Methods: Consecutive patients with heartburn and/or acid regurgit

Methods: Consecutive patients with heartburn and/or acid regurgitation in outpatient and twenty-eight healthy controls were enrolled. The patients were considered as GERD if they had any of the following situations: reflux esophagitis (RE), abnormal esophageal 24 hrs pH monitoring and/or positive symptom index (SI), positive response to proton pump inhibitor (PPI) test. HRM were performed in GERD and healthy controls with ten wet swallows and ten viscous swallows in supine position. Results: Ninety-six GERD were enrolled including 37 RE patients and 61 males. GERD had lower bolus clearance rate and lower distal contractile integral (DCI) for both wet swallows and viscous swallows

comparing with healthy controls. GERD had decreased DCI (1078.5 ± 697.0 VS. 950.0 ± 616.0 mmHg●s●cm, Fer-1 research buy P = 0.001) and decreased contractile http://www.selleckchem.com/products/MK-2206.html front velocity (CFV) (4.8 ± 1.5 VS. 4.4 ± 1.4 cm/s, P = 0.000) in viscous swallows than that in wet swallows. RE patients had lower DCI (764.7 ± 675.4 VS. 1067.2 ± 550.6 mmHg●s●cm,

P = 0.031) than non-erosive reflux disease (NERD) in viscous swallows. Patients with abnormal pH monitoring and normal pH monitoring showed no significant differences in DCI. Conclusion: Esophageal peristalsis in GERD patients was weaker comparing with healthy controls and during viscous swallows. The peristaltic function of distal esophagus in GERD was probably related to mucosal break rather than acid exposure. Key Word(s): 1. GERD; 2. HRM; 3. NERD; Presenting Author: JIAYUAN ZHUANG Additional Authors: ZEHAO ZHUANG, DUPENG TANG, LIBIN LI, YILIN ZEN, JINGWEN SUN, FANGMING ZOU, JINGJING WEI Corresponding Author: ZEHAO ZHUANG Affiliations: The college of nurse, Fujian Medical University; Department of Gastroenterology, The first affiliated hospital of Fujian Medical University; Department of Gastroenterology,

Xiamen hospital of TCM; Department of Gastroenterology, Fuqing municipal hospital Objective: There are few data on the epidemiology of gastro-esophageal reflux disease (GERD) in Hakka population. This study was aimed medchemexpress to assess the prevalence of GERD symptoms in Hakka population and to evaluate the effects of GERD symptoms on health-related quality of life. Methods: A face-to-face interview was carried out using a validated Chinese Gastro-esophageal reflux disease Questionnaire (CGQ) to evaluate the prevalence of GERD symptoms in a selected Hakka population in Youding County, Fujian Province. A randomly clustered sampling of permanent inhabitants aged 18 to 82 years was carried out in this Hakka’s community. The effects of GERD symptoms on health-related quality of life were evaluated by SF-36 (Chinese version). Results: A total of 203 residents (104 M, 99 F) were investigated. Median age of the responders was 43 years; while the response rate was 97.6%.

91 ± 1579 year) in our hospital 304 DBE examination after 83 or

91 ± 15.79 year) in our hospital. 304 DBE examination after 83 oral intakemirr and 74 times through the anus into the mirror 147 times into the mirror oral anal, in which patients received oral, anal examination, six patients were treated with oral examination, 1 patient received three times through the mouth into the mirror,and once mirror into oral and anal, 3 patients were treated with 2 rectal examination. 130 patients who was suspected small bowel disease patients (78 males,

find more 52 females, average age was 51.37 ± 17.50 year) the system iodine water angiography. Nine cases accept the DBE and the system iodine water angiography at the same time. By pathologic examination, laparotomy or conservative treatment results, compare two kinds of inspection methods for the detection rate and the diagnosis rate.in the suspected small bowel disease. Results: 291 routine the DBE checking patients in 141 patients with clinical manifestations of unexplained gastrointestinal bleeding, including one case with fever; 116 patients showed unexplained abdominal pain, three of which were accompanied by fever; 30 patients with clinical manifestations

