandwidth, 62.5 kHz; section thickness, 5.0 mm; overlap, 2.0 mm; field of view (FOV), 24 cm × 32 cm; and matrix, 256 mm × 192 mm. Subsequently, dynamic 3-D contrast enhanced imaging was performed with a bolus injection of gadolinium chelate (Magnevist; Berlex Laboratories, Wayne, NJ, USA) via an automated pump injector (Spectris MR Injection System; Medrad, Indianola, PA, USA) into an antecubital vein according to 0.2 mmol/L per kilogram of bodyweight at the rate of 3.5 mL/s followed by a 20-mL saline solution flush. The scanning delays for triphasic MR imaging were 14 s, 1 min and 3 min after initiation of the contrast injection, representing the arterial, portal and delayed phases, respectively.

31 Our in vivo results further support the role of β-catenin-medi

31 Our in vivo results further support the role of β-catenin-mediated PI3K/Akt in the regulation of hepatic oncotic necrosis/apoptosis. Thus, defective β-catenin down-regulated Bcl-2/Bcl-xL but up-regulated cleaved caspase-3 and its activity, which in turn enhanced apoptotic cell death in IR-stressed livers. Thus, our results

highlight the function of β-catenin to trigger PI3K/Akt signaling and ameliorate liver cell death in IRI pathology. Figure 8 depicts putative molecular mechanisms by which β-catenin signaling may regulate immune responses in the mechanism of liver IRI. STAT3 triggers β-catenin activation by way of GSK-3β phosphorylation. After translocating to the nucleus, β-catenin activates transcription of its target genes, depresses PTEN activity, and promotes PI3K/Akt signaling,

to provide a negative TLR4 regulatory feedback to inhibit NF-κB/IRF3 activity, and ultimately suppress check details proinflammatory gene programs in the liver. Furthermore, PI3K/Akt inhibits IL-12 production and promotes antiapoptotic Bcl-2/Bcl-xL function, which may also limit the hepatocyte death. In conclusion, this study extends our recent findings on the role of Akt/β-catenin/Foxo1 axis in the mechanism of macrophage innate activation32 by demonstrating that β-catenin may program DC development and regulate innate-adaptive interface in IR-stressed liver. By identifying molecular pathways PCI-32765 molecular weight MCE公司 critical for β-catenin function, our study provides the rationale for novel therapeutic approaches to ameliorate IR-triggered liver inflammation and damage. Additional Supporting Information may be found in the online version of this article. “
“Hepatitis B virus (HBV) and hepatitis C virus (HCV) cause a large proportion of acute

and chronic liver disease worldwide. Over the past decades many immunological studies defined host immune responses that mediate spontaneous clearance of acute HBV and HCV infection. However, host immune responses are also relevant in the context of treatment-induced clearance of chronic HBV and HCV infection. First, the pretreatment level of interferon-stimulated genes as well as genetic determinants of innate immune responses, such as single nucleotide polymorphisms near the IFNL3 gene, are strong predictors of the response to IFN-α-based therapy. Second, IFN-α, which has been a mainstay of HBV and HCV therapy over decades, and ribavirin, which has also been included in interferon-free direct antiviral therapy for HCV, modulate host immune responses. Third, both IFN-α-based and IFN-α-free treatment regimens of HBV and HCV infection alter the short-term and long-term adaptive immune response against these viruses. Finally, treatment studies have not just improved the clinical outcomes, but also provided opportunities to study virus-host interaction.

We describe the conventional MR imaging, perfusion MRI, proton MR

We describe the conventional MR imaging, perfusion MRI, proton MR spectroscopy (1H MRS), histopathology, immunohistochemistry, and chromosomal analysis in two cases of these tumors, with some features which have not been previously well described. Both tumor types demonstrated markedly elevated cerebral blood volume on perfusion MRI and had 1p19q chromosomal codeletions. Both tumor types showed an elevated Cho/Cr ratio, but extraventricular ganglioneurocytoma showed a preserved NAA/Cr ratio. These tumors should be considered in the differential diagnosis of intra-axial

brain tumors. “
“To report the brain imaging selleck kinase inhibitor features on magnetic resonance imaging (MRI) in inadvertent intrathecal gadolinium administration. A 67-year-old female with gadolinium encephalopathy from inadvertent high dose intrathecal gadolinium administration during an epidural steroid injection was studied with

multisequence 3T MRI. T1-weighted imaging shows pseudo-T2 appearance with diffusion of gadolinium into the brain parenchyma, olivary bodies, and membranous labyrinth. Nulling of cerebrospinal fluid (CSF) signal is absent PLX4032 research buy on fluid attenuation recovery (FLAIR). Susceptibility-weighted imaging (SWI) demonstrates features similar to subarachnoid hemorrhage. CT may demonstrate a pseudo-cerebral edema pattern given the high attenuation characteristics of gadolinium. Intrathecal gadolinium demonstrates characteristic imaging features on MRI of the brain and may mimic subarachnoid hemorrhage on susceptibility-weighted imaging. Identifying high dose gadolinium within the CSF spaces on MRI is essential to avoid diagnostic and therapeutic errors. “
“Postpartum cerebral angiopathy mostly occurs in the large or medium-sized cerebral arteries. In this 上海皓元 case, we aimed to report a case of postpartum cerebral angiopathy presented as an asymmetrical penetrating arterial territory infarct with severe surrounding vasogenic edema. A 26-year-old woman admitted because of sudden headache after an attack of seizure. On initial computerized tomography

(CT), hypodense lesion in the right basal ganglia was observed. The diffusion-weighted image on 5th day revealed focal acute ischemic infarction with surrounding extensive vasogenic edema in right basal ganglia. The CT angiography showed multifocal arterial narrowing of intracranial cerebral arteries that completely resolved on the follow-up study. This case suggested that asymmetrical small penetrating arterial territory infarct can occur as an atypical presentation of postpartum cerebral angiopathy. “
“To describe a case of successful intracranial angioplasty and stenting of a symptomatic middle cerebral artery (MCA) stenosis using a transcervical approach. A 73-year-old woman presented with several ischemic strokes in the left MCA distribution.

