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Sample records for acute ischemic colitis

  1. Ischemic Colitis

    PubMed Central

    FitzGerald, James F.; Hernandez III, Luis O.

    2015-01-01

    Most clinicians associate ischemic colitis with elderly patients who have underlying cardiovascular comorbidities. While the majority of cases probably occur in this population, the disease can present in younger patients as a result of different risk factors, making the diagnosis challenging. While a majority of patients respond to medical management, surgery is required in approximately 20% of the cases and is associated with high morbidity and mortality. PMID:26034405

  2. Surgical Management and Outcome in Acute Ischemic Colitis

    PubMed Central

    Beck, David E.; de Aguilar-Nascimento, Jose Eduardo

    2011-01-01

    Background Ischemic colitis is the most common form of gastrointestinal ischemia. Patients usually present with abdominal discomfort and bloody diarrhea. Treatment is contingent on the severity of disease. Mucosal/nongangrenous ischemia requires only supportive measures and medical management, whereas transmural/gangrenous ischemia may require prompt surgical intervention. The purpose of this study was to review the surgical management of ischemic colitis in a tertiary referral center. Methods Retrospective chart review of patients with ischemic colitis managed from 1995 to 2000 at the Ochsner Foundation Hospital. Results Forty-eight patients were identified. Ten of these had disease significant enough to require surgery (21%) and are the basis of this review. Eight were women, and the mean age was 71.4 years (range 43-85 years). Distribution of the disease was the right colon in 4 cases, pancolitis in 3, sigmoid in 2, and the left colon in 1. Nine patients underwent bowel resection: primary anastomosis in 3 and creation of a stoma in the other 6 (5 ileostomies and 1 transverse colostomy). Follow-up ranged from 3 days to 13.8 years. One patient died perioperatively. Conclusion Surgical management produced good results. PMID:21960763

  3. Acute ischemic colitis secondary to air embolism after diving.

    PubMed

    Payor, Austin Daniel; Tucci, Veronica

    2011-01-01

    Ischemic colitis (IC) secondary to air embolism from decompression sickness or barotrauma during diving is an extremely rare condition. After extensive review of the available literature, we found that there has been only one reported case of IC secondary to air embolism from diving. Although air embolization from diving and the various medical complications that follow have been well documented, the clinical manifestation of IC from an air embolism during diving is very rare and thus far unstudied. Common symptoms of IC include abdominal pain, bloody or non-bloody diarrhea or nausea or vomiting or any combination. Emergency physicians and Critical Care specialists should consider IC as a potential diagnosis for a patient with the above-mentioned symptoms and a history of recent diving. We report a case of IC from air embolism after a routine dive to 75 feet below sea level in a 53-year-old White female who presented to a community Emergency Department complaining of a 2-day history of diffuse abdominal pain and nausea. She was diagnosed by colonoscopy with biopsies and treated conservatively with antibiotics, bowel rest, and a slow advancement in diet.

  4. Acute ischemic colitis during scuba diving: report of a unique case.

    PubMed

    Goumas, Konstantinos; Poulou, Androniki; Tyrmpas, Ioannis; Dandakis, Dimitrios; Bartzokis, Stavros; Tsamouri, Magdalini; Barbati, Kalipso; Soutos, Dimitrios

    2008-05-28

    The presentation of clinical symptoms due to decompression during diving, varies significantly, as mainly minor disturbances for the gastrointestinal tract in particular have been reported. The following case debates whether diving can cause severe symptoms from the gastrointestinal system. We describe a clinical case of ischemic colitis presented in a 27-year-old male, who manifested abdominal pain while in the process of scuba diving 20 meters undersea, followed by bloody diarrhoea as soon as he ascended to sea level. Taking into account his past medical history, the thorough, impeccable clinical and laboratory examinations and presence of no other factors predisposing to ischemia of the colon, we assume that a possible relationship between diving conditions and the pathogenesis of ischemic colitis may exist. This unusual case might represent a hematologic manifestation of decompression sickness, due to increased coagulability and/or transient air emboli, occurring during a routine scuba diving ascent to sea level.

  5. Magnetic resonance imaging: Is there a role in clinical management for acute ischemic colitis?

    PubMed Central

    Mazzei, Maria Antonietta; Guerrini, Susanna; Cioffi Squitieri, Nevada; Imbriaco, Giusi; Chieca, Raffaele; Civitelli, Serenella; Savelli, Vinno; Mazzei, Francesco Giuseppe; Volterrani, Luca

    2013-01-01

    AIM: To validate the utility of magnetic resonance imaging (MRI) for the clinical management of acute ischemic colitis (IC). METHODS: This is a magnetic resonance (MR) prospective evaluation of 7 patients who were proved to have acute IC on the basis of clinical, endoscopic and computed tomography (CT) findings and who were imaged in our institution between February 2011 and July 2012. The mean age of the patients was 72.28 years. Abdominal CTs were obtained using a 64-detector row configuration for all patients with un-enhanced and contrast-enhanced scans, in the late arterial phase (start delay 45-50 s) and in the portal venous phase (start delay 70-80 s). The MR examinations were performed using a 1.5T superconducting magnet, using Fast Imaging Employing Steady State Acquisition and T2-weighted fast-recovery fast-spin echo sequences in axial and coronal plane. CT and MRI examinations were analysed for the presence of colonic abnormalities and associated findings. RESULTS: Segmental involvement was seen in 6 patients (85.71%), with a mean length of involvement of 412 mm (range 145.5-1000 mm). Wall thickness varied between 6 mm and 17.5 mm (mean 10.52 mm) upon CT examinations and from 5 to 15 mm (mean 8.8 mm) upon MR examinations. The MRI appearance of the colonic wall varied over the time: Type I appearance with a 3 layer sandwich sign was seen in 5 out of 12 examinations (41.66%), patients underwent MR within a mean of 36 h (ranging from 1 to 54 h) after the CT examination. Type II and III appearance with a 2 layer sign, was seen in 4 examinations (33.33%), patients underwent MR within a mean of 420.5 h (ranging from 121 to 720 h) after the CT examination. In the remaining three MRI examinations, performed within a mean of 410 h (ranging from 99.5 to 720 h) the colonic wall appeared normal. CONCLUSION: MRI, only using precontrast images, may be used as a substitute for invasive procedures in diagnosis and follow-up of acute IC. PMID:23483002

  6. Ischemic colitis associated with acute carbon monoxide poisoning--a case report.

    PubMed

    Weaver, Lindell K; Deru, Kayla

    2016-01-01

    Carbon monoxide (CO) poisoning is common, but it has rarely been reported to cause ischemic colitis. In this case, a 34-year-old female with depression presented to an emergency department after a period of unconsciousness, with urinary and bowel incontinence, following exposure to car exhaust. Her carboxyhemoglobin level was 23%. She had metabolic acidosis. She was transferred to our facility for hyperbaric oxygen treatment, where she had intractable nausea/vomiting with abdominal pain and bright-red bleeding per rectum. She exhibited lower abdominal tenderness and hypoactive bowel sounds. Vital signs were: temperature 36.8 degrees C; blood pressure 137/ 86 mmHg; heart rate 114 beats/minute; respiratory rate 28 breaths/minute. The patient's electrocardiogram showed sinus tachycardia with T-wave inversions in leads I, aVL and V3-V6. The troponin I level peaked at 3.7 ng/ml. Echocardiogram showed a reduced ejection fraction of 30%-35%, with akinesis in the posterior lateral and distal anterior distributions. Computed tomography of the abdomen revealed diffuse colonic mural thickening, supporting mesenteric ischemia. Sigmoidoscopy showed edematous friable pale mucosa from rectum to distal sigmoid colon. Hyperbaric oxygen was deferred based on the patient's status. Over three days, the initial hematochezia progressed to melena and then resolved. Adenosine cardiac stress MRI was normal. She was transferred to the psychiatry service and discharged four days later. Four years later, she has no gastrointestinal, cardiac or cognitive problems. PMID:27265995

  7. Ischemic colitis associated with acute carbon monoxide poisoning--a case report.

    PubMed

    Weaver, Lindell K; Deru, Kayla

    2016-01-01

    Carbon monoxide (CO) poisoning is common, but it has rarely been reported to cause ischemic colitis. In this case, a 34-year-old female with depression presented to an emergency department after a period of unconsciousness, with urinary and bowel incontinence, following exposure to car exhaust. Her carboxyhemoglobin level was 23%. She had metabolic acidosis. She was transferred to our facility for hyperbaric oxygen treatment, where she had intractable nausea/vomiting with abdominal pain and bright-red bleeding per rectum. She exhibited lower abdominal tenderness and hypoactive bowel sounds. Vital signs were: temperature 36.8 degrees C; blood pressure 137/ 86 mmHg; heart rate 114 beats/minute; respiratory rate 28 breaths/minute. The patient's electrocardiogram showed sinus tachycardia with T-wave inversions in leads I, aVL and V3-V6. The troponin I level peaked at 3.7 ng/ml. Echocardiogram showed a reduced ejection fraction of 30%-35%, with akinesis in the posterior lateral and distal anterior distributions. Computed tomography of the abdomen revealed diffuse colonic mural thickening, supporting mesenteric ischemia. Sigmoidoscopy showed edematous friable pale mucosa from rectum to distal sigmoid colon. Hyperbaric oxygen was deferred based on the patient's status. Over three days, the initial hematochezia progressed to melena and then resolved. Adenosine cardiac stress MRI was normal. She was transferred to the psychiatry service and discharged four days later. Four years later, she has no gastrointestinal, cardiac or cognitive problems.

  8. [Ischemic colitis: an uncommon manifestation in systemic lupus erythematosus].

    PubMed

    Medina, Viviana; Bulgach, Valeria; Lagandara, Pamela; Berner, Enrique

    2013-04-01

    We present the case of an adolescent with ischemic colitis, an infrequent pathology in this age group, worsened in the presence of systemic lupus erythematosus (SLE). The patient, aged 20, was diagnosed SLE at 6. She consulted for fever, abdominal pain in the side and right iliac fossa and diarrhea lasting 48 hours. It was assumed as acute gastroenteritis but given the persistent pain, incoercible vomiting and abdominal distension she was hospitalized. The abdominal X-ray showed distended loops, abundant feces, without air-fluid levels. The ultrasound showed erosions and ulcerations, edema and bleeding in the descending colon submucosal layer. The CT scan evidenced an ischemic lesion in the right colon. Ischemic colitis is a severe condition, infrequent in young individuals. Signs, symptoms, abdominal CT scan and colonoscopy are the elements of choice for the diagnosis.

  9. [Ischemic colitis: an uncommon manifestation in systemic lupus erythematosus].

    PubMed

    Medina, Viviana; Bulgach, Valeria; Lagandara, Pamela; Berner, Enrique

    2013-04-01

    We present the case of an adolescent with ischemic colitis, an infrequent pathology in this age group, worsened in the presence of systemic lupus erythematosus (SLE). The patient, aged 20, was diagnosed SLE at 6. She consulted for fever, abdominal pain in the side and right iliac fossa and diarrhea lasting 48 hours. It was assumed as acute gastroenteritis but given the persistent pain, incoercible vomiting and abdominal distension she was hospitalized. The abdominal X-ray showed distended loops, abundant feces, without air-fluid levels. The ultrasound showed erosions and ulcerations, edema and bleeding in the descending colon submucosal layer. The CT scan evidenced an ischemic lesion in the right colon. Ischemic colitis is a severe condition, infrequent in young individuals. Signs, symptoms, abdominal CT scan and colonoscopy are the elements of choice for the diagnosis. PMID:23568076

  10. Amphetamine-related ischemic colitis causing gastrointestinal bleeding

    PubMed Central

    Panikkath, Deepa

    2016-01-01

    A 43-year-old woman presented with acute lower intestinal bleeding requiring blood transfusion. Multiple initial investigations did not reveal the cause of the bleeding. Colonoscopy performed 2 days later showed features suggestive of ischemic colitis. On detailed history, the patient admitted to using amphetamines, and her urine drug screen was positive for them. She was managed conservatively and advised not to use amphetamines again. She did not have any recurrence on 2-year follow-up. PMID:27365888

  11. Isolated naratriptan-associated ischemic colitis

    PubMed Central

    Nissan, George; Chaudhry, Priyanka; Rangasamy, Priya; Mudrovich, Steven

    2016-01-01

    We report a 41-year-old woman who developed histology- and colonoscopy-proven ischemic colitis with the use of naratriptan not exceeding the maximum 2 doses a day and 3 days per week and without a known medical or cardiovascular history. By exclusion of other causes of colonic ischemia, naratriptan was considered the sole causal agent. Discontinuation of naratriptan resulted in a complete clinical recovery. To date, our patient is the youngest known patient to develop ischemic colitis on isolated naratriptan in the setting of no known medical risk factors or predisposing medical condition. Even though triptans are commonly used for the abortive treatment of migraine headaches, such a reported side effect is rare; however, careful assessment and individual patient-based treatment is advised.

  12. Isolated naratriptan-associated ischemic colitis

    PubMed Central

    Nissan, George; Chaudhry, Priyanka; Rangasamy, Priya; Mudrovich, Steven

    2016-01-01

    We report a 41-year-old woman who developed histology- and colonoscopy-proven ischemic colitis with the use of naratriptan not exceeding the maximum 2 doses a day and 3 days per week and without a known medical or cardiovascular history. By exclusion of other causes of colonic ischemia, naratriptan was considered the sole causal agent. Discontinuation of naratriptan resulted in a complete clinical recovery. To date, our patient is the youngest known patient to develop ischemic colitis on isolated naratriptan in the setting of no known medical risk factors or predisposing medical condition. Even though triptans are commonly used for the abortive treatment of migraine headaches, such a reported side effect is rare; however, careful assessment and individual patient-based treatment is advised. PMID:27695179

  13. Ischemic Colitis in an Endurance Runner

    PubMed Central

    Grames, Chase; Berry-Cabán, Cristóbal S.

    2012-01-01

    A 20-year-old female running the Marine Corps Marathon developed diarrhea at mile 12. After finishing the race she noted that she was covered in bloody stool. A local emergency department suspected ischemic colitis. After discharge, her primary care physician instructed her to discontinue the use of all nonsteroidal anti-inflammatory drugs. Her symptoms resolved and she returned to running without any complications. This paper describes the pathophysiology, diagnostic approach, and management options. PMID:23091744

  14. Fucoidan Extracts Ameliorate Acute Colitis.

    PubMed

    Lean, Qi Ying; Eri, Rajaraman D; Fitton, J Helen; Patel, Rahul P; Gueven, Nuri

    2015-01-01

    Inflammatory bowel diseases (IBD), such as ulcerative colitis and Crohn's disease, are an important cause of morbidity and impact significantly on quality of life. Overall, current treatments do not sustain a long-term clinical remission and are associated with adverse effects, which highlight the need for new treatment options. Fucoidans are complex sulphated, fucose-rich polysaccharides, found in edible brown algae and are described as having multiple bioactivities including potent anti-inflammatory effects. Therefore, the therapeutic potential of two different fucoidan preparations, fucoidan-polyphenol complex (Maritech Synergy) and depyrogenated fucoidan (DPF) was evaluated in the dextran sulphate sodium (DSS) mouse model of acute colitis. Mice were treated once daily over 7 days with fucoidans via oral (Synergy or DPF) or intraperitoneal administration (DPF). Signs and severity of colitis were monitored daily before colons and spleens were collected for macroscopic evaluation, cytokine measurements and histology. Orally administered Synergy and DPF, but not intraperitoneal DPF treatment, significantly ameliorated symptoms of colitis based on retention of body weight, as well as reduced diarrhoea and faecal blood loss, compared to the untreated colitis group. Colon and spleen weight in mice treated with oral fucoidan was also significantly lower, indicating reduced inflammation and oedema. Histological examination of untreated colitis mice confirmed a massive loss of crypt architecture and goblet cells, infiltration of immune cells and oedema, while all aspects of this pathology were alleviated by oral fucoidan. Importantly, in this model, the macroscopic changes induced by oral fucoidan correlated significantly with substantially decreased production of at least 15 pro-inflammatory cytokines by the colon tissue. Overall, oral fucoidan preparations significantly reduce the inflammatory pathology associated with DSS-induced colitis and could therefore represent

  15. Cytomegalovirus colitis followed by ischemic colitis in a non-immunocompromised adult: a case report.

    PubMed

    Hasegawa, Tsuyoshi; Aomatsu, Kazuki; Nakamura, Masanori; Aomatsu, Naoki; Aomatsu, Keiho

    2015-03-28

    We report a rare case of cytomegalovirus (CMV) colitis followed by severe ischemic colitis in a non-immunocompromised patient. An 86-year-old woman was admitted after experiencing episodes of vomiting and diarrhea. The next day, hematochezia was detected without abdominal pain. The initial diagnosis of ischemic colitis was based on colonoscopy and histological findings. The follow-up colonoscopy revealed a prolonged colitis. Immunohistochemical staining detected CMV-positive cells following conservative therapy. Intravenous ganciclovir therapy led to successful healing of ulcers and disappearance of CMV-positive cells. The prevalence of CMV infection is common in adults. CMV colitis is relatively common in immunocompromised patients; however, it is rare in immunocompetent patients. In our case, CMV infection was allowed to be established due to the disruption of the colonic mucosa by the prior severe ischemic colitis. Our experience suggests that biopsies may be necessary to detect CMV and the prompt management of CMV colitis should be instituted when intractable ischemic colitis is observed.

  16. "Cat scratch colon" in a patient with ischemic colitis.

    PubMed

    Park, Eui Ju; Lee, Joon Seong; Lee, Tae Hee; Choi, Dae Han; Kim, Eui Bae; Jeon, Seong Ran; Hong, Su Jin; Kim, Jin-Oh

    2015-03-01

    "Cat scratch colon" is a gross finding characterized by hemorrhagic mucosal scratches on colonoscopy. It is usually associated with a normal colon and is rarely associated with collagenous colitis. In a previous report, cat scratch colon was noted in the cecum and ascending colon, but has also been observed in the distal transverse colon. The patient in this study was also diagnosed with ischemic colitis that may have played a role in the development of cat scratch colon.

  17. Acute ischemic stroke update.

    PubMed

    Baldwin, Kathleen; Orr, Sean; Briand, Mary; Piazza, Carolyn; Veydt, Annita; McCoy, Stacey

    2010-05-01

    Stroke is the third most common cause of death in the United States and is the number one cause of long-term disability. Legislative mandates, largely the result of the American Heart Association, American Stroke Association, and Brain Attack Coalition working cooperatively, have resulted in nationwide standardization of care for patients who experience a stroke. Transport to a skilled facility that can provide optimal care, including immediate treatment to halt or reverse the damage caused by stroke, must occur swiftly. Admission to a certified stroke center is recommended for improving outcomes. Most strokes are ischemic in nature. Acute ischemic stroke is a heterogeneous group of vascular diseases, which makes targeted treatment challenging. To provide a thorough review of the literature since the 2007 acute ischemic stroke guidelines were developed, we performed a search of the MEDLINE database (January 1, 2004-July 1, 2009) for relevant English-language studies. Results (through July 1, 2009) from clinical trials included in the Internet Stroke Center registry were also accessed. Results from several pivotal studies have contributed to our knowledge of stroke. Additional data support the efficacy and safety of intravenous alteplase, the standard of care for acute ischemic stroke since 1995. Due to these study results, the American Stroke Association changed its recommendation to extend the time window for administration of intravenous alteplase from within 3 hours to 4.5 hours of symptom onset; this recommendation enables many more patients to receive the drug. Other findings included clinically useful biomarkers, the role of inflammation and infection, an expanded role for placement of intracranial stents, a reduced role for urgent carotid endarterectomy, alternative treatments for large-vessel disease, identification of nontraditional risk factors, including risk factors for women, and newly published pediatric stroke guidelines. In addition, new devices for

  18. Ischemic colitis induced by the newly reformulated multicomponent weight-loss supplement Hydroxycut®

    PubMed Central

    Sherid, Muhammed; Samo, Salih; Sulaiman, Samian; Gaziano, Joseph H

    2013-01-01

    Ischemic colitis accounts for 6%-18% of causes of acute lower gastrointestinal bleeding. It is more often multifactorial and more common in elderly. Drugs are considered important causative agents of this disease with different mechanisms. In this paper, we describe a 37-year-old otherwise healthy female presented with sudden onset diffuse abdominal pain and bloody stool. Radiologic, colonoscopic and histopathologic findings were all consistent with ischemic colitis. Her only suspected factor was hydroxycut which she had been taking for a period of 1 mo prior to her presentation. Her condition improved uneventfully after cessation of hydroxycut, bowel rest, intravenous hydration, and antibiotics. This is a first case of ischemic colitis with clear relationship with hydroxycut use (Naranjo score of 7). Our case demonstrates the importance of questioning patients regarding the usage of dietary supplements; especially since many patients consider them safe and do not disclose their use voluntarily to their physicians. Hydroxycut has to be considered as a potential trigger for otherwise unexplained ischemic colitis. PMID:23596542

  19. [Ischemic colitis after renal transplantation:etiology and pathogenesis].

    PubMed

    Alperovich, G; Idiarte, L; Besasso, O; Avagnina, A

    2003-01-01

    Ischemic colitis is a well-recognized complication occurring in renal transplant recipients. It has often been associated with cytomegalovirus (CMV) vasculitis. However, the diagnosis of this pathology in the absence of CMV suggests that other etiological factors might be involved. Drugs inducing mesenteric vasoconstriction, such as non-steroidal anti-inflamatory drugs (NSAIDs) and cyclosporine could be related to this entity.

  20. Imaging acute ischemic stroke.

    PubMed

    González, R Gilberto; Schwamm, Lee H

    2016-01-01

    Acute ischemic stroke is common and often treatable, but treatment requires reliable information on the state of the brain that may be provided by modern neuroimaging. Critical information includes: the presence of hemorrhage; the site of arterial occlusion; the size of the early infarct "core"; and the size of underperfused, potentially threatened brain parenchyma, commonly referred to as the "penumbra." In this chapter we review the major determinants of outcomes in ischemic stroke patients, and the clinical value of various advanced computed tomography and magnetic resonance imaging methods that may provide key physiologic information in these patients. The focus is on major strokes due to occlusions of large arteries of the anterior circulation, the most common cause of a severe stroke syndrome. The current evidence-based approach to imaging the acute stroke patient at the Massachusetts General Hospital is presented, which is applicable for all stroke types. We conclude with new information on time and stroke evolution that imaging has revealed, and how it may open the possibilities of treating many more patients. PMID:27432672

  1. [Cerebrolysin for acute ischemic stroke].

    PubMed

    iganshina, L E; Abakumova, T R

    2013-01-01

    The review discusses existing evidence of benefits and risks of cerebrolysin--a mixture of low-molecular-weight peptides and amino acids derived from pigs' brain tissue with proposed neuroprotective and neurotrophic properties, for acute ischemic stroke. The review presents results of systematic search and analysis of randomised clinical trials comparing cerebrolysin with placebo in patients with acute ischemic stroke. Only one trial was selected as meeting quality criteria. No difference in death and adverse events between cerebrolysin and placebo was established. The authors conclude about insufficiency of evidence to evaluate the effect of cerebrolysin on survival and dependency in people with acute ischemic stroke.

  2. Passage of a sigmoid colon cast in a patient with ischemic colitis.

    PubMed

    Abe, Shinya; Yamaguchi, Hironori; Murono, Koji; Kanazawa, Takamitsu; Ishihara, Souichirou; Sunami, Eiji; Watanabe, Toshiaki

    2014-01-01

    Colon cast passage, which is the spontaneous passage of a full-thickness, infarcted colonic segment per rectum, is a rare occurrence. The main cause is acute ischemic colitis resulting from a circulation compromise. Most of the colon cast cases reported were secondary to abdominal aortic aneurysm repairs or colorectal surgery. We report a case of an 80-year-old woman with ischemic colitis who excreted a 20-cm colon cast. In most cases that involve a colon cast containing a muscle layer component, invasive therapy is required owing to colonic obstruction or stenosis. However, in the present case, the colon cast consisted only of a mucosa layer and was not associated with severe stenosis or obstruction; therefore, it was successfully treated by conservative therapy. Histologic examination of the colon segment may be crucial in determining the appropriate treatment.

  3. Clinical Characteristics of Ischemic Colitis According to Location

    PubMed Central

    Chang, Ho Jin; Chung, Chul Woon; Ko, Kwang Hyun

    2011-01-01

    Purpose The aim of this study was to analyze various clinical characteristics of ischemic colitis according to its location. Methods The medical records of 92 cases of gastrointestinal ischemic colitis (IC) diagnosed at Bundang CHA Hospital from 1995 to 2008 were reviewed and analyzed retrospectively. The patients were diagnosed by using colonoscopic biopsies or laparotomy findings. The patients were divided into two groups, right and left, according to the main involvement area of the IC at the embryologic boundary line of the distal transverse colon, and the two groups were compared as to clinical characteristics and co-morbid diseases. Results Left IC was present in 59 patients (64.1%) and right IC in 33 patients (35.9%). No differences between the two groups in terms of clinical characteristics, cardiovascular disease and diabetes mellitus were observed. However, in 16 cases with renal failure, 10 patient had right IC and 6 patients had left IC, and this difference had statistical significance (P = 0.014). Among the 16, the 11 patients requiring hemodialysis included 8 with right IC (24.2%) and 3 with left IC (5.1%; P = 0.009). Among the 19 cases of severe IC requiring surgical treatment or involving mortality, irrespective of surgery, 11 patients showed right IC and 8 patients showed left IC (P = 0.024). Conclusion Right-side ischemic colitis was significantly associated with renal failure and disease severity, so patients with right-side colon ischemia should be more carefully observed and managed. PMID:22259742

  4. [Pregnancy and acute ischemic stroke].

    PubMed

    Bereczki, Dániel

    2016-05-15

    Pregnancy-related ischemic strokes play an important role in both maternal and fetal morbidity and mortality. Changes in hemostaseology and hemodynamics as well as risk factors related to or independent from pregnancy contribute to the increased stroke-risk during gestation and the puerperium. Potential teratogenic effects make diagnostics, acute therapy and prevention challenging. Because randomized, controlled trials are not available, a multicenter registry of patients with gestational stroke would be desirable. Until definite guidelines emerge, management of acute ischemic stroke during pregnancy remains individual, involving experts and weighing the risks and benefits.

  5. Factors precipitating acute ulcerative colitis.

    PubMed

    Puri, A S; Chaubal, C C; Midha, Vandana

    2014-08-01

    Ulcerative colitis is characterized by mucosal inflammation of a variable length of the colon starting from the rectum. The precise etiopathogenesis is unknown but it occurs in genetically susceptible individuals who manifest an abnormal immunological response against gut commensal bacteria. The disease course is-characterized by multiple spontaneous relapses and remissions. Two pathogens namely CMV and C. difficile have been associated with disease exacerbation in specific clinical situations. Whereas C. difficile may produce worsening of the disease in those exposed to broad spectrum antibiotics, CMV reactivation is seen only in patients with moderate to severe steroid refractory disease. The importance of these two super-infections can be gauged by the fact that both the ACG and the ECCO recommend testing for these two pathogens in appropriate clinical situations. The applicability of these guidelines in the Indian scenario has yet to be determined in view of the bacterial and parasitic infections endemic in tropical countries. The guidelines for diagnosis and management of these two super-infections in the presence of ulcerative colitis are discussed in this review. PMID:25735121

  6. Risk factors associated with the development of ischemic colitis

    PubMed Central

    Fernández, Joaquín Cubiella; Calvo, Luisa Núñez; Vázquez, Elvira González; García, Maria Jesús García; Pérez, Maria Teresa Alves; Silva, Isabel Martínez; Seara, Javier Fernández

    2010-01-01

    AIM: To ascertain the role of cardiovascular risk factors, cardiovascular diseases, standard treatments and other diseases in the development of ischemic colitis (IC). METHODS: A retrospective, case-control study was designed, using matched data and covering 161 incident cases of IC who required admission to our hospital from 1998 through 2003. IC was diagnosed on the basis of endoscopic findings and diagnostic or compatible histology. Controls were randomly chosen from a cohort of patients who were admitted in the same period and required a colonoscopy, excluding those with diagnosis of colitis. Cases were matched with controls (ratio 1:2), by age and sex. A conditional logistic regression was performed. RESULTS: A total of 483 patients (161 cases, 322 controls) were included; mean age 75.67 ± 10.03 years, 55.9% women. The principal indications for colonoscopy in the control group were lower gastrointestinal hemorrhage (35.4%), anemia (33.9%), abdominal pain (19.9%) and diarrhea (9.6%). The endoscopic findings in this group were hemorrhoids (25.5%), diverticular disease (30.4%), polyps (19.9%) and colorectal cancer (10.2%). The following variables were associated with IC in the univariate analysis: arterial hypertension (P = 0.033); dyslipidemia (P < 0.001); diabetes mellitus (P = 0.025); peripheral arterial disease (P = 0.004); heart failure (P = 0.026); treatment with hypotensive drugs (P = 0.023); angiotensin-converting enzyme inhibitors; (P = 0.018); calcium channel antagonists (P = 0.028); and acetylsalicylic acid (ASA) (P < 0.001). Finally, the following variables were independently associated with the development of IC: diabetes mellitus [odds ratio (OR) 1.76, 95% confidence interval (CI): 1.001-3.077, P = 0.046]; dyslipidemia (OR 2.12, 95% CI: 1.26-3.57, P = 0.004); heart failure (OR 3.17, 95% CI: 1.31-7.68, P = 0.01); peripheral arterial disease (OR 4.1, 95% CI: 1.32-12.72, P = 0.015); treatment with digoxin (digitalis) (OR 0.27, 95% CI: 0.084-0.857, P

  7. [Stunned myocardium after acute ischemic stroke].

    PubMed

    Varela, Daniel; Díaz, Fernanda; Hlavnicka, Alejandro; Wainsztein, Néstor; Leiguarda, Ramón

    2006-01-01

    The so-called stunned myocardium, defined as transitory myocardial contractile dysfunction, has been clearly demonstrated in diverse clinical situations. However, stunned myocardium related to ischemic stroke has been poorly identified. We describe two patients with diagnosis of acute ischemic stroke who developed eletrocardiographic changes, cardiac enzyme increasing levels and myocardial dysfunction secondary to abnormal cardiac wall motion. At the same time the patients developed acute lung injury with rapid resolution, perhaps as a consequence of neurocardiogenic components.

  8. Acute colitis in the renal allograft recipient.

    PubMed Central

    Perloff, L J; Chon, H; Petrella, E J; Grossman, R A; Barker, C F

    1976-01-01

    Four renal allograft recipients with evidence of ischemic damage to the colon are presented and compared with 11 cases from 5 major series. Similarities in the patients included: deterioration of renal function, multiple immunosuppressive and antibiotic regimens, the use of cadaver renal allografts, and diagnostic and therapeutic measures requiring frequent enemas with barium and ion-exchange resins. Two of our patients underwent surgery for the removal of segments of necrotic colon after several weeks of fever and abdominal pain initially attributed to either acute rejection, viral infection, or pancreatitis. One patient had three days of melena and responded to non-operative therapy. The fourth patient developed ischemic colonic changes 10 weeks after allograft nephrectomy and was receiving no immunosuppression at the time. Broad spectrum antibiotics were used at various times in all patients. Early aggressive evaluation of gastrointestinal complaints--including barium enema, upper gastrointestinal series with small bowel follow-through, proctosigmoidoscopy or colonoscopy, and arteriography--is indicated, in view of the lethality of the complication of colonic ulceration. The clinical pictures presented emphasize the fact that recipients of renal allografts are commonly heir to many complications which may be considered rare in the normal population. Images Fig. 1. Fig. 2. Fig. 3. Fig. 4a. Fig. 4b. PMID:1108814

  9. Acute ischaemic colitis associated with oral phenylephrine decongestant use.

    PubMed

    Ward, Paul W; Shaneyfelt, Terrence M; Roan, Ronald M

    2014-01-01

    In this case, the authors have presented for the first time that ischaemic colitis may be associated with phenylephrine use. Since phenylephrine is the more common active ingredient in over-the-counter (OTC) cold medications, other presentations may follow this case. A MEDLINE search was performed for all case reports or case series of ischaemic colitis secondary to pseudoephedrine or phenylephrine use published between 1966 and 2013. The search resulted in four case reports and one case series describing patients with acute onset ischaemic colitis with exposure to pseudoephedrine immediately prior to onset. However, we found no case reports of ischaemic colitis associated with phenylephrine use. We present this case as an unexpected clinical outcome of phenylephrine, which has not been associated with ischaemic colitis in the literature. Also, this case serves as a reminder of the important clinical lesson to question all patients' use of OTC and prescribed medications.

  10. Ischemic Colitis Has a Worse Prognosis When Isolated to the Right Side of the Colon

    PubMed Central

    Sotiriadis, John; Brandt, Lawrence J.; Behin, Daniel S.; Southern, William N.

    2009-01-01

    BACKGROUND In general, ischemic colitis has a very good prognosis, but there is concern that when ischemia affects the right side of the colon in an isolated fashion, the prognosis may not be so favorable. OBJECTIVE The aim of this study was to compare the clinical features and outcomes of ischemia isolated to the right side of the colon with those of ischemia involving other areas of the colon. METHODS A retrospective study was undertaken of patients with colon ischemia hospitalized at the Moses and Weiler Divisions of the Montefiore Medical Center during the interval 1998–2005. Patients were identified using computerized searches of ICD-9 codes for colon ischemia and were divided into two groups: those with isolated right colon ischemia (IRCI) and those with colon ischemia not involving the right colon in an isolated fashion (non-IRCI). Only patients with biopsy-proven ischemic colitis were entered into our study. RESULTS A total of 273 cases of biopsy-proven ischemic colitis were identified, of which 71 (26.0%) were isolated to the right side. Of these IRCI cases, 59.2% had an unfavorable outcome compared with 17.3% of cases of non-ICRI: 54.9% of IRCI patients required surgery compared with 10.9% of non-IRCI patients; mortality in patients with IRCI was 22.5% compared with 11.9% in patients with non-IRCI. CONCLUSIONS A total of 273 cases of biopsy-proven ischemic colitis were identified of which 71 (26.0%) involved only the right side. Patients with IRCI had a worse outcome than those with colon ischemia involving other colon regions, including a fivefold need for surgery and a twofold mortality. PMID:17561968

  11. Endovascular treatment of acute ischemic stroke.

    PubMed

    Leslie-Mazwi, Thabele; Rabinov, James; Hirsch, Joshua A

    2016-01-01

    Endovascular thrombectomy is an effective treatment for major acute ischemic stroke syndromes caused by major anterior circulation artery occlusions (commonly referred to as large vessel occlusion) and is superior to intravenous thrombolysis and medical management. Treatment should occur as quickly as is reasonably possible. All patients with moderate to severe symptoms (National Institutes of Health stroke scale >8) and a treatable occlusion should be considered. The use of neuroimaging is critical to exclude hemorrhage and large ischemic cores. Very shortly after stroke onset (<3 hours) computed tomography (CT) and CT angiography provide sufficient information to proceed; diffusion magnetic resonance imaging (MRI) is less reliable during this early stage. After 3 hours from onset diffusion MRI is the most reliable method to define ischemic core size and should be used in centers that can offer it rapidly. Recanalization is highly effective with a stentriever or using a direct aspiration technique, with the patient awake or under conscious sedation rather than general anesthesia, if it may be performed safely. After thrombectomy the patient should be admitted to an intensive care setting and inpatient rehabilitation undertaken as soon as feasible. Patient outcomes should be assessed at 3 months, preferably using the modified Rankin score. PMID:27430469

  12. MANAGEMENT OF ACUTE SEVERE ULCERATIVE COLITIS: A CLINICAL UPDATE

    PubMed Central

    SOBRADO, Carlos Walter; SOBRADO, Lucas Faraco

    2016-01-01

    ABSTRACT Introduction: Acute severe colitis is a potentially lethal medical emergency and, even today, its treatment remains a challenge for clinicians and surgeons. Intravenous corticoid therapy, which was introduced into the therapeutic arsenal in the 1950s, continues to be the first-line treatment and, for patients who are refractory to this, the rescue therapy may consist of clinical measures or emergency colectomy. Objective: To evaluate the indications for and results from drug rescue therapy (cyclosporine, infliximab and tacrolimus), and to suggest a practical guide for clinical approaches. Methods: The literature was reviewed using the Medline/PubMed, Cochrane library and SciELO databases, and additional information from institutional websites of interest, by cross-correlating the following keywords: acute severe colitis, fulminating colitis and treatment. Results: Treatments for acute severe colitis have avoided colectomy in 60-70% of the cases, provided that they have been started early on, with multidisciplinary follow-up. Despite the adverse effects of intravenous cyclosporine, this drug has been indicated in cases of greater severity with an imminent risk of colectomy, because of its fast action, short half-life and absence of increased risk of surgical complications. Therapy using infliximab has been reserved for less severe cases and those in which immunosuppressants are being or have been used (AZA/6-MP). Indication of biological agents has recently been favored because of their ease of therapeutic use, their good short and medium-term results, the possibility of maintenance therapy and also their action as a "bridge" for immunosuppressant action (AZA/6-MP). Colectomy has been reserved for cases in which there is still no response five to seven days after rescue therapy and in cases of complications (toxic megacolon, profuse hemorrhage and perforation). Conclusion: Patients with a good response to rescue therapy who do not undergo emergency

  13. Predicting Hemorrhagic Transformation of Acute Ischemic Stroke

    PubMed Central

    Marsh, Elisabeth B.; Llinas, Rafael H.; Schneider, Andrea L.C.; Hillis, Argye E.; Lawrence, Erin; Dziedzic, Peter; Gottesman, Rebecca F.

    2016-01-01

    Abstract Hemorrhagic transformation (HT) increases the morbidity and mortality of ischemic stroke. Anticoagulation is often indicated in patients with atrial fibrillation, low ejection fraction, or mechanical valves who are hospitalized with acute stroke, but increases the risk of HT. Risk quantification would be useful. Prior studies have investigated risk of systemic hemorrhage in anticoagulated patients, but none looked specifically at HT. In our previously published work, age, infarct volume, and estimated glomerular filtration rate (eGFR) significantly predicted HT. We created the hemorrhage risk stratification (HeRS) score based on regression coefficients in multivariable modeling and now determine its validity in a prospectively followed inpatient cohort. A total of 241 consecutive patients presenting to 2 academic stroke centers with acute ischemic stroke and an indication for anticoagulation over a 2.75-year period were included. Neuroimaging was evaluated for infarct volume and HT. Hemorrhages were classified as symptomatic versus asymptomatic, and by severity. HeRS scores were calculated for each patient and compared to actual hemorrhage status using receiver operating curve analysis. Area under the curve (AUC) comparing predicted odds of hemorrhage (HeRS score) to actual hemorrhage status was 0.701. Serum glucose (P < 0.001), white blood cell count (P < 0.001), and warfarin use prior to admission (P = 0.002) were also associated with HT in the validation cohort. With these variables, AUC improved to 0.854. Anticoagulation did not significantly increase HT; but with higher intensity anticoagulation, hemorrhages were more likely to be symptomatic and more severe. The HeRS score is a valid predictor of HT in patients with ischemic stroke and indication for anticoagulation. PMID:26765425

  14. Severe acute ulcerative colitis: the pediatric perspective.

    PubMed

    Turner, Dan

    2009-01-01

    Many features of pediatric ulcerative colitis (UC) are similar to adult-onset disease, but the rate of extensive disease is doubled in children. It is, therefore, not surprising that the admission rate for severe UC is higher in childhood-onset UC, reaching 28% by the age of 16 years. Approximately 30-40% of children will fail corticosteroids and require second-line medical therapy or colectomy. A pediatric UC activity index (PUCAI) score of >65 indicates severe disease and the index can assist in determining the need and timing of second-line medical therapy or colectomy early during the admission. A PUCAI score of >45 points on day 3 identify patients likely to fail corticosteroids (negative predictive value 90-95%), and a score >70 points on day 5 identify patients who will require short-term treatment escalation (positive predicting value 95-100%). Data in children are limited, but it seems that cyclosporine, tacrolimus and infliximab achieve a similar short-term response rate, in the range of 60-80%. Infliximab has the advantage that it may be given for a prolonged period of time while calcineurin inhibitors should not be used for more than 3-4 months, bridging to a thiopurine regimen. Colectomy is indicated in toxic megacolon or in cases refractory to one salvage therapy. The choice of colectomy in other cases should carefully consider its effect on the patient's quality of life, its impact on the physical and emotional development at a critical age of personality development, and its association with a high infertility rate in females undergoing pouch procedure before childbearing age.

  15. "Mass-forming" variant of ischemic colitis is a distinct entity with predilection for the proximal colon.

    PubMed

    Khor, Tze S; Lauwers, Gregory Y; Odze, Robert D; Srivastava, Amitabh

    2015-09-01

    We systematically evaluated the clinicopathologic features and outcome of a rare, unusual variant of ischemic colitis that presents as a mass lesion mimicking malignancy on imaging or colonoscopy. A retrospective search was performed for cases with a histologic diagnosis of ischemic colitis and a clinical impression of malignancy. Of the 23 patients initially identified, 4 were excluded because clinical and histologic review showed mucosal prolapse (n=1), discrete colon polyp (n=2), and a diverticular mass (n=1) without concern for malignancy. The mass-forming variant of ischemic colitis (n=19) was seen predominantly in elderly (mean age 71.8 y) women (63.2%) with a striking predilection for the right colon (13/19), particularly the cecum (n=6). Abdominal pain (52.6%) and hematochezia (26.3%) were the most common presenting symptoms. A computed tomography scan showed segmental thickening suspicious for malignancy in 6/8 patients. Colonoscopy revealed an exophytic (n=16) or stricturing (n=3) mass with a mean size of 4.67 cm. Mucosal biopsies showed features typical for ischemic colitis in all cases. A colectomy was performed in 4 cases. In 2, the mass-like appearance was due to marked submucosal and mural edema, whereas in the other 2 cases, with a malignant stricture-like lesion, marked submucosal fibrosis and cholesterol emboli were present. No malignancy was identified on follow-up in any patient (mean 39.9 mo). Follow-up colonoscopy was performed in 7 patients 1 to 32 weeks after initial presentation and showed resolution of the mass in all cases. Awareness of this rare variant of ischemic colitis will prevent unnecessary resections in these patients. PMID:26034865

  16. "Mass-forming" variant of ischemic colitis is a distinct entity with predilection for the proximal colon.

    PubMed

    Khor, Tze S; Lauwers, Gregory Y; Odze, Robert D; Srivastava, Amitabh

    2015-09-01

    We systematically evaluated the clinicopathologic features and outcome of a rare, unusual variant of ischemic colitis that presents as a mass lesion mimicking malignancy on imaging or colonoscopy. A retrospective search was performed for cases with a histologic diagnosis of ischemic colitis and a clinical impression of malignancy. Of the 23 patients initially identified, 4 were excluded because clinical and histologic review showed mucosal prolapse (n=1), discrete colon polyp (n=2), and a diverticular mass (n=1) without concern for malignancy. The mass-forming variant of ischemic colitis (n=19) was seen predominantly in elderly (mean age 71.8 y) women (63.2%) with a striking predilection for the right colon (13/19), particularly the cecum (n=6). Abdominal pain (52.6%) and hematochezia (26.3%) were the most common presenting symptoms. A computed tomography scan showed segmental thickening suspicious for malignancy in 6/8 patients. Colonoscopy revealed an exophytic (n=16) or stricturing (n=3) mass with a mean size of 4.67 cm. Mucosal biopsies showed features typical for ischemic colitis in all cases. A colectomy was performed in 4 cases. In 2, the mass-like appearance was due to marked submucosal and mural edema, whereas in the other 2 cases, with a malignant stricture-like lesion, marked submucosal fibrosis and cholesterol emboli were present. No malignancy was identified on follow-up in any patient (mean 39.9 mo). Follow-up colonoscopy was performed in 7 patients 1 to 32 weeks after initial presentation and showed resolution of the mass in all cases. Awareness of this rare variant of ischemic colitis will prevent unnecessary resections in these patients.

  17. CXCR2 knockout mice are protected against DSS-colitis-induced acute kidney injury and inflammation.

    PubMed

    Ranganathan, Punithavathi; Jayakumar, Calpurnia; Manicassamy, Santhakumar; Ramesh, Ganesan

    2013-11-15

    Organ cross talk exists in many diseases of the human and animal models of human diseases. A recent study demonstrated that inflammatory mediators can cause acute kidney injury and neutrophil infiltration in a mouse model of dextran sodium sulfate (DSS)-colitis. However, the chemokines and their receptors that may mediate distant organ effects in colitis are unknown. We hypothesized that keratinocyte chemoattractant (KC)/IL-8 receptor chemokine (C-X-C motif) ligand 2 (CXCL2) mediates DSS-colitis-induced acute kidney injury. Consistent with our hypothesis, wild-type (WT) mice developed severe colitis with DSS treatment, which was associated with inflammatory cytokine and chemokine expression and neutrophil infiltration in the colon. DSS-colitis in WT was accompanied by acute kidney injury and enhanced expression of inflammatory cytokines in the kidney. However, CXCR2 knockout mice were protected against DSS-colitis as well as acute kidney injury. Moreover, the expression of cytokines and chemokines and neutrophil infiltration was blunted in CXCR2 knockout mice in the colon and kidney. Administration of recombinant KC exacerbated DSS-colitis-induced acute kidney injury. Our results suggest that KC/IL-8 and its receptor CXCR2 are critical and major mediators of organ cross talk in DSS colitis and neutralization of CXCR2 will help to reduce the incidence of acute kidney injury due to ulcerative colitis and Crohn's disease in humans.

  18. Acute ischemic stroke in a pediatric patient.

    PubMed

    Gorchynski, Julie; Herrick, John; Cortes, Edgar

    2008-11-01

    Acute ischemic stroke in a pediatric patient is a complex disease with a variety of etiologies that differ from adults. Though rare, they are a real phenomenon with potentially devastating consequences. Some treating institutions are using anti-thrombotic drug therapy with unclear benefits. Available literature, which is limited to case reports and retrospective reviews of databases, clouds this topic with both positive and negative outcomes. Emergency department management should focus on stabilization and resuscitation with immediate involvement of a pediatric neurologist and intensivist. The decision to use anti-thrombotic drug therapy, including anti-platelet drugs and thrombolytics, should be in consult with the specialists involved until randomized controlled trials determine their safety and efficacy in the pediatric population.