of insufficiency of small intestine obstruction; 3 patients showed diarrhea; 1 cases PET-CT found multiple small bowel selleck kinase inhibitor metabolism increased requests for sexual DBE examination, three cases of postoperative gastrointestinal. 198 cases of endoscopic observation of patients found lesions, the overall detection rate was 68.0% (198/291), endoscopic diagnosis of small bowel 上海皓元 disease 16 small bowel tumors (mesenchymal tumors, lymphoma, lipoma, hemangioma), diverticulitis, polyps, non-specific inflammation, nonspecific ulcer, duplication narrow, small intestine, intestinal tuberculosis (Crohn’s disease?), Crohn’s disease (intestinal tuberculosis?), vascular malformations, small

bowel obstruction, hookworm disease, parenteral narrow lesions oppression and mucosal erosions, adhesions, diospyrobezoar. By biopsy or laparotomy 109 patients pathological diagnosis, pathology results are mainly benign and malignant tumors of small intestine (stromal tumor, adenocarcinoma, lymphoma, tubular adenoma, leiomyosarcoma, leiomyoma, villous adenomas, vascular, lipoma, carcinoid, metastatic carcinoma invasion), mucosa of chronic inflammation, diverticulitis, duplication, Crohn’s disease, ulcerative colitis with granulation tissue and scar formation, and vascular malformations. Combined endoscopic observation and histopathology results of 192 patients found that lesions The total positive diagnosis was 66.0% (192/291), 66 patients underwent surgical treatment. Water system iodine 130 patients underwent angiography, 31 patients with postoperative gastrointestinal. 71 cases found in patients with small bowel disease, the overall detection rate was 54.

91 ± 1579 year) in our hospital 304 DBE examination after 83 or

91 ± 15.79 year) in our hospital. 304 DBE examination after 83 oral intakemirr and 74 times through the anus into the mirror 147 times into the mirror oral anal, in which patients received oral, anal examination, six patients were treated with oral examination, 1 patient received three times through the mouth into the mirror,and once mirror into oral and anal, 3 patients were treated with 2 rectal examination. 130 patients who was suspected small bowel disease patients (78 males,

buy Deforolimus 52 females, average age was 51.37 ± 17.50 year) the system iodine water angiography. Nine cases accept the DBE and the system iodine water angiography at the same time. By pathologic examination, laparotomy or conservative treatment results, compare two kinds of inspection methods for the detection rate and the diagnosis rate.in the suspected small bowel disease. Results: 291 routine the DBE checking patients in 141 patients with clinical manifestations of unexplained gastrointestinal bleeding, including one case with fever; 116 patients showed unexplained abdominal pain, three of which were accompanied by fever; 30 patients with clinical manifestations

of insufficiency of small intestine obstruction; 3 patients showed diarrhea; 1 cases PET-CT found multiple small bowel this website metabolism increased requests for sexual DBE examination, three cases of postoperative gastrointestinal. 198 cases of endoscopic observation of patients found lesions, the overall detection rate was 68.0% (198/291), endoscopic diagnosis of small bowel MCE disease 16 small bowel tumors (mesenchymal tumors, lymphoma, lipoma, hemangioma), diverticulitis, polyps, non-specific inflammation, nonspecific ulcer, duplication narrow, small intestine, intestinal tuberculosis (Crohn’s disease?), Crohn’s disease (intestinal tuberculosis?), vascular malformations, small

bowel obstruction, hookworm disease, parenteral narrow lesions oppression and mucosal erosions, adhesions, diospyrobezoar. By biopsy or laparotomy 109 patients pathological diagnosis, pathology results are mainly benign and malignant tumors of small intestine (stromal tumor, adenocarcinoma, lymphoma, tubular adenoma, leiomyosarcoma, leiomyoma, villous adenomas, vascular, lipoma, carcinoid, metastatic carcinoma invasion), mucosa of chronic inflammation, diverticulitis, duplication, Crohn’s disease, ulcerative colitis with granulation tissue and scar formation, and vascular malformations. Combined endoscopic observation and histopathology results of 192 patients found that lesions The total positive diagnosis was 66.0% (192/291), 66 patients underwent surgical treatment. Water system iodine 130 patients underwent angiography, 31 patients with postoperative gastrointestinal. 71 cases found in patients with small bowel disease, the overall detection rate was 54.

In the present study, we report two novel causative mutations of

In the present study, we report two novel causative mutations of the F10 gene in a Chinese proband with severe FX deficiency EGFR inhibitor and mild clinical symptoms.