We describe the conventional MR imaging, perfusion MRI, proton MR

We describe the conventional MR imaging, perfusion MRI, proton MR spectroscopy (1H MRS), histopathology, immunohistochemistry, and chromosomal analysis in two cases of these tumors, with some features which have not been previously well described. Both tumor types demonstrated markedly elevated cerebral blood volume on perfusion MRI and had 1p19q chromosomal codeletions. Both tumor types showed an elevated Cho/Cr ratio, but extraventricular ganglioneurocytoma showed a preserved NAA/Cr ratio. These tumors should be considered in the differential diagnosis of intra-axial

brain tumors. “
“To report the brain imaging CX-5461 clinical trial features on magnetic resonance imaging (MRI) in inadvertent intrathecal gadolinium administration. A 67-year-old female with gadolinium encephalopathy from inadvertent high dose intrathecal gadolinium administration during an epidural steroid injection was studied with

multisequence 3T MRI. T1-weighted imaging shows pseudo-T2 appearance with diffusion of gadolinium into the brain parenchyma, olivary bodies, and membranous labyrinth. Nulling of cerebrospinal fluid (CSF) signal is absent PR-171 nmr on fluid attenuation recovery (FLAIR). Susceptibility-weighted imaging (SWI) demonstrates features similar to subarachnoid hemorrhage. CT may demonstrate a pseudo-cerebral edema pattern given the high attenuation characteristics of gadolinium. Intrathecal gadolinium demonstrates characteristic imaging features on MRI of the brain and may mimic subarachnoid hemorrhage on susceptibility-weighted imaging. Identifying high dose gadolinium within the CSF spaces on MRI is essential to avoid diagnostic and therapeutic errors. “
“Postpartum cerebral angiopathy mostly occurs in the large or medium-sized cerebral arteries. In this MCE case, we aimed to report a case of postpartum cerebral angiopathy presented as an asymmetrical penetrating arterial territory infarct with severe surrounding vasogenic edema. A 26-year-old woman admitted because of sudden headache after an attack of seizure. On initial computerized tomography

(CT), hypodense lesion in the right basal ganglia was observed. The diffusion-weighted image on 5th day revealed focal acute ischemic infarction with surrounding extensive vasogenic edema in right basal ganglia. The CT angiography showed multifocal arterial narrowing of intracranial cerebral arteries that completely resolved on the follow-up study. This case suggested that asymmetrical small penetrating arterial territory infarct can occur as an atypical presentation of postpartum cerebral angiopathy. “
“To describe a case of successful intracranial angioplasty and stenting of a symptomatic middle cerebral artery (MCA) stenosis using a transcervical approach. A 73-year-old woman presented with several ischemic strokes in the left MCA distribution.

Asghar and collaborators35 examined the diameter of extracranial

Asghar and collaborators35 examined the diameter of extracranial and intracranial vessels in subjects suffering from migraine without aura, seeking to avoid a premature dismissal of vascular mechanisms. A novel high-resolution direct MRA imaging technique was used to measure arterial circumference of the extracranial

MMA and the intracranial middle cerebral artery (MCA). The study found dilation of both MMA and MCA during migraine attack. Sumatriptan administration caused amelioration of headache and contraction of MMA, but the MCA remained unchanged. Exploratory analysis revealed www.selleckchem.com/p38-MAPK.html that in attacks with unilateral headache, there was only dilation of the ipsilateral Selleckchem CP673451 and no dilation of the contralateral MMA and of the MCA. In bilateral headache, bilateral vasodilation of both MMA and MCA became apparent. These data suggest that migraine without aura is accompanied by dilation of extracerebral and intracerebral arteries and that the headache location correlates with the location of the vasodilation. Furthermore, contraction of extracerebral, and not intracerebral arteries, is associated with amelioration of headache. Taken together,

these observations support a role for vasodilation and potential perivascular release of vasoactive substances in migraine generation. Functional Correlates.— With improved neurophysiological and functional MCE公司 imaging techniques, it became evident that migraine is associated with distinct patterns of neuronal and glial activation.36 The correct interpretation of imaging data, however, relies on distinguishing the signal alterations induced by migraine from those of a general pain response. One way of achieving this is to compare areas of activation and deactivation present during the migraine attack, to signal changes occurring after effective abortive therapy.7 The areas responsible for pain are expected to change following

effective therapy. Persistence of hyperactivity in an area represents evidence in favor of its role as a migraine-triggering site (see Table 2 for a list of neuroimaging findings during migraine attack). In several studies after sumatriptan administration, for example, the dorsal pons remained activated.37-39 An important early PET study from Weiller and collaborators39 demonstrated specific changes in blood flow during migraine attacks that do not follow a neurovascular distribution and are distinct from the patterns of blood flow seen during other primary headache disorders. Increased blood flow was found during spontaneous attacks in the brainstem and in the cingulate, auditory, and visual association cortices. Only contalateral brainstem activation, however, persisted after sumatriptan injection had induced complete relief from headache and phonophobia and photophobia.