  19. Ischemic Colitis Due to a Mesenteric Arteriovenous Malformation in a Patient with a Connective Tissue Disorder

    PubMed Central

    Poullos, Peter D.; Thompson, Atalie C.; Holz, Grant; Edelman, Lauren A.; Jeffrey, R. Brooke

    2014-01-01

    Ischemic colitis is a rare, life-threatening, consequence of mesenteric arteriovenous malformations. Ischemia ensues from a steal phenomenon through shunting, and may be compounded by the resulting portal hypertension. Computed tomographic angiography is the most common first-line test because it is quick, non-invasive, and allows for accurate anatomic characterization. Also, high-resolution three-dimensional images can be created for treatment planning. Magnetic resonance angiography is similarly sensitive for vascular mapping. Conventional angiography remains the gold standard for diagnosis and also allows for therapeutic endovascular embolization. Our patient underwent testing using all three of these modalities. We present the first reported case of this entity in a patient with a vascular connective tissue disorder. PMID:25926912

  20. Management of Acute Hypertensive Response in Patients With Ischemic Stroke

    PubMed Central

    Qureshi, Adnan I.

    2016-01-01

    High blood pressure (BP) >140/90 mm Hg is seen in 75% of patients with acute ischemic stroke and in 80% of patients with acute intracerebral hemorrhages and is independently associated with poor functional outcome. While BP reduction in patients with chronic hypertension remains one of the most important factors in primary and secondary stroke prevention, the proper management strategy for acute hypertensive response within the first 72 hours of acute ischemic stroke has been a matter of debate. Recent guidelines recommend clinical trials to ascertain whether antihypertensive therapy in the acute phase of stroke is beneficial. This review summarizes the current data on acute hypertensive response or elevated BP management during the first 72 hours after an acute ischemic stroke. Based on the potential deleterious effect of lowering BP observed in some clinical trials in patients with acute ischemic stroke and because of the lack of convincing evidence to support acute BP lowering in those situations, aggressive BP reduction in patients presenting with acute ischemic stroke is currently not recommended. While the early use of angiotensin receptor antagonists may help reduce cardiovascular events, this benefit is not necessarily related to BP reduction. PMID:27366297

  1. Developing practice recommendations for endovascular revascularization for acute ischemic stroke

    PubMed Central

    Lazzaro, Marc A.; Alexandrov, Andrei V.; Darkhabani, Ziad; Edgell, Randall C.; English, Joey; Frei, Donald; Jamieson, Dara G.; Janardhan, Vallabh; Janjua, Nazli; Janjua, Rashid M.; Katzan, Irene; Khatri, Pooja; Kirmani, Jawad F.; Liebeskind, David S.; Linfante, Italo; Nguyen, Thanh N.; Saver, Jeffrey L.; Shutter, Lori; Xavier, Andrew; Yavagal, Dileep; Zaidat, Osama O.

    2012-01-01

    Guidelines have been established for the management of acute ischemic stroke; however, specific recommendations for endovascular revascularization therapy are lacking. Burgeoning investigation of endovascular revascularization therapies for acute ischemic stroke, rapid device development, and a diverse training background of the providers performing the procedures underscore the need for practice recommendations. This review provides a concise summary of the Society of Vascular and Interventional Neurology endovascular acute ischemic stroke roundtable meeting. This document was developed to review current clinical efficacy of pharmacologic and mechanical revascularization therapy, selection criteria, periprocedure management, and endovascular time metrics and to highlight current practice patterns. It therefore provides an outline for the future development of multisociety guidelines and recommendations to improve patient selection, procedural management, and organizational strategies for revascularization therapies in acute ischemic stroke. PMID:23008406

  2. Perfusion Angiography in Acute Ischemic Stroke

    PubMed Central

    Liebeskind, David S.

    2016-01-01

    Visualization and quantification of blood flow are essential for the diagnosis and treatment evaluation of cerebrovascular diseases. For rapid imaging of the cerebrovasculature, digital subtraction angiography (DSA) remains the gold standard as it offers high spatial resolution. This paper lays out a methodological framework, named perfusion angiography, for the quantitative analysis and visualization of blood flow parameters from DSA images. The parameters, including cerebral blood flow (CBF) and cerebral blood volume (CBV), mean transit time (MTT), time-to-peak (TTP), and Tmax, are computed using a bolus tracking method based on the deconvolution of the time-density curve on a pixel-by-pixel basis. The method is tested on 66 acute ischemic stroke patients treated with thrombectomy and/or tissue plasminogen activator (tPA) and also evaluated on an estimation task with known ground truth. This novel imaging tool provides unique insights into flow mechanisms that cannot be observed directly in DSA sequences and might be used to evaluate the impact of endovascular interventions more precisely. PMID:27446232

  3. “Bath Salts” intoxication with multiorgan failure and left-sided ischemic colitis: a case report

    PubMed Central

    Gavriilidis, G; Kyriakoudi, A; Tiniakos, D; Rovina, N; Koutsoukou, A

    2015-01-01

    Background: In the recent years, a new group of designer drugs, under the brand name of bath salts has emerged as a new trend. They are mainly b-ketone amphetamine analogs and are derivatives of cathinone, a monoamine alkaloid. They are abused for psychostimulant effects. Their primary ingredient 3,4-methylenedioxypyrovalerone (MDPV), has alerted authorities worldwide due to its severe physiological and behavioral toxicities. Description of Case:We present the case of a 47-year-old man with coma, seizures, multi-organ failure and ischemic colitis after intoxication with bath salts containing MDPV. After supportive care, he had a successful outcome. To our knowledge, this report is the first to describe ischemic colitis after MDPV intoxication. Clinicians need to be especially alert since MDPV is not detected by routine screens, and its overdose can be life-threatening. Conclusion: Ischemic colitis should be recognized as a potential complication of bath salts ingestion in order to prevent unnecessary interventions, such as diagnostic laparotomy, which could worsen patient’s condition. Hippokratia 2015; 19 (4): 363-365.

  4. Outbreak of acute colitis on a horse farm associated with tetracycline-contaminated sweet feed.

    PubMed Central

    Keir, A A; Stämpfli, H R; Crawford, J

    1999-01-01

    Exposure of a group of horses to tetracycline-contaminated feed resulted in acute colitis and subsequent death in one horse and milder diarrhea in 3 others. The most severely affected animal demonstrated clinical and pathological findings typical of colitis X. The other herdmates responded well to administration of zinc bacitracin. PMID:10572668

  5. Characteristics of Misclassified CT Perfusion Ischemic Core in Patients with Acute Ischemic Stroke

    PubMed Central

    Geuskens, Ralph R. E. G.; Borst, Jordi; Lucas, Marit; Boers, A. M. Merel; Berkhemer, Olvert A.; Roos, Yvo B. W. E. M.; van Walderveen, Marianne A. A.; Jenniskens, Sjoerd F. M.; van Zwam, Wim H.; Dippel, Diederik W. J.; Majoie, Charles B. L. M.; Marquering, Henk A.

    2015-01-01

    Background CT perfusion (CTP) is used to estimate the extent of ischemic core and penumbra in patients with acute ischemic stroke. CTP reliability, however, is limited. This study aims to identify regions misclassified as ischemic core on CTP, using infarct on follow-up noncontrast CT. We aim to assess differences in volumetric and perfusion characteristics in these regions compared to areas that ended up as infarct on follow-up. Materials and Methods This study included 35 patients with >100 mm brain coverage CTP. CTP processing was performed using Philips software (IntelliSpace 7.0). Final infarct was automatically segmented on follow-up noncontrast CT and used as reference. CTP and follow-up noncontrast CT image data were registered. This allowed classification of ischemic lesion agreement (core on CTP: rMTT≥145%, aCBV<2.0 ml/100g and infarct on follow-up noncontrast CT) and misclassified ischemic core (core on CTP, not identified on follow-up noncontrast CT) regions. False discovery ratio (FDR), defined as misclassified ischemic core volume divided by total CTP ischemic core volume, was calculated. Absolute and relative CTP parameters (CBV, CBF, and MTT) were calculated for both misclassified CTP ischemic core and ischemic lesion agreement regions and compared using paired rank-sum tests. Results Median total CTP ischemic core volume was 49.7ml (IQR:29.9ml-132ml); median misclassified ischemic core volume was 30.4ml (IQR:20.9ml-77.0ml). Median FDR between patients was 62% (IQR:49%-80%). Median relative mean transit time was 243% (IQR:198%-289%) and 342% (IQR:249%-432%) for misclassified and ischemic lesion agreement regions, respectively. Median absolute cerebral blood volume was 1.59 (IQR:1.43–1.79) ml/100g (P<0.01) and 1.38 (IQR:1.15–1.49) ml/100g (P<0.01) for misclassified ischemic core and ischemic lesion agreement, respectively. All CTP parameter values differed significantly. Conclusion For all patients a considerable region of the CTP ischemic core

  6. Anesthesia for Endovascular Approaches to Acute Ischemic Stroke.

    PubMed

    Avitsian, Rafi; Machado, Sandra B

    2016-09-01

    Involvement of the Anesthesiologist in the early stages of care for acute ischemic stroke patient undergoing endovascular treatment is essential. Anesthetic management includes the anesthetic technique (general anesthesia vs sedation), a matter of much debate and an area in need of well-designed prospective studies. The large numbers of confounding factors make the design of such studies a difficult process. A universally agreed point in the endovascular management of acute ischemic stroke is the importance of decreasing the time to revascularization. Hemodynamic and ventilatory management and implementation of neuroprotective modalities and treatment of acute procedural complications are important components of the anesthetic plan. PMID:27521194

  7. Heart Failure in Acute Ischemic Stroke

    PubMed Central

    Cuadrado-Godia, Elisa; Ois, Angel; Roquer, Jaume

    2010-01-01

    Heart failure (HF) is a complex clinical syndrome that can result from any structural or functional cardiac disorder that impairs the ability of the ventricle to fill with or eject blood. Due to the aging of the population it has become a growing public health problem in recent decades. Diagnosis of HF is clinical and there is no diagnostic test, although some basic complementary testing should be performed in all patients. Depending on the ejection fraction (EF), the syndrome is classified as HF with low EF or HF with normal EF (HFNEF). Although prognosis in HF is poor, HFNEF seems to be more benign. HF and ischemic stroke (IS) share vascular risk factors such as age, hypertension, diabetes mellitus, coronary artery disease and atrial fibrillation. Persons with HF have higher incidence of IS, varying from 1.7% to 10.4% per year across various cohort studies. The stroke rate increases with length of follow-up. Reduced EF, independent of severity, is associated with higher risk of stroke. Left ventricular mass and geometry are also related with stroke incidence, with concentric hypertrophy carrying the greatest risk. In HF with low EF, the stroke mechanism may be embolism, cerebral hypoperfusion or both, whereas in HFNEF the mechanism is more typically associated with chronic endothelial damage of the small vessels. Stroke in patients with HF is more severe and is associated with a higher rate of recurrence, dependency, and short term and long term mortality. Cardiac morbidity and mortality is also high in these patients. Acute stroke treatment in HF includes all the current therapeutic options to more carefully control blood pressure. For secondary prevention, optimal control of all vascular risk factors is essential. Antithrombotic therapy is mandatory, although the choice of a platelet inhibitor or anticoagulant drug depends on the cardiac disease. Trials are ongoing to evaluate anticoagulant therapy for prevention of embolism in patients with low EF who are at

  8. Anticoagulation for the Acute Management of Ischemic Stroke

    PubMed Central

    Robinson, Austin A.; Ikuta, Kevin; Soverow, Jonathan

    2014-01-01

    Few prospective studies support the use of anticoagulation during the acute phase of ischemic stroke, though observational data suggest a role in certain populations. Depending on the mechanism of stroke, systemic anticoagulation may prevent recurrent cerebral infarction, but concomitantly carries a risk of hemorrhagic transformation. In this article, we describe a case where anticoagulation shows promise for ischemic stroke and review the evidence that has discredited its use in some circumstances while showing its potential in others. PMID:24910565

  9. Differential acute effects of selenomethionine and sodium selenite on the severity of colitis.

    PubMed

    Hiller, Franziska; Oldorff, Lisa; Besselt, Karolin; Kipp, Anna Patricia

    2015-04-01

    The European population is only suboptimally supplied with the essential trace element selenium. Such a selenium status is supposed to worsen colitis while colitis-suppressive effects were observed with adequate or supplemented amounts of both organic selenomethionine (SeMet) and inorganic sodium selenite. In order to better understand the effect of these selenocompounds on colitis development we examined colonic phenotypes of mice fed supplemented diets before the onset of colitis or during the acute phase. Colitis was induced by treating mice with 1% dextran sulfate sodium (DSS) for seven days. The selenium-enriched diets were either provided directly after weaning (long-term) or were given to mice with a suboptimal selenium status after DSS withdrawal (short-term). While long-term selenium supplementation had no effect on colitis development, short-term selenite supplementation, however, resulted in a more severe colitis. Colonic selenoprotein expression was maximized in all selenium-supplemented groups independent of the selenocompound or intervention time. This indicates that the short-term selenite effect appears to be independent from colonic selenoprotein expression. In conclusion, a selenite supplementation during acute colitis has no health benefits but may even aggravate the course of disease. PMID:25867950

  10. Evolving Role of Endovascular Treatment of Acute Ischemic Stroke

    PubMed Central

    del Zoppo, Gregory J.

    2014-01-01

    The perceived advantages of endovascular treatment for acute ischemic stroke in terms of recanalization, the multimodal and targeted approaches, and perhaps the more permissive rules on devices than on medications for their licensing favored the assumption that endovascular treatment is superior to intravenous thrombolysis for acute treatment of ischemic stroke, and its adoption in more advanced stroke centers. However, this assumption has been questioned by recent clinical trial experience showing that endovascular treatment is not superior to intravenous thrombolysis. The new evidence has changed the perception and the importance of conducting randomized trials in this area. This summary examines the background and outcomes of the latest experience with endovascular techniques in acute stroke treatment based on historical data. The new challenge is how to study the latest generation of devices called stent retrievers, which are faster in recanalizing and easier to use, in selected patients with acute ischemic stroke. In the meantime, the available evidence does not provide support for the use of endovascular treatment of acute ischemic stroke in clinical practice. PMID:24258466

  11. Imaging Recommendations for Acute Stroke and Transient Ischemic Attack Patients

    PubMed Central

    Wintermark, Max; Sanelli, Pina C.; Albers, Gregory W.; Bello, Jacqueline A.; Derdeyn, Colin P.; Hetts, Steven W.; Johnson, Michele H.; Kidwell, Chelsea S.; Lev, Michael H.; Liebeskind, David S.; Rowley, Howard A.; Schaefer, Pamela W.; Sunshine, Jeffrey L.; Zaharchuk, Greg; Meltzer, Carolyn C.

    2014-01-01

    In the article entitled “Imaging Recommendations for Acute Stroke and Transient Ischemic Attack Patients: A Joint Statement by the American Society of Neuroradiology, the American College of Radiology and the Society of NeuroInterventional Surgery”, we are proposing a simple, pragmatic approach that will allow the reader to develop an optimal imaging algorithm for stroke patients at their institution. PMID:23948676

  12. Platelet-Derived CCL5 Regulates CXC Chemokine Formation and Neutrophil Recruitment in Acute Experimental Colitis.

    PubMed

    Yu, Changhui; Zhang, Songen; Wang, Yongzhi; Zhang, Su; Luo, Lingtao; Thorlacius, Henrik

    2016-02-01

    Accumulating data suggest that platelets not only regulate thrombosis and haemostasis but also inflammatory processes. Platelets contain numerous potent pro-inflammatory compounds, including the chemokines CCL5 and CXCL4, although their role in acute colitis remains elusive. The aim of this study is to examine the role of platelets and platelet-derived chemokines in acute colitis. Acute colitis is induced in female Balb/c mice by administration of 5% dextran sodium sulfate (DSS) for 5 days. Animals receive a platelet-depleting, anti-CCL5, anti-CXCL4, or a control antibody prior to DSS challenge. Colonic tissue is collected for quantification of myeloperoxidase (MPO) activity, CXCL5, CXCL2, interleukin-6 (IL-6), and CCL5 levels as well as morphological analyses. Platelet depletion reduce tissue damage and clinical disease activity index in DSS-exposed animals. Platelet depletion not only reduces levels of CXCL2 and CXCL5 but also levels of CCL5 in the inflamed colon. Immunoneutralization of CCL5 but not CXCL4 reduces tissue damage, CXC chemokine expression, and neutrophil recruitment in DSS-treated animals. These findings show that platelets play a key role in acute colitis by regulating CXC chemokine generation, neutrophil infiltration, and tissue damage in the colon. Moreover, our results suggest that platelet-derived CCL5 is an important link between platelet activation and neutrophil recruitment in acute colitis.

  13. MDCT of acute colitis in adults: an update in current imaging features.

    PubMed

    Barral, M; Boudiaf, M; Dohan, A; Hoeffel, C; Camus, M; Pautrat, K; Fishman, E K; Cohen, S; Soyer, P

    2015-02-01

    Acute colitis is often diagnosed on multidetector row computed tomography (MDCT) because patients with this condition present with abdominal pain and a variety of nonspecific symptoms. Acute colitis has multiple causes with varying degrees of severity. Analysis of the extent of colonic involvement, presence of specific MDCT imaging features and associated signs should help radiologist narrow the diagnosis. Integrating the results of clinical examination and biological tests is mandatory, and in case of ambiguous or nonspecific MDCT findings, endoscopy and colon biopsy should always be considered for a definite diagnosis. The purpose of this review is to discuss and illustrate MDCT features that are helpful for characterizing acute colitis in adults and to provide an update in current MDCT features. PMID:24835625

  14. MDCT of acute colitis in adults: an update in current imaging features.

    PubMed

    Barral, M; Boudiaf, M; Dohan, A; Hoeffel, C; Camus, M; Pautrat, K; Fishman, E K; Cohen, S; Soyer, P

    2015-02-01

    Acute colitis is often diagnosed on multidetector row computed tomography (MDCT) because patients with this condition present with abdominal pain and a variety of nonspecific symptoms. Acute colitis has multiple causes with varying degrees of severity. Analysis of the extent of colonic involvement, presence of specific MDCT imaging features and associated signs should help radiologist narrow the diagnosis. Integrating the results of clinical examination and biological tests is mandatory, and in case of ambiguous or nonspecific MDCT findings, endoscopy and colon biopsy should always be considered for a definite diagnosis. The purpose of this review is to discuss and illustrate MDCT features that are helpful for characterizing acute colitis in adults and to provide an update in current MDCT features.

  15. Orally Administered Enoxaparin Ameliorates Acute Colitis by Reducing Macrophage-Associated Inflammatory Responses

    PubMed Central

    Lean, Qi Ying; Eri, Rajaraman D.; Randall-Demllo, Sarron; Sohal, Sukhwinder Singh; Stewart, Niall; Peterson, Gregory M.; Gueven, Nuri; Patel, Rahul P.

    2015-01-01

    Inflammatory bowel diseases, such as ulcerative colitis, cause significant morbidity and decreased quality of life. The currently available treatments are not effective in all patients, can be expensive and have potential to cause severe side effects. This prompts the need for new treatment modalities. Enoxaparin, a widely used antithrombotic agent, is reported to possess anti-inflammatory properties and therefore we evaluated its therapeutic potential in a mouse model of colitis. Acute colitis was induced in male C57BL/6 mice by administration of dextran sulfate sodium (DSS). Mice were treated once daily with enoxaparin via oral or intraperitoneal administration and monitored for colitis activities. On termination (day 8), colons were collected for macroscopic evaluation and cytokine measurement, and processed for histology and immunohistochemistry. Oral but not intraperitoneal administration of enoxaparin significantly ameliorated DSS-induced colitis. Oral enoxaparin-treated mice retained their body weight and displayed less diarrhea and fecal blood loss compared to the untreated colitis group. Colon weight in enoxaparin-treated mice was significantly lower, indicating reduced inflammation and edema. Histological examination of untreated colitis mice showed a massive loss of crypt architecture and goblet cells, infiltration of immune cells and the presence of edema, while all aspects of this pathology were alleviated by oral enoxaparin. Reduced number of macrophages in the colon of oral enoxaparin-treated mice was accompanied by decreased levels of pro-inflammatory cytokines. Oral enoxaparin significantly reduces the inflammatory pathology associated with DSS-induced colitis in mice and could therefore represent a novel therapeutic option for the management of ulcerative colitis. PMID:26218284

  16. [Current registry studies of acute ischemic stroke].

    PubMed

    Veltkamp, R; Jüttler, E; Pfefferkorn, T; Purrucker, J; Ringleb, P

    2012-10-01

    Study registries offer the opportunity to evaluate the effects of new therapies or to observe the consequences of new treatments in clinical practice. The SITS-MOST registry confirmed the validity of findings from randomized trials on intravenous thrombolysis concerning safety and efficacy in the clinical routine. Current study registries concerning new interventional thrombectomy techniques suggest a high recanalization rate; however, the clinical benefit can only be evaluated in randomized, controlled trials. Similarly, the experiences of the BASICS registry on basilar artery occlusion have led to the initiation of a controlled trial. The benefit of hemicraniectomy in malignant middle cerebral artery infarction has been demonstrated by the pooled analysis of three randomized trials. Numerous relevant aspects are currently documented in the DESTINY-R registry. Finally, the recently started RASUNOA registry examines diagnostic and therapeutic aspects of ischemic and hemorrhagic stroke occurring during therapy with new oral anticoagulants.

  17. [Uncaria tomentosa and acute ischemic kidney injury in rats].

    PubMed

    de Fátima Fernandes Vattimo, Maria; da Silva, Natalia Oliveira

    2011-03-01

    The objective of this study was to evaluate the renoprotective effects of Uncaria Tomentosa (cat's claw) on ischemic acute kidney injury induced by renal clamping in rats. The hypoxia and hypoperfusion increase the production of reactive species already present in the inflammatory process. Results showed that the renal function evaluated by creatinine clearance, the urinary excretion of peroxides and malondealdehyde indexes demonstrated that UT induced renoprotection, probably related to its antioxidant activities.

  18. Reperfusion Therapies for Acute Ischemic Stroke: An Update

    PubMed Central

    Dorado, Laura; Millán, Mònica; Dávalos, Antoni

    2014-01-01

    Acute ischemic stroke is a major cause of morbidity and mortality in developed countries. Intravenous thrombolysis with tissue plasminogen activator (tPA) within 4.5 hours of symptoms onset significantly improves clinical outcomes in patients with acute ischemic stroke. This narrow window for treatment leads to a small proportion of eligible patients to be treated. Intravenous or intra-arterial trials, combined intravenous/intra-arterial trials, and newer devices to mechanically remove the clot from intracranial arteries have been investigated or are currently being explored to increase patient eligibility and to improve arterial recanalization and clinical outcome. New retrievable stent-based devices offer higher revascularization rates with shorter time to recanalization and are now generally preferred to first generation thrombectomy devices such as Merci Retriever or Penumbra System. These devices have been shown to be effective for opening up occluded vessels in the brain but its efficacy for improving outcomes in patients with acute stroke has not yet been demonstrated in a randomized clinical trial. We summarize the results of the major systemic thrombolytic trials and the latest trials employing different endovascular approaches to ischemic stroke. PMID:24646159

  19. Neuroanatomical correlates of severe cardiac arrhythmias in acute ischemic stroke.

    PubMed

    Seifert, Frank; Kallmünzer, Bernd; Gutjahr, Isabell; Breuer, Lorenz; Winder, Klemens; Kaschka, Iris; Kloska, Stephan; Doerfler, Arnd; Hilz, Max-Josef; Schwab, Stefan; Köhrmann, Martin

    2015-05-01

    Neurocardiological interactions can cause severe cardiac arrhythmias in patients with acute ischemic stroke. The relationship between the lesion location in the brain and the occurrence of cardiac arrhythmias is still discussed controversially. The aim of the present study was to correlate the lesion location with the occurrence of cardiac arrhythmias in patients with acute ischemic stroke. Cardiac arrhythmias were systematically assessed in patients with acute ischemic stroke during the first 72 h after admission to a monitored stroke unit. Voxel-based lesion-symptom mapping (VLSM) was used to correlate the lesion location with the occurrence of clinically relevant severe arrhythmias. Overall 150 patients, 56 with right-hemispheric and 94 patients with a left-hemispheric lesion, were eligible to be included in the VLSM study. Severe cardiac arrhythmias were present in 49 of these 150 patients (32.7%). We found a significant association (FDR correction, q < 0.05) between lesions in the right insular, right frontal and right parietal cortex as well as the right amygdala, basal ganglia and thalamus and the occurrence of cardiac arrhythmias. Because left- and right-hemispheric lesions were analyzed separately, the significant findings rely on the 56 patients with right-hemispheric lesions. The data indicate that these areas are involved in central autonomic processing and that right-hemispheric lesions located to these areas are associated with an elevated risk for severe cardiac arrhythmias.

  20. Loss of n-6 fatty acid induced pediatric obesity protects against acute murine colitis

    PubMed Central

    Nagy-Szakal, Dorottya; Mir, Sabina A. V.; Harris, R. Alan; Dowd, Scot E.; Yamada, Takeshi; Lacorazza, H. Daniel; Tatevian, Nina; Smith, C. Wayne; de Zoeten, Edwin F.; Klein, John; Kellermayer, Richard

    2015-01-01

    Dietary influences may affect microbiome composition and host immune responses, thereby modulating propensity toward inflammatory bowel diseases (IBDs): Crohn disease (CD) and ulcerative colitis (UC). Dietary n-6 fatty acids have been associated with UC in prospective studies. However, the critical developmental period when (n-6) consumption may induce UC is not known. We examined the effects of transiently increased n-6 consumption during pediatric development on subsequent dextran-sulfate-sodium (DSS)-induced acute murine colitis. The animals transiently became obese then rapidly lost this phenotype. Interestingly, mice were protected against DSS colitis 40 days after n-6 consumption. The transient high n-6-induced protection against colitis was fat type- and dietary reversal-dependent and could be transferred to germ-free mice by fecal microbiota transplantation. We also detected decreased numbers of chemokine receptor (Cxcr)5+ CD4+ T cells in the mesenteric lymph nodes (MLNs) of transiently n-6-fed mice. Further experiments revealed that anti-chemokine ligand (Cxcl)13 (the ligand of Cxcr5) antibody treatment decreased DSS colitis severity, implicating the importance of the Cxcr5-Cxcl13 pathway in mammalian colitis. Consecutively, we found elevated CXCL13 concentrations (CD: 1.8-fold, P = 0.0077; UC: 1.9-fold, P = 0.056) in the serum of untreated pediatric IBD patients. The human serologic observations supported the translational relevance of our findings.—Nagy-Szakal, D., Mir, S. A. V., Harris, R. A., Dowd, S. E., Yamada, T., Lacorazza, H. D., Tatevian, N., Smith, C. W., de Zoeten, E. F., Klein, J., Kellermayer, R. Loss of n-6 fatty acid induced pediatric obesity protects against acute murine colitis. PMID:25903104

  1. Jumihaidokuto effectively inhibits colon inflammation and apoptosis in mice with acute colitis.

    PubMed

    Sreedhar, Remya; Arumugam, Somasundaram; Karuppagounder, Vengadeshprabhu; Thandavarayan, Rajarajan A; Giridharan, Vijayasree V; Pitchaimani, Vigneshwaran; Afrin, Mst Rejina; Harima, Meilei; Nakamura, Takashi; Nakamura, Masahiko; Suzuki, Kenji; Watanabe, Kenichi

    2015-12-01

    Jumihaidokuto, a Japanese kampo medicine, is prescribed in Japan for its anti-inflammatory activity. Here we have examined its beneficial effects against acute colitis induced by dextran sulfate sodium (DSS) in mice. We have used C57BL/6 female mice, divided into two groups and received 3% DSS in drinking water during the experimental period (8days). Treatment group mice received 1g/kg/day dose of Jumihaidokuto orally whereas DSS control group received equal volume of distilled water. Normal control group mice received plain drinking water. Jumihaidokuto treatment attenuated the colitis symptoms along with suppression of various inflammatory marker proteins such as IL-1β, IL-2Rα, IL-4, CTGF and RAGE. It has also down-regulated the oxidative stress and apoptotic signaling in the colons of mice with colitis. The present study has confirmed the beneficial effects of Jumihaidokuto on DSS induced acute colitis in mice and suggests that it can be a potential agent for the treatment of colitis.

  2. Ginseng Berry Extract Attenuates Dextran Sodium Sulfate-Induced Acute and Chronic Colitis

    PubMed Central

    Zhang, Wei; Xu, Li; Cho, Si-Young; Min, Kyung-Jin; Oda, Tatsuya; Zhang, LiJun; Yu, Qing; Jin, Jun-O

    2016-01-01

    This study investigates the in vivo functions of ginseng berry extract (GB) as a therapy for dextran sodium sulfate (DSS)-induced colitis. C57BL/6 mice were given drinking water containing DSS (3%) for eight days to induce acute colitis. At the same time, the mice received an oral dose of GB (50 mg/kg) once daily. The GB-treated mice were less susceptible to the development of acute colitis than were control mice treated with saline, as determined by weight loss, disease activity, and colon histology. The administration of GB to DSS-treated mice also reduced the numbers and inhibited the activation of colon-infiltrating T cells, neutrophils, intestinal CD103−CD11c+ dendritic cells (cDCs), and macrophages. In addition, GB treatment promoted the migration of CD103+CD11c+ cDCs and expansion of Foxp3+ regulatory T cells in the colons of DSS-treated mice. Similarly, in the DSS-induced chronic colitis model, GB treatment improved the macroscopic and histological appearance of the colon wall when compared to untreated control mice, as indicated by longer colon length and lower histological scores. This is the first report to show that oral administration of GB suppresses immune activation and protects against experimentally induced colitis. PMID:27058552

  3. Endovascular treatment of acute ischemic stroke.

    PubMed

    Kidwell, Chelsea S; Jahan, Reza

    2015-05-01

    Endovascular therapy for acute stroke has evolved with the use of intra-arterial thrombolytics, intravenous/intra-arterial bridging strategies, and mechanical thrombectomy/aspiration devices. Despite widespread use in clinical practice, randomized trials of first-generation devices failed to demonstrate improved outcomes compared with standard care. New-generation stent retriever devices demonstrate higher rates of revascularization and clinical outcomes compared with first-generation devices. Additional randomized trials are underway and have the potential to confirm clinical efficacy of new-generation devices compared with standard care. The role of additional advanced imaging for patient selection remains unclear, and further trials are needed to demonstrate the role of these techniques for patient selection. PMID:25907913

  4. Magnetic Resonance Imaging in Acute Ischemic Stroke Treatment

    PubMed Central

    Kim, Bum Joon; Kang, Hyun Goo; Kim, Hye-Jin; Ahn, Sung-Ho; Kim, Na Young; Warach, Steven

    2014-01-01

    Although intravenous administration of tissue plasminogen activator is the only proven treatment after acute ischemic stroke, there is always a concern of hemorrhagic risk after thrombolysis. Therefore, selection of patients with potential benefits in overcoming potential harms of thrombolysis is of great importance. Despite the practical issues in using magnetic resonance imaging (MRI) for acute stroke treatment, multimodal MRI can provide useful information for accurate diagnosis of stroke, evaluation of the risks and benefits of thrombolysis, and prediction of outcomes. For example, the high sensitivity and specificity of diffusion-weighted image (DWI) can help distinguish acute ischemic stroke from stroke-mimics. Additionally, the lesion mismatch between perfusion-weighted image (PWI) and DWI is thought to represent potential salvageable tissue by reperfusion therapy. However, the optimal threshold to discriminate between benign oligemic areas and the penumbra is still debatable. Signal changes of fluid-attenuated inversion recovery image within DWI lesions may be a surrogate marker for ischemic lesion age and might indicate risks of hemorrhage after thrombolysis. Clot sign on gradient echo image may reflect the nature of clot, and their location, length and morphology may provide predictive information on recanalization by reperfusion therapy. However, previous clinical trials which solely or mainly relied on perfusion-diffusion mismatch for patient selection, failed to show benefits of MRI-based thrombolysis. Therefore, understanding the clinical implication of various useful MRI findings and comprehensively incorporating those variables into therapeutic decision-making may be a more reasonable approach for expanding the indication of acute stroke thrombolysis. PMID:25328872

  5. Dextran Sulfate Sodium (DSS)-Induced Acute Colitis in the Rat.

    PubMed

    Martin, Jérôme C; Bériou, Gaëlle; Josien, Régis

    2016-01-01

    Inflammatory bowel diseases (IBDs) are complex multifactorial disease thought to result from inappropriate immune responses to the gut microbiota, in genetically susceptible individuals, under the influence of environmental factors. Among the different animal models developed to help in understanding IBDs pathophysiological mechanisms as well as to achieve pharmacological preclinical studies, the dextran sulfate sodium (DSS)-induced colitis model is the most widely used because of its simplicity, cost-effectiveness, and similarity with human IBDs. This section provides with a detailed protocol that we validated in our laboratory to perform DSS-induced acute colitis in the Sprague-Dawley (SPD) rat.

  6. TNFR1-dependent pulmonary apoptosis during ischemic acute kidney injury.

    PubMed

    White, Laura E; Santora, Rachel J; Cui, Yan; Moore, Frederick A; Hassoun, Heitham T

    2012-09-01

    Despite advancements in renal replacement therapy, the mortality rate for acute kidney injury (AKI) remains unacceptably high, likely due to remote organ injury. Kidney ischemia-reperfusion injury (IRI) activates cellular and soluble mediators that incite a distinct pulmonary proinflammatory and proapoptotic response. Tumor necrosis factor receptor 1 (TNFR1) has been identified as a prominent death receptor activated in the lungs during ischemic AKI. We hypothesized that circulating TNF-α released from the postischemic kidney induces TNFR1-mediated pulmonary apoptosis, and we aimed to elucidate molecular pathways to programmed cell death. Using an established murine model of kidney IRI, we characterized the time course for increased circulatory and pulmonary TNF-α levels and measured concurrent upregulation of pulmonary TNFR1 expression. We then identified TNFR1-dependent pulmonary apoptosis after ischemic AKI using TNFR1-/- mice. Subsequent TNF-α signaling disruption with Etanercept implicated circulatory TNF-α as a key soluble mediator of pulmonary apoptosis and lung microvascular barrier dysfunction during ischemic AKI. We further elucidated pathways of TNFR1-mediated apoptosis with NF-κB (Complex I) and caspase-8 (Complex II) expression and discovered that TNFR1 proapoptotic signaling induces NF-κB activation. Additionally, inhibition of NF-κB (Complex I) resulted in a proapoptotic phenotype, lung barrier leak, and altered cellular flice inhibitory protein signaling independent of caspase-8 (Complex II) activation. Ischemic AKI activates soluble TNF-α and induces TNFR1-dependent pulmonary apoptosis through augmentation of the prosurvival and proapoptotic TNFR1 signaling pathway. Kidney-lung crosstalk after ischemic AKI represents a complex pathological process, yet focusing on specific biological pathways may yield potential future therapeutic targets.

  7. TNFR1-dependent pulmonary apoptosis during ischemic acute kidney injury

    PubMed Central

    White, Laura E.; Santora, Rachel J.; Cui, Yan; Moore, Frederick A.

    2012-01-01

    Despite advancements in renal replacement therapy, the mortality rate for acute kidney injury (AKI) remains unacceptably high, likely due to remote organ injury. Kidney ischemia-reperfusion injury (IRI) activates cellular and soluble mediators that incite a distinct pulmonary proinflammatory and proapoptotic response. Tumor necrosis factor receptor 1 (TNFR1) has been identified as a prominent death receptor activated in the lungs during ischemic AKI. We hypothesized that circulating TNF-α released from the postischemic kidney induces TNFR1-mediated pulmonary apoptosis, and we aimed to elucidate molecular pathways to programmed cell death. Using an established murine model of kidney IRI, we characterized the time course for increased circulatory and pulmonary TNF-α levels and measured concurrent upregulation of pulmonary TNFR1 expression. We then identified TNFR1-dependent pulmonary apoptosis after ischemic AKI using TNFR1−/− mice. Subsequent TNF-α signaling disruption with Etanercept implicated circulatory TNF-α as a key soluble mediator of pulmonary apoptosis and lung microvascular barrier dysfunction during ischemic AKI. We further elucidated pathways of TNFR1-mediated apoptosis with NF-κB (Complex I) and caspase-8 (Complex II) expression and discovered that TNFR1 proapoptotic signaling induces NF-κB activation. Additionally, inhibition of NF-κB (Complex I) resulted in a proapoptotic phenotype, lung barrier leak, and altered cellular flice inhibitory protein signaling independent of caspase-8 (Complex II) activation. Ischemic AKI activates soluble TNF-α and induces TNFR1-dependent pulmonary apoptosis through augmentation of the prosurvival and proapoptotic TNFR1 signaling pathway. Kidney-lung crosstalk after ischemic AKI represents a complex pathological process, yet focusing on specific biological pathways may yield potential future therapeutic targets. PMID:22728466

  8. Acute adenosinergic cardioprotection in ischemic-reperfused hearts.

    PubMed

    Headrick, John P; Hack, Ben; Ashton, Kevin J

    2003-11-01

    Cells of the cardiovascular system generate and release purine nucleoside adenosine in increasing quantities when constituent cells are "stressed" or subjected to injurious stimuli. This increased adenosine can interact with surface receptors in myocardial, vascular, fibroblast, and inflammatory cells to modulate cellular function and phenotype. Additionally, adenosine is rapidly reincorporated back into 5'-AMP to maintain the adenine nucleotide pool. Via these receptor-dependent and independent (metabolic) paths, adenosine can substantially modify the acute response to ischemic insult, in addition to generating a more sustained ischemia-tolerant phenotype (preconditioning). However, the molecular basis for acute adenosinergic cardioprotection remains incompletely understood and may well differ from more widely studied preconditioning. Here we review current knowledge and some controversies regarding acute cardioprotection via adenosine and adenosine receptor activation.

  9. Neutrophils Are a Source of Gamma Interferon during Acute Salmonella enterica Serovar Typhimurium Colitis

    PubMed Central

    Spees, Alanna M.; Kingsbury, Dawn D.; Wangdi, Tamding; Xavier, Mariana N.; Tsolis, Renée M.

    2014-01-01

    Gamma interferon (IFN-γ) is an important driver of intestinal inflammation during colitis caused by Salmonella enterica serovar Typhimurium. Here we used the mouse colitis model to investigate the cellular sources of IFN-γ in the cecal mucosa during the acute phase of an S. Typhimurium infection. While IFN-γ staining was detected in T cells, NK cells, and inflammatory monocytes at 2 days after infection, the majority of IFN-γ-positive cells in the cecal mucosa were neutrophils. Furthermore, neutrophil depletion blunted mucosal Ifng expression and reduced the severity of intestinal lesions during S. Typhimurium infection. We conclude that neutrophils are a prominent cellular source of IFN-γ during the innate phase of S. Typhimurium-induced colitis. PMID:24421037

  10. Plasminogen Activators and Ischemic Stroke: Conditions for Acute Delivery

    PubMed Central

    del Zoppo, Gregory J

    2013-01-01

    Appropriate acute treatment with plasminogen activators (PAs) can significantly increase the probability of minimal or no disability in selected ischemic stroke patients. There is a great deal of evidence showing that intravenous recombinant tissue PAs (rt-PA) infusion accomplishes this goal, recanalization with other PAs has also been demonstrated in the development of this treatment. Recanalization of symptomatic, documented carotid or vertebrobasilar arterial territory occlusions have also been achieved by local intra-arterial PA delivery, although only a single prospective double-blinded randomized placebo-controlled study has been reported. The increase in intracerebral hemorrhage with these agents by either delivery approach underscores the need for careful patient selection, dose-appropriate safety and efficacy, proper clinical trial design, and an understanding of the evolution of cerebral tissue injury due to focal ischemia. Principles underlying the evolution of focal ischemia have been expanded by experience with acute PA intervention. Several questions remain open that concern the manner in which PAs can be applied acutely in ischemic stroke and how injury development can be limited. PMID:23539414

  11. Innate immune inflammatory response in the acutely ischemic myocardium.

    PubMed

    Deftereos, Spyridon; Angelidis, Christos; Bouras, Georgios; Raisakis, Konstantinos; Gerckens, Ulrich; Cleman, Michael W; Giannopoulos, Georgios

    2014-01-01

    The "holy grail" of modern interventional cardiology is the salvage of viable myocardial tissue in the distribution of an acutely occluded coronary artery. Thrombolysis and percutaneous coronary interventions, provided they can be delivered on time, can interrupt the occlusion and save tissue. At the same time restoring the patency of the coronary vessels and providing the ischemic myocardium with blood can cause additional tissue damage. A key element of ischemic and reperfusion injury and major determinant of the evolution of damage in the injured myocardium is the inflammatory response. The innate immune system initiates and directs this response which is a prerequisite for subsequent healing. The complement cascade is set in motion following the release of subcellular membrane constituents. Endogenous 'danger' signals known as danger-associated molecular patterns (DAMPs) released from ischemic and dying cells alert the innate immune system and activate several signal transduction pathways through interactions with the highly conserved Toll like receptors (TLRs). Reactive oxygen species (ROS) generation directly induces pro-inflammatory cascades and triggers formation of the inflammasome. The challenge lies into designing strategies that specifically block the inflammatory cascades responsible for tissue damage without affecting those concerned with tissue healing.

  12. Imaging-based management of acute ischemic stroke patients: current neuroradiological perspectives.

    PubMed

    Na, Dong Gyu; Sohn, Chul-Ho; Kim, Eung Yeop

    2015-01-01

    Advances in imaging-based management of acute ischemic stroke now provide crucial information such as infarct core, ischemic penumbra/degree of collaterals, vessel occlusion, and thrombus that helps in the selection of the best candidates for reperfusion therapy. It also predicts thrombolytic efficacy and benefit or potential hazards from therapy. Thus, radiologists should be familiar with various imaging studies for patients with acute ischemic stroke and the applicability to clinical trials. This helps radiologists to obtain optimal rapid imaging as well as its accurate interpretation. This review is focused on imaging studies for acute ischemic stroke, including their roles in recent clinical trials and some guidelines to optimal interpretation.

  13. Acute oxalate nephropathy associated with Clostridium difficile colitis.

    PubMed

    Cohen-Bucay, Abraham; Garimella, Pranav; Ezeokonkwo, Chukwudi; Bijol, Vanesa; Strom, James A; Jaber, Bertrand L

    2014-01-01

    We report the case of a 69-year-old man who presented with acute kidney injury in the setting of community-acquired Clostridium difficile-associated diarrhea and biopsy-proven acute oxalate nephropathy. We discuss potential mechanisms, including increased colonic permeability to oxalate. We conclude that C difficile-associated diarrhea is a potential cause of acute oxalate nephropathy. PMID:24183111

  14. Colitis after Hibiclens enema.

    PubMed

    Hardin, R D; Tedesco, F J

    1986-10-01

    Acute colitis occurred after a Hibiclens cleanser enema. Endoscopic and histologic features were not helpful in distinguishing this colitis from an infectious or idiopathic colitis, and a careful history proved invaluable. We review the complications of using soapsuds and various chemical-containing enemas; these complications range from mild colitis to death. Because soap and other chemicals are damaging to colonic mucosa, these enemas should be included as a cause of acute colitis.

  15. Ulcerative colitis presenting as acute infectious gastroenteritis with a paralytic ileus

    PubMed Central

    Schoenmaker, Suzanne Gerdien; Tjon a Ten, Walther E

    2012-01-01

    A 15-year-old girl who presented with signs of acute infectious gastroenteritis, just as two members of her family is described. As the patient did not improve, a sigmoidoscopy was performed and the diagnosis of ulcerative colitis (UC) was made. Our hypothesis is that an infection triggered the development of UC. Her paralytic ileus was probably triggered by the increased nitric oxide produced in the macrophages and smooth muscles of the inflamed bowel. PMID:22605860

  16. Intestinal Epithelial Cell Tyrosine Kinase 2 Transduces IL-22 Signals To Protect from Acute Colitis

    PubMed Central

    Hainzl, Eva; Rauch, Isabella; Heider, Susanne; Berry, David; Lassnig, Caroline; Schwab, Clarissa; Rosebrock, Felix; Milinovich, Gabriel; Schlederer, Michaela; Wagner, Michael; Schleper, Christa; Loy, Alexander; Urich, Tim; Kenner, Lukas; Han, Xiaonan; Decker, Thomas; Strobl, Birgit

    2015-01-01

    In the intestinal tract, IL-22 activates STAT3 to promote intestinal epithelial cell (IEC) homeostasis and tissue healing. The mechanism has remained obscure, but we demonstrate that IL-22 acts via tyrosine kinase 2 (Tyk2), a member of the Jak family. Using a mouse model for colitis, we show that Tyk2 deficiency is associated with an altered composition of the gut microbiota and exacerbates inflammatory bowel disease. Colitic Tyk2−/− mice have less p-STAT3 in colon tissue and their IECs proliferate less efficiently. Tyk2-deficient primary IECs show reduced p-STAT3 in response to IL-22 stimulation, and expression of IL-22–STAT3 target genes is reduced in IECs from healthy and colitic Tyk2−/− mice. Experiments with conditional Tyk2−/− mice reveal that IEC-specific depletion of Tyk2 aggravates colitis. Disease symptoms can be alleviated by administering high doses of rIL-22–Fc, indicating that Tyk2 deficiency can be rescued via the IL-22 receptor complex. The pivotal function of Tyk2 in IL-22–dependent colitis was confirmed in Citrobacter rodentium–induced disease. Thus, Tyk2 protects against acute colitis in part by amplifying inflammation-induced epithelial IL-22 signaling to STAT3. PMID:26432894

  17. Glutaraldehyde-induced colitis

    PubMed Central

    Stein, Barry L.; Lamoureux, Esther; Miller, Mark; Vasilevsky, Carol-Ann; Julien, Lynne; Gordon, Philip H.