Furthermore, the molecular mechanisms of the two mutations were analysed. The proband, a 36-year-old Chinese male patient born from non-consanguineous parents, was diagnosed with FX deficiency in routine preoperative coagulation assay. He has exhibited numerous bleeding episodes since early childhood with recurrent epistaxis and gums bleeding after brushing his teeth and dental extraction. However, he had not experienced severe bleeding diathesis. One of his brothers had similar bleeding symptoms, but other family members had no history of bleeding. After informed consent, blood from the proband and family members was collected in 0.109 m trisodium citrate. FX:C assay was performed based on both prothrombin time (PT) and activated partial thromboplastin time (APTT) using

a one-stage clotting method on ACL-TOP automatic coagulometer (HemosILTM, IL, USA). FX amidolytic activity based on RVV was performed using a chromogenic assay kit (Hyphen Biomed, Neucille suroise, France) according to the manufacturer’s instructions. FX:Ag level was measured with a sandwich enzyme-linked immunoadsorbent assay (ELISA) using rabbit anti-human polyclonal FX antibody (Dako, Glostrup, Denmark) as a capture antibody, and horseradish peroxidase (HRP)

conjugated antibody (Dako) as a 上海皓元 detection antibody. Both FX:C and FX:Ag values are expressed Epacadostat supplier as the percentage of pooled plasma levels obtained from 30 healthy, unrelated individuals. Screening for inhibitors was performed by APTT and PT mixing assays. Genomic DNA of the proband and family members was extracted from peripheral blood leucocytes using a standard protocol. Genetic defect analysis of the F10 gene was performed as previously described [3]. TA-cloning with the pMD19-T Simple vector (TaKaRa, Shiga, Japan) and DNA sequencing were used to detect for the heterozygous deletion. All variants were confirmed by reverse sequencing using a second amplicon. The variant was reported in accordance with standard international nomenclature guidelines as recommended by the Human Genome Variation Society (HGVS, http://www.hgvs.org/mutnomen/recs.html) with nucleotide +1 as the A of the ATG translation initiation codon. The genomic DNA (GenBank:12738260) and cDNA (GenBank: M57285) sequences of the F10 gene were used as reference sequences. Ectopic transcription was used to analyse the splice pattern of the IVS5+1G>A mutation in the F10 gene. Briefly, total RNA of the proband and one healthy control was isolated from peripheral leucocytes using the TRIzol reagent (Invitrogen, Carlsbad, CA, USA).

On the other hand, the exacerbated inflammatory response could ju

On the other hand, the exacerbated inflammatory response could just be secondary to increased hepatic lipid accumulation in ethanol-fed

lipin-1LKO mice. Up-regulation of hepatic proinflammatory cytokines and excess production of reactive oxygen species (ROS) in lipin-1LKO mice are likely to contribute to markedly elevated serum makers of liver injury. Additional studies evaluating the ability of lipin-1 to repress the activity of transcriptional factors such as NFATc4 or NF-κB and to attenuate the production of cytokines or ROS in response to LPS or ethanol in Kupffer cells are currently under investigation in our laboratory. The Lieber-DeCarli liquid diets enriched in polyunsaturated fat promotes ethanol-induced liver injury in rodents.[1] Our present study used a modified Lieber-DeCarli low-fat ethanol-containing liquid diet.[17] It find more is possible that hepatic lipin-1 may be influenced by dietary fat and composition. We are currently investigating the effects of dietary fat and composition on ethanol-mediated impairments of lipin-1. The present study demonstrates that ethanol metabolism by

way of ADH and ALDH2 induces nucleocytoplasmic shuttling of lipin-1α, inhibiting PGC-1α activity and causing fat accumulation in cultured hepatocytes. These in vitro findings further support the notion that depletion of hepatic nuclear lipin-1 in lipin-1LKO mice may largely contribute to the drastic liver responsiveness to ethanol challenge. The role of hepatic ethanol metabolism-induced production of metabolites, redox RO4929097 state shift, or ROS in regulation