    2001-01-01

    Objective To describe the etiology and clinical course of acute colitis occurring after flexible endoscopy. Design Chart review. Setting A university teaching hospital. Patients Eight patients who sought assessment of potential colonic disease. Intervention Colonoscopy in 5 patients and flexible sigmoidoscopy in 3 patients. The indication for endoscopy was screening in 5 patients, cancer surveillance in 2 patients and preoperative evaluation of colon carcinoma in 1 patient. Outcome measures The relation of presenting symptoms to glutaraldehyde exposure, the response to therapy and the need for further therapy. Results All patients had abdominal pain, mucus diarrhea and rectal bleeding within 48 hours after endoscopy. Most patients reported that the symptoms started within 12 hours of the procedure. All patients were confirmed by sigmoidoscopy to have colitis within 72 hours of the first endoscopic procedure. One patient required hospitalization. In the first 7 patients several stool cultures were negative for Clostridium difficile using the cytotoxin assay by the cell culture method. Four patients had negative cultures for Yersinia, Salmonella and Shigella spp. Three patients were treated with metronidazole initially. Two patients underwent endoscopic biopsy and examination of the biopsy specimen showed fibrinoleukocytic exudate and ischemic type injury. One patient underwent the scheduled sigmoid resection within 48 hours of endoscopy for a Dukes’ stage B adenocarcinoma. Concomitant acute ischemic colitis limited to the mucosa and submucosa was noted in the resected specimen. Symptoms resolved in all patients and follow-up endoscopy revealed normal mucosa. Conclusion The entity of glutaraldehyde-induced colitis should be recognized and special attention should be given during instrument cleansing to minimize the risk of its development. PMID:11308232

  18. Preventive use of Lactobacillus plantarum LS/07 and inulin to relieve symptoms of acute colitis.

    PubMed

    Hijová, Emília; Šoltésová, Alena; Salaj, Rastislav; Kuzma, Jozef; Strojný, Ladislav; Bomba, Alojz; Gregová, Kristína

    2015-01-01

    The aim of presented study was to investigate the influence of Lactobacillus plantarum LS/07 and inulin on the activity of β-glucuronidase enzyme, and counts of coliform and lactobacilli in fresh caecal digesta, cytokine levels (IL-6, IL-8), and trancription nuclear factor kappa beta (NFκB) activities in colon tissue and blood samples of rats with dextran sulphate sodium (DSS) induced acute colitis. The rats were randomly divided into four groups - CG, AC, AC+PRE and AC+PRO. Colitis was induced using of 5% DSS in drinking water for 7d. DSS application increased activity of β-glucuronidase (P < 0.001), increased counts of coliforms, and decreased lactobacilli counts (P < 0.05) in comparison to control group. Serum and tissue levels of IL-6 and IL-8 as well as tissue NFκB activities showed increased expression in acute colitis group. Inulin diet modified counts of microorganims and decreased β-glucuronidase activity, suppressed NFκB activities (P < 0.001) and down regulate synthesis of IL-6 (P < 0.01) in serum and colon tissue and tissue IL-8 (P < 0.05). Lactobacillus plantarum LS/07 decreased β-glucuronidase activity (P < 0.05), levels of IL-6 and IL-8 (P < 0.001). These results were consistent with the addition of histological findings. Our results indicate that dietary intake of Lactobacillus plantarum LS/07 and inulin suppressed expression observed markers, which play an important role in the inflammatory process, which predisposes their use in prevention or treatment of acute colitis.

  19. Emergency EEG and continuous EEG monitoring in acute ischemic stroke.

    PubMed

    Jordan, Kenneth G

    2004-01-01

    There is physiologic coupling of EEG morphology, frequencies, and amplitudes with cerebral blood flow. Intraoperative continuous electroencephalographic monitoring (CEEG) is an established modality that has been used for 30 years to detect cerebral ischemia during carotid surgery. These facts have generated interest in applying EEG/CEEG in the intensive care unit to monitor cerebral ischemia. However, its use in acute ischemic stroke (AIS) has been limited, and its value has been questioned in comparison with modern MRI imaging techniques and the clinical neurologic examination. This review presents evidence that EEG/CEEG adds value to early diagnosis, outcome prediction, patient selection for treatment, clinical management, and seizure detection in AIS. Research studies correlating EEG/CEEG and advanced imaging techniques in AIS are encouraged. Improvements in real-time ischemia detection systems are needed for EEG/CEEG to have wider application in AIS. PMID:15592008

  20. Laryngeal Elevation Velocity and Aspiration in Acute Ischemic Stroke Patients

    PubMed Central

    Zhang, Jing; Zhou, Yun; Wei, Na; Yang, Bo; Wang, Anxin; Zhou, Hai; Zhao, Xingquan; Wang, Yongjun; Liu, Liping; Ouyoung, Melody; Villegas, Brenda; Groher, Michael

    2016-01-01

    Objectives Aspiration after stroke has been associated with aspiration pneumonia, which contributes to increased mortality of stroke. Laryngeal elevation is a core mechanism for protection from aspiration. Few studies have explored the predictive value of laryngeal elevation velocity for aspiration after stroke. This study aimed to explore the ability of laryngeal elevation velocity to predict aspiration in patients with acute ischemic stroke. Methods This was a prospective cohort study that included consecutive acute ischemic stroke patients treated at a teaching hospital during a 10-month period. Patients underwent magnetic resonance imaging (MRI) to confirm the diagnosis of acute ischemic stroke. Patients who were at risk of aspiration and could swallow 5 ml of diluted barium (40%, w/v) for a videofluoroscopic swallowing (VFS) study were included. The association between abnormal indices in the oral and pharyngeal phase of the VFS study and aspiration was examined using univariate analyses. These indices included the lip closure, tongue movement and control, laryngeal elevation velocity and range, the latency of pharyngeal swallowing, pharyngeal transit time (PTT), abnormal epiglottis tilt, residual barium in the pharynx, and the duration of upper esophageal sphincter (UES) opening. The laryngeal elevation velocity (%/s) was calculated as the range of laryngeal elevation (%) from the resting position to the maximum superior position or to the position where the laryngeal vestibule is fully closed divided by the corresponding duration of laryngeal elevation. The range of laryngeal elevation (%) was the percentage calculated as the distance between the resting laryngeal position and the maximum superior excursion position or position where the laryngeal vestibule is fully closed divided by the distance between the resting laryngeal position and the lowest edge of the mandible. A logistic regression analysis was used to determine the predictive value for aspiration

  1. Absence of stearoyl-CoA desaturase-1 does not promote DSS-induced acute colitis

    PubMed Central

    MacDonald, Marcia L.E.; Bissada, Nagat; Vallance, Bruce A.; Hayden, Michael R.

    2009-01-01

    Absence of stearoyl-CoA desaturase-1 (SCD1) in mice leads to chronic inflammation of the skin and increased susceptibility to atherosclerosis, while also increasing plasma inflammatory markers. A recent report suggested that SCD1 deficiency also increases disease severity in a mouse model of inflammatory bowel disease, induced by dextran sulfate sodium (DSS). However, SCD1-deficient mice are known to consume increased amounts of water, which would also be expected to increase the intake of DSS-treated water. The aim of this study was to determine the effect of SCD1 deficiency on DSS-induced acute colitis with DSS dosing adjusted to account for genotype differences in fluid consumption. Wild-type controls were treated with 3.5% DSS for 5 days to induce moderately severe colitis, while the concentration of DSS given to SCD1-deficient mice was lowered to 2.5% to control for increased fluid consumption. Colonic inflammation was assessed by clinical and histological scoring. Although SCD1-deficient mice consumed a total intake of DSS that was greater than that of wild-type controls, colonic inflammation, colon length and fecal blood were not altered by SCD1-deficiency in DSS-induced colitis, while diarrhea and total weight loss were modestly improved. Despite SCD1 deficiency leading to chronic inflammation of the skin and increased susceptibility to atherosclerosis, it does not accelerate inflammation in the DSS-induced model of acute colitis when DSS intake is controlled. These observations suggest that SCD1 deficiency does not play a significant role in colonic inflammation in this model. PMID:19695343

  2. Current trends in the management of acute ischemic stroke.

    PubMed

    Paramasivam, Srinivasan

    2015-01-01

    Stroke is the leading cause of disability and most of the cases are those of ischemic stroke. Management strategies especially for large vessel occlusive stroke have undergone a significant change in the recent years that include widespread use of thrombolytic medications followed by endovascular clot removal. For successful treatment by endovascular thrombectomy, the important factors are patient selection based on clinical criterion including age, time of onset, premorbid clinical condition, co-morbidities, National Institute of Health Stroke Scale, and imaging criterion including computed tomography (CT) head, CT angiogram and CT perfusion. Patients presenting within 4.5 hours of onset are considered for intravenous (IV) recombinant tissue plasminogen activator treatment. Mechanical clot retrieval devices have evolved over the past decade. The Mechanical Embolus Removal in Cerebral Ischemia device was approved first followed by the penumbra revascularization system. They have proven in various studies to improve recanalization with acceptable rates of symptomatic intra-cerebral hemorrhage. Introduction of stent retrievers has led to a new era in the interventional management of acute ischemic stroke (AIS). Recent trials namely MRCLEAN, ESCAPE, SWIFT PRIMEs, and EXTEND-IA have used the stent retriever predominantly and have shown unequivocal benefit in the outcome at 90 days for AIS patients with large vessel occlusion. More recently, a new catheter namely 5 MAX ACE was introduced along with improvement in the suction device. This has led to a direct aspiration first pass technique resulting in faster recanalization. Advancements in the endovascular management of AIS with large vessel occlusion have resulted in a paradigm shift in the way this disease is managed. Improvements in patient selection using clinical and imaging criterion along with technical and technological advancements in mechanical thrombectomy have made possible a significantly improved outcome

  3. Current trends in the management of acute ischemic stroke.

    PubMed

    Paramasivam, Srinivasan

    2015-01-01

    Stroke is the leading cause of disability and most of the cases are those of ischemic stroke. Management strategies especially for large vessel occlusive stroke have undergone a significant change in the recent years that include widespread use of thrombolytic medications followed by endovascular clot removal. For successful treatment by endovascular thrombectomy, the important factors are patient selection based on clinical criterion including age, time of onset, premorbid clinical condition, co-morbidities, National Institute of Health Stroke Scale, and imaging criterion including computed tomography (CT) head, CT angiogram and CT perfusion. Patients presenting within 4.5 hours of onset are considered for intravenous (IV) recombinant tissue plasminogen activator treatment. Mechanical clot retrieval devices have evolved over the past decade. The Mechanical Embolus Removal in Cerebral Ischemia device was approved first followed by the penumbra revascularization system. They have proven in various studies to improve recanalization with acceptable rates of symptomatic intra-cerebral hemorrhage. Introduction of stent retrievers has led to a new era in the interventional management of acute ischemic stroke (AIS). Recent trials namely MRCLEAN, ESCAPE, SWIFT PRIMEs, and EXTEND-IA have used the stent retriever predominantly and have shown unequivocal benefit in the outcome at 90 days for AIS patients with large vessel occlusion. More recently, a new catheter namely 5 MAX ACE was introduced along with improvement in the suction device. This has led to a direct aspiration first pass technique resulting in faster recanalization. Advancements in the endovascular management of AIS with large vessel occlusion have resulted in a paradigm shift in the way this disease is managed. Improvements in patient selection using clinical and imaging criterion along with technical and technological advancements in mechanical thrombectomy have made possible a significantly improved outcome

  4. [Amebic colitis and liver abscess complicated by high serum procalcitonin in acute myeloid leukemia].

    PubMed

    Oku, Eijiro; Nomura, Kei; Nakamura, Takayuki; Morishige, Satoshi; Seki, Ritsuko; Imamura, Rie; Hashiguchi, Michitoshi; Osaki, Kouichi; Mizuno, Shinichi; Nagafuji, Koji; Okamura, Takashi

    2012-11-01

    We present a case of amebic colitis and liver abscess complicated by acute myeloid leukemia (AML) with high serum procalcitonin (PCT). A 61-year-old Japanese man seen at our hospital for severe diarrhea and high fever was found to have multiple ulcers in the transverse and sigmoid colon and rectum by colonoscopy and biopsies were conducted. Immature leukocytes with mild anemia and thrombocytopenia were seen in peripheral blood, necessitating bone marrow aspiration and biopsy that yielded a diagnosis of AML (FAB M4Eo). Serum C-reactive protein and PCT were extremely elevated. Blood cultures for bacteria and fungi were negative. Multiple low-density areas in the liver were found in abdominal computed tomography. Histological colon biopsy findings revealed amebic colitis, strongly suggesting amebic liver abscess. Metronidazole treatment was initiated for amebiasis and subsequent standard chemotherapy for AML was followed after fever was lowered. Hematological and cytogenetic CR was maintained with good clinical condition. Few case reports have been published in Japan to date on amebic colitis and liver abscess complicated by AML and no reports have been made on PCT elevation caused by amebiasis. In conclusion, differential diagnosis of amebiasis is necessary in addition to that of bacterial or fungal infection in serum PCT elevation. PMID:23367854

  5. Dietary unsaponifiable fraction from extra virgin olive oil supplementation attenuates acute ulcerative colitis in mice.

    PubMed

    Sánchez-Fidalgo, S; Cárdeno, A; Sánchez-Hidalgo, M; Aparicio-Soto, M; Villegas, I; Rosillo, M A; de la Lastra, C Alarcón

    2013-02-14

    Extra virgin olive oil (EVOO) has demonstrated immunomodulatory and antiinflammatory properties in murine experimental ulcerative colitis (UC). In addition to its high monounsaturated fatty acid content, evidences have accumulated on the favorable properties of minor, although highly bioactive, components present in the unsaponifiable fraction (UF). The present study was designed to evaluate the effects of dietary EVOO's UF supplementation on acute UC. C57BL/6 mice were fed from weaning with sunflower oil (SD), EVOO diet and UF-enriched SD at 5% oil (SD+UF). After 30 days, mice were exposed to 3% dextran sulfate sodium (DSS) for 5 days developing acute colitis. After 4 days of DSS removal, animals were sacrificed and colons were histological and biochemically processed. Disease activity index and microscopic damage score were significantly improved in EVOO and SD+UF dietary groups versus SD group. In addition, both dietary treatments significantly induced decreases in MCP-1 and TNF-α levels, iNOS and COX-2 overexpression and p38 MAPKs activation in colon mucosa. Moreover, an upregulation of IκB expression was also observed after feeding the animals with both diets. However, no statistically differences between data from mice fed with EVOO or UF+SD diets were observed. Dietary enrichment with EVOO's UF reduces the damage in acute colitis model, alleviating the oxidative events and returning proinflammatory proteins expression to basal levels probably through p38 MAPK and NFκB signalling pathways. EVOO's UF diet might provide a basis for developing a new strategy in dietary supplementation for the prevention of UC.

  6. Traditional Chinese Patent Medicine for Acute Ischemic Stroke

    PubMed Central

    Zhang, Xin; Liu, Xue-Ting; Kang, De-Ying

    2016-01-01

    Abstract The aim of the study is to conduct an overview of systematic reviews (SRs) to provide a contemporary review of the evidence for delivery of Traditional Chinese Patent Medicine (TCPMs) for patients with acute ischemic stroke. SRs were assessed for quality using the Assessment of Multiple Systematic Reviews (AMSTAR) tool and the Oxman-Guyatt Overview Quality Assessment Questionnaire (OQAQ). We assessed the quality of the evidence of high methodological quality (an AMSTAR score ≥9 or an OQAQ score ≥7) for reported outcomes using the GRADE (the Grading of Recommendations Assessment, Development and Evaluation) approach. (1) Dan Shen agents: tiny trends toward the improvement in different neurological outcomes (RR = 1.16, 1.10, 1.23, 1.08, 1.12); (2) Mailuoning: a tiny trend toward improvement in the neurological outcome (RR = 1.18); (3) Ginkgo biloba: tiny trends toward improvement in the neurological outcome (RR = 1.18, MD = 0.81); (4) Dengzhanhua: a tiny trend toward an improvement in neurological (RR = 1.23); (5) Acanthopanax: a small positive (RR = 1.17, 1.31) result on neurological improvement reported; (6) Chuanxiong-type preparations: neurological functional improved (MD = 2.90);(7) Puerarin: no better effect on the rate of death or disability (OR = 0.81, 95% CI 0.35–1.87); (8) Milk vetch: no better effect on the rate of death (OR = 0.66, 95% CI: 0.11–2.83);(9) Qingkailing: rate of death reduced (OR = 0.66, 95% CI: 0.11–2.83). Limitations in the methodological quality of the RCTs, inconsistency and imprecision led to downgrading of the quality of the evidence, which varied by review and by outcome. Consequently, there are currently only weak evidences to support those TCPMs. The 9 TCPMs may be effective in the treatment of acute ischemic stroke, as the GRADE approach indicated a weak recommendation for those TCPMs’ usage. PMID:27015174

  7. Cardiovascular risk factors for acute stroke: Risk profiles in the different subtypes of ischemic stroke.

    PubMed

    Arboix, Adrià

    2015-05-16

    Timely diagnosis and control of cardiovascular risk factors is a priority objective for adequate primary and secondary prevention of acute stroke. Hypertension, atrial fibrillation and diabetes mellitus are the most common risk factors for acute cerebrovascular events, although novel risk factors, such as sleep-disordered breathing, inflammatory markers or carotid intima-media thickness have been identified. However, the cardiovascular risk factors profile differs according to the different subtypes of ischemic stroke. Atrial fibrillation and ischemic heart disease are more frequent in patients with cardioembolic infarction, hypertension and diabetes in patients with lacunar stroke, and vascular peripheral disease, hypertension, diabetes, previous transient ischemic attack and chronic obstructive pulmonary disease in patients with atherothrombotic infarction. This review aims to present updated data on risk factors for acute ischemic stroke as well as to describe the usefulness of new and emerging vascular risk factors in stroke patients.

  8. Cardiovascular risk factors for acute stroke: Risk profiles in the different subtypes of ischemic stroke.

    PubMed

    Arboix, Adrià

    2015-05-16

    Timely diagnosis and control of cardiovascular risk factors is a priority objective for adequate primary and secondary prevention of acute stroke. Hypertension, atrial fibrillation and diabetes mellitus are the most common risk factors for acute cerebrovascular events, although novel risk factors, such as sleep-disordered breathing, inflammatory markers or carotid intima-media thickness have been identified. However, the cardiovascular risk factors profile differs according to the different subtypes of ischemic stroke. Atrial fibrillation and ischemic heart disease are more frequent in patients with cardioembolic infarction, hypertension and diabetes in patients with lacunar stroke, and vascular peripheral disease, hypertension, diabetes, previous transient ischemic attack and chronic obstructive pulmonary disease in patients with atherothrombotic infarction. This review aims to present updated data on risk factors for acute ischemic stroke as well as to describe the usefulness of new and emerging vascular risk factors in stroke patients. PMID:25984516

  9. Cardiovascular risk factors for acute stroke: Risk profiles in the different subtypes of ischemic stroke

    PubMed Central

    Arboix, Adrià

    2015-01-01

    Timely diagnosis and control of cardiovascular risk factors is a priority objective for adequate primary and secondary prevention of acute stroke. Hypertension, atrial fibrillation and diabetes mellitus are the most common risk factors for acute cerebrovascular events, although novel risk factors, such as sleep-disordered breathing, inflammatory markers or carotid intima-media thickness have been identified. However, the cardiovascular risk factors profile differs according to the different subtypes of ischemic stroke. Atrial fibrillation and ischemic heart disease are more frequent in patients with cardioembolic infarction, hypertension and diabetes in patients with lacunar stroke, and vascular peripheral disease, hypertension, diabetes, previous transient ischemic attack and chronic obstructive pulmonary disease in patients with atherothrombotic infarction. This review aims to present updated data on risk factors for acute ischemic stroke as well as to describe the usefulness of new and emerging vascular risk factors in stroke patients. PMID:25984516

  10. Pseudomembranous Colitis

    PubMed Central

    Farooq, Priya D.; Urrunaga, Nathalie H.; Tang, Derek M.; von Rosenvinge, Erik C.

    2015-01-01

    Pseudomembranous colitis is an inflammatory condition of the colon characterized by elevated yellow-white plaques that coalesce to form pseudomembranes on the mucosa. Patients with the condition commonly present with abdominal pain, diarrhea, fever, and leukocytosis. Because pseudomembranous colitis is often associated with C. difficile infection, stool testing and empiric antibiotic treatment should be initiated when suspected. When results of C. difficile testing are negative and symptoms persist despite escalating empiric treatment, early gastroenterology consultation and lower endoscopy would be the next step in the appropriate clinical setting. If pseudomembranous colitis is confirmed endoscopically, colonic biopsies should be obtained, as histology can offer helpful clues to the underlying diagnosis. The less common non-C. difficile causes of pseudomembranous colitis should be entertained, as a number of etiologies can result in this condition. Examples include Behcet’s disease, collagenous colitis, inflammatory bowel disease, ischemic colitis, other infections organisms (e.g. bacteria, parasites, viruses), and a handful of drugs and toxins. Pinpointing the correct underlying etiology would better direct patient care and disease management. Surgical specialists would be most helpful in colonic perforation, gangrenous colon, or severe disease. PMID:25769243

  11. MAR binding protein SMAR1 favors IL-10 mediated regulatory T cell function in acute colitis

    SciTech Connect

    Mirlekar, Bhalchandra; Patil, Sachin; Bopanna, Ramanamurthy; Chattopadhyay, Samit

    2015-08-21

    T{sub reg} cells are not only crucial for controlling immune responses to autoantigens but also prevent those directed towards commensal pathogens. Control of effector immune responses by T{sub reg} cells depend on their capacity to accumulate at inflammatory site and accordingly accommodate to inflammatory environment. Till date, the factors associated with maintaining these aspects of T{sub reg} phenotype is not understood properly. Here we have shown that a known nuclear matrix binding protein SMAR1 is selectively expressed more in colonic T{sub reg} cells and is required for their ability to accumulate at inflammatory site and to sustain high levels of Foxp3 and IL-10 expression during acute colitis. Elimination of anti-inflammatory subsets revealed a protective role for IL-10 producing T{sub reg} cells in SMAR1{sup −/−} mice. Moreover, a combined action of Foxp3 and SMAR1 restricts effector cytokine production and enhance the production of IL-10 by colonic T{sub reg} cells that controls acute colitis. This data highlights a critical role of SMAR1 in maintaining T{sub reg} physiology during inflammatory disorders. - Highlights: • SMAR1 is essential to sustain high level of Foxp3 and IL-10 in T{sub reg} cells. • SMAR1{sup −/−} T{sub reg} cells produce pro-inflammatory cytokine IL-17 leads to inflammation. • IL-10 administration can control the inflammation in SMAR1{sup −/−} mice. • Both Foxp3 and SMAR1 maintain T{sub reg} phenotype that controls colitis.

  12. Gut microbiota affects sensitivity to acute DSS-induced colitis independently of host genotype.

    PubMed

    Brinkman, Brigitta M; Becker, Anne; Ayiseh, Rene B; Hildebrand, Falk; Raes, Jeroen; Huys, Geert; Vandenabeele, Peter

    2013-11-01

    Caspase-deficient mice and wild-type (WT) mice show significant differences in their gut microbiota composition. These differences coincide with the observation that caspase-3-deficient mice carrying a natural caspase-11 mutation (Casp3/11(-/-)) are less sensitive to acute dextran sodium sulfate-induced colitis than WT mice. For these reasons, we investigated the role of the microbiota in the development of colitis by cohousing WT and Casp3/11(-/-) mice. Microbial community fingerprinting by denaturing gradient gel electrophoresis analysis revealed that the similarities in gut microbial composition of WT and Casp3/11(-/-) mice increased after cohousing. In the acute dextran sodium sulfate-induced colitis model, Casp3/11(-/-) mice that were cohoused with WT mice showed increased weight loss and disease activity scores and increased neutrophil infiltration and inflammatory cytokine levels in their colon tissue compared with Casp3/11(-/-) mice that were not cohoused with WT mice. Also, we demonstrate that only the microbiota of the Casp3/11(-/-) mice cohoused with WT mice showed an important increase in Prevotella species. In conclusion, our cohousing experiments revealed that the colitogenic activity of the WT microbiota is transferable to Casp3/11(-/-) mice and that Prevotella species are likely to be involved. By contrast, the relative protection of Casp3/11(-/-) mice against dextran sodium sulfate damage is not transferred to WT mice after cohousing. These results underscore the need for in-depth studies of the bilateral interaction of host genes and microbiota to gain insight into the mechanisms of disease pathogenesis. Our findings also have important implications for the experimental design of disease studies in genetically modified mice and conclusions drawn from them. PMID:24105395

  13. Current knowledge on the neuroprotective and neuroregenerative properties of citicoline in acute ischemic stroke

    PubMed Central

    Martynov, Mikhail Yu; Gusev, Eugeny I

    2015-01-01

    Ischemic stroke is one of the leading causes of long-lasting disability and death. Two main strategies have been proposed for the treatment of ischemic stroke: restoration of blood flow by thrombolysis or mechanical thrombus extraction during the first few hours of ischemic stroke, which is one of the most effective treatments and leads to a better functional and clinical outcome. The other direction of treatment, which is potentially applicable to most of the patients with ischemic stroke, is neuroprotection. Initially, neuroprotection was mainly targeted at protecting gray matter, but during the past few years there has been a transition from a neuron-oriented approach toward salvaging the whole neurovascular unit using multimodal drugs. Citicoline is a multimodal drug that exhibits neuroprotective and neuroregenerative effects in a variety of experimental and clinical disorders of the central nervous system, including acute and chronic cerebral ischemia, intracerebral hemorrhage, and global cerebral hypoxia. Citicoline has a prolonged therapeutic window and is active at various temporal and biochemical stages of the ischemic cascade. In acute ischemic stroke, citicoline provides neuroprotection by attenuating glutamate exitotoxicity, oxidative stress, apoptosis, and blood–brain barrier dysfunction. In the subacute and chronic phases of ischemic stroke, citicoline exhibits neuroregenerative effects and activates neurogenesis, synaptogenesis, and angiogenesis and enhances neurotransmitter metabolism. Acute and long-term treatment with citicoline is safe and in most clinical studies is effective and improves functional outcome. PMID:27186142

  14. Acute extensive ischemic enteritis in a young man diagnosed with wireless capsule endoscopy: a case report.

    PubMed

    Jeong, Woo Seong; Song, Hyun Joo; Na, Soo Young; Boo, Sun Jin; Kim, Heung Up; Kim, Jinseok; Choi, Guk Myung

    2013-03-25

    Ischemic enteritis is caused by either the interruption or significant reduction of arterial inflow to the small intestine. Risk factors are old age, diabetes mellitus and cardiovascular disease. It is very rare in young patients. We experienced a 21-year-old man with recurrent acute ischemic enteritis who was diagnosed with capsule endoscopy. He had previously taken medications for pulmonary hypertension and obstruction of both carotid arteries, and about 20 months earlier, he had been admitted due to hematochezia. Two sessions of angiography did not reveal the cause of hematochezia. At that time, capsule endoscopy showed mucosal edema and erythema in the terminal ileum, suggesting healed ischemic enteritis. The patient was admitted again due to hematochezia. Abdominal computed tomography showed focal celiac trunk stenosis and diffuse wall thickening of the small intestine, suggesting ischemic enteritis. Capsule endoscopy showed multiple active ulcers and severe hemorrhage with exudate, extending from the proximal jejunum to the terminal ileum. Using capsule endoscopy, the patient was diagnosed with acute extensive ischemic enteritis. Because endoscopic images of ischemic enteritis have rarely been reported, we report a case of a 21-year-old man who was diagnosed acute extensive ischemic enteritis with capsule endoscopy.

  15. The Quest for Arterial Recanalization in Acute Ischemic Stroke-The Past, Present and the Future

    PubMed Central

    L.L.Yeo, Leonard; Sharma, Vijay K

    2013-01-01

    Ischemic stroke is one of the major causes of mortality and long-term disability. In the recent past, only very few treatment options were available and a considerable proportion of stroke survivors remained permanently disabled. However, over the last 2 decades rapid advances in acute stroke care have resulted in a corresponding improvement in mortality rates and functional outcomes. In this review, we describe the evolution of systemic thrombolytic agents and various interventional devices, their current status as well as some of the future prospects. We reviewed literature pertaining to acute ischemic stroke reperfusion treatment. We explored the current accepted treatment strategies to attain cerebral reperfusion via intravenous modalities and compare and contrast them within the boundaries of their clinical trials. Subsequently we reviewed the trials for interventional devices for acute ischemic stroke, categorizing them into thrombectomy devices, aspiration devices, clot disruption devices and thrombus entrapment devices. Finally we surveyed several of the alternative reperfusion strategies available. We also shed some light on the controversies surrounding the current strategies of treatment of acute ischemic stroke. Acute invasive interventional strategies continue to improve along with the noninvasive modalities. Both approaches appear promising. We conducted a comprehensive chronological review of the existing treatments as well as upcoming remedies for acute ischemic stroke. PMID:23864913

  16. Update on medical and surgical options for patients with acute severe ulcerative colitis: What is new?

    PubMed Central

    Andrew, Rachel E; Messaris, Evangelos

    2016-01-01

    Acute severe ulcerative colitis (UC) is a highly morbid condition that requires both medical and surgical management through the collaboration of gastroenterologists and colorectal surgeons. First line treatment for patients presenting with acute severe UC consists of intravenous steroids, but those who do not respond require escalation of therapy or emergent colectomy. The mortality of emergent colectomy has declined significantly in recent decades, but due to the morbidity of this procedure, second line agents such as cyclosporine and infliximab have been used as salvage therapy in an attempt to avoid emergent surgery. Unfortunately, protracted medical therapy has led to patients presenting for surgery in a poorer state of health leading to poorer post-operative outcomes. In this era of multiple medical modalities available in the treatment of acute severe UC, physicians must consider the advantages and disadvantages of prolonged medical therapy in an attempt to avoid surgery. Colectomy remains a mainstay in the treatment of severe ulcerative colitis not responsive to corticosteroids and rescue therapy, and timely referral for surgery allows for improved post-operative outcomes with lower risk of sepsis and improved patient survival. Options for reconstructive surgery include three-stage ileal pouch-anal anastomosis or a modified two-stage procedure that can be performed either open or laparoscopically. The numerous avenues of medical and surgical therapy have allowed for great advances in the treatment of patients with UC. In this era of options, it is important to maintain a global view, utilize biologic therapy when indicated, and then maintain an appropriate threshold for surgery. The purpose of this review is to summarize the growing number of medical and surgical options available in the treatment of acute, severe UC. PMID:27721922

  17. Mechanical thrombectomy for acute ischemic stroke in pregnancy using the penumbra system.

    PubMed

    Aaron, Sanjith; Shyamkumar, N K; Alexander, Sunithi; Babu, P Suresh; Prabhakar, A T; Moses, Vinu; Murthy, T V; Alexander, Mathew

    2016-01-01

    Even though intravenous thrombolysis with tissue plasminogen activator (IV tPA) is the standard of care in acute ischemic stroke, its use in pregnancy is not clearly defined. Mechanical thrombectomy devices can be an option; however, literature on the use of such mechanical devices in stroke in pregnancy is lacking. Here we describe two cases that developed acute embolic stroke during pregnancy who were successfully treated by mechanical clot retrieval using the Penumbra system 28 (Penumbra Inc., Alameda, California, USA). To the best of our knowledge, these are the only case reports on the use of the Penumbra device in pregnant patients with acute ischemic stroke. PMID:27293343

  18. IL-33 Aggravates DSS-Induced Acute Colitis in Mouse Colon Lamina Propria by Enhancing Th2 Cell Responses.

    PubMed

    Zhu, Junfeng; Yang, Fangli; Sang, Lixuan; Zhai, Jingbo; Zhang, Xiaoqing; Yue, Dan; Li, Shengjun; Li, Yan; Lu, Changlong; Sun, Xun

    2015-01-01

    Interleukin- (IL-) 33, a member of the IL-1 cytokine family, is an important modulator of the immune system associated with several immune-mediated diseases. IL-33 was expressed in high level on epithelial cells of intestinal tract. It suggested that IL-33 plays a potential role in inflammatory bowel diseases (IBD). We investigated the role of interleukin- (IL-) 33 in dextran sulphate sodium- (DSS-) induced acute colitis in mice using recombinant mouse IL-33 protein (rIL-33). We found that DSS-induced acute colitis was aggravated by rIL-33 treatment. rIL-33-treated DSS mice showed markedly reduced levels of interferon- (IFN-)γ and IL-17A in their colon lamina propria lymphocytes (LPL), but the levels of Th2 cytokines, such as IL-5 and IL-13, in these cells were significantly increased, compared to DSS mice treated with PBS. Our results suggested that IL-33 stimulated CD4(+)T cells and caused the cell to adopt a Th2-type response but at the same time suppressed Th17 and Th1 cell responses. Therefore, IL-33 may be involved in pathogenesis of DSS-induced acute colitis by promoting Th2 cell response in intestinal mucosa of mice. Modulation of IL-33/ST2 signaling by monoclonal antibody (mAb) could be a novel biological therapy in DSS-induced acute colitis.

  19. εPKC confers acute tolerance to cerebral ischemic reperfusion injury

    PubMed Central

    Bright, Rachel; Sun, Guo-Hua; Yenari, Midori A.; Steinberg, Gary K.; Mochly-Rosen, Daria

    2008-01-01

    In response to mild ischemic stress, the brain elicits endogenous survival mechanisms to protect cells against a subsequent lethal ischemic stress, referred to as ischemic tolerance. The molecular signals that mediate this protection are thought to involve the expression and activation of multiple kinases, including protein kinase C (PKC). Here we demonstrate that εPKC mediates cerebral ischemic tolerance in vivo. Systemic delivery of ψεRACK, an εPKC-selective peptide activator, confers neuroprotection against a subsequent cerebral ischemic event when delivered immediately prior to stroke. In addition, activation of εPKC by ψεRACK treatment decreases vascular tone in vivo, as demonstrated by a reduction in microvascular cerebral blood flow. Here we demonstrate the role of acute and transient εPKC in early cerebral tolerance in vivo and suggest that extra-parenchymal mechanisms, such as vasoconstriction, may contribute to the conferred protection. PMID:18586397

  20. Thrombin induces ischemic LTP (iLTP): implications for synaptic plasticity in the acute phase of ischemic stroke

    PubMed Central

    Stein, Efrat Shavit; Itsekson-Hayosh, Zeev; Aronovich, Anna; Reisner, Yair; Bushi, Doron; Pick, Chaim G.; Tanne, David; Chapman, Joab; Vlachos, Andreas; Maggio, Nicola

    2015-01-01

    Acute brain ischemia modifies synaptic plasticity by inducing ischemic long-term potentiation (iLTP) of synaptic transmission through the activation of N-Methyl-D-aspartate receptors (NMDAR). Thrombin, a blood coagulation factor, affects synaptic plasticity in an NMDAR dependent manner. Since its activity and concentration is increased in brain tissue upon acute stroke, we sought to clarify whether thrombin could mediate iLTP through the activation of its receptor Protease-Activated receptor 1 (PAR1). Extracellular recordings were obtained in CA1 region of hippocampal slices from C57BL/6 mice. In vitro ischemia was induced by acute (3 minutes) oxygen and glucose deprivation (OGD). A specific ex vivo enzymatic assay was employed to assess thrombin activity in hippocampal slices, while OGD-induced changes in prothrombin mRNA levels were assessed by (RT)qPCR. Upon OGD, thrombin activity increased in hippocampal slices. A robust potentiation of excitatory synaptic strength was detected, which occluded the ability to induce further LTP. Inhibition of either thrombin or its receptor PAR1 blocked iLTP and restored the physiological, stimulus induced LTP. Our study provides important insights on the early changes occurring at excitatory synapses after ischemia and indicates the thrombin/PAR1 pathway as a novel target for developing therapeutic strategies to restore synaptic function in the acute phase of ischemic stroke. PMID:25604482

  1. Effect of acute and chronic DSS induced colitis on plasma eicosanoid and oxylipin levels in the rat.

    PubMed

    Willenberg, Ina; Ostermann, Annika I; Giovannini, Samoa; Kershaw, Olivia; von Keutz, Anne; Steinberg, Pablo; Schebb, Nils Helge

    2015-07-01

    Eicosanoids and oxylipins are potent lipid mediators involved in the regulation of inflammation. In order to evaluate their role and suitability as biomarkers in colitis, we analyzed their systemic levels in the acute and chronic phase of dextran sulfate sodium (DSS) induced colitis. Male Fischer 344 rats were treated in three cycles with 4% DSS in the drinking water (4 days followed by 10 days recovery) and blood was drawn 3 days prior to the first DSS treatment and on days 4, 11, 32 and 39. Histopathological evaluation of the colon tissue after 42 days showed that the animals developed a mild to severe chronic colitis. Consistently, prostaglandin levels were massively (twofold) elevated in the colonic tissue. LC-MS based targeted metabolomics was used to determine plasma oxylipin levels at the different time points. In the acute phase of inflammation directly after DSS treatment, epoxy-fatty acid (FA), dihydroxy-FA and hydroxy-FA plasma concentrations were uniformly elevated. With each treatment cycle the increase in these oxylipin levels was more pronounced. Our data suggest that in the acute phase of colitis release of polyunsaturated FAs from membranes in the inflamed tissue is reflected by a uniform increase of oylipins formed in different branches of the arachidonic acid cascade. However, during the recovery phases the systemic oxylipin pattern is not or only moderately altered and does not allow to evaluate the onset of chronic inflammation in the colon.

  2. Acute Stress Decreases but Chronic Stress Increases Myocardial Sensitivity to Ischemic Injury in Rodents

    PubMed Central

    Eisenmann, Eric D.; Rorabaugh, Boyd R.; Zoladz, Phillip R.

    2016-01-01

    Cardiovascular disease (CVD) is the largest cause of mortality worldwide, and stress is a significant contributor to the development of CVD. The relationship between acute and chronic stress and CVD is well evidenced. Acute stress can lead to arrhythmias and ischemic injury. However, recent evidence in rodent models suggests that acute stress can decrease sensitivity to myocardial ischemia–reperfusion injury (IRI). Conversely, chronic stress is arrhythmogenic and increases sensitivity to myocardial IRI. Few studies have examined the impact of validated animal models of stress-related psychological disorders on the ischemic heart. This review examines the work that has been completed using rat models to study the effects of stress on myocardial sensitivity to ischemic injury. Utilization of animal models of stress-related psychological disorders is critical in the prevention and treatment of cardiovascular disorders in patients experiencing stress-related psychiatric conditions. PMID:27199778

  3. Loss of n-6 fatty acid induced pediatric obesity protects against acute murine colitis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Dietary influences may affect microbiome composition and host immune responses, thereby modulating propensity toward inflammatory bowel diseases: Crohn disease and ulcerative colitis. Dietary n-6 fatty acids have been associated with ulcetative colitis in prospective studies. However, the critical d...

  4. Oral caffeine administration ameliorates acute colitis by suppressing chitinase 3-like 1 expression in intestinal epithelial cells

    PubMed Central

    Lee, In-Ah; Low, Daren; Kamba, Alan; Llado, Victoria; Mizoguchi, Emiko

    2013-01-01

    Background The initial trigger of inflammatory bowel disease (IBD) can be partly attributed towards the interaction and invasion of intestinal epithelial cells (IECs) and submucosal compartments. Identifying safe and economical methods to block these interactions may help prevent the onset of early colitis. Chitinase 3-like 1 is an inducible host protein that facilitates bacterial attachment and invasion on/into IECs. Therefore, we test the hypothesis of inhibiting CHI3L1 using the pan-chitinase inhibitor caffeine to reduce the likelihood of early colitis onset. Methods IEC lines were treated with caffeine (2.5 mM or 5 mM) and analyzed for CHI3L1 expression and the impact on bacterial invasion. In vivo, mice were treated with 2.5 mM caffeine and induced with 3.5% dextran sulfate sodium (DSS)-mediated colitis and subsequently analyzed colitis development. Results In vitro, caffeine treatment in IEC lines down-regulated CHI3L1 mRNA expression, which resulted in the reduction of bacterial invasion in a caffeine dose-dependent manner. In vivo, mice treated with caffeine displayed delayed response towards DSS-induced colitis, characterized by lower body weight loss, clinical and histological scores. Bacterial translocation into other organs and pro-inflammatory cytokines production were also reduced in the caffeine-treated mice with DSS-induced colitis. Caffeine treatment also resulted in the loss of CHI3L1-associated AKT signaling pathway activation both in vitro and in vivo. Conclusion Development of acute colitis is reduced upon caffeine treatment. The mechanism involves the down-regulation of CHI3L1 expression and its associated bacterial interaction effect. Therefore caffeine is proposed as a safe and economical candidate for successful IBD management. PMID:23925589

  5. Novel guggulsterone derivative GG-52 inhibits NF-kappaB signaling in intestinal epithelial cells and attenuates acute murine colitis.

    PubMed

    Kim, Jung Mogg; Kang, Hyoun Woo; Cha, Mi Yeon; Yoo, Doyoung; Kim, Nayoung; Kim, In-Kyoung; Ku, Jeounghun; Kim, Sunil; Ma, Sang-Ho; Jung, Hyun Chae; Song, In Sung; Kim, Joo Sung

    2010-07-01

    We already showed that the plant sterol guggulsterone has been reported to inhibit nuclear factor-kappaB (NF-kappaB) signaling in intestinal epithelial cells (IECs) and to attenuate dextran sulfate sodium (DSS)-induced colitis. This study investigates the anti-inflammatory effects of novel guggulsterone derivatives on IEC and preventive and therapeutic murine models of DSS-induced colitis. Novel guggulsterone derivates with high lipophilicity were designed and four derivates, including GG-46, GG-50B, GG-52, and GG-53, were synthesized. Two guggulsterone derivatives, GG-50B and GG-52, significantly inhibited the activated NF-kappaB signals and the upregulated expression of interleukin-8 (IL-8) in COLO 205 cells stimulated with tumor necrosis factor-alpha (TNF-alpha). Pretreatment with GG-50B and GG-52 attenuated the increased IkappaB kinase (IKK) and IkappaBalpha phsophorylation induced by TNF-alpha. In preventive and therapeutic models of murine colitis, administration of GG-52 significantly reduced the severity of DSS-induced colitis, as assessed by disease activity index, colon length, and histology. In contrast, GG-50B did not show a significant reduction in the colitis severity. Moreover, the efficacy on attenuating colitis by GG-52 was comparable to that by sulfasalazine or prednisolone. These results indicate that the novel guggulsterone derivative GG-52 blocks NF-kappaB activation in IEC and ameliorates DSS-induced acute murine colitis, which suggests that GG-52 is a potential therapeutic agent for the treatment of inflammatory bowel diseases.

  6. Applying Pharmacokinetics to Optimize Dosing of Anti-TNF Biologics in Acute Severe Ulcerative Colitis

    PubMed Central

    Rosen, Michael J.; Minar, Philip; Vinks, Alexander A.

    2015-01-01

    Background Acute severe ulcerative colitis (ASUC), the most aggressive presentation ulcerative colitis (UC), occurs in 15 percent of adults and children with UC. First line therapy with intravenous corticosteroids is ineffective in half of adults and one third of children. Therapeutic monoclonal antibodies against TNF (anti-TNF therapy) are emerging as a common treatment for ASUC due to their similar efficacy to calcineurin inhibitors and more favorable adverse effect profile. Aim To comprehensively review the evidence for anti-TNF therapy for ASUC in children and adults with regard to outcomes and pharmacokinetics. Methods PubMed and recent conference proceedings were searched using the terms “ulcerative colitis”, “acute severe ulcerative colitis”, “anti-TNF”, “pharmacokinetics”, and the generic names of specific anti-TNF agents. Results Outcomes after anti-TNF therapy for ASUC remain suboptimal with aboutone half of children and adults undergoing colectomy. While several randomized controlled trials have demonstrated the efficacy of anti-TNF therapy for ambulatory patients with moderate to severely active UC, patients in these studies were less ill than those with ASUC. Patients with ASUC may exhibit more rapid clearance of anti-TNF biologics due pharmacokinetic mechanisms influenced by disease severity. Conclusions Conventional weight-based dosing effective in patients with moderately to severely active UC, may not be equally effective in those with ASUC. Personalized anti-TNF dosing strategies that integratepatient factors and early measures of pharmacokinetics and response hold promise for ensuring sustained drug exposure and maximizing early mucosal healing in patients with ASUC. PMID:25809869

  7. Matrix Metalloproteinases and Blood-Brain Barrier Disruption in Acute Ischemic Stroke

    PubMed Central

    Lakhan, Shaheen E.; Kirchgessner, Annette; Tepper, Deborah; Leonard, Aidan

    2013-01-01

    Ischemic stroke continues to be one of the most challenging diseases in translational neurology. Tissue plasminogen activator (tPA) remains the only approved treatment for acute ischemic stroke, but its use is limited to the first hours after stroke onset due to an increased risk of hemorrhagic transformation over time resulting in enhanced brain injury. In this review we discuss the role of matrix metalloproteinases (MMPs) in blood-brain barrier (BBB) disruption as a consequence of ischemic stroke. MMP-9 in particular appears to play an important role in tPA-associated hemorrhagic complications. Reactive oxygen species can enhance the effects of tPA on MMP activation through the loss of caveolin-1 (cav-1), a protein encoded in the cav-1 gene that serves as a critical determinant of BBB permeability. This review provides an overview of MMPs’ role in BBB breakdown during acute ischemic stroke. The possible role of MMPs in combination treatment of acute ischemic stroke is also examined. PMID:23565108

  8. Noninvasive ventilatory correction as an adjunct to an experimental systemic reperfusion therapy in acute ischemic stroke.

    PubMed

    Barlinn, Kristian; Balucani, Clotilde; Palazzo, Paola; Zhao, Limin; Sisson, April; Alexandrov, Andrei V

    2010-01-01

    Background. Obstructive sleep apnea (OSA) is a common condition in patients with acute ischemic stroke and associated with early clinical deterioration and poor functional outcome. However, noninvasive ventilatory correction is hardly considered as a complementary treatment option during the treatment phase of acute ischemic stroke. Summary of Case. A 55-year-old woman with an acute middle cerebral artery (MCA) occlusion received intravenous tissue plasminogen activator (tPA) and enrolled into a thrombolytic research study. During tPA infusion, she became drowsy, developed apnea episodes, desaturated and neurologically deteriorated without recanalization, re-occlusion or intracerebral hemorrhage. Urgent noninvasive ventilatory correction with biphasic positive airway pressure (BiPAP) reversed neurological fluctuation. Her MCA completely recanalized 24 hours later. Conclusions. Noninvasive ventilatory correction should be considered more aggressively as a complementary treatment option in selected acute stroke patients. Early initiation of BiPAP can stabilize cerebral hemodynamics and may unmask the true potential of other therapies. PMID:21052540

  9. Early treatment of hypertension in acute ischemic and intracerebral hemorrhagic stroke: progress achieved, challenges, and perspectives.

    PubMed

    Feldstein, Carlos A

    2014-03-01

    Hypertension is the leading risk factor for ischemic and intracerebral hemorrhagic subtypes of stroke. Additionally, high blood pressure (BP) in the acute cerebrovascular event is associated with poor outcome, and a high percentage of stroke survivors have inadequate control of hypertension. The present is a systematic review of prospective, randomized, and controlled trials carried out on safety and efficacy of antihypertensive treatment of both subtypes of acute stroke. Six trials involving 7512 patients were included, which revealed controversies on the speed and the goals of treatment. These controversies could be due at least in part, from the fact that some studies analyzed the results of antihypertensive treatment in ischemic and intracerebral hemorrhagic subtypes of acute stroke together, and from a different prevalence of past-stroke in the randomized groups. Further research is necessary to establish whether standard antihypertensive treatment provides greater benefit than simple observation in patients with ischemic acute stroke and Stage 2 hypertension of JNC 7, albeit they were not candidates for acute reperfusion. In that case, the target reduction in BP could be 10% to 15% within 24 hours. The recently published INTERACT 2 has provided evidence that patients with hemorrhagic stroke may receive intensive antihypertensive treatment safely with the goal of reducing systolic BP to levels no lower than 130 mm Hg. It is important to take into account that marked BP lowering in acute stroke increases the risk of poor outcome by worsening cerebral ischemia from deterioration of cerebral blood flow autoregulation. PMID:24220549

  10. Telmisartan treatment targets inflammatory cytokines to suppress the pathogenesis of acute colitis induced by dextran sulphate sodium.

    PubMed

    Arumugam, Somasundaram; Sreedhar, Remya; Thandavarayan, Rajarajan A; Giridharan, Vijayasree V; Karuppagounder, Vengadeshprabhu; Pitchaimani, Vigneshwaran; Afrin, Mst Rejina; Miyashita, Shizuka; Nomoto, Mayumi; Harima, Meilei; Suzuki, Hiroshi; Nakamura, Takashi; Nakamura, Masahiko; Suzuki, Kenji; Watanabe, Kenichi

    2015-08-01

    The renin angiotensin system (RAS) is essential for the regulation of cardiovascular and renal functions to maintain the fluid and electrolyte homeostasis. Recent studies have demonstrated a locally expressed RAS in various tissues of mammals, which is having pathophysiological roles in those organ system. Interestingly, local RAS has important role during the inflammatory bowel disease pathogenesis. Further to delineate its role and also to identify the potential effects of telmisartan, an angiotensin receptor blocker, we have used a mouse model of acute colitis induced by dextran sulphate sodium. We have used 0.01 and 5mg/kg body weight doses of telmisartan and administered as enema to facilitate the on-site action and to reduce the systemic adverse effects. Telmisartan high dose treatment significantly reduced the disease activity index score when compared with the colitis control mice. In addition, oxidative stress and endoplasmic reticulum stress markers expression were also significantly reduced when compared with the colitis control mice. Subsequent experiments were carried out to investigate some of the mechanisms underlying its anti-inflammatory effects and identified that the mRNA levels of pro-inflammatory cytokines such as tumour necrosis factor α, interleukin 1β, interleukin 6 and monocyte chemoattractant protein 1 as well as cellular DNA damage were significantly suppressed when compared with the colitis control mice. Similarly the apoptosis marker proteins such as cleaved caspase 3 and 7 levels were down-regulated and anti-apoptotic protein Bcl2 level was significantly upregulated by telmisartan treatment. These results indicate that blockade of RAS by telmisartan can be an effective therapeutic option against acute colitis.

  11. Oxaloacetate: a novel neuroprotective for acute ischemic stroke.

    PubMed

    Campos, Francisco; Sobrino, Tomás; Ramos-Cabrer, Pedro; Castillo, José

    2012-02-01

    It is well established that glutamate acts as an important mediator of neuronal degeneration during cerebral ischemia. Different kind of glutamate antagonists have been used to reduce the deleterious effects of glutamate. However, their preclinical success failed to translate into practical treatments. Far from the classical use of glutamate antagonists employed so far, the systemic administration of oxaloacetate represents a novel neuroprotective strategy to minimize the deleterious effect of glutamate in the brain tissue after ischemic stroke. The neuroprotective effect of oxaloacetate is based on the capacity of this molecule to reduce the brain and blood glutamate levels as a result of the activation of the blood-resident enzyme glutamate-oxaloacetate transaminase. Here we review the recent experimental and clinical results where it is demonstrated the potential applicability of oxaloacetate as a novel and powerful neuroprotective treatment against ischemic stroke.

  12. Anti-inflammatory effect of Helichrysum oligocephalum DC extract on acetic acid — Induced acute colitis in rats

    PubMed Central

    Minaiyan, Mohsen; Ghassemi-Dehkordi, Nasrollah; Mahzouni, Parvin; Ahmadi, Najme-Sadat

    2014-01-01

    Background: Helichrysum oligocephalum DC. from Asteraceae family is an endemic plant growing wild in Iran. This study was carried out to investigate the effect of H. oligocephalum hydroalcoholic extract (HOHE) on ulcerative colitis (UC) induced by acetic acid (AA) in rats. Materials and Methods: Rats were grouped (n = 6) and fasted for 24 h before colitis induction. Treatments were started 2 h before the induction of colitis and continued for two consecutive days with different doses of HOHE (100, 200, and 400 mg/kg) orally (p.o.) and intraperitoneally (i.p.). The colon tissue was removed and tissue damages were scored after macroscopic and histopathologic assessments. Results: Among the examined doses of HOHE, 100 mg/kg was the most effective dose that reduced the extent of UC lesions and resulted in significant alleviation. Weight/length ratio as an index of tissue inflammation and extravasation was also diminished in the treatment group administered HOHE at a dose of 100 mg/kg, and the results showed correlation with macroscopic and histopathologic evaluations. These data suggest that HOHE (100 mg/kg) administered either p.o. or i.p. was effective in diminishing inflammation and ulcer indices in this murine model of acute colitis in a non–dose-related manner. Conclusions: H. oligocephalum could be considered as a suitable anticolitis alternative; however, further studies are needed to support this hypothesis for clinical setting. PMID:24761395

  13. [Changes of homeostasis and immunity in the acute period of ischemic stroke].

    PubMed

    Burtsev, E M; Grinshteĭn, V B; Nazarov, S B

    2001-01-01

    We studied homeostasis, immunity and rheological blood properties in the acute period of ischemic stroke. As intravascular blood coagulation and depression of fibrinolysis happen the amount of "rough" red blood cells increased as well as their aggregates enlarged in size. These changes haven't been seen in patients with lacunar stroke and transient ischemic attacks. Deep depression of T-cell immunity in stroke and inhibition of total fibrinolysis were observed. The most significant depression of cells immunity was found in patients with poor outcome. We recommend to evaluate T-cell immunity in stroke patients and proceed immunocorrection of necessity. PMID:12830541

  14. Quality Improvement in Acute Ischemic Stroke Care in Taiwan: The Breakthrough Collaborative in Stroke

    PubMed Central

    Chern, Chang-Ming; Lee, Tsong-Hai; Tang, Sung-Chun; Tsai, Li-Kai; Liao, Hsun-Hsiang; Chang, Hang; LaBresh, Kenneth A.; Lin, Hung-Jung; Chiou, Hung-Yi; Chiu, Hou-Chang; Lien, Li-Ming

    2016-01-01

    In the management of acute ischemic stroke, guideline adherence is often suboptimal, particularly for intravenous thrombolysis or anticoagulation for atrial fibrillation. We sought to improve stroke care quality via a collaborative model, the Breakthrough Series (BTS)-Stroke activity, in a nationwide, multi-center activity in Taiwan. A BTS Collaborative, a short-term learning system for a large number of multidisciplinary teams from hospitals, was applied to enhance acute ischemic stroke care quality. Twenty-four hospitals participated in and submitted data for this stroke quality improvement campaign in 2010–2011. Totally, 14 stroke quality measures, adopted from the Get With The Guideline (GWTG)-Stroke program, were used to evaluate the performance and outcome of the ischemic stroke patients. Data for a one-year period from 24 hospitals with 13,181 acute ischemic stroke patients were analyzed. In 14 hospitals, most stroke quality measures improved significantly during the BTS-activity compared with a pre-BTS-Stroke activity period (2006–08). The rate of intravenous thrombolysis increased from 1.2% to 4.6%, door-to-needle time ≤60 minutes improved from 7.1% to 50.8%, symptomatic hemorrhage after intravenous thrombolysis decreased from 11.0% to 5.6%, and anticoagulation therapy for atrial fibrillation increased from 32.1% to 64.1%. The yearly composite measures of five stroke quality measures revealed significant improvements from 2006 to 2011 (75% to 86.3%, p<0.001). The quarterly composite measures also improved significantly during the BTS-Stroke activity. In conclusion, a BTS collaborative model is associated with improved guideline adherence for patients with acute ischemic stroke. GWTG-Stroke recommendations can be successfully applied in countries besides the United States. PMID:27487190

  15. Quality Improvement in Acute Ischemic Stroke Care in Taiwan: The Breakthrough Collaborative in Stroke.

    PubMed

    Hsieh, Fang-I; Jeng, Jiann-Shing; Chern, Chang-Ming; Lee, Tsong-Hai; Tang, Sung-Chun; Tsai, Li-Kai; Liao, Hsun-Hsiang; Chang, Hang; LaBresh, Kenneth A; Lin, Hung-Jung; Chiou, Hung-Yi; Chiu, Hou-Chang; Lien, Li-Ming

    2016-01-01

    In the management of acute ischemic stroke, guideline adherence is often suboptimal, particularly for intravenous thrombolysis or anticoagulation for atrial fibrillation. We sought to improve stroke care quality via a collaborative model, the Breakthrough Series (BTS)-Stroke activity, in a nationwide, multi-center activity in Taiwan. A BTS Collaborative, a short-term learning system for a large number of multidisciplinary teams from hospitals, was applied to enhance acute ischemic stroke care quality. Twenty-four hospitals participated in and submitted data for this stroke quality improvement campaign in 2010-2011. Totally, 14 stroke quality measures, adopted from the Get With The Guideline (GWTG)-Stroke program, were used to evaluate the performance and outcome of the ischemic stroke patients. Data for a one-year period from 24 hospitals with 13,181 acute ischemic stroke patients were analyzed. In 14 hospitals, most stroke quality measures improved significantly during the BTS-activity compared with a pre-BTS-Stroke activity period (2006-08). The rate of intravenous thrombolysis increased from 1.2% to 4.6%, door-to-needle time ≤60 minutes improved from 7.1% to 50.8%, symptomatic hemorrhage after intravenous thrombolysis decreased from 11.0% to 5.6%, and anticoagulation therapy for atrial fibrillation increased from 32.1% to 64.1%. The yearly composite measures of five stroke quality measures revealed significant improvements from 2006 to 2011 (75% to 86.3%, p<0.001). The quarterly composite measures also improved significantly during the BTS-Stroke activity. In conclusion, a BTS collaborative model is associated with improved guideline adherence for patients with acute ischemic stroke. GWTG-Stroke recommendations can be successfully applied in countries besides the United States. PMID:27487190

  16. Oral administration of sodium butyrate attenuates inflammation and mucosal lesion in experimental acute ulcerative colitis.

    PubMed

    Vieira, Erica L M; Leonel, Alda J; Sad, Alexandre P; Beltrão, Nathália R M; Costa, Thaís F; Ferreira, Talita M R; Gomes-Santos, Ana C; Faria, Ana M C; Peluzio, Maria C G; Cara, Denise C; Alvarez-Leite, Jacqueline I

    2012-05-01

    Butyrate is a four-carbon short-chain fatty acid that improves colonic trophism. Although several studies have shown the benefits of butyrate enemas in ulcerative colitis (UC), studies using the oral route are rare in the literature. In the present study, we evaluated the effect of butyrate intake in the immune response associated to UC. For that, mice were fed control or butyrate (0.5% sodium butyrate) diets for 14 days. Acute UC was induced by dextran sulphate sodium (DSS, 2.5%), replacing drinking water. The results showed that, in UC animals, oral butyrate significantly improved trophism and reduced leukocyte (eosinophil and neutrophil) infiltration in the colon mucosa and improved the inflammatory profile (activated macrophage, B and T lymphocytes) in cecal lymph nodes. In the small intestine, although mucosa histology was similar among groups, DSS treatment reduced duodenal transforming growth factor-β, increased interleukin-10 concentrations and increased memory T lymphocytes and dendritic cells in Peyer's patches. Butyrate supplementation was able to revert these alterations. When cecal butyrate concentration was analyzed in cecal content, it was still higher in the healthy animals receiving butyrate than in the UC+butyrate and control groups. In conclusion, our results show that oral administration of sodium butyrate improves mucosa lesion and attenuates the inflammatory profile of intestinal mucosa, local draining lymph nodes and Peyer's patches of DSS-induced UC. Our results also highlight the potential use of butyrate supplements as adjuvant in UC treatment.

  17. Acute necrotizing colitis with pneumatosis intestinalis in an Amazonian manatee calf.

    PubMed

    Guerra Neto, Guilherme; Galvão Bueno, Marina; Silveira Silva, Rodrigo Otavio; Faria Lobato, Francisco Carlos; Plácido Guimarães, Juliana; Bossart, Gregory D; Marmontel, Miriam

    2016-08-01

    On 25 January 2014, a 1 mo old female Amazonian manatee Trichechus inunguis calf weighing 12 kg was rescued by air transport in Guajará, Brazil, and transferred to Mamirauá Institute's Community-based Amazonian Manatee Rehabilitation Center. The calf presented piercing/cutting lesions on the back, neck, and head, in addition to dehydration and intermittent involuntary buoyancy. X-ray analysis revealed a large amount of gases in the gastrointestinal tract. Daily procedures included wound cleaning and dressing, clinical and laboratory monitoring, treatment for intestinal tympanism, and artificial feeding. Adaptation to the nursing formula included 2 kinds of whole milk. Up to 20 d post-rescue the calf presented appetite, was active, and gained weight progressively. Past this period the calf started losing weight and presented constant involuntary buoyancy and died after 41 d in rehabilitation. The major findings at necropsy were pneumatosis intestinalis in cecum and colon, pulmonary edema, and hepatomegaly. The microscopic examination revealed pyogranulomatous and necrohemohrragic colitis with multinucleated giant cells, acute multifocal lymphadenitis with lymphoid depletion in cortical and paramedullary regions of mesenteric lymph nodes, and diffuse severe acinar atrophy of the pancreas. Anaerobic cultures of fragments of cecum and colon revealed colonies genotyped as Clostridium perfringens type A. We speculate that compromised immunity, thermoregulatory failure, and intolerance to artificial diet may have been contributing factors to the infection, leading to enterotoxemia and death. PMID:27503914

  18. Protective role of G-CSF in dextran sulfate sodium-induced acute colitis through generating gut-homing macrophages.

    PubMed

    Meshkibaf, Shahab; Martins, Andrew J; Henry, Garth T; Kim, Sung Ouk

    2016-02-01

    Granulocyte colony-stimulating factor (G-CSF) is a pleiotropic cytokine best known for its role in promoting the generation and function of neutrophils. G-CSF is also found to be involved in macrophage generation and immune regulation; however, its in vivo role in immune homeostasis is largely unknown. Here, we examined the role of G-CSF in dextran sulfate sodium (DSS)-induced acute colitis using G-CSF receptor-deficient (G-CSFR(-/-)) mice. Mice were administered with 1.5% DSS in drinking water for 5days, and the severity of colitis was measured for the next 5days. GCSFR(-/-) mice were more susceptible to DSS-induced colitis than G-CSFR(+/+) or G-CSFR(-/+) mice. G-CSFR(-/-) mice harbored less F4/80(+) macrophages, but a similar number of neutrophils, in the intestine. In vitro, bone marrow-derived macrophages prepared in the presence of both G-CSF and macrophage colony-stimulating factor (M-CSF) (G-BMDM) expressed higher levels of regulatory macrophage markers such as programmed death ligand 2 (PDL2), CD71 and CD206, but not in arginase I, transforming growth factor (TGF)-β, Ym1 (chitinase-like 3) and FIZZ1 (found in inflammatory zone 1), and lower levels of inducible nitric oxide synthase (iNOS), CD80 and CD86 than bone marrow-derived macrophages prepared in the presence of M-CSF alone (BMDM), in response to interleukin (IL)-4/IL-13 and lipopolysaccharide (LPS)/interferon (IFN)-γ, respectively. Adoptive transfer of G-BMDM, but not BMDM, protected G-CSFR(-/-) mice from DSS-induced colitis, and suppressed expression of tumor necrosis factor (TNF)-α, IL-1β and iNOS in the intestine. These results suggest that G-CSF plays an important role in preventing colitis, likely through populating immune regulatory macrophages in the intestine.

  19. Plasma C-Reactive Protein and Clinical Outcomes after Acute Ischemic Stroke: A Prospective Observational Study

    PubMed Central

    Matsuo, Ryu; Ago, Tetsuro; Hata, Jun; Wakisaka, Yoshinobu; Kuroda, Junya; Kuwashiro, Takahiro; Kitazono, Takanari; Kamouchi, Masahiro

    2016-01-01

    Background and Purpose Although plasma C-reactive protein (CRP) is elevated in response to inflammation caused by brain infarction, the association of CRP with clinical outcomes after acute ischemic stroke remains uncertain. This study examined whether plasma high-sensitivity CRP (hsCRP) levels at onset were associated with clinical outcomes after acute ischemic stroke independent of conventional risk factors and acute infections after stroke. Methods We prospectively included 3653 patients with first-ever ischemic stroke who had been functionally independent and were hospitalized within 24 h of onset. Plasma hsCRP levels were measured on admission and categorized into quartiles. The association between hsCRP levels and clinical outcomes, including neurological improvement, neurological deterioration, and poor functional outcome (modified Rankin scale ≥3 at 3 months), were investigated using a logistic regression analysis. Results Higher hsCRP levels were significantly associated with unfavorable outcomes after adjusting for age, sex, baseline National Institutes of Health Stroke Scale score, stroke subtype, conventional risk factors, intravenous thrombolysis and endovascular therapy, and acute infections during hospitalization (multivariate-adjusted odds ratios [95% confidence interval] in the highest quartile versus the lowest quartile as a reference: 0.80 [0.65–0.97] for neurological improvement, 1.72 [1.26–2.34] for neurological deterioration, and 2.03 [1.55–2.67] for a poor functional outcome). These associations were unchanged after excluding patients with infectious diseases occurring during hospitalization, or those with stroke recurrence or death. These trends were similar irrespective of stroke subtypes or baseline stroke severity, but more marked in patients aged <70 years (Pheterogeneity = 0.001). Conclusions High plasma hsCRP is independently associated with unfavorable clinical outcomes after acute ischemic stroke. PMID:27258004

  20. Proton relaxation in acute and subacute ischemic brain edema

    SciTech Connect

    Boisvert, D.P.; Handa, Y.; Allen, P.S. )

    1990-01-01

    The relation between regional ischemic brain edema and tissue proton relaxation rates (R1 = 1/T1; R2 = 1/T2) were studied in 16 macaque monkeys subjected to MCA occlusion. In vivo R2 measurements were obtained from multiple spin-echo (eight echoes) images taken at 2-, 3-, 4-, and 72-hr postischemia. In vitro R1 and R2 values were determined for corresponding regions after sacrifice at 4 hr (n = 8) or at 72-hr postischemia in seven surviving animals. The water content of the white and gray matter tissue samples was measured by the wet/dry method. Four animals (25%) showed ipsilateral regions of increased signal intensity as early as 2 hr after MCA occlusion. All seven animals imaged at 72 hr displayed such regions. Despite the absence of measured changes in tissue water content, significant decreases in R2, but not in R1, occurred at 4 hr. At this stage, R2 values correlated more closely than R1 with individual variations in water content. At 72 hr, marked decreases in both R1 and R2 were measured in ischemic deep gray matter and white matter. Cortical gray matter was unchanged. In edematous gray and white matter, both R1 and R2 correlated closely with tissue water content, but R2 was consistently 10 to 20 times more sensitive than R1. Biexponential R2 decay was observed at 4 and 72 hr, but only in the white matter region that became severely edematous at 72 hr.

  1. Targets of vascular protection in acute ischemic stroke differ in type 2 diabetes.

    PubMed

    Kelly-Cobbs, Aisha I; Prakash, Roshini; Li, Weiguo; Pillai, Bindu; Hafez, Sherif; Coucha, Maha; Johnson, Maribeth H; Ogbi, Safia N; Fagan, Susan C; Ergul, Adviye

    2013-03-15

    Hemorrhagic transformation is an important complication of acute ischemic stroke, particularly in diabetic patients receiving thrombolytic treatment with tissue plasminogen activator, the only approved drug for the treatment of acute ischemic stroke. The objective of the present study was to determine the effects of acute manipulation of potential targets for vascular protection [i.e., NF-κB, peroxynitrite, and matrix metalloproteinases (MMPs)] on vascular injury and functional outcome in a diabetic model of cerebral ischemia. Ischemia was induced by middle cerebral artery occlusion in control and type 2 diabetic Goto-Kakizaki rats. Treatment groups received a single dose of the peroxynitrite decomposition catalyst 5,10,15,20-tetrakis(4-sulfonatophenyl)prophyrinato iron (III), the nonspecific NF-κB inhibitor curcumin, or the broad-spectrum MMP inhibitor minocycline at reperfusion. Poststroke infarct volume, edema, hemorrhage, neurological deficits, and MMP-9 activity were evaluated. All acute treatments reduced MMP-9 and hemorrhagic transformation in diabetic groups. In addition, acute curcumin and minocycline therapy reduced edema in these animals. Improved neurological function was observed in varying degrees with treatment, as indicated by beam-walk performance, modified Bederson scores, and grip strength; however, infarct size was similar to untreated diabetic animals. In control animals, all treatments reduced MMP-9 activity, yet bleeding was not improved. Neuroprotection was only conferred by curcumin and minocycline. Uncovering the underlying mechanisms contributing to the success of acute therapy in diabetes will advance tailored stroke therapies. PMID:23335797

  2. Assessment of arterial collateralization and its relevance to intra-arterial therapy for acute ischemic stroke.

    PubMed

    Ramaiah, Siva Seeta; Mitchell, Peter; Dowling, Richard; Yan, Bernard

    2014-03-01

    Evidence from recent randomized controlled studies comparing intra-arterial (IA) therapy with intravenous tissue plasminogen activator highlighted the mismatch between recanalization success and clinical outcomes in patients presenting with acute ischemic stroke. There is emerging interest in the impact of arterial collateralization, as determined by leptomeningeal anastomoses (LMAs), on the treatment outcomes of IA therapy. The system of LMA constitutes the secondary network of cerebral collateral circulation apart from the Circle of Willis. Both anatomic and angiographic studies confirmed significant interindividual variability in LMA. This review aims to outline the current understanding of arterial collateralization and its impact on outcomes after IA therapy for acute ischemic stroke, underpinning the possible role of arterial collateralization assessment as a selection tool for patients most likely to benefit from IA therapy.

  3. Transient ischemic attack as an unusual initial manifestation of acute promyelocytic leukemia.

    PubMed

    Liu, Lifeng; Yuan, Xiaoling

    2016-07-01

    Patients with acute promyelocytic leukemia (APL) are prone to both bleeding and thrombosis. Both of these have a significant impact on the morbidity and mortality of patients with this disease. Here we report a case of a 41-year-old male, who presented with transient ischemic attack (TIA) and early neurological deterioration (END) as initial manifestations prior to an ultimate diagnosis of APL. This patient had no cerebrovascular risk factors or familial cerebrovascular disease. The patient experienced an acute ischemic stroke, verified by magnetic resonance imaging (MRI), in less than 24 h after his second hospital admission. Some APL patients suffer from cerebral ischemia as an initial manifestation or during induction therapy, and patients presenting this condition may continue to deteriorate until their death during hospitalization. Thus, APL should be considered as a possible underlying disease in patients with TIA without cerebrovascular risk factors. Delayed diagnosis and treatment of APL can be fatal.

  4. Meta-Analysis of Local Endovascular Therapy for Acute Ischemic Stroke.

    PubMed

    Kennedy, Sean A; Baerlocher, Mark O; Baerlocher, Felix; Socko, Daniel; Sacks, David; Nikolic, Boris; Wojak, Joan C; Haskal, Ziv J

    2016-03-01

    A meta-analysis was performed to assess randomized controlled trials comparing local endovascular therapy (with and without intravenous thrombolysis) versus standard care (intravenous thrombolysis alone when appropriate) for acute ischemic stroke. Local endovascular therapy showed a significant improvement in functional independence versus standard care (odds ratio, 1.779; 95% confidence interval, 1.262-2.507; P < .001). This benefit strengthened further on subgroup analyses of trials in which a majority of cases used stent retrievers, trials with intravenous thrombolysis use in both arms when appropriate, and trials that required preprocedural imaging of all patients. There were no significant differences between arms in terms of mortality, hemicraniectomy, intracranial hemorrhage, and cerebral edema rates (P > .05). In conclusion, in the treatment of acute ischemic stroke, local endovascular therapy leads to improved functional independence compared with standard care. PMID:26803573

  5. Effect of IMOD™ on the inflammatory process after acute ischemic stroke: a randomized clinical trial

    PubMed Central

    2013-01-01

    Background and purpose of the study Considering the role of inflammation in acute cerebrovascular accidents, anti-inflammatory treatment has been considered as an option in cerebrovascular diseases. Regarding the properties of Setarud (IMOD™) in immune regulation, the aim of the present study was to evaluate the role of this medication in treating patients with acute ischemic stroke. Methods In this randomized clinical trial, 99 patients with their first ever acute ischemic stroke were divided into two groups of IMOD™ (n = 49) and control (n = 50). The control group underwent routine treatment and the intervention group underwent routine treatment plus daily intermittent infusion of IMOD™ (250mg on the first day and then 375mg into DW5% serum during a 30-minute period for 7 days). The serum levels of inflammatory markers were evaluated on the first day (baseline) and on 4th and 7th days. Data were analyzed and the results were compared. Results and major conclusion 58 males (58.6%) and 41 females (41.4%) with a mean age of 67.00 ± 8.82 years, who had their first ever stroke attack, were enrolled in this trial. Treatment with IMOD™ showed a decreasing trend in IL-6 levels compared to the control group (p = 0.04). In addition, the treatment resulted in the control of increasing serum levels of hsCRP after 7 days compared to the control group (p = 0.02). There was an insignificant decrease in TNF-α and IL-1 levels in the IMOD™ group. Considering the prominent role of inflammation after an ischemic cerebral damage, it appears that treatment with IMOD™ improves the inflammatory profile. Therefore, IMOD™ (Setarud) might be considered as a therapeutic option in the acute ischemic stroke. However, future studies are necessary on its long-term results and clinical efficacy. PMID:23514014

  6. Prevalence of intracranial artery stenosis in Iranian patients with acute ischemic stroke using transcranial Doppler ultrasonography

    PubMed Central

    Shariat, Abdolhamid; Niknam, Leila; Izadi, Sadegh; Salehi, Alireza

    2016-01-01

    Background: The aim of this study is to determine the frequency of intracranial artery stenosis in patients with acute ischemic stroke in Iran. Methods: A total of 169 patients with acute ischemic stroke were eligible to participate and were enrolled in this study from January 2012 to February 2013. All the patients were admitted to the Nemazee ‎Hospital, affiliated to Shiraz University of Medical Sciences, Iran. They underwent transcranial Doppler (TCD) ultrasonography. Mean flow velocity (MFV) of basilar artery, vertebral artery, middle cerebral artery (MCA), anterior cerebral artery (ACA), and posterior cerebral artery (PCA) were evaluated. Results: A mean of patients’ age was 67.80 ± 8.14 years. There were 83 men (49.1%) and 86 women (50.9%). Overall, 43 patients (25.4%), with a mean age of 66.7 ± 6.2 years, had intracranial stenosis. The number of men and women with intracranial stenosis was comparable (52.4% men vs. 47.6% women). Hypertension (P < 0.001), hyperlipidemia (P < 0.001), and diabetes mellitus (DM) (P < 0.001) were major risk factors for intracranial stenosis. Conclusion: The prevalence of intracranial artery stenosis in patients with acute ischemic stroke is 25.4% which is comparable with previous reports from Iran and other Middle East countries. PMID:27648174

  7. Bioreducible Polymer-Transfected Skeletal Myoblasts for VEGF Delivery to Acutely Ischemic Myocardium

    PubMed Central

    McGinn, Arlo N.; Nam, Hye Yeong; Ou, Mei; Straub, Catherine M.; Hu, Norman; Yockman, James W.; Bull, David A.; Kim, Sung Wan

    2010-01-01

    Implantation of skeletal myoblasts to the heart has been investigated as a means to regenerate and protect the myocardium from damage after myocardial infarction. While several animal studies utilizing skeletal myoblasts have reported positive findings, results from clinical studies have been mixed. In this study we utilize a newly developed bioreducible polymer system to transfect skeletal myoblasts with a plasmid encoding vascular endothelial growth factor (VEGF) prior to implantation into acutely ischemic myocardium. VEGF has been demonstrated to promote revascularization of the myocardium following myocardial infarction. We report that implanting VEGF expressing skeletal myoblasts into acutely ischemic myocardium produces superior results compared to implantation of untransfected skeletal myoblasts. Skeletal myoblasts expressing secreted VEGF were able to restore cardiac function to non-diseased levels as measured by ejection fraction, to limit remodeling of the heart chamber as measured by end systolic and diastolic volumes, and to prevent myocardial wall thinning. Additionally, arteriole and capillary formation, retention of viable cardiomyocytes, and prevention of apoptosis was significantly improved by VEGF expressing skeletal myoblasts compared to untransfected myoblasts. This work demonstrates the feasibility of using bioreducible cationic polymers to create engineered skeletal myoblasts to treat acutely ischemic myocardium. PMID:20970850

  8. Electroacupuncture for Acute Ischemic Stroke: A Meta-Analysis of Randomized Controlled Trials.

    PubMed

    Liu, Ai-Ju; Li, Ji-Huang; Li, Hui-Qin; Fu, Deng-Lei; Lu, Lin; Bian, Zhao-Xiang; Zheng, Guo-Qing

    2015-01-01

    Electroacupuncture (EA) is an extension technique of acupuncture based on traditional acupuncture combined with modern electrotherapy. Here, we conducted a systematic review specifically to assess the effectiveness and safety of EA for acute ischemic stroke. Eight databases were searched for randomized-controlled clinical trials (RCTs) of EA for acute ischemic stroke published from inception to June 2013. Ultimately, 67 studies claimed to be RCTs. Eighteen studies with 1411 individuals were selected for the analyses, which got ≥ 4 "yes" in the domains of Cochrane risk of bias tool. The meta-analysis showed a significant effect of EA for improving Barthel Index (p < 0.00001), Fugl-Meyer Assessment (p < 0.00001), National Institutes of Health Stroke Scale (p < 0.00001), and Revised Scandinavian Stroke Scale (p < 0.00001) compared with western conventional treatments (WCTs). In an analysis of the total clinical efficacy rate, there was a significant difference between EA and WCTs (p=0.0002). Adverse effects were monitored in 6 studies, and were well tolerated in all stroke patients. According to the GRADE approach, the quality of evidence was mostly high or moderate. In conclusion, this systematic review revealed the evidence in support of the use of EA for acute ischemic stroke, although further larger sample-size and rigorously designed RCTs are required. PMID:26621442

  9. Platelets Proteomic Profiles of Acute Ischemic Stroke Patients

    PubMed Central

    Baykal, Ahmet Tarik; Sener, Azize

    2016-01-01

    Platelets play a crucial role in the pathogenesis of stroke and antiplatelet agents exist for its treatment and prevention. Through the use of LC-MS based protein expression profiling, platelets from stroke patients were analyzed and then correlated with the proteomic analyses results in the context of this disease. This study was based on patients who post ischemic stroke were admitted to hospital and had venous blood drawn within 24 hrs of the incidence. Label-free protein expression analyses of the platelets’ tryptic digest was performed in triplicate on a UPLC-ESI-qTOF-MS/MS system and ProteinLynx Global Server (v2.5, Waters) was used for tandem mass data extraction. The peptide sequences were searched against the reviewed homo sapiens database (www.uniprot.org) and the quantitation of protein variation was achieved through Progenesis LC-MS software (V4.0, Nonlinear Dynamics). These Label-free differential proteomics analysis of platelets ensured that 500 proteins were identified and 83 of these proteins were found to be statistically significant. The differentially expressed proteins are involved in various processes such as inflammatory response, cellular movement, immune cell trafficking, cell-to-cell signaling and interaction, hematological system development and function and nucleic acid metabolism. The expressions of myeloperoxidase, arachidonate 12-Lipoxygenase and histidine-rich glycoprotein are involved in cellular metabolic processes, crk-like protein and ras homolog gene family member A involved in cell signaling with vitronectin, thrombospondin 1, Integrin alpha 2b, and integrin beta 3 involved in cell adhesion. Apolipoprotein H, immunoglobulin heavy constant gamma 1 and immunoglobulin heavy constant gamma 3 are involved in structural, apolipoprotein A-I, and alpha-1-microglobulin/bikunin precursor is involved in transport, complement component 3 and clusterin is involved in immunity proteins as has been discussed. Our data provides an insight

  10. Platelets Proteomic Profiles of Acute Ischemic Stroke Patients.

    PubMed

    Cevik, Ozge; Baykal, Ahmet Tarik; Sener, Azize

    2016-01-01

    Platelets play a crucial role in the pathogenesis of stroke and antiplatelet agents exist for its treatment and prevention. Through the use of LC-MS based protein expression profiling, platelets from stroke patients were analyzed and then correlated with the proteomic analyses results in the context of this disease. This study was based on patients who post ischemic stroke were admitted to hospital and had venous blood drawn within 24 hrs of the incidence. Label-free protein expression analyses of the platelets' tryptic digest was performed in triplicate on a UPLC-ESI-qTOF-MS/MS system and ProteinLynx Global Server (v2.5, Waters) was used for tandem mass data extraction. The peptide sequences were searched against the reviewed homo sapiens database (www.uniprot.org) and the quantitation of protein variation was achieved through Progenesis LC-MS software (V4.0, Nonlinear Dynamics). These Label-free differential proteomics analysis of platelets ensured that 500 proteins were identified and 83 of these proteins were found to be statistically significant. The differentially expressed proteins are involved in various processes such as inflammatory response, cellular movement, immune cell trafficking, cell-to-cell signaling and interaction, hematological system development and function and nucleic acid metabolism. The expressions of myeloperoxidase, arachidonate 12-Lipoxygenase and histidine-rich glycoprotein are involved in cellular metabolic processes, crk-like protein and ras homolog gene family member A involved in cell signaling with vitronectin, thrombospondin 1, Integrin alpha 2b, and integrin beta 3 involved in cell adhesion. Apolipoprotein H, immunoglobulin heavy constant gamma 1 and immunoglobulin heavy constant gamma 3 are involved in structural, apolipoprotein A-I, and alpha-1-microglobulin/bikunin precursor is involved in transport, complement component 3 and clusterin is involved in immunity proteins as has been discussed. Our data provides an insight into

  11. Platelets Proteomic Profiles of Acute Ischemic Stroke Patients.

    PubMed

    Cevik, Ozge; Baykal, Ahmet Tarik; Sener, Azize

    2016-01-01

    Platelets play a crucial role in the pathogenesis of stroke and antiplatelet agents exist for its treatment and prevention. Through the use of LC-MS based protein expression profiling, platelets from stroke patients were analyzed and then correlated with the proteomic analyses results in the context of this disease. This study was based on patients who post ischemic stroke were admitted to hospital and had venous blood drawn within 24 hrs of the incidence. Label-free protein expression analyses of the platelets' tryptic digest was performed in triplicate on a UPLC-ESI-qTOF-MS/MS system and ProteinLynx Global Server (v2.5, Waters) was used for tandem mass data extraction. The peptide sequences were searched against the reviewed homo sapiens database (www.uniprot.org) and the quantitation of protein variation was achieved through Progenesis LC-MS software (V4.0, Nonlinear Dynamics). These Label-free differential proteomics analysis of platelets ensured that 500 proteins were identified and 83 of these proteins were found to be statistically significant. The differentially expressed proteins are involved in various processes such as inflammatory response, cellular movement, immune cell trafficking, cell-to-cell signaling and interaction, hematological system development and function and nucleic acid metabolism. The expressions of myeloperoxidase, arachidonate 12-Lipoxygenase and histidine-rich glycoprotein are involved in cellular metabolic processes, crk-like protein and ras homolog gene family member A involved in cell signaling with vitronectin, thrombospondin 1, Integrin alpha 2b, and integrin beta 3 involved in cell adhesion. Apolipoprotein H, immunoglobulin heavy constant gamma 1 and immunoglobulin heavy constant gamma 3 are involved in structural, apolipoprotein A-I, and alpha-1-microglobulin/bikunin precursor is involved in transport, complement component 3 and clusterin is involved in immunity proteins as has been discussed. Our data provides an insight into

  12. Delayed Surgery for Aortic Dissection after Intravenous Thrombolysis in Acute Ischemic Stroke

    PubMed Central

    Choi, Nari; Yoon, Jee-Eun; Park, Byoung-Won; Chang, Won-Ho; Kim, Hyun-Jo; Lee, Kyung Bok

    2016-01-01

    We report a case of aortic dissection masquerading as acute ischemic stroke followed by intravenous thrombolysis. A 59-year-old man presented with dizziness. After examination, the patient had a seizure with bilateral Babinski signs. Soon after identifying multiple acute infarctions in both hemispheres on diffusion-weighted brain magnetic resonance (MR) imaging, tissue plasminogen activator (t-PA) was administered. Both common carotid arteries were invisible on MR angiography, and subsequent chest computed tomography revealed an aortic dissection. The emergency operation was delayed for 13 hours due to t-PA administration. The patient died of massive bleeding. PMID:27734002

  13. Treatment Strategies for Acute Ischemic Stroke Caused by Carotid Artery Occlusion

    PubMed Central

    Li, Wei; Yin, Qin; Xu, Gelin; Liu, Xinfeng

    2016-01-01

    Background: Acute ischemic stroke caused by internal carotid artery (ICA) occlusion usually has a poor prognosis, especially the T occlusion cases without functional collaterals. The efficacy of intravenous (IV) or intra-arterial (IA) thrombolysis with recombinant tissue plasminogen activator (rt-PA) remains ambiguous in these patients. Eendovascular recanalization of the occluded carotid has been attempted in recent years as a potential strategy. However, the different etiologies of ICA occlusion pose a significant challenge to neurointerventionists. Recently, several endovascular evolvements have been reported in treating carotid occlusion-related stroke. This review summarizes the current status of treatment for acute ICA occlusion.

  14. Absence of Intestinal PPARγ Aggravates Acute Infectious Colitis in Mice through a Lipocalin-2–Dependent Pathway

    PubMed Central

    Kundu, Parag; Ling, Teo Wei; Korecka, Agata; Li, Yinghui; D'Arienzo, Rossana; Bunte, Ralph M.; Berger, Thorsten; Arulampalam, Velmurugesan; Chambon, Pierre; Mak, Tak Wah; Wahli, Walter; Pettersson, Sven

    2014-01-01

    To be able to colonize its host, invading Salmonella enterica serovar Typhimurium must disrupt and severely affect host-microbiome homeostasis. Here we report that S. Typhimurium induces acute infectious colitis by inhibiting peroxisome proliferator-activated receptor gamma (PPARγ) expression in intestinal epithelial cells. Interestingly, this PPARγ down-regulation by S. Typhimurium is independent of TLR-4 signaling but triggers a marked elevation of host innate immune response genes, including that encoding the antimicrobial peptide lipocalin-2 (Lcn2). Accumulation of Lcn2 stabilizes the metalloproteinase MMP-9 via extracellular binding, which further aggravates the colitis. Remarkably, when exposed to S. Typhimurium, Lcn2-null mice exhibited a drastic reduction of the colitis and remained protected even at later stages of infection. Our data suggest a mechanism in which S. Typhimurium hijacks the control of host immune response genes such as those encoding PPARγ and Lcn2 to acquire residence in a host, which by evolution has established a symbiotic relation with its microbiome community to prevent pathogen invasion. PMID:24465207

  15. Prostaglandin E2 and reactive oxygen metabolite damage in the cecum in a pony model of acute colitis

    PubMed Central

    McConnico, Rebecca S.; Argenzio, Robert A.; Roberts, Malcolm C.

    2002-01-01

    The objective of this project was to determine early tissue biochemical events associated with increased colonic secretion during the acute stage of castor-oil-induced colitis by measuring cecal mucosal and submucosal malondialdehyde (MDA) and prostaglandin E2 (PGE2), levels in ponies. Intestinal tissue (inflamed or healthy) samples were obtained from 4 age- and sex-matched Shetland ponies. Biochemical methods were used to determine MDA and PGE2 levels in intestinal tissue samples from inflamed and healthy equine intestine. Inflamed tissue MDA and PGE2 levels increased with time after castor oil challenge and correlated with granulocyte infiltration, as determined by myeloperoxidase levels in a companion study. Elevated intestinal tissue MDA levels suggest that lipid peroxidation could be attributed to reactive oxygen metabolites (ROM) released from stimulated, recruited, and resident granulocytes. Tissue levels of MDA and PGE2 suggest a role for granulocyte-derived mediators of intestinal inflammation in the massive secretory response in cases of acute equine colitis. Tissue MDA and PGE2 levels may be useful laboratory tools to quantify and characterize intestinal secretory inflammatory responses in acute inflammatory conditions in the equine colon. PMID:11858649

  16. Effects of Dietary Plant Sterols and Stanol Esters with Low- and High-Fat Diets in Chronic and Acute Models for Experimental Colitis.

    PubMed

    te Velde, Anje A; Brüll, Florence; Heinsbroek, Sigrid E M; Meijer, Sybren L; Lütjohann, Dieter; Vreugdenhil, Anita; Plat, Jogchum

    2015-10-15

    In this study, we evaluated the effects of dietary plant sterols and stanols as their fatty acid esters on the development of experimental colitis. The effects were studied both in high- and low-fat diet conditions in two models, one acute and another chronic model of experimental colitis that resembles gene expression in human inflammatory bowel disease (IBD). In the first experiments in the high fat diet (HFD), we did not observe a beneficial effect of the addition of plant sterols and stanols on the development of acute dextran sulphate sodium (DSS) colitis. In the chronic CD4CD45RB T cell transfer colitis model, we mainly observed an effect of the presence of high fat on the development of colitis. In this HFD condition, the presence of plant sterol or stanol did not result in any additional effect. In the second experiments with low fat, we could clearly observe a beneficial effect of the addition of plant sterols on colitis parameters in the T cell transfer model, but not in the DSS model. This positive effect was related to the gender of the mice and on Treg presence in the colon. This suggests that especially dietary plant sterol esters may improve intestinal inflammation in a T cell dependent manner.

  17. Effects of Dietary Plant Sterols and Stanol Esters with Low- and High-Fat Diets in Chronic and Acute Models for Experimental Colitis.

    PubMed

    te Velde, Anje A; Brüll, Florence; Heinsbroek, Sigrid E M; Meijer, Sybren L; Lütjohann, Dieter; Vreugdenhil, Anita; Plat, Jogchum

    2015-10-01

    In this study, we evaluated the effects of dietary plant sterols and stanols as their fatty acid esters on the development of experimental colitis. The effects were studied both in high- and low-fat diet conditions in two models, one acute and another chronic model of experimental colitis that resembles gene expression in human inflammatory bowel disease (IBD). In the first experiments in the high fat diet (HFD), we did not observe a beneficial effect of the addition of plant sterols and stanols on the development of acute dextran sulphate sodium (DSS) colitis. In the chronic CD4CD45RB T cell transfer colitis model, we mainly observed an effect of the presence of high fat on the development of colitis. In this HFD condition, the presence of plant sterol or stanol did not result in any additional effect. In the second experiments with low fat, we could clearly observe a beneficial effect of the addition of plant sterols on colitis parameters in the T cell transfer model, but not in the DSS model. This positive effect was related to the gender of the mice and on Treg presence in the colon. This suggests that especially dietary plant sterol esters may improve intestinal inflammation in a T cell dependent manner. PMID:26501315

  18. Hypothermia inhibits the propagation of acute ischemic injury by inhibiting HMGB1.

    PubMed

    Lee, Jung Ho; Yoon, Eun Jang; Seo, Jeho; Kavoussi, Adriana; Chung, Yong Eun; Chung, Sung Phil; Park, Incheol; Kim, Chul Hoon; You, Je Sung

    2016-01-01

    Acute ischemic stroke causes significant chronic disability worldwide. We designed this study to clarify the mechanism by which hypothermia helps alleviate acute ischemic stroke. In a middle cerebral artery occlusion model (4 h ischemia without reperfusion), hypothermia effectively reduces mean infarct volume. Hypothermia also prevents neurons in the infarct area from releasing high mobility group box 1 (HMGB1), the most well-studied damage-associated molecular pattern protein. By preventing its release, hypothermia also prevents the typical middle cerebral artery occlusion-induced increase in serum HMGB1. We also found that both glycyrrhizin-mediated inhibition of HMGB1 and intracerebroventricular neutralizing antibody treatments before middle cerebral artery occlusion onset diminish infarct volume. This suggests a clear neuroprotective effect of HMGB1 inhibition by hypothermia in the brain. We next used real-time polymerase chain reaction to measure the levels of pro-inflammatory cytokines in peri-infarct regions. Although middle cerebral artery occlusion increases the expression of interleukin-1β and tissue necrosis factor-α, this elevation is suppressed by both hypothermia and glycyrrhizin treatment. We show that hypothermia reduces the production of inflammatory cytokines and helps salvage peri-infarct regions from the propagation of ischemic injury via HMGB1 blockade. In addition to suggesting a potential mechanism for hypothermia's therapeutic effects, our results suggest HMGB1 modulation may lengthen the therapeutic window for stroke treatments. PMID:27544687

  19. Severe envenomation by Cerastes cerastes viper: an unusual mechanism of acute ischemic stroke.

    PubMed

    Rebahi, Houssam; Nejmi, Hicham; Abouelhassan, Taoufik; Hasni, Khadija; Samkaoui, Mohamed-Abdenasser

    2014-01-01

    Cerebral complications after snake bites--particularly ischemic complications--are rare. Very few cases of cerebral infarction resulting from a viper bite have been reported, and we call attention to this uncommon etiology. We discuss 3 authenticated reports of acute ischemic cerebrovascular accidents after 3 typical severe envenomations by Cerastes cerastes vipers. The 3 patients developed extensive local swelling and life-threatening systemic envenomation characterized by disseminated intravascular coagulopathy, increased fibrinolysis, thrombocytopenia, microangiopathic hemolytic anemia, and acute renal failure. This clinical picture involved atypical neurologic manifestations. These patients had either low Glasgow Coma Scale (GCS) or hemiparesis within hours to 4 days after being bitten, and they were found to have computed tomographic evidence of single or multiple ischemic (nonhemorrhagic) strokes of small- to large-vessel territories of the brain. One patient had good clinical recovery without neurologic deficits. Thrombotic complications occurred an average of 36 hours after being bitten, and their importance depends on the degree of envenomation. The possible mechanisms for cerebral infarction in these cases include generalized prothrombotic action of the venom (consumptive coagulopathy), toxin-induced vasculitis, and endothelial damage.