of lipin-1α nucleocytoplasmic shuttling merits investigation. In summary, using liver-specific lipin-1-null mice fed an ethanol-containing diet, we demonstrated for the first time that liver-specific deletion of lipin-1 leads to the rapid onset and progression of alcoholic steatohepatitis, providing novel insights into the biological MCE function of lipin-1 in alcoholic steatohepatitis. Our present findings suggest that the development of nutritional or pharmacological agents to enhance nuclear lipin-1 activity could be a promising approach toward developing new options for the prevention and treatment of human alcoholic steatohepatitis. Additional Supporting Information may be found in the online version of this article. “
“Crohn’s disease (CD) is a multifactorial disorder with a pivotal role of the genetic component. A single nucleotide polymorphism in heat shock protein 70-2 (HSP70-2) has been shown to be associated with a severe clinical course in CD. The purpose of this study was to identify associations between the HSP70-2 polymorphism and the clinical courses of CD in the Chinese population. One hundred patients with CD and 190 healthy individuals were genotyped for the HSP70-2 PstI polymorphism by restriction fragment length polymorphism analysis. The genotype frequency of the PstI polymorphism did not differ between patients and controls.

The latter will be less heterogenous (with less force peaks) with

The latter will be less heterogenous (with less force peaks) with an increasing proportion of low-angle enamel ridges. While the validity of these explanations will have to be tested in further studies,

the enamel ridge alignment represents a clear signal that deviates from an arbitrary distribution and hence most likely represents a functional adaptation. “
“Between the Middle Jurassic and Holocene, birds evolved an enormous diversity of behaviours. The distribution and antiquity of these behaviours is difficult to establish given a relatively poor fossil record. Rare crop, stomach and gut contents typically reveal diets consistent with morphology but stem-members of some lineages (including Cariamae and Coraciiformes) seem to have been different in ecology from their extant relatives. Most of our ideas about the behaviour Microtubule Associated inhibitor of fossil birds are based on analogy Navitoclax solubility dmso (with skull form, limb proportions and claw curvature being used to guide hypotheses). However, this has limitations given that some extinct taxa lack extant analogues and that some extant taxa do not behave as predicted by osteology. Reductionist methods have been used to test predation style and running ability in fossil taxa including moa, Gastornis and phorusrhacids. Virtually nothing is

known of nesting and nest-building behaviour but colonial nesting is known from the Cretaceous onwards. Rare vegetative nests demonstrate

modern nest-building from the Eocene onwards. Ornamental rectrices indicate that sexually driven display drove some aspects of feather evolution and evidence for loud vocal behaviour and intraspecific combat is known for some taxa. Our knowledge of fossil bird behaviour indicates that ‘modern’ behaviours are at least as old as crown birds. Stem-members of extant lineages, however, may sometimes or often have differed from extant taxa. “
“This paper presents an analysis of molar occlusal morphology and its relation to diet in modern bovids. The work develops previous research by analysing samples from 86 species from all major subfamilies and medchemexpress from across their geographical distribution. Molar surfaces are characterized by the length, thickness and shape of enamel formations. Discriminant function analysis (DFA) is used to characterize the dental anatomy of each group and permits interpretations as to the selective pressures governing occlusal form. Grazers and most browsers are very different and distinguishable, the former possessing long and thickened enamel with a bimodal distribution of central ridge enamel alignment. Frugivorous duikers possess thickened enamel and large surface areas, traits interpreted as adaptations for hard-object feeding.

1, 95% CI = 64–142, P < 00001) Central obesity, defined as wa

1, 95% CI = 6.4–14.2, P < 0.0001). Central obesity, defined as waist circumference > 80 cm in women and > 90 cm in men, was another independent risk factor of unreliable LSM (OR = 1.3, buy LBH589 95% CI = 1.0–1.6, P = 0.04) and LSM failure (OR = 5.8, 95% CI = 2.9–11.5, P < 0.0001). Conclusion:  BMI ≥ 28.0 kg/m2 and central obesity were the independent risk factors of unreliable LSM and LSM failure in Chinese, and these rates

were significantly higher in patients with extreme BMI. “
“Patients with chronic hepatitis C with partial virologic response or nonresponse to interferon-based therapies can experience treatment-related improvements in liver histology. This retrospective analysis assessed the histologic response to treatment in patients with varying degrees of virologic response (sustained virologic response [SVR], breakthrough, relapse, or nonresponse), time to hepatitis C virus (HCV) RNA undetectability, and duration of viral suppression. Patients (HCV

genotypes 1-6) with baseline and follow-up liver biopsies from eight phase 2 to phase 4 interferon-based trials were analyzed. Selumetinib Blinded biopsies were evaluated by a single pathologist. Improvements or worsening of METAVIR necroinflammatory activity and fibrosis were defined as increase or decrease of ≥1 grading category from baseline to 24 weeks after end of treatment. A majority of the 1571 patients with paired biopsy data were white, male, with HCV genotype 1/4, baseline HCV RNA levels >800,000 IU/mL, and baseline alanine aminotransferase levels ≤3 × upper limit of the normal medchemexpress range; mean baseline activity and fibrosis scores were 1.8 and 1.7, respectively.