  20. High-Performance Upconversion Nanoprobes for Multimodal MR Imaging of Acute Ischemic Stroke.

    PubMed

    Wang, Jing; Zhang, Hua; Ni, Dalong; Fan, Wenpei; Qu, Jianxun; Liu, Yanyan; Jin, Yingying; Cui, Zhaowen; Xu, Tianyong; Wu, Yue; Bu, Wenbo; Yao, Zhenwei

    2016-07-01

    Multimodal magnetic resonance (MR) imaging, including MR angiography (MRA) and MR perfusion (MRP), plays a critical role in the diagnosis and surveillance of acute ischemic stroke. However, these techniques are hindered by the low T1 relaxivity, short circulation time, and high leakage rate from vessels of clinical Magnevist. To address these problems, nontoxic polyethylene glycol (PEG)ylated upconversion nanoprobes (PEG-UCNPs) are synthesized and first adopted for excellent MRA and MRP imaging, featuring high diagnostic sensitivity toward acute ischemic stroke in high-resolution imaging. The investigations show that the agent possesses superior advantages over clinical Magnevist, such as much higher relaxivity, longer circulation time, and lower leakage rate, which guarantee much better imaging efficiency. Remarkably, an extremely small dosage (5 mg Gd kg(-1) ) of PEG-UCNPs provides high-resolution MRA imaging with the vascular system delineated much clearer than the Magnevist with clinical dosage as high as 108 mg Gd kg(-1) . On the other hand, the long circulation time of PEG-UCNPs enables the surveillance of the progression of ischemic stroke using MRA or MRP. Once translated, these PEG-UCNPs are expected to be a promising candidate for substituting the clinical Magnevist in MRA and MRP, which will significantly lengthen the imaging time window and improve the overall diagnostic efficiency. PMID:27219071

  1. An evidence-based causative classification system for acute ischemic stroke.

    PubMed

    Ay, Hakan; Furie, Karen L; Singhal, Aneesh; Smith, Wade S; Sorensen, A Gregory; Koroshetz, Walter J

    2005-11-01

    Regular, evidence-based assignment of patients to etiologic stroke categories is essential to enable valid comparison among studies. We designed an algorithm (SSS-TOAST) that incorporated recent advances in stroke imaging and epidemiology to identify the most probable TOAST category in the presence of evidence for multiple mechanisms. Based on the weight of evidence, each TOAST subtype was subdivided into 3 subcategories as "evident", "probable", or "possible". Classification into the subcategories was determined via predefined specific clinical and imaging criteria. These criteria included published risks of ischemic stroke from various mechanisms and published reports of the strength of associations between clinical and imaging features and particular stroke mechanisms. Two neurologists independently assessed 50 consecutively admitted patients with acute ischemic stroke through reviews of abstracted data from medical records. The number of patients classified as "undetermined-unclassified" per the original TOAST system decreased from 38-40% to 4% using the SSS-TOAST system. The kappa value for inter-examiner reliability was 0.78 and 0.90 for the original TOAST and SSS-TOAST respectively. The SSS-TOAST system successfully classifies patients with acute ischemic stroke into determined etiologic categories without sacrificing reliability. The SSS-TOAST is a dynamic algorithm that can accommodate modifications as new epidemiological data accumulate and diagnostic techniques advance. PMID:16240340

  2. Phase-based metamorphosis of diffusion lesion in relation to perfusion values in acute ischemic stroke.

    PubMed

    Rekik, Islem; Allassonnière, Stéphanie; Luby, Marie; Carpenter, Trevor K; Wardlaw, Joanna M

    2015-01-01

    Examining the dynamics of stroke ischemia is limited by the standard use of 2D-volume or voxel-based analysis techniques. Recently developed spatiotemporal models such as the 4D metamorphosis model showed promise for capturing ischemia dynamics. We used a 4D metamorphosis model to evaluate acute ischemic stroke lesion morphology from the acute diffusion-weighted imaging (DWI) to final T2-weighted imaging (T2-w). In 20 representative patients, we metamorphosed the acute lesion to subacute lesion to final infarct. From the DWI lesion deformation maps we identified dynamic lesion areas and examined their association with perfusion values inside and around the lesion edges, blinded to reperfusion status. We then tested the model in ten independent patients from the STroke Imaging Repository (STIR). Perfusion values varied widely between and within patients, and were similar in contracting and expanding DWI areas in many patients in both datasets. In 25% of patients, the perfusion values were higher in DWI-contracting than DWI-expanding areas. A similar wide range of perfusion values and ongoing expansion and contraction of the DWI lesion were seen subacutely. There was more DWI contraction and less expansion in patients who received thrombolysis, although with widely ranging perfusion values that did not differ. 4D metamorphosis modeling shows promise as a method to improve use of multimodal imaging to understand the evolution of acute ischemic tissue towards its fate. PMID:26288755

  3. Ischemic penumbra in acute stroke: Demonstration by PET with fluorine-18 fluoromisonidazole

    SciTech Connect

    Yeh, S.H.; Liu, R.S.; Hu, H.H.

    1994-05-01

    Ischemic penumbra (IP) in acute stroke has gained clinical interest since tissue functions may be recovered if perfusion can be reestablished. However, such therapeutic intervention is {open_quotes}blind{close_quotes} since clinical examination can not distinguish IP from developing infarction. In vivo demonstration of IP may have significance for stroke patient management. This study was a preliminary evaluation of detecting IP in vivo by F-18 fluoromisonidazole ([F-18]-FMISO), a hypoxic imaging agent. Static PET imaging was performed after IV injection of 370 MBq of [F-18]-FMISO at 20 and 120 min. Tomograms were reconstructed and evaluated visually in correlation with CT or MR scans. In acute stroke, patients (pts) were called back for the second PET study one month after the initial study. CT was used for confirming infarction. In 6 pts with acute cerebral infarction, three of them had intense [F-18]-FMISO retention in the penumbra surrounding the central, eclipse-like zone of absent radio-activity (infarction) at 2 hr in the acute state, and the penumbra disappeared in association with increased area of infarction on CT in one case in the chronic state. In five pts with chronic infarction, all had no penumbra of [F-18]-FMISO retention. In summary, our preliminary results demonstrate the feasibility of using [F-18]-FMISO PET to detect ischemic penumbra in vivo.

  4. Combined iron sucrose and protoporphyrin treatment protects against ischemic and toxin-mediated acute renal failure.

    PubMed

    Zager, Richard A; Johnson, Ali C M; Frostad, Kirsten B

    2016-07-01

    Tissue preconditioning, whereby various short-term stressors initiate organ resistance to subsequent injury, is well recognized. However, clinical preconditioning of the kidney for protection against acute kidney injury (AKI) has not been established. Here we tested whether a pro-oxidant agent, iron sucrose, combined with a protoporphyrin (Sn protoporphyrin), can induce preconditioning and protect against acute renal failure. Mice were pretreated with iron sucrose, protoporphyrin, cyanocobalamin, iron sucrose and protoporphyrin, or iron sucrose and cyanocobalamin. Eighteen hours later, ischemic, maleate, or glycerol models of AKI were induced, and its severity was assessed the following day (blood urea nitrogen, plasma creatinine concentrations; post-ischemic histology). Agent impact on cytoprotective gene expression (heme oxygenase 1, hepcidin, haptoglobin, hemopexin, α1-antitrypsin, α1-microglobulin, IL-10) was assessed as renal mRNA and protein levels. AKI-associated myocardial injury was gauged by plasma troponin I levels. Combination agent administration upregulated multiple cytoprotective genes and, unlike single agent administration, conferred marked protection against each tested model of acute renal failure. Heme oxygenase was shown to be a marked contributor to this cytoprotective effect. Preconditioning also blunted AKI-induced cardiac troponin release. Thus, iron sucrose and protoporphyrin administration can upregulate diverse cytoprotective genes and protect against acute renal failure. Associated cardiac protection implies potential relevance to both AKI and its associated adverse downstream effects. PMID:27165818

  5. Pseudoradial Nerve Palsy Caused by Acute Ischemic Stroke

    PubMed Central

    Tahir, Hassan; Daruwalla, Vistasp; Meisel, Jeremy; Kodsi, Samir E.

    2016-01-01

    Pseudoperipheral palsy has been used to characterize isolated monoparesis secondary to stroke. Isolated hand nerve palsy is a rare presentation for acute cerebral stroke. Our patient presented with clinical features of typical peripheral radial nerve palsy and a normal computed tomography scan of the head, which, without a detailed history and neurological examination, could have been easily misdiagnosed as a peripheral nerve lesion deferring further investigation for a stroke. We stress the importance of including cerebral infarction as a critical differential diagnosis in patients presenting with sensory-motor deficit in an isolated peripheral nerve pattern. A good history and physical exam can differentiate stroke from peripheral neuropathy as the cause of radial nerve palsy. PMID:27493976

  6. Pseudoradial Nerve Palsy Caused by Acute Ischemic Stroke.

    PubMed

    Tahir, Hassan; Daruwalla, Vistasp; Meisel, Jeremy; Kodsi, Samir E

    2016-01-01

    Pseudoperipheral palsy has been used to characterize isolated monoparesis secondary to stroke. Isolated hand nerve palsy is a rare presentation for acute cerebral stroke. Our patient presented with clinical features of typical peripheral radial nerve palsy and a normal computed tomography scan of the head, which, without a detailed history and neurological examination, could have been easily misdiagnosed as a peripheral nerve lesion deferring further investigation for a stroke. We stress the importance of including cerebral infarction as a critical differential diagnosis in patients presenting with sensory-motor deficit in an isolated peripheral nerve pattern. A good history and physical exam can differentiate stroke from peripheral neuropathy as the cause of radial nerve palsy. PMID:27493976

  7. Whole-Brain CT Perfusion to Quantify Acute Ischemic Penumbra and Core.

    PubMed

    Lin, Longting; Bivard, Andrew; Krishnamurthy, Venkatesh; Levi, Christopher R; Parsons, Mark W

    2016-06-01

    underestimated when brain coverage was 40 mm or less (P < .0001). Conclusion Correct threshold setting and whole-brain coverage CT perfusion allowed differentiation of the penumbra from the ischemic core in patients with acute ischemic stroke. (©) RSNA, 2016 Online supplemental material is available for this article.

  8. The Relation Between GABA and L-Arginine Levels With Some Stroke Risk Factors in Acute Ischemic Stroke Patients

    PubMed Central

    Hosinian, Mohsen; Qujeq, Durdi; Ahmadi Ahangar, Alijan

    2016-01-01

    Changes in extra and intracellular neurotransmitter amino acids concentration in the early stage of acute cerebral ischemia have been reported. In this the study, serum level of gamma aminobutyric acid (GABA) and L-Arginine in acute ischemic stroke patients was assessed. 60 patients with acute ischemic stroke and sixthy healthy volunteers as a control group were assessed. Serum GABA was measured with modified enzymatic method and serum L- Arginine was measured by modified Sakaguchi method. Serum GABA level in stroke cases was lower than that of the control group. There was no relationship between GABA level and age or gender. Also, no significant correlation was observed between GABA levels with ischemic stroke risk factors such as smoking, diabetes mellitus, and hypertension. Serum L- Arginine level in patients was slightly increased in comparison with control group. There was a positive relationship between serum L- Arginine level and acute ischemic stroke risk factors. Serum GABA level was reduced in patients and had no correlation with acute ischemic stroke risk factors. PMID:27478806

  9. Copolymer-1 Promotes Neurogenesis and Improves Functional Recovery after Acute Ischemic Stroke in Rats

    PubMed Central

    Cruz, Yolanda; Lorea, Jonathan; Mestre, Humberto; Kim-Lee, Jennifer Hyuna; Herrera, Judith; Mellado, Raúl; Gálvez, Vanesa; Cuellar, Leopoldo; Musri, Carolina; Ibarra, Antonio

    2015-01-01

    Stroke triggers a systemic inflammatory response that exacerbates the initial injury. Immunizing with peptides derived from CNS proteins can stimulate protective autoimmunity (PA). The most renowned of these peptides is copolymer-1 (Cop-1) also known as glatiramer acetate. This peptide has been approved for use in the treatment of multiple sclerosis. Cop-1-specific T cells cross the blood-brain barrier and secrete neurotrophins and anti-inflammatory cytokines that could stimulate proliferation of neural precursor cells and recruit them to the injury site; making it an ideal therapy for acute ischemic stroke. The aim of this work was to evaluate the effect of Cop-1 on neurogenesis and neurological recovery during the acute phase (7 days) and the chronic phase of stroke (60 days) in a rat model of transient middle cerebral artery occlusion (tMCAo). BDNF and NT-3 were quantified and infarct volumes were measured. We demonstrated that Cop-1 improves neurological deficit, enhances neurogenesis (at 7 and 60 days) in the SVZ, SGZ, and cerebral cortex through an increase in NT-3 production. It also decreased infarct volume even at the chronic phase of tMCAo. The present manuscript fortifies the support for the use of Cop-1 in acute ischemic stroke. PMID:25821957

  10. Effectiveness of CT Computed Tomography Perfusion in Diagnostics of Acute Ischemic Stroke

    PubMed Central

    Menzilcioglu, Mehmet Sait; Mete, Ahmet; Ünverdi, Zeyni

    2015-01-01

    Summary Background Stroke is the third most common death reason after the cardiovascular disorders and cancer. Cerebral ischemia is a pathology that stems from a decrease in cerebral perfusion. Computed Tomography Perfusion (CTP) is an additional method to the conventional Computed Tomography (CT) that could be performed by using developed softwares, in a short period of time and with a low risk of complications. CTP not only allows early detection of cerebral ischemia but also gives valuable information on the ischemic penumbra which are very important in early diagnosis and treatment. Acute Ischemic Stroke (AIS) can be cured by trombolytic treapy within 3–6 hours after symptom onset. Since rapid screening and accurate diagnosis increase the success of the treatment, the role of neuroradiology in acute ischemia diagnostics and treatment has become more important. Our aim was to define CT skills in early diagnosis of AIS, to define its contribution to patient’s diagnosis and treatment and to define its importance regarding patient’s prognosis. Material/Methods We included 42 patients that presented to the emergency service and neurology outpatient clinic with the symptoms of acute cerebral incidence. Results In our study, we found that Cerebral Blood Flow (CBF) is 90.91% sensitive and 100% specific in examining ischemia. Conclusions Tissue hemodynamic data, especially sensitivity and specificity rates, which cannot be acquired by conventional CT and MRI methods, can be acquired by the CTP method. PMID:26740827

  11. Urine specific gravity as a predictor of early neurological deterioration in acute ischemic stroke.

    PubMed

    Lin, L C; Fann, W C; Chou, M H; Chen, H W; Su, Y C; Chen, J C

    2011-07-01

    We previously found that a blood urea nitrogen/creatinine (BUN/Cr) ratio>15 is an independent predictor of early neurological deterioration after acute ischemic stroke, which suggests that dehydration may be a cause of early deterioration. The aim of this study was to determine whether urine specific gravity, which is another indicator of hydration status and one that is more easily obtained, is also an independent predictor of early deterioration or stroke-in-evolution (SIE). Demographic and clinical data were recorded at admission from patients with acute ischemic stroke who were prospectively enrolled from October 2007 to June 2010. We compared patients with and without stroke-in-evolution (based on an increase of 3 points or more points on the National Institutes of Health Stroke Scale within 3 days). Univariate and multivariate statistical analyses were carried out. A total of 317 patients (43 SIE and 274 non-SIE) were enrolled; the first 196 patients comprised the cohort of our previous study. The only two independent predictors of early deterioration or SIE were BUN/Cr>15 and urine specific gravity>1.010. After adjusting for age and gender, patients with a urine specific gravity>1.010 were 2.78 times more likely to develop SIE (95% CI=1.11-6.96; P=0.030). Urine specific gravity may be useful as an early predictor of early deterioration in patients with acute ischemic stroke. Patients with urine specific gravity ≤ 1.010 therefore may have a reduced likelihood of early neurological deterioration.

  12. Protein Kinase D2 Protects against Acute Colitis Induced by Dextran Sulfate Sodium in Mice

    PubMed Central

    Xiong, Jing; Zhou, Ming-feng; Wang, Ya-dong; Chen, Li-ping; Xu, Wan-fu; Wang, Yao-dong; Deng, Fan; Liu, Si-de

    2016-01-01

    Inflammatory bowel disease is characterized by dysregulation of the mucosal immune system resulting from impaired intestinal epithelial barrier function. Protein kinase D2 has been implicated in the regulation of immune responses. The present study was to define PKD2 might affect murine colitis. Colitis was induced in wild-type mice (PKD2WT/WT) and PKD2 catalytic activity deficient mice (PKD2SSAA/SSAA) with dextran sulfate sodium. PKD2SSAA-knockin mice displayed catalytic activity deficiency and increased susceptibility to DSS-induced colitis with enhanced weight loss, colonic inflammation compared with PKD2WT/WT mice. Furthermore, crucial inflammatory cytokines mRNA levels in PKD2SSAA-knockin mice were higher than controls accompanied with down-regulation of ZO-1, MUC2 and intestinal barrier dysfunction. However, there were no differences in the proliferation or apoptosis of intestinal epithelial cells in PKD2SSAA-knockin mice compared with wild-type controls. In addition, PKD2 expression was repressed in patients with IBD compared with healthy controls. These studies suggested that activation of PKD2 in the colonic epithelium microenvironment may contribute to protect against DSS-induced colitis through regulation of intestinal mucosal immunity and barrier function. PMID:27659202

  13. Memory deficit associated with increased brain proinflammatory cytokine levels and neurodegeneration in acute ischemic stroke.

    PubMed

    Silva, Bruno; Sousa, Larissa; Miranda, Aline; Vasconcelos, Anilton; Reis, Helton; Barcelos, Lucíola; Arantes, Rosa; Teixeira, Antonio; Rachid, Milene Alvarenga

    2015-08-01

    The present study aimed to investigate behavioral changes and neuroinflammatory process following left unilateral common carotid artery occlusion (UCCAO), a model of cerebral ischemia. Post-ischemic behavioral changes following 15 min UCCAO were recorded 24 hours after reperfusion. The novel object recognition task was used to assess learning and memory. After behavioral test, brains from sham and ischemic mice were removed and processed to evaluate central nervous system pathology by TTC and H&E techniques as well as inflammatory mediators by ELISA. UCCAO promoted long-term memory impairment after reperfusion. Infarct areas were observed in the cerebrum by TTC stain. Moreover, the histopathological analysis revealed cerebral necrotic cavities surrounded by ischemic neurons and hippocampal neurodegeneration. In parallel with memory dysfunction, brain levels of TNF-a, IL-1b and CXCL1 were increased post ischemia compared with sham-operated group. These findings suggest an involvement of central nervous system inflammatory mediators and brain damage in cognitive impairment following unilateral acute ischemia.

  14. Pseudomembranous colitis

    MedlinePlus

    Antibiotic-associated colitis; Colitis - pseudomembranous; Necrotizing colitis; C difficile - pseudomembranous ... The C difficile bacteria normally lives in the intestine. However, too much of these bacteria may grow when you ...

  15. A systematic review and critical appraisal of quality measures for the emergency care of acute ischemic stroke.

    PubMed

    Sauser, Kori; Burke, James F; Reeves, Mathew J; Barsan, William G; Levine, Deborah A

    2014-09-01

    Acute stroke is an important focus of quality improvement efforts. There are many organizations involved in quality measurement for acute stroke, and a complex landscape of quality measures exists. Our objective is to describe and evaluate existing US quality measures for the emergency care of acute ischemic stroke patients in the emergency department (ED) setting. We performed a systematic review of the literature to identify the existing quality measures for the emergency care of acute ischemic stroke. We then convened a panel of experts to appraise how well the measures satisfy the American College of Cardiology/American Heart Association (ACC/AHA) criteria for performance measure development (strength of the underlying evidence, clinical importance, magnitude of the relationship between performance and outcome, and cost-effectiveness). We identified 7 quality measures relevant to the emergency care of acute ischemic stroke that fall into 4 main categories: brain imaging, thrombolytic administration, dysphagia screening, and mortality. Three of the 7 measures met all 4 of the ACC/AHA evaluation criteria: brain imaging within 24 hours, thrombolytic therapy within 3 hours of symptom onset, and thrombolytic therapy within 60 minutes of hospital arrival. Measures not satisfying all evaluation criteria were brain imaging report within 45 minutes, consideration for thrombolytic therapy, dysphagia screening, and mortality rate. There remains room for improvement in the development and use of measures that reflect high-quality emergency care of acute ischemic stroke patients in the United States.

  16. Lactobacillus casei secreting alpha-MSH induces the therapeutic effect on DSS-induced acute colitis in Balb/c Mice.

    PubMed

    Yoon, Sun-Woo; Lee, Chul-Ho; Kim, Jeong-Yoon; Kim, Jie-Youn; Sung, Moon-Hee; Poo, Haryoung

    2008-12-01

    The neuropeptide alpha-melanocyte-stimulating hormone (alpha- MSH) has anti-inflammatory property by downregulating the expressions of proinflammatory cytokines. Because alpha-MSH elicits the anti-inflammatory effect in various inflammatory disease models, we examined the therapeutic effect of oral administration of recombinant Lactobacillus casei, which secretes alpha-MSH (L. casei-alpha-MSH), on dextran sulfate sodium (DSS)-induced colitis in Balb/c mice. Thus, we constructed the alpha-MSH-secreting Lactobacillus casei by the basic plasmid, pLUAT-ss, which was composed of a PldhUTLS promoter and alpha-amylase signal sequence from Streptococcus bovis strain. Acute colitis was induced by oral administration of 5% DSS in drinking water for 7 days. To investigate the effect of L. casei-alpha-MSH on the colitis, L. casei or L. casei-alpha-MSH was orally administered for 7 days and their effects on body weight, mortality rate, cytokine production, and tissue myeloperoxidase (MPO) activity were observed. Administration of L. casei-alpha-MSH reduced the symptom of acute colitis as assessed by body weight loss (DSS alone: 14.45+/-0. 2 g; L. casei-alpha- MSH: 18.2+/-0.12 g), colitis score (DSS alone: 3.6+/-0.4; L. casei-alpha-MSH: 1.4+/-0.6), MPO activity (DSS alone: 42.7+/-4.5 U/g; L. casei-alpha-MSH: 10.25+/-0.5 U/g), survival rate, and histological damage compared with the DSS alone mice. L. casei-alpha-MSH-administered entire colon showed reduced in vitro production of proinflammatory cytokines and NF-kappaB activation. The alpha-MSH-secreting recombinant L. casei showed significant anti-inflammatory effects in the murine model of acute colitis and suggests a potential therapeutic role for this agent in clinical inflammatory bowel diseases.

  17. Targeting IL-12/IL-23 by Employing a p40 Peptide-Based Vaccine Ameliorates TNBS-Induced Acute and Chronic Murine Colitis

    PubMed Central

    Guan, Qingdong; Ma, Yanbing; Hillman, China-Li; Qing, Gefei; Ma, Allan G; Weiss, Carolyn R; Zhou, Gang; Bai, Aiping; Warrington, Richard J; Bernstein, Charles N; Peng, Zhikang

    2011-01-01

    Interleukin (IL)-12 and IL-23 both share the p40 subunit and are key cytokines in the pathogenesis of Crohn’s disease. Previously, we have developed and identified three mouse p40 peptide-based and virus-like particle vaccines. Here, we evaluated the effects and immune mechanisms of the optimal vaccine in downregulating intestinal inflammation in murine acute and chronic colitis, induced by intrarectal administrations of trinitrobenzene sulfonic acid (TNBS). Mice were injected subcutaneously with vaccine, vaccine carrier or saline three times, and then intrarectally administered TNBS weekly for 2 wks (acute colitis) or 7 wks (chronic colitis). The severity of colitis was evaluated by body weight, histology and collagen and cytokine levels in colon tissue. Th1 and Th17 cells in mesenteric lymph nodes (MLN) were determined. Our results showed the vaccine induced high level and long-lasting specific IgG antibodies to p40, IL-12 and IL-23. After administrations of TNBS, vaccinated mice had significantly less body weight loss and a significant decrease of inflammatory scores, collagen deposition and expression of p40, IL-12, IL-23, IL-17, TNF, iNOS and Bcl-2 in colon tissues, compared with carrier and saline groups. Moreover, vaccinated mice exhibited a trend to lower percentages of Th1 cells in acute colitis and of Th17 cells in chronic colitis in MLN than in controls. In summary, administration of the vaccine induced specific antibodies to IL-12 and IL-23, which was associated with improvement of intestinal inflammation and fibrosis. This suggests that the vaccine may provide a potential approach for the long-term treatment of Crohn’s disease. PMID:21424108

  18. Elevated Homocysteine Level Related to Poor Outcome After Thrombolysis in Acute Ischemic Stroke.

    PubMed

    Yao, En-Sheng; Tang, Yan; Xie, Min-Jie; Wang, Ming-Huan; Wang, Hong; Luo, Xiang

    2016-01-01

    BACKGROUND Hyperhomocysteinemia (HHcy) is a well-known risk factor for ischemic stroke. However, whether HHcy can influence the treatment outcome of acute ischemic stroke (AIS) patients has yet to be fully determined. In this study, we investigated the relationship between serum homocysteine (Hcy) level and prognosis in AIS patients who received tissue plasminogen activator (tPA) treatment. MATERIAL AND METHODS Patients were recruited according to the research criteria and grouped by their serum Hcy levels. Neurological outcome was evaluated by National Institute of Health Stroke Scale (NIHSS) score system before and 1 week after treatment, and functional outcome was evaluated by modified Rankin Scale (MRS) score system after 3 months. All patients took CT/MRI examination to detect cerebral hemorrhage in 24 hours after tPA treatment. Receiver operating characteristic curve (ROC) was employed to assess if serum homocysteine level can be used as an index to predict the outcome after tPA treatment. RESULTS The mean (±SD) serum Hcy level of 194 patients was 22.62±21.23 μmol/L. After 1-week tPA treatment, the NIHSS scores of high Hcy level group were significantly higher than those of low level group (p<0.05), meantime the high Hcy group showed obvious symptomatic intracerebral hemorrhage risk after 24 hours (p<0.05). Poor outcome was presented in mRS score results after 3 months in high Hcy level group, which compared with low Hcy level group (p<0.01). The ROC showed that Hcy level was a moderately sensitive and specific index to predict the prognosis with an optimal cut-off value at 19.95 µmol/L (sensitivity [58.2%], specificity [80.3%]). CONCLUSIONS High serum homocysteine level could potentially predict poor prognosis in acute ischemic stroke patients after tPA treatment. PMID:27629768

  19. Elevated Homocysteine Level Related to Poor Outcome After Thrombolysis in Acute Ischemic Stroke

    PubMed Central

    Yao, En-Sheng; Tang, Yan; Xie, Min-Jie; Wang, Ming-Huan; Wang, Hong; Luo, Xiang

    2016-01-01

    Background Hyperhomocysteinemia (HHcy) is a well-known risk factor for ischemic stroke. However, whether HHcy can influence the treatment outcome of acute ischemic stroke (AIS) patients has yet to be fully determined. In this study, we investigated the relationship between serum homocysteine (Hcy) level and prognosis in AIS patients who received tissue plasminogen activator (tPA) treatment. Material/Methods Patients were recruited according to the research criteria and grouped by their serum Hcy levels. Neurological outcome was evaluated by National Institute of Health Stroke Scale (NIHSS) score system before and 1 week after treatment, and functional outcome was evaluated by modified Rankin Scale (MRS) score system after 3 months. All patients took CT/MRI examination to detect cerebral hemorrhage in 24 hours after tPA treatment. Receiver operating characteristic curve (ROC) was employed to assess if serum homocysteine level can be used as an index to predict the outcome after tPA treatment. Results The mean (±SD) serum Hcy level of 194 patients was 22.62±21.23 μmol/L. After 1-week tPA treatment, the NIHSS scores of high Hcy level group were significantly higher than those of low level group (p<0.05), meantime the high Hcy group showed obvious symptomatic intracerebral hemorrhage risk after 24 hours (p<0.05). Poor outcome was presented in mRS score results after 3 months in high Hcy level group, which compared with low Hcy level group (p<0.01). The ROC showed that Hcy level was a moderately sensitive and specific index to predict the prognosis with an optimal cut-off value at 19.95 μmol/L (sensitivity [58.2%], specificity [80.3%]). Conclusions High serum homocysteine level could potentially predict poor prognosis in acute ischemic stroke patients after tPA treatment. PMID:27629768

  20. Preventive Antibacterial Therapy in Acute Ischemic Stroke: A Randomized Controlled Trial

    PubMed Central

    Klehmet, Juliane; Rogge, Witold; Drenckhahn, Christoph; Göhler, Jos; Bereswill, Stefan; Göbel, Ulf; Wernecke, Klaus Dieter; Wolf, Tilo; Arnold, Guy; Halle, Elke; Volk, Hans-Dieter; Dirnagl, Ulrich; Meisel, Andreas

    2008-01-01

    Background Pneumonia is a major risk factor of death after acute stroke. In a mouse model, preventive antibacterial therapy with moxifloxacin not only prevents the development of post-stroke infections, it also reduces mortality, and improves neurological outcome significantly. In this study we investigate whether this approach is effective in stroke patients. Methods Preventive ANtibacterial THERapy in acute Ischemic Stroke (PANTHERIS) is a randomized, double-blind, placebo-controlled trial in 80 patients with severe, non-lacunar, ischemic stroke (NIHSS>11) in the middle cerebral artery (MCA) territory. Patients received either intravenous moxifloxacin (400 mg daily) or placebo for 5 days starting within 36 hours after stroke onset. Primary endpoint was infection within 11 days. Secondary endpoints included neurological outcome, survival, development of stroke-induced immunodepression, and induction of bacterial resistance. Findings On intention-to treat analysis (79 patients), the infection rate at day 11 in the moxifloxacin treated group was 15.4% compared to 32.5% in the placebo treated group (p = 0.114). On per protocol analysis (n = 66), moxifloxacin significantly reduced infection rate from 41.9% to 17.1% (p = 0.032). Stroke associated infections were associated with a lower survival rate. In this study, neurological outcome and survival were not significantly influenced by treatment with moxifloxacin. Frequency of fluoroquinolone resistance in both treatment groups did not differ. On logistic regression analysis, treatment arm as well as the interaction between treatment arm and monocytic HLA-DR expression (a marker for immunodepression) at day 1 after stroke onset was independently and highly predictive for post-stroke infections. Interpretation PANTHERIS suggests that preventive administration of moxifloxacin is superior in reducing infections after severe non-lacunar ischemic stroke compared to placebo. In addition, the results emphasize the

  1. Albumin Administration in Acute Ischemic Stroke: Safety Analysis of the ALIAS Part 2 Multicenter Trial

    PubMed Central

    Hill, Michael D.; Martin, Renee H.; Palesch, Yuko Y.; Moy, Claudia S.; Tamariz, Diego; Ryckborst, Karla J.; Jones, Elizabeth B.; Weisman, David; Pettigrew, Creed; Ginsberg, Myron D.

    2015-01-01

    Background Albumin treatment of ischemic stroke was associated with cardiopulmonary adverse events in previous studies and a low incidence of intracranial hemorrhage. We sought to describe the neurological and cardiopulmonary adverse events in the ALIAS Part 2 Multicenter Trial. Methods Ischemic stroke patients, aged 18–83 and a baseline NIHSS ≥ 6, were randomized to treatment with ALB or saline control within 5 hours of stroke onset. Neurological adverse events included symptomatic intracranial hemorrhage, hemicraniectomy, neurological deterioration and neurological death. Cardiopulmonary adverse events included pulmonary edema/congestive heart failure, acute coronary syndromes, atrial fibrillation, pneumonia and pulmonary thromboembolism. Results Among 830 patients, neurological and cardiopulmonary adverse events were not differentially associated with poor outcome between ALB and saline control subjects. The rate of symptomatic intracranial hemorrhage in the first 24h was low overall (2.9%, 24/830) but more common in the ALB treated subjects (RR = 2.4, CI95 1.01–5.8). The rate of pulmonary edema/CHF in the first 48h was 7.9% (59/830) and was more common among ALB treated subjects (RR = 10.7, CI95 4.3–26.6); this complication was expected and was satisfactorily managed with mandated diuretic administration and intravenous fluid guidelines. Troponin elevations in the first 48h were common, occurring without ECG change or cardiac symptoms in 52 subjects (12.5%). Conclusions ALB therapy was associated with an increase in symptomatic ICH and pulmonary edema/congestive heart failure but this did not affect final outcomes. Troponin elevation occurs routinely in the first 48 hours after acute ischemic stroke. Trial Registration ClincalTrials.gov NCT00235495 PMID:26325387

  2. Safety and Efficacy of Acute Clopidogrel Load in Patients with Moderate and Severe Ischemic Strokes

    PubMed Central

    Monlezun, Dominique J.; Rincon, Natalia; Tiu, Jonathan; Valmoria, Melisa

    2016-01-01

    Objective. To study the safety and efficacy of a clopidogrel loading dose in patients with moderate and severe acute ischemic strokes. Background. The safety of clopidogrel loading has been extensively investigated in patients with minor strokes and transient ischemic attacks. Methods. Acute ischemic stroke patients presenting consecutively to our center from 07/01/08 to 07/31/13 were screened. Clopidogrel loading was defined as at least 300 mg dose (with or without aspirin) given within 6 hours of admission. We compared outcomes in patients with baseline NIHSS > 3 with and without clopidogrel loading. Results. Inclusion criteria were met for 1011 patients (43.6% females, 69.1% black, median age 63). Patients with clopidogrel loading had lower baseline NIHSS than patients who were not loaded (8 versus 9, p = 0.005). The two groups had similar risk for hemorrhagic transformation (p = 0.918) and symptomatic hemorrhage (p = 0.599). Patients who were loaded had a lower rate of neurological worsening (38.9% versus 48.3%, p = 0.031) and less in-hospital mortality (4.3% versus 13.4%, p = 0.001) compared to those who were not loaded. The likelihood of having a poor functional outcome did not differ between the two groups after adjusting for NIHSS on admission (OR = 0.71, 95% CI 0.4633–1.0906, p = 0.118). Conclusion. Clopidogrel loading dose was not associated with increased risk for hemorrhagic transformation or symptomatic intracranial hemorrhage in our retrospective study and was associated with reduced rates of neuroworsening following moderate and severe stroke.

  3. Serum Phenylalanine, Tyrosine, and their Ratio in Acute Ischemic Stroke: on the Trail of a Biomarker?

    PubMed

    Ormstad, Heidi; Verkerk, Robert; Sandvik, Leiv

    2016-01-01

    Fast diagnosis and appropriate treatment are of utmost importance to improving the outcome in patients with acute ischemic stroke (AIS). A rapid and sensitive blood test for ischemic stroke is required. The aim of this study was to examine the usefulness of phenylalanine (PHE) and tyrosine (TYR) as diagnostic biomarkers in AIS. Serum levels of PHE and TYR, measured using HPLC, and their ratio (PHE/TYR) were compared between 45 patients with AIS and 40 healthy control subjects. The relationship between PHE/TYR and the serum levels of several cytokines were also examined. PHE/TYR was significantly higher in AIS patients than in healthy controls (1.75 vs 1.24, p < 0.001). A receiver operating characteristic (ROC) curve analysis of PHE/TYR in AIS patients relative to healthy controls revealed promising sensitivity and specificity, which at an optimal cutoff of 1.45 were 76 and 85 %, respectively. PHE/TYR was positively correlated with interleukin (IL)-1β (r = 0.37, p = 0.011) and IL-6 (r = 0.33, p = 0.025). This study shows that PHE/TYR is highly elevated in the acute phase of AIS, and that this elevation is coupled to the inflammatory response. The ROC analysis documents the possible value of PHE/TYR as a biomarker for AIS and demonstrates its clinical potential as a blood-based test for AIS.

  4. Saving the limb in diabetic patients with ischemic foot lesions complicated by acute infection.

    PubMed

    Clerici, Giacomo; Faglia, Ezio

    2014-12-01

    Ischemia and infection are the most important factors affecting the prognosis of foot ulcerations in diabetic patients. To improve the outcome of these patients, it is necessary to aggressively treat 2 important pathologies--namely, occlusive arterial disease affecting the tibial and femoral arteries and infection of the ischemic diabetic foot. Each of these 2 conditions may lead to major limb amputation, and the presence of both critical limb ischemia (CLI) and acute deep infection is a major risk factor for lower-extremity amputation. Thus, the management of diabetic foot ulcers requires specific therapeutic approaches that vary significantly depending on whether foot lesions are complicated by infection and/or ischemia. A multidisciplinary team approach is the key to successful treatment of a diabetic foot ulcer: ischemic diabetic foot ulcers complicated by acute deep infection pose serious treatment challenges because high levels of skill, organization, accuracy, and timing of intervention are required to maximize the chances of limb salvage: these complex issues are better managed by a multidisciplinary clinical group.

  5. Surgical Management of Severe Colitis in the Intensive Care Unit.

    PubMed

    Halaweish, Ihab; Alam, Hasan B

    2015-12-01

    Severe colitis, an umbrella encompassing several entities, is one of the most common acute gastrointestinal disorders resulting in critical illness. Clostridium difficile infection is responsible for the majority of nosocomial diarrhea with fulminant C difficile colitis (CDC) carrying a high mortality. Optimal outcomes can be achieved by early identification and treatment of fulminant CDC, with appropriate surgical intervention when indicated. Ischemic colitis, on the other hand, is uncommon with a range of etiological factors including abdominal aortic surgery, inotropic drugs, rheumatoid diseases, or often no obvious triggering factor. Most cases resolve with nonsurgical management; however, prompt recognition of full-thickness necrosis and gangrene is crucial for good patient outcomes. Fulminant colitis is a severe disease secondary to progressive ulcerative colitis with systemic deterioration. Surgical intervention is indicated for hemorrhage, perforation, or peritonitis and failure of medical therapy to control the disease. Although, failure of medical management is the most common indication, it can be difficult to define objectively and requires a collaborative multidisciplinary approach. This article proposes some simple management algorithms for these clinical entities, with a focus on critically ill patients.

  6. Hyperhomocysteinemia, a Biochemical Tool for Differentiating Ischemic and Nonischemic Central Retinal Vein Occlusion during the Early Acute Phase

    PubMed Central

    Mukherjee, Somnath; Ghosh, Sambuddha; Mukherjee, Suman; Dutta, Jayanta; Datta, Himadri; Das, Harendra Nath

    2015-01-01

    Purpose The purpose of the study was to differentiate ischemic central retinal vein occlusion (CRVO) from nonischemic CRVO during the early acute phase using plasma homocysteine as a biochemical marker. Methods Fasting plasma homocysteine, serum vitamin B12, and folate levels were measured in 108 consecutive unilateral elderly adult (age >50 years) ischemic CRVO patients in the absence of local and systemic disease and compared with a total of 144 age and sex matched nonischemic CRVO patients and 120 age and sex matched healthy control subjects. Results Homocysteine level was significantly increased in the patients with ischemic CRVO in comparison with nonischemic CRVO patients (p = 0.009) and also in comparison with control subjects (p < 0.001). Analysis also showed that hyperhomocysteinemia was associated with increased incidence of ischemic CRVO (odds ratio, 18) than that for nonischemic CRVO (odds ratio, 4.5). Serum vitamin B12 and folate levels were significantly lower (p < 0.001) in CRVO patients compared to the control but were not significantly different between nonischemic and ischemic CRVO patients (p > 0.1). Conclusions Hyperhomocysteinemia can be regarded as useful in differentiating nonischemic and ischemic CRVO during the early acute phase in absence of local and systemic disease in the elderly adult (age >50 years) population. PMID:25829824

  7. Promoting inflammatory lymphangiogenesis by vascular endothelial growth factor-C (VEGF-C) aggravated intestinal inflammation in mice with experimental acute colitis

    PubMed Central

    Wang, X.L.; Zhao, J.; Qin, L.; Qiao, M.

    2016-01-01

    Angiogenesis and lymphangiogenesis are thought to play a role in the pathogenesis of inflammatory bowel diseases (IBD). However, it is not understood if inflammatory lymphangiogenesis is a pathological consequence or a productive attempt to resolve the inflammation. This study investigated the effect of lymphangiogenesis on intestinal inflammation by overexpressing a lymphangiogenesis factor, vascular endothelial growth factor-C (VEGF-C), in a mouse model of acute colitis. Forty eight-week-old female C57BL/6 mice were treated with recombinant adenovirus overexpressing VEGF-C or with recombinant VEGF-C156S protein. Acute colitis was then established by exposing the mice to 5% dextran sodium sulfate (DSS) for 7 days. Mice were evaluated for disease activity index (DAI), colonic inflammatory changes, colon edema, microvessel density, lymphatic vessel density (LVD), and VEGFR-3mRNA expression in colon tissue. When acute colitis was induced in mice overexpressing VEGF-C, there was a significant increase in colonic epithelial damage, inflammatory edema, microvessel density, and neutrophil infiltration compared to control mice. These mice also exhibited increased lymphatic vessel density (73.0±3.9 vs 38.2±1.9, P<0.001) and lymphatic vessel size (1974.6±104.3 vs 1639.0±91.5, P<0.001) compared to control mice. Additionally, the expression of VEGFR-3 mRNA was significantly upregulated in VEGF-C156S mice compared to DSS-treated mice after induction of colitis (42.0±1.4 vs 3.5±0.4, P<0.001). Stimulation of lymphangiogenesis by VEGF-C during acute colitis promoted inflammatory lymphangiogenesis in the colon and aggravated intestinal inflammation. Inflammatory lymphangiogenesis may have pleiotropic effects at different stages of IBD. PMID:27074165

  8. Gingko biloba extract (Ginaton) ameliorates dextran sulfate sodium (DSS)-induced acute experimental colitis in mice via reducing IL-6/STAT3 and IL-23/IL-17.

    PubMed

    Sun, Yan; Lin, Lian-Jie; Lin, Yan; Sang, Li-Xuan; Jiang, Min; Zheng, Chang-Qing

    2015-01-01

    This study explored the underlying mechanism of Gingko biloba extract (Ginaton) on dextran sulfate sodium (DSS)-induced acute experimental colitis in mice. 40 male C57BL/6 mice were randomly divided into four groups: normal control group, Ginaton group, Ginaton treatment group, and DSS group. After 7 days administration, mice were sacrificed and colons were collected for H-E staining, immunohistochemistry, real-time PCR and Western blot. By observing clinical disease activity and histological damage, we assessed the effect of Ginaton on DSS-induced acute experimental colitis in mice and observed the effect of Ginaton on normal mice. We also explored the specific mechanism of Ginaton on DSS-induced acute experimental colitis in mice through examining the expression of inflammatory related mediators (gp130, STAT3, p-STAT3, ROR-γt) and cytokines (IL-6, IL-17, IL-23). Ginaton-treated DSS mice showed significant improvement over untreated DSS mice. Specifically, Ginaton improved clinical disease activity (DAI score, weight closs, colon shortening, and bloody stool) and histological damage, and reduced the expression of inflammatory-related mediators (p-STAT3, gp130, ROR-γt) and cytokines (IL-6, IL-17, IL-23). In addition, clinical disease activity, histological damage, the expression of inflammatory related mediators (STAT3, p-STAT3, gp130, ROR-t) and cytokines (IL-6, IL-17, IL-23) in mice of Ginaton group were similar to normal control group. In conclusion, Ginaton ameliorates DSS-induced acute experimental colitis in mice by reducing IL-17 production, which is at least partly involved in inhibiting IL-6/STAT3 signaling pathway and IL-23/IL-17 axis. Moreover, Ginaton itself does not cause inflammatory change in normal mice. These results support that Ginaton can be as a potential clinical treatment for ulcerative colitis (UC).

  9. Detecting anti-prothrombin antibodies in young women with acute ischemic stroke.

    PubMed

    Cojocaru, Inimioara Mihaela; Cojocaru, M; Tănăsescu, R; Burcin, Cecilia; Mitu, Andreea Cristina; Iliescu, Iuliana; Dumitrescu, Laura; Pavel, Isabela; Silosi, Isabela

    2008-01-01

    Prothrombin (PT) is a target for antibodies with lupus anticoagulant (LA) activity. Anti-prothrombin antibodies (aPT) were recently identified as antibodies directed toward a phospholipid-binding protein. aPT are a new serologic marker of antiphospholipid syndrome. The objective was to detect aPT in a group of 46 patients with acute ischemic stroke in order to correlate their presence with clinical diagnosis, laboratory and neuroradiological findings. We tested aPT, lupus anticoagulant (LA), anticardiolipin (aCL), and anti-beta2-glycoprotein I antibodies (anti-bbeta2-GPI) in 46 young women with acute ischemic stroke aged 34-45 years and 43 patients with nonischemic neurologic diseases and 141 normal controls. Anti-prothrombin antibodies were detected by calcium-containing aPT ELISA, aCL and anti-beta2-GPI by ELISA. All samples were screened using the activated partial thromboplastin time (aPTT); the dilute Russell viper venous time (dRVV) coagulation test was performed. The results were statistically analyzed. Anti-prothrombin antibodies were found in 26 (57%) of 46 stroke patients. Out of 43 patients with nonischemic neurological disorders, 2 (4.18%) were positive for aPT. aPT were detected in one (0.70%) of the normal controls. Ten stroke patients (21%) were positive for IgG aPT only, 9 stroke patients (18.2%) for IgM aPT only, and 8 stroke patients (16.9%) for both IgG and IgM isotypes of aPT. Two nonischemic neurological disorders patients (4.18%) presented IgM isotype of aPT. Patients with ischemic stroke presented aPT much more frequently than the healthy controls (OR 182.00 [95% CI 23.382-1416.6]. p < 0.0001). Patients with ischemic stroke presented aPT much frequently than the nonischemic neurological disorders patients (OR 26.650 [95% CI 5.743-123.66], p < 0.0001). When IgG or IgM aPT were considered separately, they were more frequently found in patients with ischemic stroke than in healthy control group (OR 38.889 [95% CI 4.817-313.95], p < 0.0001) and

  10. Urgent carotid endarterectomy in patients with acute neurological ischemic events within six hours after symptoms onset.

    PubMed

    Gajin, P; Radak, Dj; Tanaskovic, S; Babic, S; Nenezic, D

    2014-06-01

    To analyze the outcome of urgent carotid endarterectomy (CEA) performed within less than six hours in patients with crescendo transient ischemic attack (TIA) and stroke in progression. From January 1998 to December 2008, 58 urgent CEAs were done for acute neurological ischemic events--46 patients with crescendo TIA and 12 patients with stroke in progression. Brain computed tomography (CT) was done prior and after the surgery. Disability level was assessed prior to and after urgent CEA using modified Rankin scale. Median follow-up was 42.1 ± 16.6 months. In the early postoperative period stroke rate was 0% for the patients in crescendo TIA group while in patients with stroke in progression group 3 patients (25%) had positive postoperative brain CT, yet neurological status significantly improved. Mid-term stroke rate was 2.2% in crescendo TIA group and 8.3% in stroke in progression group. In the early postoperative period there were no lethal outcomes, mid-term mortality was 8.3% in stroke in progression while in crescendo TIA group lethal outcomes were not observed. In conclusion, based on our results urgent CEA is a safe and effective treatment option for patients with crescendo TIA and stroke in progression with acceptable rate of postoperative complications.