Overall, 80% of patients received peginterferon alfa-2a monotherapy or peginterferon alfa-2a/ribavirin combination therapy. Mean treatment duration was 46 weeks. There was a positive correlation between the degree of virologic response and improvements in METAVIR activity and fibrosis, and an inverse correlation with worsening activity and fibrosis (all comparisons, P < 0.0001). Patients with SVR had the greatest histologic benefit. As a combined group, relapsers and patients with breakthrough had significantly greater benefits than nonresponders (activity, P = 0.0001; fibrosis, P = 0.003). Consistent with these results, a better histologic response was correlated with a shorter time to undetectable HCV RNA and a longer duration of viral suppression (all comparisons, P < 0.0001). Conclusion: In patients with chronic hepatitis C who were treated with interferon-based therapies, histologic benefits may be observed even in the absence of an SVR. (HEPATOLOGY 2010;) Although viral clearance is the primary goal of hepatitis C virus (HCV) treatment, improvements in liver histology, characterized by decreases in inflammatory and fibrosis scores, have also been documented in numerous clinical trials.

In terms of CV risk, factor deficiency may not be protective The

In terms of CV risk, factor deficiency may not be protective. The problem is that we just do not know exactly what happens because the current

literature is contradictory. HIV and hepatitis C are major confounders in our patient population and they FK228 are likely to remain with us for several years to come. Overall, there are very few studies and we lack the scientific best evidence which can help create best practice guidelines. Some immediate challenges ahead: 1  What is the optimal antiplatelet therapy (single vs. double)? While morbidity associated with changes in bone mineral density (BMD) clearly increases with age it is not a disorder restricted to the elderly patients, and osteoporosis can occur at all ages. Osteoporosis is a systemic disease characterized by low BMD and microarchitectural deterioration of bone tissue. A decrease in BMD, as evidenced by a low peak bone mass, results from excessive bone resorption once peak bone mass has been attained and decreased

bone formation during remodelling. Figure 1 shows how bone mass is attained over time in healthy men and women, with peak levels being achieved by the age of 30 years. The impact of ageing and specific events such as menopause is also highlighted. Reductions in BMD produce bone tissue which becomes increasingly fragile with an increased risk of fracture, most notably in the hip, vertebrae and wrist. There are a number of factors that contribute to low BMD/osteoporosis including non-modifiable genetic factors (race, gender) and modifiable environmental factors (exercise, smoking, alcohol, vitamin D and calcium). In addition JQ1 supplier medchemexpress to these, there is a wide range of risk factors such as age, female gender, menopause, certain hormone/metabolic related disorders, steroid therapy and so forth [25–27]. With regards its prevalence: 34 million Americans have low bone mass and 10 million are estimated to have osteoporosis [25,26]. Furthermore, 75 million people in the US, Europe and Japan are affected by the disorder and one in five

men >50 years of age will experience an osteoporosis-related fracture. Osteoporosis is associated with significant morbidity and every 30 s someone in the European Union suffers an osteoporosis-related hip fracture. Prognosis after a hip fracture is poor: the mortality rate within 1 year is about 20%, 30% will have permanent disability, 40% will require assistance with walking and 80% will be unable to perform at least one independent activity of daily living [25,26]. Osteoporosis causes more disability than all cancers other than lung cancer, and the ensuing significant morbidity leads to loss of normal functioning, loss of independence, high levels of pain and impaired quality of life and overall well-being [25,26]. Peak bone mass is a primary determinant of osteoporosis risk and weight bearing exercises are crucial to help bone tissue/structure development.