  11. Complexity of Heart Rate Variability Can Predict Stroke-In-Evolution in Acute Ischemic Stroke Patients.

    PubMed

    Chen, Chih-Hao; Huang, Pei-Wen; Tang, Sung-Chun; Shieh, Jiann-Shing; Lai, Dar-Ming; Wu, An-Yu; Jeng, Jiann-Shing

    2015-12-01

    About one-third of acute stroke patients may experience stroke-in-evolution, which is often associated with a worse outcome. Recently, we showed that multiscale entropy (MSE), a non-linear method for analysis of heart rate variability (HRV), is an early outcome predictor in non-atrial fibrillation (non-AF) stroke patients. We aimed to further investigate MSE as a predictor of SIE. We included 90 non-AF ischemic stroke patients admitted to the intensive care unit (ICU). Nineteen (21.1%) patients met the criteria of SIE, which was defined as an increase in the National Institutes of Health Stroke Scale score of ≥2 points within 3 days of admission. The MSE of HRV was analyzed from 1-hour continuous ECG signals during the first 24 hours of admission. The complexity index was defined as the area under the MSE curve. Compared with patients without SIE, those with SIE had a significantly lower complexity index value (21.3 ± 8.5 vs 26.5 ± 7.7, P = 0.012). After adjustment for clinical variables, patients with higher complexity index values were significantly less likely to have SIE (odds ratio = 0.897, 95% confidence interval 0.818-0.983, P = 0.020). In summary, early assessment of HRV by MSE can be a potential predictor of SIE in ICU-admitted non-AF ischemic stroke patients.

  12. Serum Levels of Substance P and Mortality in Patients with a Severe Acute Ischemic Stroke.

    PubMed

    Lorente, Leonardo; Martín, María M; Almeida, Teresa; Pérez-Cejas, Antonia; Ramos, Luis; Argueso, Mónica; Riaño-Ruiz, Marta; Solé-Violán, Jordi; Hernández, Mariano

    2016-01-01

    Substance P (SP), a member of tachykinin family, is involved in the inflammation of the central nervous system and in the appearance of cerebral edema. Higher serum levels of SP have been found in 18 patients with cerebral ischemia compared with healthy controls. The aim of our multi-center study was to analyze the possible association between serum levels of SP and mortality in ischemic stroke patients. We included patients with malignant middle cerebral artery infarction (MMCAI) and a Glasgow Coma Scale (GCS) lower than 9. Non-surviving patients at 30 days (n = 31) had higher serum concentrations of SP levels at diagnosis of severe MMCAI than survivors (n = 30) (p < 0.001). We found in multiple regression an association between serum concentrations of SP higher than 362 pg/mL and mortality at 30 days (Odds Ratio = 5.33; 95% confidence interval = 1.541-18.470; p = 0.008) after controlling for age and GCS. Thus, the major novel finding of our study was the association between serum levels of SP and mortality in patients suffering from severe acute ischemic stroke. PMID:27338372

  13. Serum Levels of Substance P and Mortality in Patients with a Severe Acute Ischemic Stroke

    PubMed Central

    Lorente, Leonardo; Martín, María M.; Almeida, Teresa; Pérez-Cejas, Antonia; Ramos, Luis; Argueso, Mónica; Riaño-Ruiz, Marta; Solé-Violán, Jordi; Hernández, Mariano

    2016-01-01

    Substance P (SP), a member of tachykinin family, is involved in the inflammation of the central nervous system and in the appearance of cerebral edema. Higher serum levels of SP have been found in 18 patients with cerebral ischemia compared with healthy controls. The aim of our multi-center study was to analyze the possible association between serum levels of SP and mortality in ischemic stroke patients. We included patients with malignant middle cerebral artery infarction (MMCAI) and a Glasgow Coma Scale (GCS) lower than 9. Non-surviving patients at 30 days (n = 31) had higher serum concentrations of SP levels at diagnosis of severe MMCAI than survivors (n = 30) (p < 0.001). We found in multiple regression an association between serum concentrations of SP higher than 362 pg/mL and mortality at 30 days (Odds Ratio = 5.33; 95% confidence interval = 1.541–18.470; p = 0.008) after controlling for age and GCS. Thus, the major novel finding of our study was the association between serum levels of SP and mortality in patients suffering from severe acute ischemic stroke. PMID:27338372

  14. Abnormal EEG Complexity and Functional Connectivity of Brain in Patients with Acute Thalamic Ischemic Stroke

    PubMed Central

    Liu, Shuang; Guo, Jie; Meng, Jiayuan; Wang, Zhijun; Yao, Yang; Yang, Jiajia; Qi, Hongzhi; Ming, Dong

    2016-01-01

    Ischemic thalamus stroke has become a serious cardiovascular and cerebral disease in recent years. To date the existing researches mostly concentrated on the power spectral density (PSD) in several frequency bands. In this paper, we investigated the nonlinear features of EEG and brain functional connectivity in patients with acute thalamic ischemic stroke and healthy subjects. Electroencephalography (EEG) in resting condition with eyes closed was recorded for 12 stroke patients and 11 healthy subjects as control group. Lempel-Ziv complexity (LZC), Sample Entropy (SampEn), and brain network using partial directed coherence (PDC) were calculated for feature extraction. Results showed that patients had increased mean LZC and SampEn than the controls, which implied the stroke group has higher EEG complexity. For the brain network, the stroke group displayed a trend of weaker cortical connectivity, which suggests a functional impairment of information transmission in cortical connections in stroke patients. These findings suggest that nonlinear analysis and brain network could provide essential information for better understanding the brain dysfunction in the stroke and assisting monitoring or prognostication of stroke evolution. PMID:27403202

  15. Evidence-based guideline: The role of diffusion and perfusion MRI for the diagnosis of acute ischemic stroke

    PubMed Central

    Schellinger, P.D.; Bryan, R.N.; Caplan, L.R.; Detre, J.A.; Edelman, R.R.; Jaigobin, C.; Kidwell, C.S.; Mohr, J.P.; Sloan, M.; Sorensen, A.G.; Warach, S.

    2010-01-01

    Objective: To assess the evidence for the use of diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI) in the diagnosis of patients with acute ischemic stroke. Methods: We systematically analyzed the literature from 1966 to January 2008 to address the diagnostic and prognostic value of DWI and PWI. Results and Recommendations: DWI is established as useful and should be considered more useful than noncontrast CT for the diagnosis of acute ischemic stroke within 12 hours of symptom onset. DWI should be performed for the most accurate diagnosis of acute ischemic stroke (Level A); however, the sensitivity of DWI for the diagnosis of ischemic stroke in a general sample of patients with possible acute stroke is not perfect. The diagnostic accuracy of DWI in evaluating cerebral hemorrhage is outside the scope of this guideline. On the basis of Class II and III evidence, baseline DWI volumes probably predict baseline stroke severity in anterior territory stroke (Level B) but possibly do not in vertebrobasilar artery territory stroke (Level C). Baseline DWI lesion volumes probably predict (final) infarct volumes (Level B) and possibly predict early and late clinical outcome measures (Level C). Baseline PWI volumes predict to a lesser degree the baseline stroke severity compared with DWI (Level C). There is insufficient evidence to support or refute the value of PWI in diagnosing acute ischemic stroke (Level U). GLOSSARY ADC = apparent diffusion coefficient; ASPECTS = Alberta Stroke Program Early CT Score; CBF = cerebral blood flow; CI = confidence interval; DWI = diffusion-weighted imaging; ICH = intracerebral hemorrhage; MR = magnetic resonance; NIHSS = National Institute of Health Stroke Scale; PWI = perfusion-weighted imaging; tPA = tissue plasminogen activator. PMID:20625171

  16. Prognostic value of intravenous dipyridamole thallium scintigraphy after an acute myocardial ischemic event

    SciTech Connect

    Younis, L.T.; Byers, S.; Shaw, L.; Barth, G.; Goodgold, H.; Chaitman, B.R.

    1989-07-15

    Seventy-seven patients recovering from an acute coronary event were studied by intravenous dipyridamole thallium scintigraphy to evaluate the prognostic value and safety of the test in this patient subset. Forty-four patients (58%) had unstable angina and 33 (42%) had an acute myocardial infarction. One death occurred within 24 hours of testing. Sixty-eight patients were followed for an average of 12 months; 25, 31 and 23% had a fixed, reversible or combined thallium defect on their predischarge thallium scan. During follow-up, 10 patients died or had a nonfatal myocardial infarction; in each case, a reversible or combined myocardial thallium defect was present. Univariate analysis of 17 clinical, scintigraphic and angiographic variables showed that a reversible thallium defect and the angiographically determined extent of coronary artery disease were predictors of future cardiac events. The extent of coronary disease and global left ventricular ejection fraction were predictors of subsequent reinfarction or death. Logistic regression analyses revealed that a reversible thallium defect (p less than 0.001) and the extent of coronary disease (p less than 0.009) were the only significant predictors of a cardiac event. When death or reinfarction were the outcome variables, the extent of coronary disease (p less than 0.02) and left ventricular ejection fraction (p less than 0.06) were the only variables selected. Thus, intravenous dipyridamole thallium scintigraphy after an acute coronary ischemic syndrome is a useful and relatively safe noninvasive test to predict subsequent cardiac events.

  17. Mechanical Thrombectomy in Patients With Acute Ischemic Stroke: A Health Technology Assessment

    PubMed Central

    2016-01-01

    Background In Ontario, current treatment for eligible patients who have an acute ischemic stroke is intravenous thrombolysis (IVT). However, there are some limitations and contraindications to IVT, and outcomes may not be favourable for patients with stroke caused by a proximal intracranial occlusion. An alternative is mechanical thrombectomy with newer devices, and a number of recent studies have suggested that this treatment is more effective for improving functional independence and clinical outcomes. The objective of this health technology assessment was to evaluate the clinical effectiveness and cost-effectiveness of new-generation mechanical thrombectomy devices (with or without IVT) compared to IVT alone (if eligible) in patients with acute ischemic stroke. Methods We conducted a systematic review of the literature, limited to randomized controlled trials that examined the effectiveness of mechanical thrombectomy using stent retrievers and thromboaspiration devices for patients with acute ischemic stroke. We assessed the quality of the evidence using the GRADE approach. We developed a Markov decision-analytic model to assess the cost-effectiveness of mechanical thrombectomy (with or without IVT) versus IVT alone (if eligible), calculated incremental cost-effectiveness ratios using a 5-year time horizon, and conducted sensitivity analyses to examine the robustness of the estimates. Results There was a substantial, statistically significant difference in rate of functional independence (GRADE: high quality) between those who received mechanical thrombectomy (with or without IVT) and IVT alone (odds ratio [OR] 2.39, 95% confidence interval [CI] 1.88–3.04). We did not observe a difference in mortality (GRADE: moderate quality) (OR 0.80, 95% CI 0.60–1.07) or symptomatic intracerebral hemorrhage (GRADE: moderate quality) (OR 1.11, 95% CI 0.66–1.87). In the base-case cost-utility analysis, which had a 5 year time horizon, the costs and effectiveness for

  18. [Clinical thinking about treating acute ischemic stroke by targeting the neurovascular unit of Chinese medicine].

    PubMed

    Lei, Ya-Ling; Liu, Qing; Luo, Yi

    2013-09-01

    Neurovascular unit (NVU) concept proposed for the treatment of acute ischemic stroke (AIS) provides a new target, i.e., we should target as an integrity including neurons, glia, and microcirculation, thus supplementing limitations of previous treatment targeting neurons or blood vessels alone. Meanwhile, many clinical trials have failed after NVU protection against AIS drug research has developed at home and abroad. Chinese medicine has multi-component, multi-target, and overall regulation advantages, and is in line with clinical requirement for overall treatment targeting multiple targets of NVU. Currently clinical studies of Chinese medicine treatment of AIS targeting NVU are few. Standardized and systematic clinical efficacy evaluation is lack. Clinical studies for improving AIS-NVU injured blood markers by Chinese medicine are rarer. We hope to pave the way for performing clinical studies on Chinese medicine treatment of AIS targeting NVU.

  19. Developments in mechanical thrombectomy devices for the treatment of acute ischemic stroke.

    PubMed

    Mordasini, Pasquale; Gralla, Jan

    2016-01-01

    Several recent prospective randomized controlled trials of endovascular stroke therapy using latest generation thrombectomy devices, so called stent-retrievers, have shown significantly improved clinical outcome compared to the standard treatment with intra-venous thrombolysis using r-tPA alone. Despite some differences in inclusion criteria between these studies, all required non-invasive vessel imaging to proof occlusion of a major brain supplying vessel. Furthermore, in most studies additional imaging techniques were used to exclude patients with already established large cerebral infarction or unfavorable collateral or penumbral status. Patients with small infarct volume, severe neurological deficits and in whom thrombectomy can be initiated within the first 6 hours after symptom onset seem to benefit the most. Therefore, mechanical thrombectomy using stent-retrievers in addition to intra-venous thrombolysis is recommended for the treatment of acute ischemic stroke with proven major vessel occlusion in the anterior circulation.

  20. Review of technology development and clinical trials of transcranial laser therapy for acute ischemic stroke treatment

    NASA Astrophysics Data System (ADS)

    Catanzaro, Brian E.; Streeter, Jackson; de Taboada, Luis

    2010-02-01

    Stroke is the one of the leading causes of mortality in the United States, claiming 600,000 lives each year. Evidence suggests that near infrared (NIR) illumination has a beneficial effect on a variety of cells when these cells are exposed to adverse conditions. Among these conditions is the hypoxic state produced by acute ischemic stroke (AIS). To demonstrate the impact NIR Transcranial Laser Therapy (TLT) has on AIS in humans, a series of double blind, placebo controlled clinical trials were designed using the NeuroThera(R) System (NTS). The NTS was designed and developed to treat subjects non-invasively using 808 nm NIR illumination. TLT, as it applies to stroke therapy, and the NTS will be described. The results of the two clinical trials: NeuroThera(R) Safety and Efficacy Trial 1 (NEST-1) and NeuroThera(R) Safety and Efficacy Trial 2 (NEST-2) will be reviewed and discussed.

  1. Acute ischemic optic neuropathy with extended prone position ventilation in a lung transplant recipient.

    PubMed

    Panchabhai, Tanmay S; Bandyopadhyay, Debabrata; Kapoor, Aanchal; Akindipe, Olufemi; Lane, Charles; Krishnan, Sudhir

    2016-01-01

    Prone position ventilation (PPV) improves mortality in severe acute respiratory distress syndrome (ARDS), but outcomes following its use in lung transplant recipients are not known. We report the case of a 42-year-old Caucasian man who presented with severe ARDS from Bordetella pertussis, 5 years after bilateral sequential lung transplant for cystic fibrosis. He was managed with PPV for 22 days and had a prolonged ICU stay complicated by hypoxic ischemic optic neuropathy leading to blindness. Since his discharge from the ICU 6 months ago, his FEV1 has recovered to 47% predicted compared to his pre-ICU peak FEV1 of 85% predicted, suggesting recovery of lung function. This is the first report of optic nerve damage and vision loss in patients undergoing PPV. Our report also suggests that, in appropriately selected lung transplant recipients, severe hypoxemia could potentially be managed with prone ventilation. PMID:27051622

  2. Acute mesenteric ischemia.

    PubMed

    Sise, Michael J

    2014-02-01

    Acute mesenteric ischemia is uncommon and always occurs in the setting of preexisting comorbidities. Mortality rates remain high. The 4 major types of acute mesenteric ischemia are acute superior mesenteric artery thromboembolic occlusion, mesenteric arterial thrombosis, mesenteric venous thrombosis, and nonocclusive mesenteric ischemia, including ischemic colitis. Delays in diagnosis are common and associated with high rates of morbidity and mortality. Prompt diagnosis requires attention to history and physical examination, a high index of suspicion, and early contract CT scanning. Selective use of nonoperative therapy has an important role in nonocclusive mesenteric ischemia of the small bowel and colon.

  3. Intramitochondrial Zn2+ accumulation via the Ca2+ uniporter contributes to acute ischemic neurodegeneration

    PubMed Central

    Medvedeva, Yuliya V.; Weiss, John H.

    2014-01-01

    Ca2+ and Zn2+ have both been implicated in the induction of acute ischemic neurodegeneration. We recently examined changes in intracellular Zn2+ and Ca2+ in CA1 pyramidal neurons subjected to oxygen glucose deprivation (OGD), and found that Zn2+ rises precede and contribute to the onset of terminal Ca2+ rises (“Ca2+ deregulation”), which are causatively linked to a lethal loss of membrane integrity. The present study seeks to examine the specific role of intramitochondrial Zn2+ accumulation in ischemic injury, using blockers of the mitochondrial Ca2+ uniporter (MCU), through which both Zn2+ and Ca2+ appear able to enter the mitochondrial matrix. In physiological extracellular Ca2+, treatment with the MCU blocker, Ruthenium Red (RR), accelerated the Ca2+ deregulation, most likely by disrupting mitochondrial Ca2+ buffering and thus accelerating the lethal cytosolic Ca2+ overload. However, when intracellular Ca2+ overload was slowed, either by adding blockers of major Ca2+ entry channels or by lowering the concentration of Ca2+ in the extracellular buffer, Ca2+ deregulation was delayed, and under these conditions either Zn2+ chelation or MCU blockade resulted in similar further delays of the Ca2+ deregulation. In parallel studies using the reactive oxygen species (ROS) indicator, hydroethidine, lowering Ca2+ surprisingly accelerated OGD induced ROS generation, and in these low Ca2+ conditions, either Zn2+ chelation or MCU block slowed the ROS generation. These studies suggest that, during acute ischemia, Zn2+ entry into mitochondria via the MCU induces mitochondrial dysfunction (including ROS generation) that occurs upstream of, and contributes to the terminal Ca2+ deregulation. PMID:24787898

  4. Cerebrolysin effects on neurological outcomes and cerebral blood flow in acute ischemic stroke

    PubMed Central

    Amiri-Nikpour, Mohammad Reza; Nazarbaghi, Surena; Ahmadi-Salmasi, Babak; Mokari, Tayebeh; Tahamtan, Urya; Rezaei, Yousef

    2014-01-01

    Background Cerebrolysin, a brain-derived neuropeptide, has been shown to improve the neurological outcomes of stroke, but no study has demonstrated its effect on cerebral blood flow. This study aimed to determine the cerebrolysin impact on the neurological outcomes and cerebral blood flow. Methods In a randomized, double-blinded, placebo-controlled trial, 46 patients who had acute focal ischemic stroke were randomly assigned into two groups to receive intravenously either 30 mL of cerebrolysin diluted in normal saline daily for 10 days (n=23) or normal saline alone (n=23) adjunct to 100 mg of aspirin daily. All patients were examined using the National Institutes of Health Stroke Scale and transcranial Doppler to measure the mean flow velocity and pulsatility index (PI) of their cerebral arteries at baseline as well as on days 30, 60, and 90. Results The patients’ mean age was 60±9.7 years, and 51.2% of patients were male. The National Institutes of Health Stroke Scale was significantly lower in the cerebrolysin group compared with the placebo group on day 60 (median 10, interquartile range 9–11, P=0.008) and day 90 (median 11, interquartile range 10–13.5, P=0.001). The median of PI in the right middle cerebral artery was significantly lower in the cerebrolysin group compared with the placebo group on days 30, 60, and 90 (P<0.05). One patient in the cerebrolysin group and two patients in the placebo group died before day 30 (4.3% versus 8.7%). Conclusion Cerebrolysin can be useful to improve the neurological outcomes and the PI of middle cerebral artery in patients with acute focal ischemic stroke. PMID:25516711

  5. Intramitochondrial Zn2+ accumulation via the Ca2+ uniporter contributes to acute ischemic neurodegeneration.

    PubMed

    Medvedeva, Yuliya V; Weiss, John H

    2014-08-01

    Ca(2+) and Zn(2+) have both been implicated in the induction of acute ischemic neurodegeneration. We recently examined changes in intracellular Zn(2+) and Ca(2+) in CA1 pyramidal neurons subjected to oxygen glucose deprivation (OGD), and found that Zn(2+) rises precede and contribute to the onset of terminal Ca(2+) rises ("Ca(2+) deregulation"), which are causatively linked to a lethal loss of membrane integrity. The present study seeks to examine the specific role of intramitochondrial Zn(2+) accumulation in ischemic injury, using blockers of the mitochondrial Ca(2+) uniporter (MCU), through which both Zn(2+) and Ca(2+) appear able to enter the mitochondrial matrix. In physiological extracellular Ca(2+), treatment with the MCU blocker, Ruthenium Red (RR), accelerated the Ca(2+) deregulation, most likely by disrupting mitochondrial Ca(2+) buffering and thus accelerating the lethal cytosolic Ca(2+) overload. However, when intracellular Ca(2+) overload was slowed, either by adding blockers of major Ca(2+) entry channels or by lowering the concentration of Ca(2+) in the extracellular buffer, Ca(2+) deregulation was delayed, and under these conditions either Zn(2+) chelation or MCU blockade resulted in similar further delays of the Ca(2+) deregulation. In parallel studies using the reactive oxygen species (ROS) indicator, hydroethidine, lowering Ca(2+) surprisingly accelerated OGD induced ROS generation, and in these low Ca(2+) conditions, either Zn(2+) chelation or MCU block slowed the ROS generation. These studies suggest that, during acute ischemia, Zn(2+) entry into mitochondria via the MCU induces mitochondrial dysfunction (including ROS generation) that occurs upstream of, and contributes to the terminal Ca(2+) deregulation.

  6. Comparison of clinical signs and outcomes between dogs with presumptive ischemic myelopathy and dogs with acute noncompressive nucleus pulposus extrusion.

    PubMed

    Fenn, Joe; Drees, Randi; Volk, Holger A; De Decker, Steven

    2016-10-01

    OBJECTIVE To compare clinical signs and outcomes between dogs with presumptive ischemic myelopathy and dogs with presumptive acute noncompressive nucleus pulposus extrusion (ANNPE). DESIGN Retrospective study. ANIMALS 51 dogs with ischemic myelopathy and 42 dogs with ANNPE examined at 1 referral hospital. PROCEDURES Medical records and MRI sequences were reviewed for dogs with a presumptive antemortem diagnosis of ischemic myelopathy or ANNPE. Information regarding signalment, clinical signs at initial examination, and short-term outcome was retrospectively retrieved from patient records. Long-term outcome information was obtained by telephone communication with referring or primary-care veterinarians and owners. RESULTS Compared with the hospital population, English Staffordshire Bull Terriers and Border Collies were overrepresented in the ischemic myelopathy and ANNPE groups, respectively. Dogs with ANNPE were significantly older at disease onset and were more likely to have a history of vocalization at onset of clinical signs, have spinal hyperesthesia during initial examination, have a lesion at C1-C5 spinal cord segments, and be ambulatory at hospital discharge, compared with dogs with ischemic myelopathy. Dogs with ischemic myelopathy were more likely to have a lesion at L4-S3 spinal cord segments and have long-term fecal incontinence, compared with dogs with ANNPE. However, long-term quality of life and outcome did not differ between dogs with ischemic myelopathy and dogs with ANNPE. CONCLUSIONS AND CLINICAL RELEVANCE Results revealed differences in clinical signs at initial examination between dogs with ischemic myelopathy and dogs with ANNPE that may aid clinicians in differentiating the 2 conditions. PMID:27654163

  7. Gene silencing of TNF-alpha in a murine model of acute colitis using a modified cyclodextrin delivery system.

    PubMed

    McCarthy, J; O'Neill, M J; Bourre, L; Walsh, D; Quinlan, A; Hurley, G; Ogier, J; Shanahan, F; Melgar, S; Darcy, R; O'Driscoll, C M

    2013-05-28

    Inflammatory bowel disease (IBD) is a chronic relapsing inflammation of the gastrointestinal tract. The cytokine TNF-alpha (TNF-α) plays a pivotal role in mediating this inflammatory response. RNA interference (RNAi) holds great promise for the specific and selective silencing of aberrantly expressed genes, such as TNF-α in IBD. The aim of this study was to investigate the efficacy of an amphiphilic cationic cyclodextrin (CD) vector for effective TNF-α siRNA delivery to macrophage cells and to mice with induced acute-colitis. The stability of CD.siRNA was examined by gel electrophoresis in biorelevant media reflecting colonic fluids. RAW264.7 cells were transfected with CD.TNF-α siRNA, stimulated with lipopolysaccharide (LPS) and TNF-α and IL-6 responses were measured by PCR and ELISA. Female C57BL/6 mice were exposed to dextran sodium sulphate (DSS) and treated by intrarectal administration with either CD.siRNA TNF-α or a control solution. In vitro, siRNA in CD nanocomplexes remained intact and stable in both fed and fasted simulated colonic fluids. RAW264.7 cells transfected with CD.TNF-α siRNA and stimulated with LPS displayed a significant reduction in both gene and protein levels of TNF-α and IL-6. CD.TNF-α siRNA-treated mice revealed a mild amelioration in clinical signs of colitis, but significant reductions in total colon weight and colonic mRNA expression of TNF-α and IL-6 compared to DSS-control mice were detected. This data indicates the clinical potential of a local CD-based TNF-α siRNA delivery system for the treatment of IBD. PMID:23500058

  8. Simultaneously Presented Acute Ischemic Stroke and Non-ST Elevation Myocardial Infarction in a Patient with Paroxysmal Atrial Fibrillation

    PubMed Central

    Kim, Hack-Lyoung; Seo, Jae-Bin; Chung, Woo-Young; Zo, Joo-Hee; Kim, Myung-A

    2013-01-01

    Although atrial fibrillation is the most frequent cause of embolic stroke, coronary embolism from atrial fibrillation is a very rare cause of acute myocardial infarction. Therefore, simultaneously presented acute ischemic stroke and acute myocardial infarction due to atrial fibrillation in the same patient has not been documented. The present report describes the case of a 58-year-old man with paroxysmal atrial fibrillation who initially presented with a large cerebral infarction due to embolic occlusion of the left middle cerebral artery. Four hours after the diagnosis of cerebral embolism, he was subsequently diagnosed with acute myocardial infarction due to concurrent coronary embolism. He underwent successful coronary revascularization with a drug-eluting stent. The possibility of combined coronary embolism as a rare etiology should be kept in mind when a patient with acute embolic stroke presents, especially when there is evidence of acute myocardial infarction. PMID:24363753

  9. Mesalizine-Induced Acute Pancreatitis and Interstitial Pneumonitis in a Patient with Ulcerative Colitis.

    PubMed

    Chung, Min Jae; Lee, Jae Hee; Moon, Kyung Rye

    2015-12-01

    Ulcerative colitis (UC) is a chronic idiopathic inflammatory bowel disease. Mesalizine for the first-line therapy of UC has adverse effects include pancreatitis, pneumonia and pericarditis. UC complicated by two coexisting conditions, however, is very rare. Moreover, drug-related pulmonary toxicity is particularly rare. An 11-year-old male patient was hospitalized for recurring upper abdominal pain after meals with vomiting, hematochezia and exertional dyspnea developing at 2 weeks of mesalizine therapy for UC. The serum level of lipase was elevated. Chest X-ray and thorax computed tomography showed interstitial pneumonitis. Mesalizine was discontinued and steroid therapy was initiated. Five days after admission, symptoms were resolved and mesalizine was resumed after a drop in amylase and lipase level. Symptoms returned the following day, however, accompanied by increased the serum levels of amylase and lipase. Mesalizine was discontinued again and recurring symptoms rapidly improved.

  10. The Relationship between C-Reactive Protein Level and Discharge Outcome in Patients with Acute Ischemic Stroke

    PubMed Central

    Geng, He-Hong; Wang, Xin-Wang; Fu, Rong-Li; Jing, Meng-Juan; Huang, Ling-Ling; Zhang, Qing; Wang, Xiao-Xiao; Wang, Pei-Xi

    2016-01-01

    Previous studies showed that C-reactive protein (CRP), an inflammatory marker, was associated with stroke severity and long-term outcome. However, the relationship between the acute-phase CRP level and discharge outcome has received little attention. We prospectively studied 301 patients with acute ischemic stroke (over a period of two weeks) from two hospital stroke wards and one rehabilitation department in Henan, China. Patients’ demographic and clinical data were collected and evaluated at admission. Poor discharge outcome was assessed in patients at discharge using the Modified Rankin Scale (MRS > 2). Multivariate logistic regression analysis was performed to determine the risk factors of poor discharge outcome after adjusting for potential confounders. Poor discharge outcome was observed in 78 patients (25.9%). Univariate analyses showed that factors significantly influencing poor discharge outcome were age, residence, recurrent acute ischemic stroke, coronary heart disease, the National Institutes of Health Stroke Scale (NIHSS) score at admission, non-lacunar stroke, time from onset of stroke to admission, CRP, TBIL (total bilirubin), direct bilirubin (DBIL), ALB (albumin), FIB (fibrinogen) and D-dimer (p < 0.05). After adjusting for age, residence, recurrent ischemic stroke, coronary heart disease, NIHSS score at admission, lacunar stroke, time from onset of stroke to admission, CRP, TBIL, DBIL, ALB, FIB and D-dimer, multivariate logistic regression analyses revealed that poor outcome at discharge was associated with recurrent acute ischemic stroke (OR, 2.115; 95% CI, 1.094–4.087), non-lacunar stroke (OR, 2.943; 95% CI, 1.436–6.032), DBIL (OR, 1.795; 95% CI, 1.311–2.458), and CRP (OR, 4.890; 95% CI, 3.063–7.808). In conclusion, the CRP level measured at admission was found to be an independent predictor of poor outcome at discharge. Recurrent acute ischemic stroke, non-lacunar stroke and DBIL were also significantly associated with discharge

  11. Role of spleen-derived monocytes/macrophages in acute ischemic brain injury.

    PubMed

    Kim, Eunhee; Yang, Jiwon; Beltran, Cesar D; Cho, Sunghee

    2014-08-01

    Monocytes/macrophages (MMs), mononuclear phagocytes, have been implicated in stroke-induced inflammation and injury. However, the presence of pro-inflammatory Ly-6C(high) and antiinflammatory Ly-6C(low) monocyte subsets raises uncertainty regarding their role in stroke pathologic assessment. With recent identification of the spleen as an immediate reservoir of MMs, this current study addresses whether the spleen-derived MMs are required for stroke pathologic assessment. We observed that the spleen was contracted in poststroke animals and the contraction was accompanied by decreased number of Ly-6C(high) and Ly-6C(low) subsets in the spleen. The deployment of these subsets from the spleen temporally coincided with respective increases in the ischemic brain. Compared to mice with the spleen, mice receiving a splenectomy just before the stroke displayed less accumulation of Ly-6C(high) and Ly-6C(low) MMs in the brain. Despite the reduced accumulation of both subsets, infarct size and swelling were not reduced in the asplenic mice. The dissociative findings of infarct size and extent of MM infiltration in the postischemic brain indicate minimal involvement of spleen-derived total MMs in acute infarct development. Selective Ly-6C(high) or Ly-6C(low) MM targeting is suggested to address the contribution of the individual subset to acute stroke pathologic assessment.

  12. Paediatric arterial ischemic stroke: acute management, recent advances and remaining issues.

    PubMed

    Rosa, Margherita; De Lucia, Silvana; Rinaldi, Victoria Elisa; Le Gal, Julie; Desmarest, Marie; Veropalumbo, Claudio; Romanello, Silvia; Titomanlio, Luigi

    2015-01-01

    Stroke is a rare disease in childhood with an estimated incidence of 1-6/100.000. It has an increasingly recognised impact on child mortality along with its outcomes and effects on quality of life of patients and their families. Clinical presentation and risk factors of paediatric stroke are different to those of adults therefore it can be considered as an independent nosological entity. The relative rarity, the age-related peculiarities and the variety of manifested symptoms makes the diagnosis of paediatric stroke extremely difficult and often delayed. History and clinical examination should investigate underlying diseases or predisposing factors and should take into account the potential territoriality of neurological deficits and the spectrum of differential diagnosis of acute neurological accidents in childhood. Neuroimaging (in particular diffusion weighted magnetic resonance) is the keystone for diagnosis of paediatric stroke and other investigations might be considered according to the clinical condition. Despite substantial advances in paediatric stroke research and clinical care, many unanswered questions remain concerning both its acute treatment and its secondary prevention and rehabilitation so that treatment recommendations are mainly extrapolated from studies on adult population. We have tried to summarize the pathophysiological and clinical characteristics of arterial ischemic stroke in children and the most recent international guidelines and practical directions on how to recognise and manage it in paediatric emergency.

  13. Is Intra-Arterial Treatment for Acute Ischemic Stroke Less Effective in Women than in Men?

    PubMed Central

    de Ridder, Inger R.; Fransen, Puck S.S.; Beumer, Debbie; Berkhemer, Olvert A.; van den Berg, Lucie A.; Wermer, Marieke J.; Lingsma, Hester; van Zwam, Wim H.; Roos, Yvo B.; van Oostenbrugge, Robert J.; Majoie, Charles B.; van der Lugt, Aad; Dippel, Diederik W.J.

    2016-01-01

    Introduction Stroke etiology and outcome after ischemic stroke differ between men and women. We examined if sex modifies the effect of intra-arterial treatment (IAT) in a randomized clinical trial of IAT for acute ischemic stroke in the Netherlands (MR CLEAN). Patients and Methods The primary outcome was the score on the modified Rankin scale at 90 days. We tested for interaction between sex and treatment and estimated the treatment effect by sex with multiple ordinal logistic regression with adjustment for prognostic factors. Results All 500 patients were included in the analysis; 292 (58.4%) were men. The treatment effect (adjusted common odds ratio) was 2.39 [95% confidence interval (CI) 1.55–3.68] in men and 0.99 (95% CI 0.60–1.66) in women (pinteraction = 0.016). In women, mortality was higher in the intervention group than in the control group (24 vs. 15%, p = 0.07). Serious adverse events occurred more often in women than in men undergoing intervention. There were no differences in neuro-imaging outcomes. Discussion and Conclusion Contrary to other studies, we found a significant interaction between sex and treatment effect in the MR CLEAN trial. Pooled analyses of all published thrombectomy trials did not confirm this finding. In MR CLEAN, women seem to have a slightly more unfavorable profile, causing higher mortality and more serious adverse events, but insufficient to explain the absence of an overall effect. This suggests a play of chance and makes it clear that IAT should not be withheld in women.

  14. Clinically-relevant reperfusion in acute ischemic stroke MTT performs better than Tmax and TTP

    PubMed Central

    Kong, Linglong; Zhu, Hongtu; Vo, Katie D.; Powers, William J.; Lin, Weili; Lee, Jin-Moo

    2014-01-01

    Background While several MRI parameters are used to assess tissue perfusion during hyperacute stroke, it is unclear which is optimal for measuring clinically-relevant reperfusion. We directly compared MTT prolongation (MTTp), TTP, and time-to-maximum (Tmax) to determine which best predicted neurological improvement and tissue salvage following early reperfusion. Methods Acute ischemic stroke patients underwent three MRI's: <4.5hr (tp1), at 6hr (tp2), and at 1 month after onset. Perfusion deficits at tp1 and tp2 were defined by MTTp, TTP, or Tmax beyond four commonly-used thresholds. Percent reperfusion (%Reperf) was calculated for each parameter and threshold. Regression analysis was used to fit %Reperf for each parameter and threshold as a predictor of neurological improvement [defined as admission National Institutes of Health Stroke Scale (NIHSS) – 1 month NIHSS (ΔNIHSS)] after adjusting for baseline clinical variables. Volume of reperfusion, for each parameter and threshold, was correlated with tissue salvage, defined as tp1 perfusion deficit volume – final infarct volume. Results 50 patients were scanned at 2.7 hours and 6.2 hours after stroke onset. %Reperf predicted ΔNIHSS for all MTTp thresholds, for Tmax > 6s and > 8s, but for no TTP thresholds. Tissue salvage significantly correlated with reperfusion for all MTTp thresholds and with Tmax > 6s, while there was no correlation with any TTP threshold. Among all parameters, reperfusion defined by MTTp was most strongly associated with ΔNIHSS (MTTp>3s, p=0.0002) and tissue salvage (MTTp> 3s and 4s, P<0.0001). Conclusion MTT-defined reperfusion was the best predictor of neurological improvement and tissue salvage in hyperacute ischemic stroke. PMID:24500786

  15. Association between neuroserpin and molecular markers of brain damage in patients with acute ischemic stroke

    PubMed Central

    2011-01-01

    Background Neuroserpin has shown neuroprotective effects in animal models of cerebral ischemia and has been associated with functional outcome after ischemic stroke. Our aim was to study whether neuroserpin serum levels could be associated to biomarkers of excitotoxicity, inflammation and blood brain barrier disruption. Methods We prospectively included 129 patients with ischemic stroke (58.1% male; mean age, 72.4 ± 9.6 years) not treated with tPA within 12 hours (h) of symptoms onset (mean time, 4.7 ± 2.1 h). Poor functional outcome at 3 months was considered as a modified Rankin scale score >2. Serum levels of neuroserpin, Interleukin 6 (IL-6), Intercellular adhesion molecule-1 (ICAM-1), active Matrix metalloproteinase 9 (MMP-9), and cellular fibronectin (cFn) (determined by ELISA) and glutamate (determined by HPLC) were measured on admission, 24 and 72 h. The main variable was considered the decrease of neuroserpin levels within the first 24 h. ROC analysis was used to select the best predictive value for neuroserpin to predict poor functional outcome due to a lack of linearity. Results The decrease of neuroserpin levels within the first 24 h was negatively correlated with serum levels at 24 hours of glutamate (r = -0.642), IL-6 (r = -0.678), ICAM-1 (r = -0.345), MMP-9 (r = -0.554) and cFn (r = -0.703) (all P < 0.0001). In the multivariate analysis, serum levels of glutamate (OR, 1.04; CI95%, 1.01-1.06, p = 0.001); IL-6 (OR, 1.4; CI95%, 1.1-1.7, p = 0.001); and cFn (OR, 1.3; CI95%, 1.1-1.6, p = 0.002) were independently associated with a decrease of neuroserpin levels <70 ng/mL at 24 h after adjusting for confounding factors. Conclusions These findings suggest that neuroprotective properties of neuroserpin may be related to the inhibition of excitotoxicity, inflammation, as well as blood brain barrier disruption that occur after acute ischemic stroke. PMID:21569344

  16. Dynamic change of collateral flow varying with distribution of regional blood flow in acute ischemic rat cortex

    NASA Astrophysics Data System (ADS)

    Wang, Zhen; Luo, Weihua; Zhou, Fangyuan; Li, Pengcheng; Luo, Qingming

    2012-12-01

    Cerebral blood flow (CBF) is critical for the maintenance of cerebral function by guaranteed constant oxygen and glucose supply to brain. Collateral channels (CCs) are recruited to provide alternatives to CBF to ischemic regions once the primary vessel is occluded during ischemic stroke. However, the knowledge of the relationship between dynamic evolution of collateral flow and the distribution of regional blood flow remains limited. In this study, laser speckle imaging was used to assess dynamic changes of CCs and regional blood flow in a rat cortex with permanent middle cerebral artery occlusion (MCAo). We found that CCs immediately provided blood flow to ischemic territories after MCAo. More importantly, there were three kinds of dynamic changes of CCs during acute stroke: persistent CC, impermanent CC, and transient CC, respectively, related to different distributions of regional blood flow. Although there was the possible occurrence of peri-infarct depolarization (PID) during ischemia, there was no obvious significance about the onset time and duration of CCs between rats with and without PID. These results suggest that the initial arising of CCs does not ensure their persistence, and that collateral flow could be varied with distribution of regional blood flow in acute ischemic stroke, which may facilitate the understanding of collateral recruitment and promote the development of collateral therapeutics in the future.

  17. Functional gain following rehabilitation of recurrent ischemic stroke in the elderly: experience of a post-acute care rehabilitation setting.

    PubMed

    Mizrahi, E H; Fleissig, Y; Arad, M; Adunsky, A

    2015-01-01

    The aim of the study was to evaluate whether rehabilitation of patients with recurrent ischemic strokes is associated with functional gain. We studied a total of 919 consecutive post-acute ischemic stroke elderly patients admitted for rehabilitation. 22% out of the patients had recurrent stroke on index day. Functional outcomes of first-ever stroke patients and recurrent ischemic stroke patients were assessed by the Functional Independence Measurement scale (FIM™) at admission and discharge. Data was analyzed by t-test, Chi-square test and by multiple linear regression analysis. There were 716 patients with first ever stroke and 203 patients with recurrent stroke. Total and motor FIM scores at admission and total, motor, gain and Montebello Rehabilitation Factor (RFG) FIM scores at discharge were similar in the two groups. A multiple linear regression analysis showed that age (beta=-0.13, p=0.001) length of stay (beta=0.21, p<0.001), Mini-Mental State Examination score (MMSE) (beta=0.1, p=0.01), and admission total FIM (beta=-0.12, p=0.01) emerged as the only independent predictors of higher gain FIM scores at discharge. The finding suggests that elderly patients with recurrent ischemic stroke admitted to rehabilitation ward, showed similar FIM gain scores at discharge, compared with first-ever stroke patients. It is concluded that recurrent stroke should not be considered as adversely affecting the short-term functional outcomes of patients in a post-acute rehabilitation setting.

  18. The Combined Approach to Lysis Utilizing Eptifibatide and rt-PA in Acute Ischemic Stroke

    PubMed Central

    Pancioli, Arthur M.; Broderick, Joseph; Brott, Thomas; Tomsick, Thomas; Khoury, Jane; Bean, Judy; del Zoppo, Gregory; Kleindorfer, Dawn; Woo, Daniel; Khatri, Pooja; Castaldo, John; Frey, James; Gebel, James; Kasner, Scott; Kidwell, Chelsea; Kwiatkowski, Thomas; Libman, Richard; Mackenzie, Richard; Scott, Phillip; Starkman, Sidney; Thurman, R. Jason

    2008-01-01

    Background and Purpose Multiple approaches are being studied to enhance the rate of thrombolysis for acute ischemic stroke. Treatment of myocardial infarction with a combination of a reduced-dose fibrinolytic agent and a glycoprotein (GP) IIb/IIIa receptor antagonist has been shown to improve the rate of recanalization versus fibrinolysis alone. The combined approach to lysis utilizing eptifibatide and recombinant tissue-type plasminogen activator (rt-PA) (CLEAR) stroke trial assessed the safety of treating acute ischemic stroke patients within 3 hours of symptom onset with this combination. Methods The CLEAR trial was a National Institutes of Health/National Institute of Neurological Disorders and Stroke–funded multicenter, double-blind, randomized, dose-escalation and safety study. Patients were randomized 3:1 to either low-dose rt-PA (tier 1=0.3 mg/kg, tier 2=0.45 mg/kg) plus eptifibatide (75 μg/kg bolus followed by 0.75 μg/kg per min infusion for 2 hours) or standard-dose rt-PA (0.9 mg/kg). The primary safety end point was the incidence of symptomatic intracerebral hemorrhage within 36 hours. Secondary analyses were performed regarding clinical efficacy. Results Ninety-four patients (40 in tier 1 and 54 in tier 2) were enrolled. The combination group of the 2 dose tiers (n=69) had a median age of 71 years and a median baseline National Institutes of Health Stroke Scale (NIHSS) score of 14, and the standard-dose rt-PA group (n=25) had a median age of 61 years and a median baseline NIHSS score of 10 (P=0.01 for NIHSS score). Fifty-two (75%) of the combination treatment group and 24 (96%) of the standard treatment group had a baseline modified Rankin scale score of 0 (P=0.04). There was 1 (1.4%; 95% CI, 0% to 4.3%) symptomatic intracranial hemorrhage in the combination group and 2 (8.0%; 95% CI, 0% to 19.2%) in the rt-PA–only arm (P=0.17). During randomization in tier 2, a review by the independent data safety monitoring board demonstrated that the safety

  19. Listeria Rhombencephalitis Complicating Anti-TNF Treatment during an Acute Flare of Crohn's Colitis

    PubMed Central

    Caddy, G. R.

    2016-01-01

    Patients with Crohn's disease often require the use of immunosuppressant drugs to control disease activity. Such medication includes steroids, azathioprine, and biologic therapy. These suppress the immune response, and the patient is more susceptible to infection. We present a case of a 69-year-old gentleman with a history of Crohn's colitis who had ongoing symptoms of diarrhoea in spite of standard treatment. Biologic therapy was considered to be the next step, and screening for infection was undertaken prior to use. Three days following anti-TNF treatment, he became drowsy, and examination revealed pyrexia, slurred speech, and nystagmus. Investigation revealed presence of Listeria rhombencephalitis. He demonstrated poor neurological recovery. Listeria monocytogenes is an infection commonly associated with food sources. Some patients develop a self-limiting diarrhoeal illness, but in the immunosuppressed population, the clinical features may be more sinister. Cotrimoxazole prophylaxis is already recommended for those on triple immunosuppression. We propose the early initiation of this treatment, including where biologic use is anticipated. In those on multiple immunosuppressants, a diet similar to that followed in pregnancy may minimise risk of acquiring this infection. Clinicians must always have a high index of suspicion for opportunistic infection in such immunocompromised patients.

  20. Listeria Rhombencephalitis Complicating Anti-TNF Treatment during an Acute Flare of Crohn's Colitis

    PubMed Central

    Caddy, G. R.

    2016-01-01

    Patients with Crohn's disease often require the use of immunosuppressant drugs to control disease activity. Such medication includes steroids, azathioprine, and biologic therapy. These suppress the immune response, and the patient is more susceptible to infection. We present a case of a 69-year-old gentleman with a history of Crohn's colitis who had ongoing symptoms of diarrhoea in spite of standard treatment. Biologic therapy was considered to be the next step, and screening for infection was undertaken prior to use. Three days following anti-TNF treatment, he became drowsy, and examination revealed pyrexia, slurred speech, and nystagmus. Investigation revealed presence of Listeria rhombencephalitis. He demonstrated poor neurological recovery. Listeria monocytogenes is an infection commonly associated with food sources. Some patients develop a self-limiting diarrhoeal illness, but in the immunosuppressed population, the clinical features may be more sinister. Cotrimoxazole prophylaxis is already recommended for those on triple immunosuppression. We propose the early initiation of this treatment, including where biologic use is anticipated. In those on multiple immunosuppressants, a diet similar to that followed in pregnancy may minimise risk of acquiring this infection. Clinicians must always have a high index of suspicion for opportunistic infection in such immunocompromised patients. PMID:27651962

  1. Listeria Rhombencephalitis Complicating Anti-TNF Treatment during an Acute Flare of Crohn's Colitis.

    PubMed

    Stratton, L; Caddy, G R

    2016-01-01

    Patients with Crohn's disease often require the use of immunosuppressant drugs to control disease activity. Such medication includes steroids, azathioprine, and biologic therapy. These suppress the immune response, and the patient is more susceptible to infection. We present a case of a 69-year-old gentleman with a history of Crohn's colitis who had ongoing symptoms of diarrhoea in spite of standard treatment. Biologic therapy was considered to be the next step, and screening for infection was undertaken prior to use. Three days following anti-TNF treatment, he became drowsy, and examination revealed pyrexia, slurred speech, and nystagmus. Investigation revealed presence of Listeria rhombencephalitis. He demonstrated poor neurological recovery. Listeria monocytogenes is an infection commonly associated with food sources. Some patients develop a self-limiting diarrhoeal illness, but in the immunosuppressed population, the clinical features may be more sinister. Cotrimoxazole prophylaxis is already recommended for those on triple immunosuppression. We propose the early initiation of this treatment, including where biologic use is anticipated. In those on multiple immunosuppressants, a diet similar to that followed in pregnancy may minimise risk of acquiring this infection. Clinicians must always have a high index of suspicion for opportunistic infection in such immunocompromised patients. PMID:27651962

  2. Changes of deceleration and acceleration capacity of heart rate in patients with acute hemispheric ischemic stroke

    PubMed Central

    Xu, Yan-Hong; Wang, Xing-De; Yang, Jia-Jun; Zhou, Li; Pan, Yong-Chao

    2016-01-01

    Background and purpose Autonomic dysfunction is common after stroke, which is correlated with unfavorable outcome. Phase-rectified signal averaging is a newly developed technique for assessing cardiac autonomic function, by detecting sympathetic and vagal nerve activity separately through calculating acceleration capacity (AC) and deceleration capacity (DC) of heart rate. In this study, we used this technique for the first time to investigate the cardiac autonomic function of patients with acute hemispheric ischemic stroke. Methods A 24-hour Holter monitoring was performed in 63 patients with first-ever acute ischemic stroke in hemisphere and sinus rhythm, as well as in 50 controls with high risk of stroke. DC, AC, heart rate variability parameters, standard deviation of all normal-to-normal intervals (SDNN), and square root of the mean of the sum of the squares of differences between adjacent normal-to-normal intervals (RMSSD) were calculated. The National Institutes of Health Stroke Scale (NIHSS) was used to assess the severity of stroke. We analyzed the changes of DC, AC, SDNN, and RMSSD and also studied the correlations between these parameters and NIHSS scores. Results The R–R (R wave to R wave on electrocardiogram) intervals, DC, AC, and SDNN in the cerebral infarction group were lower than those in controls (P=0.003, P=0.002, P=0.006, and P=0.043), but the difference of RMSSD and the D-value and ratio between absolute value of AC (|AC|) and DC were not statistically significant compared with those in controls. The DC of the infarction group was significantly correlated with |AC|, SDNN, and RMSSD (r=0.857, r=0.619, and r=0.358; P=0.000, P=0.000, and P=0.004). Correlation analysis also showed that DC, |AC|, and SDNN were negatively correlated with NIHSS scores (r=−0.279, r=−0.266, and r=−0.319; P=0.027, P=0.035, and P=0.011). Conclusion Both DC and AC of heart rate decreased in patients with hemispheric infarction, reflecting a decrease in both vagal

  3. Vascular Pathology in the Extracranial Vertebral Arteries in Patients with Acute Ischemic Stroke

    PubMed Central

    Bentsen, L.; Nygård, A.; Ovesen, C.; Christensen, A.; Rosenbaum, S.; Havsteen, I.; Christensen, H.

    2014-01-01

    Introduction Vascular pathology in the extracranial vertebral arteries remains among the possible causes in cryptogenic stroke. However, the diagnosis is challenged by the great variety in the anatomy of the vertebral arteries, clinical symptoms and difficulties in the radiological assessments. The aim of this study was to assess the prevalence of CT angiography (CTA)-detected pathological findings in the extracranial vertebral arteries in an acute stroke population and secondly to determine the frequency of posterior pathology as probable cause in patients with otherwise cryptogenic stroke. Method The analysis was based on 657 consecutive patients with symptoms of acute stroke and a final diagnosis of ischemic stroke or transient ischemic attack. On admission, a noncontrast CT cerebrum and CTA were performed. A senior consultant neuroradiologist, blinded to clinical data, reviewed all CTA scans systematically, assessing the four segments of the extracranial vertebral arteries. First, the frequency of pathological findings including stenosis, plaques, dissection, kinked artery and coiling was assessed. Subsequently, we explored the extent of the pathological findings that were the most plausible causes of stroke, namely either a possible dissection or a kinked artery. Results Findings in the extracranial vertebral arteries included significant stenosis (0.8%), atherosclerotic plaque types (3.8%), possible dissections (2.6%), kinked arteries (2.6%) and coiling (32.0%). Eighteen patients (2.8%) with pathological findings had an unknown cause of stroke, likely posterior symptoms and no clinical stroke symptoms from the anterior circuit. Of these, 3 cases were kinked arteries (0.5%) and 15 cases (2.3%) were possible dissections. Conclusion We found that in approximately 3% of the study population, the most plausible cause of the cryptogenic strokes was due to a pathological finding in the posterior extracranial vertebral arteries, being either a possible dissection or

  4. Apical leptin induces chloride secretion by intestinal epithelial cells and in a rat model of acute chemotherapy-induced colitis

    PubMed Central

    Hoda, Raschid M.; Scharl, Michael; Keely, Stephen J.; McCole, Declan F.

    2010-01-01

    The purpose of this study was to investigate whether luminal leptin alters ion transport properties of the intestinal epithelium under acute inflammatory conditions. Monolayers of human intestinal T84 epithelial cells and a rat model of chemotherapy-induced enterocolitis were used. Cells were treated with leptin and mounted in Ussing chambers to measure basal and secretagogue-induced changes in transepithelial short-circuit current (Isc). Furthermore, the role of MAPK and phosphatidylinositol 3-kinase (PI3K) signaling pathways in mediating responses to leptin was investigated. Acute colitis in Sprague-Dawley rats was induced by intraperitoneal injection of 40 mg/kg methotrexate. Leptin (100 ng/ml) induced a time-dependent increase in basal Isc in T84 intestinal epithelial cells (P < 0.01). Moreover, pretreatment of T84 cells with leptin for up to 1 h significantly potentiated carbachol- and forskolin-induced increases in Isc. Pretreatment with an inhibitor of MAPK abolished the effect of leptin on basal, carbachol- and forskolin-induced chloride secretion (P < 0.05). However, the PI3K inhibitor, wortmannin, only blunted the effect of leptin on forskolin-induced increases in Isc. Furthermore, leptin treatment evoked both ERK1/2 and Akt1 phosphorylation in T84 cells. In the rat model, luminal leptin induced significant increases in Isc across segments of proximal and, to a lesser extent, distal colon (P < 0.05). We conclude that luminal leptin is likely an intestinal chloride secretagogue, particularly when present at elevated concentrations and/or in the setting of inflammation. Our findings may provide a mechanistic explanation, at least in part, for the clinical condition of secretory diarrhea both in hyperleptinemic obese patients and in patients with chemotherapy-induced intestinal inflammation. PMID:20203064

  5. Pilot study of the safety of starting administration of low-dose aspirin and cilostazol in acute ischemic stroke.

    PubMed

    Fujita, Keishi; Komatsu, Yoji; Sato, Naoaki; Higuchi, Osamu; Kujiraoka, Yuji; Kamezaki, Takao; Suzuki, Kensuke; Matsumura, Akira

    2011-01-01

    Progressive stroke is a serious problem due to the associated morbidity and mortality. Aspirin is recommended for acute ischemic stroke, but does not reduce the frequency of stroke progression. No standard treatment has been approved for the prevention of stroke progression. Cilostazol, which reduces platelet aggregation about 3 hours after single administration, does not increase the frequency of bleeding events when compared with aspirin or a placebo. Moreover, the combination of 100 mg aspirin and 200 mg cilostazol does not increase the frequency of bleeding events compared with only 100 mg aspirin, and thus is expected to prevent stroke progression with a high degree of safety. The present study investigated the safety of this combination of two drugs administered at the above concentrations in 54 patients with acute ischemic stroke within 48 hours of stroke onset. Modified National Institutes of Health Stroke Scale (NIHSS) measurements were performed at baseline and again on day 4 to 7. Progressive stroke was defined as an increase greater than or equal to 1 point on NIHSS. Patient scores on the modified Rankin Scale (mRS) were evaluated at baseline and 3 months after enrollment. Stroke progression occurred in 11.1% of the patients. The percentages of patients with mRS score from 0 to 2 were 42.6% and 75% at baseline and 3 months, respectively. No symptomatic intracranial hemorrhage or major extracranial hemorrhage occurred. These results suggest that administration of aspirin and cilostazol is safe for acute ischemic stroke.

  6. Effects of dietary virgin olive oil polyphenols: hydroxytyrosyl acetate and 3, 4-dihydroxyphenylglycol on DSS-induced acute colitis in mice.

    PubMed

    Sánchez-Fidalgo, Susana; Villegas, Isabel; Aparicio-Soto, Marina; Cárdeno, Ana; Rosillo, Ma Ángeles; González-Benjumea, Alejandro; Marset, Azucena; López, Óscar; Maya, Inés; Fernández-Bolaños, José G; Alarcón de la Lastra, Catalina

    2015-05-01

    Hydroxytyrosol, a polyphenolic compound from extra virgin olive oil (EVOO) has exhibited an improvement in a model of DSS-induced colitis. However, other phenolic compounds present such as hydroxytyrosyl acetate (HTy-Ac) and 3,4-dihydroxyphenylglycol (DHPG) need to be explored to complete the understanding of the overall effects of EVOO on inflammatory colon mucosa. This study was designed to evaluate the effect of both HTy-Ac and DHPG dietary supplementation in the inflammatory response associated to colitis model. Six-week-old mice were randomized in four dietary groups: sham and control groups received standard diet, and other two groups were fed with HTy-Ac and DHPG, respectively, at 0.1%. After 30 days, all groups except sham received 3% DSS in drinking water for 5 days followed by a regime of 5 days of water. Acute inflammation was evaluated by Disease Activity Index (DAI), histology and myeloperoxidase (MPO) activity. Colonic expression of iNOS, COX-2, MAPKs, NF-kB and FOXP3 were determined by western blotting. Only HTy-Ac-supplemented group showed a significant DAI reduction as well as an improvement of histological damage and MPO. COX-2 and iNOS protein expression were also significantly reduced. In addition, this dietary group down-regulated JNK phosphorylation and prevented the DSS-induced nuclear translocation level of p65. However, no significant differences were observed in the FOXP3 expression. These results demonstrated, for the first time, that HTy-Ac exerts an antiinflammatory effect on acute ulcerative colitis. We concluded that HTy-Ac supplement might provide a basis for developing a new dietary strategy for the prevention of ulcerative colitis.

  7. Effects of dietary virgin olive oil polyphenols: hydroxytyrosyl acetate and 3, 4-dihydroxyphenylglycol on DSS-induced acute colitis in mice.

    PubMed

    Sánchez-Fidalgo, Susana; Villegas, Isabel; Aparicio-Soto, Marina; Cárdeno, Ana; Rosillo, Ma Ángeles; González-Benjumea, Alejandro; Marset, Azucena; López, Óscar; Maya, Inés; Fernández-Bolaños, José G; Alarcón de la Lastra, Catalina

    2015-05-01

    Hydroxytyrosol, a polyphenolic compound from extra virgin olive oil (EVOO) has exhibited an improvement in a model of DSS-induced colitis. However, other phenolic compounds present such as hydroxytyrosyl acetate (HTy-Ac) and 3,4-dihydroxyphenylglycol (DHPG) need to be explored to complete the understanding of the overall effects of EVOO on inflammatory colon mucosa. This study was designed to evaluate the effect of both HTy-Ac and DHPG dietary supplementation in the inflammatory response associated to colitis model. Six-week-old mice were randomized in four dietary groups: sham and control groups received standard diet, and other two groups were fed with HTy-Ac and DHPG, respectively, at 0.1%. After 30 days, all groups except sham received 3% DSS in drinking water for 5 days followed by a regime of 5 days of water. Acute inflammation was evaluated by Disease Activity Index (DAI), histology and myeloperoxidase (MPO) activity. Colonic expression of iNOS, COX-2, MAPKs, NF-kB and FOXP3 were determined by western blotting. Only HTy-Ac-supplemented group showed a significant DAI reduction as well as an improvement of histological damage and MPO. COX-2 and iNOS protein expression were also significantly reduced. In addition, this dietary group down-regulated JNK phosphorylation and prevented the DSS-induced nuclear translocation level of p65. However, no significant differences were observed in the FOXP3 expression. These results demonstrated, for the first time, that HTy-Ac exerts an antiinflammatory effect on acute ulcerative colitis. We concluded that HTy-Ac supplement might provide a basis for developing a new dietary strategy for the prevention of ulcerative colitis. PMID:25736481

  8. A Model for Predicting Persistent Elevation of Factor VIII among Patients with Acute Ischemic Stroke

    PubMed Central

    Samai, Alyana A.; Boehme, Amelia K.; Shaban, Amir; George, Alexander J.; Dowell, Lauren; Monlezun, Dominique J.; Leissinger, Cindy; Schluter, Laurie; El Khoury, Ramy; Martin-Schild, Sheryl

    2016-01-01

    Background and Purpose Elevated levels of coagulation factor VIII (FVIII) may persist independent of the acute-phase response; however, this relationship has not been investigated relative to acute ischemic stroke (AIS). We examined the frequency and predictors of persistently elevated FVIII in AIS patients. Methods AIS patients admitted between July 2008 and May 2014 with elevated baseline FVIII levels and repeat FVIII levels drawn for more than 7 days postdischarge were included. The patients were dichotomized by repeat FVIII level for univariate analysis at 150% and 200% activity thresholds. An adjusted model was developed to predict the likelihood of persistently elevated FVIII levels. Results Among 1616 AIS cases, 98 patients with elevated baseline FVIII had repeat FVIII levels. Persistent FVIII elevation was found in more than 75% of patients. At the 150% threshold, the prediction score ranged from 0 to 7 and included black race, female sex, prior stroke, hyperlipidemia, smoking, baseline FVIII > 200%, and baseline von Willebrand factor (vWF) level greater than 200%. At the 200% threshold, the prediction score ranged from 0–5 and included female sex, prior stroke, diabetes mellitus, baseline FVIII level greater 200%, and baseline vWF level greater than 200%. For each 1-point increase in score, the odds of persistent FVIII at both the 150% threshold (odds ratio [OR] = 10.4, 95% confidence interval [CI] 1.63–66.9, P = .0134) and 200% threshold (OR = 10.2, 95% CI 1.82–57.5, P = .0083) increased 10 times. Conclusion Because an elevated FVIII level confers increased stroke risk, our model for anticipating a persistently elevated FVIII level may identify patients at high risk for recurrent stroke. FVIII may be a target for secondary stroke prevention. PMID:26777556

  9. The velocity of collateral filling predicts recanalization in acute ischemic stroke after intravenous thrombolysis.

    PubMed

    Zhang, Sheng; Zhang, Xiaocheng; Yan, Shenqiang; Lai, Yangxiao; Han, Quan; Sun, Jianzhong; Zhang, Minming; Parsons, Mark W; Wang, Shaoshi; Lou, Min

    2016-01-01

    The aim of this study was to evaluate the impact of pretreatment quality of collaterals, involving velocity and extent of collateral filling, on recanalization after intravenous thrombolysis (IVT). A retrospective analysis was performed of 66 patients with acute middle cerebral artery (MCA) M1 segment occlusion who underwent MR perfusion (MRP) imaging before IVT. The velocity of collateral filling was defined as arrival time delay (ATD) of contrast bolus to Sylvian fissure between the normal and the affected hemisphere. The extent of collateral filling was assessed according to the Alberta Stroke Program Early CT (ASPECT) score on temporally fused maximum intensity projections (tMIP). Arterial occlusive lesion (AOL) score was used to assess the degree of arterial recanalization. ATD (OR = 0.775, 95% CI = 0.626-0.960, p = 0.020), but not tMIP-ASPECT score (OR = 1.073, 95% CI = 0.820-1.405, p = 0.607), was independently associated with recanalization (AOL score of 2 and 3) at 24 hours after IVT. When recanalization was achieved, hemorrhagic transformation (HT) occurred more frequently in patients with slow collaterals (ATD ≥ 2.3 seconds) than those with rapid collaterals (ATD < 2.3 seconds) (88.9% vs 38.1%, p = 0.011). In conclusion, the velocity of collaterals related to recanalization, which may guide the decision-making of revascularization therapy in acute ischemic stroke. PMID:27296511

  10. Automated prediction of tissue outcome after acute ischemic stroke in computed tomography perfusion images

    NASA Astrophysics Data System (ADS)

    Vos, Pieter C.; Bennink, Edwin; de Jong, Hugo; Velthuis, Birgitta K.; Viergever, Max A.; Dankbaar, Jan Willem

    2015-03-01

    Assessment of the extent of cerebral damage on admission in patients with acute ischemic stroke could play an important role in treatment decision making. Computed tomography perfusion (CTP) imaging can be used to determine the extent of damage. However, clinical application is hindered by differences among vendors and used methodology. As a result, threshold based methods and visual assessment of CTP images has not yet shown to be useful in treatment decision making and predicting clinical outcome. Preliminary results in MR studies have shown the benefit of using supervised classifiers for predicting tissue outcome, but this has not been demonstrated for CTP. We present a novel method for the automatic prediction of tissue outcome by combining multi-parametric CTP images into a tissue outcome probability map. A supervised classification scheme was developed to extract absolute and relative perfusion values from processed CTP images that are summarized by a trained classifier into a likelihood of infarction. Training was performed using follow-up CT scans of 20 acute stroke patients with complete recanalization of the vessel that was occluded on admission. Infarcted regions were annotated by expert neuroradiologists. Multiple classifiers were evaluated in a leave-one-patient-out strategy for their discriminating performance using receiver operating characteristic (ROC) statistics. Results showed that a RandomForest classifier performed optimally with an area under the ROC of 0.90 for discriminating infarct tissue. The obtained results are an improvement over existing thresholding methods and are in line with results found in literature where MR perfusion was used.

  11. The velocity of collateral filling predicts recanalization in acute ischemic stroke after intravenous thrombolysis

    PubMed Central

    Zhang, Sheng; Zhang, Xiaocheng; Yan, Shenqiang; Lai, Yangxiao; Han, Quan; Sun, Jianzhong; Zhang, Minming; Parsons, Mark W.; Wang, Shaoshi; Lou, Min

    2016-01-01

    The aim of this study was to evaluate the impact of pretreatment quality of collaterals, involving velocity and extent of collateral filling, on recanalization after intravenous thrombolysis (IVT). A retrospective analysis was performed of 66 patients with acute middle cerebral artery (MCA) M1 segment occlusion who underwent MR perfusion (MRP) imaging before IVT. The velocity of collateral filling was defined as arrival time delay (ATD) of contrast bolus to Sylvian fissure between the normal and the affected hemisphere. The extent of collateral filling was assessed according to the Alberta Stroke Program Early CT (ASPECT) score on temporally fused maximum intensity projections (tMIP). Arterial occlusive lesion (AOL) score was used to assess the degree of arterial recanalization. ATD (OR = 0.775, 95% CI = 0.626–0.960, p = 0.020), but not tMIP-ASPECT score (OR = 1.073, 95% CI = 0.820–1.405, p = 0.607), was independently associated with recanalization (AOL score of 2 and 3) at 24 hours after IVT. When recanalization was achieved, hemorrhagic transformation (HT) occurred more frequently in patients with slow collaterals (ATD ≥ 2.3 seconds) than those with rapid collaterals (ATD < 2.3 seconds) (88.9% vs 38.1%, p = 0.011). In conclusion, the velocity of collaterals related to recanalization, which may guide the decision-making of revascularization therapy in acute ischemic stroke. PMID:27296511

  12. The velocity of collateral filling predicts recanalization in acute ischemic stroke after intravenous thrombolysis.

    PubMed

    Zhang, Sheng; Zhang, Xiaocheng; Yan, Shenqiang; Lai, Yangxiao; Han, Quan; Sun, Jianzhong; Zhang, Minming; Parsons, Mark W; Wang, Shaoshi; Lou, Min

    2016-01-01

    The aim of this study was to evaluate the impact of pretreatment quality of collaterals, involving velocity and extent of collateral filling, on recanalization after intravenous thrombolysis (IVT). A retrospective analysis was performed of 66 patients with acute middle cerebral artery (MCA) M1 segment occlusion who underwent MR perfusion (MRP) imaging before IVT. The velocity of collateral filling was defined as arrival time delay (ATD) of contrast bolus to Sylvian fissure between the normal and the affected hemisphere. The extent of collateral filling was assessed according to the Alberta Stroke Program Early CT (ASPECT) score on temporally fused maximum intensity projections (tMIP). Arterial occlusive lesion (AOL) score was used to assess the degree of arterial recanalization. ATD (OR = 0.775, 95% CI = 0.626-0.960, p = 0.020), but not tMIP-ASPECT score (OR = 1.073, 95% CI = 0.820-1.405, p = 0.607), was independently associated with recanalization (AOL score of 2 and 3) at 24 hours after IVT. When recanalization was achieved, hemorrhagic transformation (HT) occurred more frequently in patients with slow collaterals (ATD ≥ 2.3 seconds) than those with rapid collaterals (ATD < 2.3 seconds) (88.9% vs 38.1%, p = 0.011). In conclusion, the velocity of collaterals related to recanalization, which may guide the decision-making of revascularization therapy in acute ischemic stroke.

  13. Effects of hyperbaric oxygenation on oxidative stress in acute transient focal cerebral ischemic rats.

    PubMed

    Wang, Ray-Yau; Chang, Heng-Chih; Chen, Chun-Hao; Tsai, Yi-Wei; Yang, Yea-Ru

    2012-01-01

    The aim of this study was to investigate the effects of hyperbaric oxygenation (HBO) after brain ischemia. Middle cerebral artery occlusion (MCAO) procedure was used to induce the brain ischemia. Rats were assigned to control or HBO group after brain ischemia. In order to examine the role of glutathione after HBO treatment, another group of brain ischemic rats were included to receive the glutathione synthesis inhibitor and HBO treatment. HBO was administered at a pressure of 3 atmospheres absolute for 1 h with 100% oxygen, starting at 3 h post brain ischemia in HBO groups. Animals in control group were placed in their home cage and exposed to normobaric room air. The infarct volume (IV), activation of astrocyte, and level of total glutathione and lipid peroxidation (LP) were assessed 24 h post-reperfusion. Significant reduction in IV was noted in HBO group when compared with control group. The activation of astrocyte was significantly increased in the right cerebral cortex and right striatum in the HBO group when compared with those of the control group. The glutathione level was higher with lower LP level in right cortex and right striatum after HBO as compared with those of the control. However, such effects of HBO treatment were markedly reduced by glutathione synthesis inhibitor administration. These results show that inhibiting glutathione synthesis dramatically reduces the effectiveness of HBO in acute transient focal cerebral ischemia.

  14. Acute ischemic gangrene of the rectum: Report of 3 cases and review of literature☆

    PubMed Central

    Azimuddin, Khawaja; Raphaeli, Tal

    2013-01-01

    INTRODUCTION Acute ischemia of the rectum resulting in full thickness necrosis is extremely uncommon because of its excellent blood supply. PRESENTATION OF CASE We present 3 cases with spontaneous ischemic gangrene of the rectum. All three patients were elderly with atherosclerotic arterial disease and presented with hypotensive shock but in none of these patients we encountered a precipitating factor such as preceding vascular surgery or shock state. DISCUSSION A high index of suspicion should be maintained in elderly patients with atherosclerotic disease who present with lower GI symptoms with hypotensive shock and an inflamed rectum on CT scan. Immediate beside proctoscopy should be offered to these patients and if the diagnosis is confirmed these patients should be taken to the operating room immediately. If the entire rectum is found to be gangrenous then an emergency APR should be performed and the perineal wound left open. If the rectum is partially gangrenous then a low anterior resection with Hartman's procedure for diversion is appropriate. CONCLUSION Prompt diagnosis and resuscitation followed by immediate surgical intervention is necessary to save these elderly patients. PMID:24240084

  15. Quantitative permeability magnetic resonance imaging in acute ischemic stroke: how long do we need to scan?

    PubMed

    Vidarsson, Logi; Thornhill, Rebecca E; Liu, Fang; Mikulis, David J; Kassner, Andrea

    2009-11-01

    Blood-brain barrier (BBB) permeability estimation with dynamic contrast-enhanced MRI (DCE-MRI) has shown significant potential for predicting hemorrhagic transformation (HT) in patients presenting with acute ischemic stroke (AIS). In this work, the effects of scan duration on quantitative BBB permeability estimates (KPS) were investigated. Data from eight patients (three with HT) aged 37-93 years old were retrospectively studied by directly calculating the standard deviation of KPS as a function of scan time. The uncertainty in KPS was reduced only slightly for a scan time of 3 min and 30 s (4% reduction in P value from .047 to .045). When more than 3 min and 30 s of data were used, quantitative permeability MRI was able to separate those patients who proceeded to HT from those who did not (P value <.05). Our findings indicate that reducing permeability acquisition times is feasible in keeping with the need to maintain time-efficient MR protocols in the setting of AIS.

  16. A polygraph study of ischemic heart disease: behavior of systolic times in acute myocardial infarction.

    PubMed

    Sardella, F; Martinotti, R; Porro, F; Monzani, V; Randazzo, A; Pieri, R

    1983-01-01

    The authors investigated systolic time intervals in 28 cases of acute myocardial infarction (AMI). Polygraph recordings were made on the first day of illness and repeated at two, three, five, and seven hospital days. The patients were divided into two groups: one with a contributory history of ischemic and/or hypertensive heart disease (Group PH for "positive history") and one without such history (Group NH for "negative history"). The influence of numerous variables on systolic times were explored in both groups, and the emerging data were processed by multiple stepwise regression analysis. The results show that the left ventricular ejection time (LVET) is invariably shortened in AMI, whereas the pre-ejection indices (PEP and ICT) afford definite differentiation of patients of Group PH (with lengthened PEP and ICT values) from those of Group NH (shortened PEP and ICT). The authors emphasize the importance of obtaining polygraph recordings very early in the course of AMI and of taking into account the patient's history in view of a correct assessment of pre-ejection times.

  17. A new approach to define acute kidney injury in term newborns with hypoxic ischemic encephalopathy

    PubMed Central

    Gupta, Charu; Massaro, An N.

    2016-01-01

    Background Current definitions of acute kidney injury (AKI) are not sufficiently sensitive to identify all newborns with AKI during the first week of life. Methods To determine whether the rate of decline of serum creatinine (SCr) during the first week of life can be used to identify newborns with AKI, we reviewed the medical records of 106 term neonates at risk of AKI who were treated with hypothermia for hypoxic ischemic encephalopathy (HIE). Results Of the newborns enrolled in the study, 69 % showed a normal rate of decline of SCr to ≥50 % and/or reached SCr levels of ≤0.6 mg/dl before the 7th day of life, and therefore had an excellent clinical outcome (control group). Thirteen newborns with HIE (12 %) developed AKI according to an established neonatal definition (AKI–KIDGO group), and an additional 20 newborns (19 %) showed a rate of decline of SCr of <33, <40, and <46 % from birth to days 3, 5, or 7 of life, respectively (delayed rise in estimated SCr clearance group). Compared to the control group, newborns in the other two groups required more days of mechanical ventilation and vasopressor drugs and had higher gentamicin levels, more fluid overload, lower urinary epidermal growth factor levels, and a prolonged length of stay. Conclusions The rate of decline of SCr provides a sensitive approach to identify term newborns with AKI during the first week of life. PMID:26857710

  18. Antiplatelet Usage Impacts Clot Density in Acute Anterior Circulation Ischemic Stroke.

    PubMed

    Pikija, Slaven; Magdic, Jozef; Lukic, Anita; Schreiber, Catharina; Mutzenbach, Johannes Sebastian; McCoy, Mark R; Sellner, Johann

    2016-01-01

    We explored whether clot density in middle cerebral artery (MCA) occlusion is related to clinical variables, stroke etiology, blood constituents, and prestroke medication. We performed a retrospective chart review of patients with acute ischemic stroke of the anterior circulation admitted to two Central European stroke centers. The acquisition of non-contrast enhanced CT (NECT) and CT angiography (CTA) within 4.5 h of symptom onset was obligatory. We assessed the site of MCA occlusion as well as density, area, and length of the clot in 150 patients. The Hounsfield unit values for the clot were divided with contralateral MCA segment to yield relative Hounsfield Unit ratio (rHU). The site of the vessel occlusion (M1 vs. M2) and antiplatelet usage, but not stroke etiology, significantly influenced rHU. We found an inverse correlation of rHU with erythrocyte count (p < 0.001). The multivariate analysis revealed that a higher rHU (i.e., clot being more hyperdense) was more likely with the use of antiplatelets (OR 4.24, CI 1.10-16.31, p = 0.036). Erythrocyte (OR 0.18, CI 0.05-0.55, p = 0.003), and thrombocyte counts (OR 0.99, CI 0.98-0.99, p = 0.029) were associated with odds for more hypodense clots (lower rHU). Our study disclosed that antiplatelet therapy impacts the composition of intracranial clots of the anterior circulation. PMID:27563874

  19. Oxidative Stress Markers and Their Dynamic Changes in Patients after Acute Ischemic Stroke

    PubMed Central

    Kollár, Branislav; Chomová, Mária; Pazderová, Petra; Andrezálová, Lucia; Ježovičová, Miriam; Koňariková, Katarína; Laubertová, Lucia; Krivošíková, Zuzana; Slezáková, Laura; Turčáni, Peter

    2016-01-01

    We have focused on determining the range of oxidative stress biomarkers and their dynamic changes in patients at different time points after the acute ischemic stroke (AIS). 82 patients with AIS were involved in our study and were tested: within 24 h from the onset of the attack (group A); at 7-day follow-up (group B); and at 3-month follow-up (group C). 81 gender and age matched volunteers were used as controls. Stroke patients in group A had significantly higher concentrations of plasma lipid peroxides and urine 8-isoprostanes when compared with controls. Protein carbonyls were not significantly different in any experimental group compared to controls. Antioxidant capacity of plasma was increased only in experimental group C. Activities of superoxide dismutase and catalase were elevated in all three experimental AIS groups compared to controls. Paraoxonase activity was reduced in groups A and B and unchanged in group C when compared to controls. Glutathione peroxide activity was elevated only in group A. Our results suggest that free radical damage is the highest within 24 h after the attack. During the next 3 months oxidative damage to lipids caused by free radicals is reduced due to activated antioxidant system. PMID:27774120

  20. Serum IL-33 Is a Novel Diagnostic and Prognostic Biomarker in Acute Ischemic Stroke

    PubMed Central

    Li, Qian; Lin, Yuanshao; Huang, Wensi; Zhou, Yulei; Chen, Xiaoli; Wang, Brian; Zhang, Wanli; Cai, Zhengyi; Xue, Jie; Zhang, Wenhui; Yu, Tieer; Wang, Hong; He, Jincai; Jin, Kunlin; Shao, Bei

    2016-01-01

    Interleukin-33 (IL-33), a newly recognized IL-1 family member, is expressed in various tissues and cells, and involved in pathogenesis of many human diseases. For example, IL-33 plays a protective role in cardiovascular diseases. However, the role of IL-33 in acute ischemic stroke (AIS) remains unclear. This study aims to investigate whether IL-33 level in AIS patient serum can be used as a potential diagnostic and prognostic marker. The study included two hundred and six patients with first-ever ischemic stroke, who were admitted within 72 hours after stroke onset. The serum level of IL-33 was measured with ELISA and the severity of AIS patients on admission was evaluated based on the National Institutes of Health Stroke Scale (NIHSS) score. The functional outcome at 3 months was determined using the Barthel index (BI). We found that serum IL-33 was significantly higher (P < 0.001) in patients with AIS [57.68 ng/L (IQR, 44.95-76.73)] compared with healthy controls [47.48 ng/L (IQR, 38.67-53.78)]. IL-33 was an independent diagnostic biomarker for AIS with an OR of 1.051 (95%Cl, 1.018-1.085; P=0.002). Serum IL-33 was higher (P < 0.05) in the stroke patients with small cerebral infarction volume compared to AIS patients with large cerebral infarction. In addition, serum IL-33 was also significantly higher (P = 0.001) in the patients with mild stroke, compared to the patients with severe stroke. Furthermore, serum IL-33 level in AIS patients with a worse outcome was higher (P < 0.001) compared to AIS patients with a better outcome. IL-33 was also an independent predictor for the functional outcome with an adjusted OR of 0.932 (95% CI, 0.882-0.986). Our results suggest that the lower level of serum IL-33 is associated with large infarction volume and greater stroke severity in AIS patients. Thus, IL-33 can be used as a novel and independent diagnostic and predicting prognostic marker in AIS. PMID:27699084

  1. Serum IL-33 Is a Novel Diagnostic and Prognostic Biomarker in Acute Ischemic Stroke

    PubMed Central

    Qian, Li; Yuanshao, Lin; Wensi, Huang; Yulei, Zhou; Xiaoli, Chen; Brian, Wang; Wanli, Zhang; Zhengyi, Cai; Jie, Xue; Wenhui, Zhang; Tieer, Yu; Hong, Wang; Jincai, He; Kunlin, Jin; Bei, Shao

    2016-01-01

    Interleukin-33 (IL-33), a newly recognized IL-1 family member, is expressed in various tissues and cells, and involved in pathogenesis of many human diseases. For example, IL-33 plays a protective role in cardiovascular diseases. However, the role of IL-33 in acute ischemic stroke (AIS) remains unclear. This study aims to investigate whether IL-33 level in AIS patient serum can be used as a potential diagnostic and prognostic marker. The study included two hundred and six patients with first-ever ischemic stroke, who were admitted within 72 hours after stroke onset. The serum level of IL-33 was measured with ELISA and the severity of AIS patients on admission was evaluated based on the National Institutes of Health Stroke Scale (NIHSS) score. The functional outcome at 3 months was determined using the Barthel index (BI). We found that serum IL-33 was significantly higher (P < 0.001) in patients with AIS [57.68 ng/L (IQR, 44.95-76.73)] compared with healthy controls [47.48 ng/L (IQR, 38.67-53.78)]. IL-33 was an independent diagnostic biomarker for AIS with an OR of 1.051 (95%Cl, 1.018-1.085; P=0.002). Serum IL-33 was higher (P < 0.05) in the stroke patients with small cerebral infarction volume compared to AIS patients with large cerebral infarction. In addition, serum IL-33 was also significantly higher (P = 0.001) in the patients with mild stroke, compared to the patients with severe stroke. Furthermore, serum IL-33 level in AIS patients with a worse outcome was higher (P < 0.001) compared to AIS patients with a better outcome. IL-33 was also an independent predictor for the functional outcome with an adjusted OR of 0.932 (95% CI, 0.882-0.986). Our results suggest that the lower level of serum IL-33 is associated with large infarction volume and greater stroke severity in AIS patients. Thus, IL-33 can be used as a novel and independent diagnostic and predicting prognostic marker in AIS.

  2. Virtual monochromatic imaging in dual-source and dual-energy CT for visualization of acute ischemic stroke

    NASA Astrophysics Data System (ADS)

    Hara, Hidetake; Muraishi, Hiroshi; Matsuzawa, Hiroki; Inoue, Toshiyuki; Nakajima, Yasuo; Satoh, Hitoshi; Abe, Shinji

    2015-07-01

    We have recently developed a phantom that simulates acute ischemic stroke. We attempted to visualize an acute-stage cerebral infarction by using dual-energy Computed tomography (DECT) to obtain virtual monochromatic images of this phantom. Virtual monochromatic images were created by using DECT voltages from 40 to 100 keV in steps of 10 keV and from 60 to 80 keV in steps of 1 keV, under three conditions of the tube voltage with thin (Sn) filters. Calculation of the CNR values allowed us to evaluate the visualization of acute-stage cerebral infarction. The CNR value of a virtual monochromatic image was the highest at 68 keV under 80 kV / Sn 140 kV, at 72 keV under 100 kV / Sn 140 kV, and at 67 keV under 140 kV / 80 kV. The CNR values of virtual monochromatic images at voltages between 65 and 75 keV were significantly higher than those obtained for all other created images. Therefore, the optimal conditions for visualizing acute ischemic stroke were achievable.

  3. RNAi-mediated silencing of TNF-α converting enzyme to down-regulate soluble TNF-α production for treatment of acute and chronic colitis.

    PubMed

    Song, Yoonsung; Kim, Ye-Ram; Kim, So Mi; Ul Ain, Qurrat; Jang, Kiseok; Yang, Chul-Su; Kim, Yong-Hee

    2016-10-10

    Elevated level of tumor necrosis factor-α (TNF-α), one of the inflammatory cytokines, is considered to be a potential target for the inflammatory bowel disease (IBD) therapy. Recently, TNF-α converting enzyme (TACE), a sheddase playing an important role in cleaving and releasing bioactive soluble TNF-α, has been challenged with inhibitors to treat inflammatory diseases. Here, we report a novel anti-TNF-α strategy using a short hairpin RNA silencing TACE (shTACE) to prevent and treat colitis. The shTACE formed stable complexes with nona-arginine-based bio-cleavable disulfide bond-linked poly (arginine) (PAs-s) for enhanced gene delivery. Systemically administered shTACE/PAs-s peptoplexes efficiently decreased TNF-α levels, increased survival and alleviated pathophysiological parameters representing colitis severity. Our results demonstrate effectiveness and safety of shTACE/PAs-s peptoplexes with the capacity of overcoming acute and chronic ulcerative colitis through modulation of excessive inflammatory responses in the colon, providing a strong potential as a therapeutic agent for a broad variety of inflammatory diseases.

  4. Treatment protocol based on assessment of clot quality during endovascular thrombectomy for acute ischemic stroke using the Trevo stent retriever.

    PubMed

    Ishikawa, Kojiro; Ohshima, Tomotaka; Nishihori, Masahiro; Imai, Tasuku; Goto, Shunsaku; Yamamoto, Taiki; Nishizawa, Toshihisa; Shimato, Shinji; Kato, Kyozo

    2016-08-01

    The optional endovascular approach for acute ischemic stroke is unclear. The Trevo stent retriever can be used as first-line treatment for fast mechanical recanalization. The authors developed a treatment protocol for acute ischemic stroke based on the assessment of clot quality during clot removal with the Trevo. This prospective single-center study included all patients admitted for acute ischemic stroke between July 2014 and February 2015, who underwent emergency endovascular treatment. According to the protocol, the Trevo was used for first-line treatment. Immediately after the Trevo was deployed, the stent delivery wire was pushed to open the stent by force (ACAPT technique). Clot quality was assessed on the basis of the perfusion status after deployment of the Trevo; continued occlusion or immediate reopening either reoccluded or maintained after the stent retriever had been in place for 5 min. If there was no obvious clot removal after the first pass with the Trevo, according to the quality of the clot, either a second pass was performed or another endovascular device was selected. Twelve consecutive patients with acute major cerebral artery occlusion were analyzed. Thrombolysis in cerebral infarction score 2b and 3 was achieved in 11 patients (91.7%) and 9 (75%) had a good clinical outcome after 90 days based on a modified Rankin scale score ≤ 2. Symptomatic intracranial hemorrhage occurred in 1 patient (8.3%). The overall mortality rate was 8.3%. Endovascular thrombectomy using the Trevo stent retriever for first-line treatment is feasible and effective. PMID:27578909

  5. Treatment protocol based on assessment of clot quality during endovascular thrombectomy for acute ischemic stroke using the Trevo stent retriever

    PubMed Central

    Ishikawa, Kojiro; Ohshima, Tomotaka; Nishihori, Masahiro; Imai, Tasuku; Goto, Shunsaku; Yamamoto, Taiki; Nishizawa, Toshihisa; Shimato, Shinji; Kato, Kyozo

    2016-01-01

    ABSTRACT The optional endovascular approach for acute ischemic stroke is unclear. The Trevo stent retriever can be used as first-line treatment for fast mechanical recanalization. The authors developed a treatment protocol for acute ischemic stroke based on the assessment of clot quality during clot removal with the Trevo. This prospective single-center study included all patients admitted for acute ischemic stroke between July 2014 and February 2015, who underwent emergency endovascular treatment. According to the protocol, the Trevo was used for first-line treatment. Immediately after the Trevo was deployed, the stent delivery wire was pushed to open the stent by force (ACAPT technique). Clot quality was assessed on the basis of the perfusion status after deployment of the Trevo; continued occlusion or immediate reopening either reoccluded or maintained after the stent retriever had been in place for 5 min. If there was no obvious clot removal after the first pass with the Trevo, according to the quality of the clot, either a second pass was performed or another endovascular device was selected. Twelve consecutive patients with acute major cerebral artery occlusion were analyzed. Thrombolysis in cerebral infarction score 2b and 3 was achieved in 11 patients (91.7%) and 9 (75%) had a good clinical outcome after 90 days based on a modified Rankin scale score ≤ 2. Symptomatic intracranial hemorrhage occurred in 1 patient (8.3%). The overall mortality rate was 8.3%. Endovascular thrombectomy using the Trevo stent retriever for first-line treatment is feasible and effective. PMID:27578909

  6. Perfusion Imaging in the 3 Hour Time Window Predicts a tPA-Associated Hemorrhage in Acute Ischemic Stroke

    PubMed Central

    Rangaraju, Srikant; Edwards, Adam; Dehkharghani, Seena; Nahab, Fadi

    2015-01-01

    Perfusion imaging is being evaluated in acute ischemic stroke patients to identify those who may benefit from reperfusion therapies beyond standard thrombolytic time windows but limited data is available on its utility in patients presenting within standard thrombolytic time windows. We report a case of a patient presenting within the 3 hour time window where computerized tomographic perfusion imaging before intravenous thrombolysis identified a large volume of severely ischemic tissue and where intravenous tissue plasminogen activator (tPA) administration subsequently resulted in a fatal intracerebral hemorrhage. Whether perfusion imaging can predict an increased risk of tPA-associated symptomatic hemorrhage in patients presenting within standard thrombolytic time windows requires further study. PMID:25692511

  7. Repurposing an old drug to improve the safety and use of tissue plasminogen activator for acute ischemic stroke: Minocycline

    PubMed Central

    Hess, David C; Fagan, Susan

    2014-01-01

    There is only 1 US Food and Drug Administration-approved drug for acute ischemic stroke: tissue plasminogen activator (tPA). Due to a short time window and fear of intracerebral hemorrhage (ICH), tPA remains underutilized. There is great interest in developing combination drugs to use with tPA to improve the odds of a favorable recovery and to reduce the risk of ICH. Minocycline is a broad spectrum antibiotic that has been found to be a neuroprotective agent in preclinical ischemic stroke models. Minocycline inhibits matrix metalloproteinase-9, a biomarker for ICH associated with tPA use. Minocycline is also an anti-inflammatory agent and inhibits poly (ADP-ribose) polymerase- 1. Minocycline has been safe and well tolerated in the clinical trials conducted to date. PMID:20575623

  8. Combined neurothrombectomy or thrombolysis with adjunctive delivery of 3K3A-activated protein C in acute ischemic stroke

    PubMed Central

    Amar, Arun Paul; Griffin, John H.; Zlokovic, Berislav V.

    2015-01-01

    In the treatment of acute ischemic stroke (AIS), vessel recanalization correlates with improved functional status and reduced mortality. Mechanical neurothrombectomy achieves a higher likelihood of revascularization than intravenous thrombolysis (IVT), but there remains significant discrepancy between rates of recanalization and rates of favorable outcome. The poor neurological recovery among some stroke patients despite successful recanalization confirms the need for adjuvant therapy, such as pharmacological neuroprotection. Prior clinical trials of neuroprotectant drugs failed perhaps due to inability of the agent to reach the ischemic tissue beyond the occluded artery. A protocol that couples mechanical neurothrombectomy with concurrent delivery of a neuroprotectant overcomes this pitfall. Activated protein C (APC) exerts pleiotropic anti-inflammatory, anti-apoptotic, antithrombotic, cytoprotective, and neuroregenerative effects in stroke and appears a compelling candidate for this novel approach. PMID:26388732

  9. Acute ischemic stroke treated with intravenous tissue plasminogen activator in a patient taking dabigatran with radiographic evidence of recanalization.

    PubMed

    Sangha, Navdeep; El Khoury, Ramy; Misra, Vivek; Lopez, George

    2012-11-01

    Dabigatran etexelate is a new oral direct thrombin inhibitor that has been approved by the US Food and Drug Administration to prevent stroke in patients with nonvalvular atrial fibrillation. A 51-year-old man with a history of atrial fibrillation who was taking dabigatran presented with an acute ischemic stroke. The patient had a normal international normalized ratio, activated partial thromboplastin time, and an elevated thrombin time of 26.4 seconds. Recanalization of the middle cerebral artery with intravenous tissue plasminogen activator was apparent on digital subtraction angiography, and there was no evidence of intracerebral hemorrhage on the repeat computed tomographic scan. This is the first report of a patient who was taking dabigatran etexilate and who had an ischemic stroke caused by a middle cerebral artery occlusion, with an elevated thrombin time and radiographic recanalization with intravenous tissue plasminogen activator without evidence of hemorrhagic transformation. PMID:22683118

  10. Similarities and differences of acute nonconvulsive seizures and other epileptic activities following penetrating and ischemic brain injuries in rats.

    PubMed

    Lu, Xi-Chun May; Mountney, Andrea; Chen, Zhiyong; Wei, Guo; Cao, Ying; Leung, Lai Yee; Khatri, Vivek; Cunningham, Tracy; Tortella, Frank C

    2013-04-01

    The similarities and differences between acute nonconvulsive seizures (NCS) and other epileptic events, for example, periodic epileptiform discharges (PED) and intermittent rhythmic delta activities (IRDA), were characterized in rat models of penetrating and ischemic brain injuries. The NCS were spontaneously induced by either unilateral frontal penetrating ballistic-like brain injury (PBBI) or permanent middle cerebral artery occlusion (pMCAO), and were detected by continuous electroencephalogram (EEG) monitoring begun immediately after the injury and continued for 72 h or 24 h, respectively. Analysis of NCS profiles (incidence, frequency, duration, and time distribution) revealed a high NCS incidence in both injury models. The EEG waveform expressions of NCS and PED exhibited intrinsic variations that resembled human electrographic manifestations of post-traumatic and post-ischemic ictal and inter-ictal events, but these waveform variations were not distinguishable between the two types of brain injury. However, the NCS after pMCAO occurred more acutely and intensely (latency=0.6 h, frequency=25 episodes/rat) compared with the PBBI-induced NCS (latency=24 h, frequency=10 episodes/rat), such that the most salient features differentiating post-traumatic and post-ischemic NCS were the intensity and time distribution of the NCS profiles. After pMCAO, nearly 50% of the seizures occurred within the first 2 h of injury, whereas after PBBI, NCS occurred sporadically (0-5%/h) throughout the 72 h recording period. The PED were episodically associated with NCS. By contrast, the IRDA appeared to be independent of other epileptic events. This study provided comprehensive comparisons of post-traumatic and post-ischemic epileptic profiles. The identification of the similarities and differences across a broad spectrum of epileptic events may lead to differential strategies for post-traumatic and post-stroke seizure interventions.