In terms of CV risk, factor deficiency may not be protective The

In terms of CV risk, factor deficiency may not be protective. The problem is that we just do not know exactly what happens because the current

literature is contradictory. HIV and hepatitis C are major confounders in our patient population and they PKC412 are likely to remain with us for several years to come. Overall, there are very few studies and we lack the scientific best evidence which can help create best practice guidelines. Some immediate challenges ahead: 1  What is the optimal antiplatelet therapy (single vs. double)? While morbidity associated with changes in bone mineral density (BMD) clearly increases with age it is not a disorder restricted to the elderly patients, and osteoporosis can occur at all ages. Osteoporosis is a systemic disease characterized by low BMD and microarchitectural deterioration of bone tissue. A decrease in BMD, as evidenced by a low peak bone mass, results from excessive bone resorption once peak bone mass has been attained and decreased

bone formation during remodelling. Figure 1 shows how bone mass is attained over time in healthy men and women, with peak levels being achieved by the age of 30 years. The impact of ageing and specific events such as menopause is also highlighted. Reductions in BMD produce bone tissue which becomes increasingly fragile with an increased risk of fracture, most notably in the hip, vertebrae and wrist. There are a number of factors that contribute to low BMD/osteoporosis including non-modifiable genetic factors (race, gender) and modifiable environmental factors (exercise, smoking, alcohol, vitamin D and calcium). In addition check details 上海皓元 to these, there is a wide range of risk factors such as age, female gender, menopause, certain hormone/metabolic related disorders, steroid therapy and so forth [25–27]. With regards its prevalence: 34 million Americans have low bone mass and 10 million are estimated to have osteoporosis [25,26]. Furthermore, 75 million people in the US, Europe and Japan are affected by the disorder and one in five

men >50 years of age will experience an osteoporosis-related fracture. Osteoporosis is associated with significant morbidity and every 30 s someone in the European Union suffers an osteoporosis-related hip fracture. Prognosis after a hip fracture is poor: the mortality rate within 1 year is about 20%, 30% will have permanent disability, 40% will require assistance with walking and 80% will be unable to perform at least one independent activity of daily living [25,26]. Osteoporosis causes more disability than all cancers other than lung cancer, and the ensuing significant morbidity leads to loss of normal functioning, loss of independence, high levels of pain and impaired quality of life and overall well-being [25,26]. Peak bone mass is a primary determinant of osteoporosis risk and weight bearing exercises are crucial to help bone tissue/structure development.

In the general population, the distribution of chronic tension-ty

In the general population, the distribution of chronic tension-type headache and chronic migraine is fairly equal, but in medical practice chronic migraine accounts for the vast majority of patients with chronic daily headache. The first step in the management of chronic daily headache, whether it concerns chronic tension-type headache or chronic migraine, is to identify the potential overuse of analgesic and/or vasoconstrictor medications. Once medication overuse, if present, HDAC inhibitor is dealt with, preventive treatment is initiated with medications and/or non-pharmacological

strategies. Chronic migraine patients who are refractory to or do not tolerate those treatments, however, may end up taking a triptan frequently, if not daily. This is illustrated by the following case history, BMN 673 clinical trial which in turn is followed by questions regarding the safety of daily or almost-daily triptan use in the context of medication-overuse headache and cardiovascular safety concerns. These issues will be addressed in this expert opinion article. Daily triptan use for chronic migraine is probably not all that rare. A retrospective audit was carried out in 9 general-medicine practices in the United Kingdom and

Ireland,[2] examining all patients 18 years and older who had a recorded diagnosis of migraine and had been prescribed a triptan during a 1-year period. A total of 77,715 patients were registered 上海皓元 with the 9 participating practices, of whom 3672 (4.7%) had a recorded diagnosis of migraine and 360 met the audit inclusion criteria. Of these 360 patients, 7.4% had received prescriptions for at least 150 tablets during the year of the audit, which, if 1 tablet is taken daily, means an average triptan use of every other day at a minimum. A French, population-based, observational study of a regional health care insurance database covering medication use of 5.3 million people, that is, 8% of the population, revealed that over a period of 18 months, 0.04% of the population or 2.4% of

all triptan users obtained 60 daily triptan doses per 3 months, averaging a daily triptan dose every 1 day.[3] If the British and French data presented above can be generalized, they suggest that roughly 5% of all triptan-using migraineurs take a triptan, on average, at least 15 days per month, this is, for abortive treatment of chronic migraine. This 50-year-old woman has a history of migraine without aura since her teens. The headaches gradually increased in frequency over time and have been daily or almost daily for the last 5 years. She tried multiple preventive medications, including topiramate, amitriptyline, propranolol, onabotulinumtoxinA, divalproex sodium, gabapentin, zonisamide, and memantine, either alone or in combination, without benefit or side effects.