  11. Neuroendocrinal, Neurodevelopmental, and Embryotoxic Effects of Recombinant Tissue Plasminogen Activator Treatment for Pregnant Women with Acute Ischemic Stroke

    PubMed Central

    Steinberg, Anna; Moreira, Tiago P.

    2016-01-01

    Thrombolysis with recombinant tissue plasminogen activator (rTPA) was the first evidence-based treatment approved for acute stroke. Ischemic stroke is relatively uncommon in fertile women but treatment is often delayed or not given. In randomized trials, pregnancy has been an exclusion criterion for thrombolysis. Physiologic TPA has been shown to have neuroendocrine effects namely in vasopressin secretion. Important TPA effects in brain function and development include neurite outgrowth, migration of cerebellar granular neurons and promotion of long-term potentiation, among others. Until now, no neuroendocrine side-effects have been reported in pregnant women treated with rTPA. The effects of rTPA exposure in the fetus following intravenous thrombolysis in pregnant women are still poorly understood. This depends on low case frequency, short-duration of exposure and the fact that rTPA molecule is too large to pass the placenta. rTPA has a short half-life of 4–5 min, with only 10% of its concentration remaining in circulation after 20 min, which may explain its safety at therapeutically doses. Ischemic stroke during pregnancy occurs most often in the third trimester. Complication rates of rTPA in pregnant women treated for thromboembolic conditions and ischemic stroke were found to be similar when compared to non-pregnant women (7–9% mortality). In embryos of animal models so far, no indications of a teratogenic or mutagenic potential were found. Pregnancy is still considered a relative contraindication when treating acute ischemic stroke with rTPA, however, treatment risk must be balanced against the potential of maternal disability and/or death. PMID:26941596

  12. Lipoic Acid Use and Functional Outcomes after Thrombolysis in Patients with Acute Ischemic Stroke and Diabetes

    PubMed Central

    Choi, Kang-Ho; Kim, Joon-Tae; Kim, Hyung-Seok; Kim, Ja-Hae; Nam, Tai-Seung; Choi, Seong-Min; Lee, Seung-Han; Kim, Byeong-Chae; Kim, Myeong-Kyu; Cho, Ki-Hyun

    2016-01-01

    Background Alpha-lipoic acid (aLA) is a strong antioxidant commonly used for treating diabetic polyneuropathy. Previously, we demonstrated the neurorestorative effects of aLA after cerebral ischemia in rats. However, its effects on patients with stroke remain unknown. We investigated whether patients treated with aLA have better functional outcomes after acute ischemic stroke (AIS) and reperfusion therapy than patients not receiving aLA. Methods In this retrospective study of 172 prospectively registered patients with diabetes and AIS treated with tissue plasminogen activator (tPA), we investigated the relationship between aLA use and functional outcome both after 3 months and after 1 year. The functional outcomes included occurrence of hemorrhagic transformation (HT), early neurological deterioration (END), and early clinical improvement (ECI). Favorable outcomes were defined as modified Rankin Scale (mRS) scores of 0–2. Results Of the 172 patients with AIS and diabetes, 47 (27.3%) used aLA. In the entire cohort, favorable outcomes occurred at significantly higher rates both at 3 months and at 1 year in those treated with aLA. The risks for END and HT were lower and the occurrence of ECI was higher in patients treated with aLA. In multivariable analysis, aLA use was associated with favorable outcomes both at 3 months and at 1 year. Age, HT, and increased National Institutes of Health Stroke Scale scores were negative predictors of a favorable outcome. Conclusions The use of aLA in patients with AIS and diabetes who are treated with tPA is associated with favorable outcomes. These results indicate that aLA could be a useful intervention for the treatment of AIS after reperfusion therapy. PMID:27677185

  13. Comparative effectiveness research on patients with acute ischemic stroke using Markov decision processes

    PubMed Central

    2012-01-01

    Background Several methodological issues with non-randomized comparative clinical studies have been raised, one of which is whether the methods used can adequately identify uncertainties that evolve dynamically with time in real-world systems. The objective of this study is to compare the effectiveness of different combinations of Traditional Chinese Medicine (TCM) treatments and combinations of TCM and Western medicine interventions in patients with acute ischemic stroke (AIS) by using Markov decision process (MDP) theory. MDP theory appears to be a promising new method for use in comparative effectiveness research. Methods The electronic health records (EHR) of patients with AIS hospitalized at the 2nd Affiliated Hospital of Guangzhou University of Chinese Medicine between May 2005 and July 2008 were collected. Each record was portioned into two "state-action-reward" stages divided by three time points: the first, third, and last day of hospital stay. We used the well-developed optimality technique in MDP theory with the finite horizon criterion to make the dynamic comparison of different treatment combinations. Results A total of 1504 records with a primary diagnosis of AIS were identified. Only states with more than 10 (including 10) patients' information were included, which gave 960 records to be enrolled in the MDP model. Optimal combinations were obtained for 30 types of patient condition. Conclusion MDP theory makes it possible to dynamically compare the effectiveness of different combinations of treatments. However, the optimal interventions obtained by the MDP theory here require further validation in clinical practice. Further exploratory studies with MDP theory in other areas in which complex interventions are common would be worthwhile. PMID:22400712

  14. Procedural Predictors of Outcome in Patients Undergoing Endovascular Therapy for Acute Ischemic Stroke

    SciTech Connect

    Rai, Ansaar T. Jhadhav, Yahodeep; Domico, Jennifer; Hobbs, Gerald R.

    2012-12-15

    Purpose: To identify factors impacting outcome in patients undergoing interventions for acute ischemic stroke (AIS). Materials and Methods: This was a retrospective analysis of patients undergoing endovascular therapy for AIS secondary during a 30 month period. Outcome was based on modified Rankin score at 3- to 6-month follow-up. Recanalization was defined as Thrombolysis in myocardial infarction score 2 to 3. Collaterals were graded based on pial circulation from the anterior cerebral artery either from an ipsilateral injection in cases of middle cerebral artery (MCA) occlusion or contralateral injection for internal carotid artery terminus (ICA) occlusion as follows: no collaterals (grade 0), some collaterals with retrograde opacification of the distal MCA territory (grade 1), and good collaterals with filling of the proximal MCA (M2) branches or retrograde opacification up to the occlusion site (grade 2). Occlusion site was divided into group 1 (ICA), group 2 (MCA with or without contiguous M2 involvement), and group 3 (isolated M2 or M3 branch occlusion). Results: A total of 89 patients were studied. Median age and National Institutes of health stroke scale (NIHSS) score was 71 and 15 years, respectively. Favorable outcome was seen in 49.4% of patients and mortality in 25.8% of patients. Younger age (P = 0.006), lower baseline NIHSS score (P = 0.001), successful recanalization (P < 0.0001), collateral support (P = 0.0008), distal occlusion (P = 0.001), and shorter procedure duration (P = 0.01) were associated with a favorable outcome. Factors affecting successful recanalization included younger age (P = 0.01), lower baseline NIHSS score (P = 0.05), collateral support (P = 0.01), and shorter procedure duration (P = 0.03). An ICA terminus occlusion (P < 0.0001), lack of collaterals (P = 0.0003), and unsuccessful recanalization (P = 0.005) were significantly associated with mortality. Conclusion: Angiographic findings and preprocedure variables can help

  15. Leukocytosis in Patients with Neurologic Deterioration after Acute Ischemic Stroke is Associated with Poor Outcomes

    PubMed Central

    Kumar, Andre D.; Boehme, Amelia K.; Siegler, James E.; Gillette, Michael; Albright, Karen C.; Martin-Schild, Sheryl

    2016-01-01

    Background Neurologic deterioration (ND) after acute ischemic stroke (AIS) has been shown to result in poor outcomes. ND is thought to arise from penumbral excitotoxic cell death caused in part by leukocytic infiltration. Elevated admission peripheral leukocyte levels are associated with poor outcomes in stroke patients who suffer ND, but little is known about the dynamic changes that occur in leukocyte counts around the time of ND. We sought to determine if peripheral leukocyte levels in the days surrounding ND are correlated with poor outcomes. Methods Patients with AIS who presented to our center within 48 hours of symptom onset between July 2008 and June 2010 were retrospectively identified by chart review and screened for ND (defined as an increase in National Institutes of Health Stroke Scale score ≥2 within a 24-hour period). Patients were excluded for steroid use during hospitalization or in the month before admission and infection within the 48 hours before or after ND. Demographics, daily leukocyte counts, and poor functional outcome (modified Rankin Scale score 3–6) were investigated. Results Ninety-six of the 292 (33%) patients screened had ND. The mean age was 69.5 years; 62.5% were male and 65.6% were black. Patients with a poor functional outcome had significantly higher leukocyte and neutrophil levels 1 day before ND (P =.048 and P =.026, respectively), and on the day of ND (P =.013 and P =.007, respectively), compared to patients with good functional outcome. Conclusions Leukocytosis at the time of ND correlates with poor functional outcomes and may represent a marker of greater cerebral damage through increased parenchymal inflammation. PMID:23031742

  16. Effect of the technique for assisting renal blood circulation on ischemic kidney in acute cardiorenal syndrome.

    PubMed

    Hanada, Shigeru; Takewa, Yoshiaki; Mizuno, Toshihide; Tsukiya, Tomonori; Taenaka, Yoshiyuki; Tatsumi, Eisuke

    2012-06-01

    The technique for assisting renal blood circulation may be a useful therapeutic method in acute cardiorenal syndrome (ACRS), because renal ischemic dysfunction due to the reduced renal blood circulation is a powerful negative prognostic factor in ACRS. We constructed a circuit assisting renal arterial pressure and flow, and performed renal-selective blood perfusion (RSP) to the left kidney in a goat model of ACRS induced by right ventricular rapid pacing (n = 8), with the right kidney left intact as an internal control. Upon induction of ACRS, renal arterial flow (RAF), creatinine clearance (CCr), and renal oxygen consumption (RVO(2)) of the left kidney decreased to 49, 48, and 63% of the respective baseline values accompanied by a significant increase in renal vascular resistance (RVR), and similar results were observed in the right kidney. Then, RSP improved RVR and increased left RAF, CCr, and RVO(2) up to 91, 86, and 93% of baseline values, respectively, without a significant change in systemic hemodynamics. The RSP-treated kidney showed significantly higher CCr and urinary excretion of water and sodium compared to the contralateral kidney. Additional infusion of prostaglandin E(1) with RSP decreased RVR further and enabled the left RAF to increase up to 129% of the baseline value, without a significant change in systemic hemodynamic parameters. The CCr and RVO(2) did not change significantly, and urinary excretion of water and sodium showed a tendency to increase. These findings suggest that the technique for assisting renal blood circulation for both kidneys may offer a new treatment strategy for patients with ACRS.

  17. Antiplatelet Usage Impacts Clot Density in Acute Anterior Circulation Ischemic Stroke

    PubMed Central

    Pikija, Slaven; Magdic, Jozef; Lukic, Anita; Schreiber, Catharina; Mutzenbach, Johannes Sebastian; McCoy, Mark R.; Sellner, Johann

    2016-01-01

    We explored whether clot density in middle cerebral artery (MCA) occlusion is related to clinical variables, stroke etiology, blood constituents, and prestroke medication. We performed a retrospective chart review of patients with acute ischemic stroke of the anterior circulation admitted to two Central European stroke centers. The acquisition of non-contrast enhanced CT (NECT) and CT angiography (CTA) within 4.5 h of symptom onset was obligatory. We assessed the site of MCA occlusion as well as density, area, and length of the clot in 150 patients. The Hounsfield unit values for the clot were divided with contralateral MCA segment to yield relative Hounsfield Unit ratio (rHU). The site of the vessel occlusion (M1 vs. M2) and antiplatelet usage, but not stroke etiology, significantly influenced rHU. We found an inverse correlation of rHU with erythrocyte count (p < 0.001). The multivariate analysis revealed that a higher rHU (i.e., clot being more hyperdense) was more likely with the use of antiplatelets (OR 4.24, CI 1.10–16.31, p = 0.036). Erythrocyte (OR 0.18, CI 0.05–0.55, p = 0.003), and thrombocyte counts (OR 0.99, CI 0.98–0.99, p = 0.029) were associated with odds for more hypodense clots (lower rHU). Our study disclosed that antiplatelet therapy impacts the composition of intracranial clots of the anterior circulation. PMID:27563874

  18. Prediction of Outcome in Diabetic Acute Ischemic Stroke Patients: A Hospital-Based Pilot Study Report

    PubMed Central

    Nayak, Amit R.; Badar, Shweta R.; Lande, Neha; Kawle, Anuja P.; Kabra, Dinesh P.; Chandak, Nitin H.; Raje, Dhananjay V.; Singh, Lokendra R.; Daginawala, Hatim F.; Kashyap, Rajpal S.

    2016-01-01

    Background Demographic and clinical characteristics are known to influence the outcome in acute ischemic stroke (AIS) patients. Purpose This study is aimed at evaluating short- and long-term outcomes in diabetic AIS patients. In addition, the study also evaluates the impact of diabetes on the performance of indigenously reported biomarker, inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4) and known biomarkers, neuron-specific enolase (NSE) and glial-derived S-100 beta beta protein (S-100ββ). Methods This study was performed on 29 diabetes and 75 non-diabetes AIS patients. Outcome of AIS patients was analyzed by using modified Rankin scale at discharge, then at 12 and 18 months after discharge. Based on the obtained scores, patients were classified as improved group (scales 1-3) and dependent/expired group (scales 3-6). Blood samples were collected during admission and at discharge/expired time. Levels of NSE, S100ββ, and ITIH4 were analyzed in all samples. Results On discharge, frequencies of dependent/expired outcome were 4/29 (14%) and 19/75 (17%) in diabetic and non-diabetic AIS patients. However, follow-up outcome at 12 and 18 months showed higher dependent/expired cases of 43 and 41% among diabetic AIS patients compared to 27 and 21% in non-diabetic patients. Multivariate analysis revealed that diabetes is an independent risk factor for dependent/expired outcome in AIS patients (OR 0.484 (at discharge); 1.307 (at 12 months) and 1.675 (at 18 months)). NSE, S100ββ, and ITIH4 showed a differential expression in both the outcome groups of AIS patients, irrespective of diabetes. Conclusion Diabetes increases the risk of dependent/expired outcome in AIS patients. Also, serum NSE, S100ββ, and ITIH4 are independent biomarkers for prognosis of outcome in AIS patients, irrespective of diabetes. PMID:27780987

  19. Acute Ischemic Stroke Involving Both Anterior and Posterior Circulation Treated by Endovascular Revascularization for Acute Basilar Artery Occlusion via Persistent Primitive Trigeminal Artery

    PubMed Central

    Fujita, Atsushi; Hosoda, Kohkichi; Kohmura, Eiji

    2016-01-01

    We report a case of acute ischemic stroke involving both the anterior and posterior circulation associated with a persistent primitive trigeminal artery (PPTA), treated by endovascular revascularization for acute basilar artery (BA) occlusion via the PPTA. An otherwise healthy 67-year-old man experienced sudden loss of consciousness and quadriplegia. Magnetic resonance imaging showed an extensive acute infarction in the right cerebral hemisphere, and magnetic resonance angiography showed occlusion of the right middle cerebral artery (MCA) and BA. Because the volume of infarction in the territory of the right MCA was extensive, we judged the use of intravenous tissue plasminogen activator to be contraindicated. Cerebral angiography revealed hypoplasia of both vertebral arteries and the presence of a PPTA from the right internal carotid artery. A microcatheter was introduced into the BA via the PPTA and revascularization was successfully performed using a Merci Retriever with adjuvant low-dose intraarterial urokinase. After treatment, his consciousness level and right motor weakness improved. Although persistent carotid-vertebrobasilar anastomoses such as a PPTA are relatively rare vascular anomalies, if the persistent primitive artery is present, it can be an access route for mechanical thrombectomy for acute ischemic stroke. PMID:27446523

  20. Ulcerative colitis - discharge

    MedlinePlus

    Inflammatory bowel disease - ulcerative colitis - discharge; Ulcerative proctitis - discharge; Colitis - discharge ... were in the hospital because you have ulcerative colitis. This is a swelling of the inner lining ...

  1. Screening of an anti-inflammatory peptide from Hydrophis cyanocinctus and analysis of its activities and mechanism in DSS-induced acute colitis

    PubMed Central

    Zheng, Zengjie; Jiang, Hailong; Huang, Yan; Wang, Jie; Qiu, Lei; Hu, Zhenlin; Ma, Xingyuan; Lu, Yiming

    2016-01-01

    Snake has been used for centuries as a traditional Chinese medicine, especially for therapeutic treatment for inflammatory diseases; however, its mechanisms of action and active constituents remain controversial. In our study, a tumor necrosis factor receptor 1 (TNFR1) selective binding peptide, Hydrostatin-SN1 (H-SN1), which was screened from a Hydrophis cyanocinctus venom gland T7 phage display library, was shown to exhibit significant anti-inflammatory activity in vitro and in vivo. As a TNFR1 antagonist, it reduced cytotoxicity mediated by TNF-α in L929 fibroblasts and effectively inhibited the combination between TNF-α with TNFR1 in surface plasmon resonance analysis. H-SN1 was also shown to suppress TNFR1–associated signaling pathways as it minimized TNF-α-induced NF-кB and MAPK activation in HEK293 embryonic kidney and HT29 adenocarcinoma cell lines. We next determined the effect of H-SN1 in vivo using a murine model of acute colitis induced by dextran sodium sulfate, demonstrating that H-SN1 lowered the clinical parameters of acute colitis including the disease activity index and histologic scores. H-SN1 also inhibited TNF/TNFR1 downstream targets at both mRNA and protein levels. These results indicate that H-SN1 might represent a suitable candidate for use in the treatment of TNF-α-associated inflammatory diseases such as inflammatory bowel diseases. PMID:27158082

  2. Mulberry fruit prevents LPS-induced NF-κB/pERK/MAPK signals in macrophages and suppresses acute colitis and colorectal tumorigenesis in mice.

    PubMed

    Qian, Zhengjiang; Wu, Zhiqin; Huang, Lian; Qiu, Huiling; Wang, Liyan; Li, Li; Yao, Lijun; Kang, Kang; Qu, Junle; Wu, Yonghou; Luo, Jun; Liu, Johnson J; Yang, Yi; Yang, Wancai; Gou, Deming

    2015-11-30

    Here, we investigated the impact of mulberry fruit (MBF) extracts on lipopolysaccharide (LPS)-induced inflammatory responses in RAW 264.7 macrophages, and the therapeutic efficacy of MBF diet in mice with dextran sulfate sodium (DSS)-induced acute colitis and MUC2(-/-) mice with colorectal cancer. In vitro, LPS-induced nitric oxide (NO) production was significantly inhibited by MBF extracts via suppressing the expression of proinflammatory molecules, including inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin-1 beta (IL-β) and IL-6. Particularly, a dose-dependent inhibition on LPS-induced inflammatory responses was observed following treatment with MBF dichloromethane extract (MBF-DE), in which linoleic acid and ethyl linolenate were identified as two active compounds. Moreover, we elucidated that MBF-DE attenuated LPS-induced inflammatory responses by blocking activation of both NF-κB/p65 and pERK/MAPK pathways. In vivo, DSS-induced acute colitis was significantly ameliorated in MBF-fed mice as gauged by weight loss, colon morphology and histological damage. In addition, MBF-fed MUC2(-/-) mice displayed significant decrease in intestinal tumor and inflammation incidence compared to control diet-fed group. Overall, our results demonstrated that MBF suppressed the development of intestinal inflammation and tumorgenesis both in vitro and in vivo, and supports the potential of MBF as a therapeutic functional food for testing in human clinical trials.

  3. Mulberry fruit prevents LPS-induced NF-κB/pERK/MAPK signals in macrophages and suppresses acute colitis and colorectal tumorigenesis in mice

    PubMed Central

    Qian, Zhengjiang; Wu, Zhiqin; Huang, Lian; Qiu, Huiling; Wang, Liyan; Li, Li; Yao, Lijun; Kang, Kang; Qu, Junle; Wu, Yonghou; Luo, Jun; Liu, Johnson J.; Yang, Yi; Yang, Wancai; Gou, Deming

    2015-01-01

    Here, we investigated the impact of mulberry fruit (MBF) extracts on lipopolysaccharide (LPS)-induced inflammatory responses in RAW 264.7 macrophages, and the therapeutic efficacy of MBF diet in mice with dextran sulfate sodium (DSS)-induced acute colitis and MUC2−/− mice with colorectal cancer. In vitro, LPS-induced nitric oxide (NO) production was significantly inhibited by MBF extracts via suppressing the expression of proinflammatory molecules, including inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin-1 beta (IL-β) and IL-6. Particularly, a dose-dependent inhibition on LPS-induced inflammatory responses was observed following treatment with MBF dichloromethane extract (MBF-DE), in which linoleic acid and ethyl linolenate were identified as two active compounds. Moreover, we elucidated that MBF-DE attenuated LPS-induced inflammatory responses by blocking activation of both NF-κB/p65 and pERK/MAPK pathways. In vivo, DSS-induced acute colitis was significantly ameliorated in MBF-fed mice as gauged by weight loss, colon morphology and histological damage. In addition, MBF-fed MUC2−/− mice displayed significant decrease in intestinal tumor and inflammation incidence compared to control diet-fed group. Overall, our results demonstrated that MBF suppressed the development of intestinal inflammation and tumorgenesis both in vitro and in vivo, and supports the potential of MBF as a therapeutic functional food for testing in human clinical trials. PMID:26615818

  4. Neuroimmunomodulatory effects of transcranial laser therapy combined with intravenous tPA administration for acute cerebral ischemic injury

    PubMed Central

    Peplow, Philip V.

    2015-01-01

    At present, the only FDA approved treatment for ischemic strokes is intravenous administration of tissue plasminogen activator within 4.5 hours of stroke onset. Owing to this brief window only a small percentage of patients receive tissue plasminogen activator. Transcranial laser therapy has been shown to be effective in animal models of acute ischemic stroke, resulting in significant improvement in neurological score and function. NEST-1 and NEST-2 clinical trials in human patients have demonstrated the safety and positive trends in efficacy of transcranial laser therapy for the treatment of ischemic stroke when initiated close to the time of stroke onset. Combining intravenous tissue plasminogen activator treatment with transcranial laser therapy may provide better functional outcomes. Statins given within 4 weeks of stroke onset improve stroke outcomes at 90 days compared to patients not given statins, and giving statins following transcranial laser therapy may provide an effective treatment for patients not able to be given tissue plasminogen activator due to time constraints. PMID:26487831

  5. Early High-dosage Atorvastatin Treatment Improved Serum Immune-inflammatory Markers and Functional Outcome in Acute Ischemic Strokes Classified as Large Artery Atherosclerotic Stroke

    PubMed Central

    Tuttolomondo, Antonino; Di Raimondo, Domenico; Pecoraro, Rosaria; Maida, Carlo; Arnao, Valentina; Corte, Vittoriano Della; Simonetta, Irene; Corpora, Francesca; Di Bona, Danilo; Maugeri, Rosario; Iacopino, Domenico Gerardo; Pinto, Antonio

    2016-01-01

    Abstract Statins have beneficial effects on cerebral circulation and brain parenchyma during ischemic stroke and reperfusion. The primary hypothesis of this randomized parallel trial was that treatment with 80 mg/day of atorvastatin administered early at admission after acute atherosclerotic ischemic stroke could reduce serum levels of markers of immune-inflammatory activation of the acute phase and that this immune-inflammatory modulation could have a possible effect on prognosis of ischemic stroke evaluated by some outcome indicators. We enrolled 42 patients with acute ischemic stroke classified as large arteries atherosclerosis stroke (LAAS) randomly assigned in a randomized parallel trial to the following groups: Group A, 22 patients treated with atorvastatin 80 mg (once-daily) from admission day until discharge; Group B, 20 patients not treated with atorvastatin 80 mg until discharge, and after discharge, treatment with atorvastatin has been started. At 72 hours and at 7 days after acute ischemic stroke, subjects of group A showed significantly lower plasma levels of tumor necrosis factor-α, interleukin (IL)-6, vascular cell adhesion molecule-1, whereas no significant difference with regard to plasma levels of IL-10, E-Selectin, and P-Selectin was observed between the 2 groups. At 72 hours and 7 days after admission, stroke patients treated with atorvastatin 80 mg in comparison with stroke subjects not treated with atorvastatin showed a significantly lower mean National Institutes of Health Stroke Scale and modified Rankin scores. Our findings provide the first evidence that atorvastatin acutely administered immediately after an atherosclerotic ischemic stroke exerts a lowering effect on immune-inflammatory activation of the acute phase of stroke and that its early use is associated to a better functional and prognostic profile. PMID:27043681

  6. Persistent Leukocytosis—Is this a Persistent Problem for Patients with Acute Ischemic Stroke?

    PubMed Central

    Boehme, Amelia K.; Kumar, Andre D.; Lyerly, Michael J.; Gillette, Michael A.; Siegler, James E.; Albright, Karen C.; Beasley, T. Mark; Martin-Schild, Sheryl

    2016-01-01

    Background In the setting of acute ischemic stroke (AIS), leukocytosis has been shown to be an indicator of inflammatory response. Although leukocytosis on admission has been shown to correlate with initial stroke severity in AIS patients, no work has been done to assess if there are differences in transient or persistent leukocytosis in patients without infection. The objective of this study is to determine the clinical significance of persistent versus transient leukocytosis during the early phase of AIS. Methods Patients who presented with AIS to our center within 48 hours of symptom onset between July 2008 and June 2010 were retrospectively identified by chart review. Patients were included if they had leukocytosis on admission (defined as white blood cell count >11,000/μL based on laboratory reference range values). A logistic regression model was used to evaluate persistent leukocytosis (leukocytosis 48 hours after admission) as a predictor of several outcome measures, including good functional outcome (discharge modified Rankin Scale score of 0-2). Marginal effects were used to estimate the probability of poor functional outcome. Results Of the 438 patients screened, 49 had leukocytosis on admission and of those 24 (49%) had persistent leukocytosis. NIHSS score correlated significantly with persistence of leukocytosis (r = .306; P =.0044). More people with transient leukocytosis (leukocytosis lasting <48 hours) had a good functional outcome (44% versus 16%; P = .006). After adjusting for baseline NIHSS score, persistent leukocytosis was not a significant independent predictor of good functional outcome, but showed an association (OR, 2.5; 95% CI, .562-10.7; P = .2322). Persistent leukocytosis after adjusting for age and NIHSS score at admission is associated with a poor functional outcome, but it is not statistically significant (OR, 2.43; 95% CI, .59-9.87; P = .2151). After controlling for age and NIHSS score on admission, for patients with persistent

  7. Metabolomic profiling of the heart during acute ischemic preconditioning reveals a role for SIRT1 in rapid cardioprotective metabolic adaptation.

    PubMed

    Nadtochiy, Sergiy M; Urciuoli, William; Zhang, Jimmy; Schafer, Xenia; Munger, Joshua; Brookes, Paul S

    2015-11-01

    Ischemic preconditioning (IPC) protects tissues such as the heart from prolonged ischemia-reperfusion (IR) injury. We previously showed that the lysine deacetylase SIRT1 is required for acute IPC, and has numerous metabolic targets. While it is known that metabolism is altered during IPC, the underlying metabolic regulatory mechanisms are unknown, including the relative importance of SIRT1. Thus, we sought to test the hypothesis that some of the metabolic adaptations that occur in IPC may require SIRT1 as a regulatory mediator. Using both ex-vivo-perfused and in-vivo mouse hearts, LC-MS/MS based metabolomics and (13)C-labeled substrate tracing, we found that acute IPC altered several metabolic pathways including: (i) stimulation of glycolysis, (ii) increased synthesis of glycogen and several amino acids, (iii) increased reduced glutathione levels, (iv) elevation in the oncometabolite 2-hydroxyglutarate, and (v) inhibition of fatty-acid dependent respiration. The majority (83%) of metabolic alterations induced by IPC were ablated when SIRT1 was acutely inhibited with splitomicin, and a principal component analysis revealed that metabolic changes in response to IPC were fundamentally different in nature when SIRT1 was inhibited. Furthermore, the protective benefit of IPC was abrogated by eliminating glucose from perfusion media while sustaining normal cardiac function by burning fat, thus indicating that glucose dependency is required for acute IPC. Together, these data suggest that SIRT1 signaling is required for rapid cardioprotective metabolic adaptation in acute IPC.

  8. Apolipoprotein A1-Unique Peptide as a Diagnostic Biomarker for Acute Ischemic Stroke

    PubMed Central

    Zhao, Xu; Yu, Yue; Xu, Wenlong; Dong, Lei; Wang, Yuan; Gao, Bing; Li, Guangyu; Zhang, Wentao

    2016-01-01

    Clinically-informative biomarkers of ischemic stroke are needed for rapid diagnosis and timely treatment. In the present study, APOA1 unique peptide (APOA1-UP), a novel peptide biomarker, was identified and quantified by multiple reaction monitoring (MRM) using labeled reference peptide (LRP). Serum samples of 94 patients in the ischemic stroke group and 37 patients in the non-stroke group were analyzed for the levels of total APOA1-UP, low density lipoprotein cholesterol (LDL-C), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and total cholesterol (TC). Median ratio of total APOA1-UP/LRP was 2.14 (interquartile range, 0.40) in the non-stroke group and 1.32 (0.44) in the ischemic stroke group (p < 0.0001). The serum level of total APOA1-UP was independently correlated with the presence of ischemic stroke by multivariate logistic regression analysis (p < 0.0001). From the receiver operating characteristic (ROC) curve, the area under the curve (AUC) was 0.9750 and the optimal cutoff value of the serum APOA1-UP level was 1.80, which yielded a sensitivity of 90.63% and a specificity of 97.14%. The diagnostic efficiency of HDL-C was lower, with an AUC of 0.7488. Therefore, the serum level of APOA1-UP is a diagnostic biomarker candidate for ischemic stroke in the early stage. PMID:27043525

  9. Inflammatory and metabolic markers and short-time outcome in patients with acute ischemic stroke in relation to TOAST subtypes.

    PubMed

    Lehmann, Marcio Francisco; Kallaur, Ana Paula; Oliveira, Sayonara Rangel; Alfieri, Daniela Frizon; Delongui, Franciele; de Sousa Parreira, Johnathan; de Araújo, Maria Caroline Martins; Rossato, Carolina; de Almeida, Jéssica Tavares; Pelegrino, Larissa Moliterno; Bragato, Erick Frank; Lehmann, Ana Lucia Cruz Fürstenberger; Morimoto, Helena Kaminami; Lozovoy, Marcell Alysson Batisti; Simão, Andrea Name Colado; Kaimen-Maciel, Damácio Ramon; Reiche, Edna Maria Vissoci

    2015-12-01

    The aim of this study was to evaluate the association between inflammatory and metabolic markers and short-time outcome with acute ischemic stroke subtypes. A total of 121 patients was classified according to TOAST criteria, such as large artery atherosclerosis (LAAS), lacunar infarct (LAC), cardioembolic infarct (CEI), other determined etiology (ODE), and undetermined etiology (UDE). The functional impairment was evaluated within the first eight hours of stroke and the outcome after three-month follow-up using the modified Rankin Scale. Blood samples were obtained up to 24 h of stroke. Compared with 96 controls, patients with LAAS, CEI, and LAC subtypes showed higher levels of white blood cells, high-sensitivity C-reactive protein (hsCRP), interleukin 6 (IL-6), metalloproteinase 9 (MMP-9), glucose, and iron (p < 0.05); and lower high-density lipoprotein cholesterol (HDL-C) (p < 0.0001); platelets, insulin, insulin resistance, and homocysteine were higher in LAC (p < 0.0001); ferritin was higher in LAAS (p < 0.0001); and total cholesterol (TC) was lower in LAAS and CEI (p < 0.01). When stroke subtypes were compared, insulin was higher in LAAS vs. LAC and in LAC vs. CEI (p < 0.05); and TC was lower in LAAS vs. LAC (p < 0.05). Outcome and rate of mortality after three-month were higher in LAAS vs. LAC (p < 0.001 and p = 0.0391 respectively). The results underscored the important role of the inflammatory response and metabolic changes in the pathogenesis of ischemic stroke subtypes that might be considered on the initial evaluation of stroke patients to identify those that could benefit with individualized therapeutic strategies that taken into account these markers after acute ischemic event. PMID:26359121

  10. Alpinetin attenuates inflammatory responses by suppressing TLR4 and NLRP3 signaling pathways in DSS-induced acute colitis

    PubMed Central

    He, Xuexiu; Wei, Zhengkai; Wang, Jingjing; Kou, Jinhua; Liu, Weijian; Fu, Yunhe; Yang, Zhengtao

    2016-01-01

    Alpinetin, a composition of Alpinia katsumadai Hayata, has been reported to have a number of biological properties, such as antibacterial, antitumor and other important therapeutic activities. However, the effect of alpinetin on inflammatory bowel disease (IBD) has not yet been reported. The purpose of this study was to investigate the anti-inflammatory effect and mechanism of alpinetin on dextran sulfate sodium (DSS)-induced colitis in mice. In vivo, DSS-induced mice colitis model was established by giving mice drinking water containing 5% (w/v) DSS for 7 days. Alpinetin (25, 50 and 100 mg/kg) were administered once a day by intraperitoneal injection 3 days before DSS treatment. In vitro, phorbol myristate acetate (PMA)-differentiated monocytic THP-1 macrophages were treated with alpinetin and stimulated by lipopolysaccharide (LPS). The results showed that alpinetin significantly attenuated diarrhea, colonic shortening, histological injury, myeloperoxidase (MPO) activity and the expressions of tumor necrosis factor (TNF-α) and interleukin (IL-1β) production in mice. In vitro, alpinetin markedly inhibited LPS-induced TNF-α and IL-1β production, as well as Toll-like receptor 4 (TLR4) mediated nuclear transcription factor-kappaB (NF-κB) and NOD-like receptor protein 3 (NLRP3) inflammasome activation. In conclusion, this study demonstrated that alpinetin had protective effects on DSS-induced colitis and may be a promising therapeutic reagent for colitis treatment. PMID:27321991

  11. Alpinetin attenuates inflammatory responses by suppressing TLR4 and NLRP3 signaling pathways in DSS-induced acute colitis.

    PubMed

    He, Xuexiu; Wei, Zhengkai; Wang, Jingjing; Kou, Jinhua; Liu, Weijian; Fu, Yunhe; Yang, Zhengtao

    2016-06-20

    Alpinetin, a composition of Alpinia katsumadai Hayata, has been reported to have a number of biological properties, such as antibacterial, antitumor and other important therapeutic activities. However, the effect of alpinetin on inflammatory bowel disease (IBD) has not yet been reported. The purpose of this study was to investigate the anti-inflammatory effect and mechanism of alpinetin on dextran sulfate sodium (DSS)-induced colitis in mice. In vivo, DSS-induced mice colitis model was established by giving mice drinking water containing 5% (w/v) DSS for 7 days. Alpinetin (25, 50 and 100 mg/kg) were administered once a day by intraperitoneal injection 3 days before DSS treatment. In vitro, phorbol myristate acetate (PMA)-differentiated monocytic THP-1 macrophages were treated with alpinetin and stimulated by lipopolysaccharide (LPS). The results showed that alpinetin significantly attenuated diarrhea, colonic shortening, histological injury, myeloperoxidase (MPO) activity and the expressions of tumor necrosis factor (TNF-α) and interleukin (IL-1β) production in mice. In vitro, alpinetin markedly inhibited LPS-induced TNF-α and IL-1β production, as well as Toll-like receptor 4 (TLR4) mediated nuclear transcription factor-kappaB (NF-κB) and NOD-like receptor protein 3 (NLRP3) inflammasome activation. In conclusion, this study demonstrated that alpinetin had protective effects on DSS-induced colitis and may be a promising therapeutic reagent for colitis treatment.

  12. Anti-inflammatory effect of Moringa oleifera Lam. seeds on acetic acid-induced acute colitis in rats

    PubMed Central

    Minaiyan, Mohsen; Asghari, Gholamreza; Taheri, Diana; Saeidi, Mozhgan; Nasr-Esfahani, Salar

    2014-01-01

    Objective: Anti-inflammatory, immuno-modulatory, and antioxidant properties of Moringa oleifera Lam. suggest that it might have beneficial effects on colitis. The present study was performed to investigate the anticolitis effect of Moringa oleifera seeds hydro-alcoholic extract (MSHE) and its chloroform fraction (MCF) on acetic acid-induced colitis in rats. Materials and Methods: Both MSHE and MCF with three increasing doses (50, 100, and 200 mg/kg) were administered orally to separate groups of male Wistar rats, 2 h before ulcer induction (using acetic acid 4%) and continued for 5 days. Prednisolone (4 mg/kg) and normal saline (1 ml/kg) were used in reference and control groups, respectively. All rats were sacrificed 24 h after the last dose (at day 6) and tissue injuries were assessed macroscopically and pathologically. Results: Extracts with three doses mentioned before were effective to reduce weight of distal colon (8 cm) as a marker for inflammation and tissue edema. Three doses of MSHE and two greater doses of MCF (100 and 200 mg/kg) were effective to reduce ulcer severity, area, and index as well as mucosal inflammation severity and extent, crypt damage, invasion involvement, total colitis index, and MPO activity compared with controls. MCF (50 mg/kg) was not significantly effective in reducing evaluated parameters of colitis compared with controls. Conclusion: It is concluded that MSHE and MCF were both effective to treat experimental colitis and this might be attributed to their similar major components, biophenols and flavonoids. Since the efficacy was evident even in low doses of MSHE, presence of active constituents with high potency in seeds is persuasive. PMID:25050310

  13. Effect of Coriandrum sativum hydroalcoholic extract and its essential oil on acetic acid- induced acute colitis in rats

    PubMed Central

    Heidari, Bahareh; Sajjadi, Seyed Ebrahim; Minaiyan, Mohsen

    2016-01-01

    Objective: The aim of this study was to determine the protective effects of Coriandrum sativum on acetic acid-inducedcolitis in rats. C. sativum (Coriander) has long been used in Iranian traditional medicine and its use as an anti-inflammatory agent is still common in some herbal formulations. Materials and Methods: Colitis was induced by intra-rectal administration of 2ml acetic acid 4% in fasted male Wistar rats. Treatment was carried out using three increasing doses of extract (250, 500, 1000 mg/kg) and essential oil (0.25, 0.5, 1 ml/kg) of coriander started 2 h before colitis induction and continued for a five-day period. Colon biopsies were taken for weighting, macroscopic scoring of injured tissue, histopathological examination and measuring myeloperoxidase (MPO) activity. Results: Colon weight was decreased in the groups treated with extract (500 and 1000 mg/kg) and essential oil (0.5 ml/kg) compared to the control group. Regarding MPO levels, ulcer severity and area as well as the total colitis index, same results indicating meaningful alleviation of colitis was achieved after treatment with oral extract and essential oil. Conclusion: Since the present experiment was made by oral fractions of coriander thus the resulting effects could be due to both the absorption of the active ingredients and/or the effect of non-absorbable materials on colitis after reaching the colon. In this regard, we propose more toxicological and clinical experiments to warranty its beneficial application in human inflammatory bowel diseases. PMID:27222834

  14. Ulcerative Colitis

    MedlinePlus

    Ulcerative colitis (UC) is a disease that causes inflammation and sores, called ulcers, in the lining of the rectum and colon. ... a group of diseases called inflammatory bowel disease. UC can happen at any age, but it usually ...

  15. Ulcerative colitis

    MedlinePlus

    ... is not clear if immune problems cause this illness. Stress and certain foods can trigger symptoms, but they ... Social support can often help with the stress of dealing with illness, and ... and coping with the condition. The Crohn's and Colitis ...

  16. Safety of early initiation of rivaroxaban or dabigatran after thrombolysis in acute ischemic stroke.

    PubMed

    Ritzenthaler, T; Derex, L; Davenas, C; Bnouhanna, W; Farghali, A; Mechtouff, L; Cho, T-H; Nighoghossian, N

    2015-09-01

    The introduction of direct oral anticoagulants (DOA) in the early stage of cerebral infarction after thrombolysis may reduce the recurrence rate but raises safety concern. We sought to study the feasibility and safety of the introduction of rivaroxaban or dabigatran in this context. Thirty-four consecutive patients admitted for ischemic stroke related to non-valvular atrial fibrillation in whom DOA were given within the first two weeks following intravenous rt-PA were studied. A clinical and radiological monitoring protocol was established to ensure the safety of the prescription. None of the patients experienced symptomatic hemorrhagic transformation or a symptomatic recurrent ischemic event after early rivaroxaban or dabigatran introduction.

  17. Loss of TMF/ARA160 Protein Renders Colonic Mucus Refractory to Bacterial Colonization and Diminishes Intestinal Susceptibility to Acute Colitis*

    PubMed Central

    Bel, Shai; Elkis, Yoav; Lerer-Goldstein, Tali; Nyska, Abraham; Shpungin, Sally; Nir, Uri

    2012-01-01

    TMF/ARA160 is a Golgi-associated protein with several cellular functions, among them direction of the NF-κB subunit, p65 RelA, to ubiquitination and proteasomal degradation in stressed cells. We sought to investigate the role of TMF/ARA160 under imposed stress conditions in vivo. TMF−/− and wild-type (WT) mice were treated with the ulcerative agent dextran sulfate sodium (DSS), and the severity of the inflicted acute colitis was determined. TMF−/− mice were found to be significantly less susceptible to DSS-induced colitis, with profoundly less bacterial penetration into the colonic epithelia. Surprisingly, unlike in WT mice, no bacterial colonies were visualized in colons of healthy untreated TMF−/− mice, indicating the constitutive resistance of TMF−/− colonic mucus to bacterial retention and penetration. Gene expression analysis of colon tissues from unchallenged TMF−/− mice revealed 5-fold elevated transcription of the muc2 gene, which encodes the major component of the colonic mucus gel, the MUC2 mucin. Accordingly, the morphology of the colonic mucus in TMF−/− mice was found to differ from the mucus structure in WT colons. The NF-κB subunit, p65, a well known transcription inducer of muc2, was up-regulated significantly in TMF−/− intestinal epithelial cells. However, this did not cause spontaneous inflammation or increased colonic crypt cell proliferation. Collectively, our findings demonstrate that absence of TMF/ARA160 renders the colonic mucus refractory to bacterial colonization and the large intestine less susceptible to the onset of colitis. PMID:22553199

  18. Emergency Care of Patients with Acute Ischemic Stroke in the Kaiser Permanente Southern California Integrated Health System

    PubMed Central

    Sauser-Zachrison, Kori; Shen, Ernest; Ajani, Zahra; Neil, William P; Sangha, Navdeep; Gould, Michael K; Sharp, Adam L

    2016-01-01

    Context: Tissue plasminogen activator (tPA) is underutilized for treatment of acute ischemic stroke. Objective: To determine whether the probability of tPA administration for patients with ischemic stroke in an integrated health care system improved from 2009 to 2013, and to identify predictors of tPA administration. Design: Retrospective analysis of all ischemic stroke presentations to 14 Emergency Departments between 2009 and 2013. A generalized linear mixed-effects model identified patient and hospital predictors of tPA. Main Outcome Measures: Primary outcome was tPA administration; secondary outcomes were door-to-imaging and door-to-needle times and tPA-related bleeding complications. Results: Of the 11,630 patients, 3.9% received tPA. The likelihood of tPA administration increased with presentation in 2012 and 2013 (odds ratio [OR] = 1.75; 95% confidence interval [CI] = 1.26–2.43; and OR = 2.58; 95% CI = 1.90–3.51), female sex (OR = 1.27; 95% CI = 1.04–1.54), and ambulance arrival (OR = 2.17; 95% CI = 1.76–2.67), and decreased with prior stroke (OR = 0.47; 95% CI = 0.25–0.89) and increased age (OR = 0.98; 95% CI = 0.97–0.99). Likelihood varied by Medical Center (pseudo-intraclass correlation coefficient 13.5%). Among tPA-treated patients, median door-to-imaging time was 15 minutes (interquartile range, 9–23 minutes), and door-to-needle time was 73 minutes (interquartile range, 55–103 minutes). The rate of intracranial hemorrhage was 4.2% and 0.9% among tPA- and non-tPA treated patients (p < 0.001). Conclusion: Acute ischemic stroke care improved over time in this integrated health system. Better understanding of differences in hospital performance will have important quality-improvement and policy implications. PMID:27043833

  19. Therapeutic Targets for Neuroprotection in Acute Ischemic Stroke: Lost in Translation?

    PubMed Central

    Stankowski, Jeannette N.

    2011-01-01

    Abstract The development of a suitable neuroprotective agent to treat ischemic stroke has failed when transitioned to the clinical setting. An understanding of the molecular mechanisms involved in neuronal injury during ischemic stroke is important, but must be placed in the clinical context. Current therapeutic targets have focused on the preservation of the ischemic penumbra in the hope of improving clinical outcomes. Unfortunately, most patients in the ultra-early time windows harbor penumbra but have tremendous variability in the size of the core infarct, the ultimate predictor of prognosis. Understanding this variability may allow for proper patient selection that may better correlate to bench models. Reperfusion therapies are rapidly evolving and have been shown to improve clinical outcomes. The use of neuroprotective agents to prolong time windows prior to reperfusion or to prevent reperfusion injury may present future therapeutic targets for the treatment of ischemic stroke. We review the molecular pathways and the clinical context from which future targets may be identified. Antioxid. Redox Signal. 14, 1841–1851. PMID:20626319

  20. Renal dysfunction and thrombolytic therapy in patients with acute ischemic stroke: a systematic review and meta-analysis.

    PubMed

    Hao, Zilong; Yang, Chunsong; Liu, Ming; Wu, Bo

    2014-12-01

    Renal dysfunction is a prevalent comorbidity in acute ischemic stroke patients requiring thrombolytic therapy. However, the effect of renal dysfunction on the clinical outcome of this population remains controversial. This study aimed to evaluate the safety and effectiveness of thrombolytic therapy in acute stroke patients with renal dysfunction using a meta-analysis. We systematically searched PubMed and EMBASE for studies that evaluated the relationship between renal dysfunction and intravenous tissue plasminogen activator (tPA) in patients with acute ischemic stroke. Poor outcome (modified Rankin Scale≥2), mortality, and symptomatic intracranial hemorrhage (ICH) and any ICH were analyzed. Fourteen studies were included (N=53,553 patients). The mean age ranged from 66 to 75 years. The proportion of male participants was 49% to 74%. The proportion of renal dysfunction varied from 21.9% to 83% according to different definitions. Based on 9 studies with a total of 7796 patients, the meta-analysis did not identify a significant difference in the odds of poor outcome (odds ratio [OR]=1.06; 95% confidence interval [CI]: 0.96-1.16; I=44.5) between patients with renal dysfunction and those without renal dysfunction. Patients with renal dysfunction were more likely to die after intravenous thrombolysis (OR=1.13; 95% CI: 1.05-1.21; I=70.3). No association was observed between symptomatic ICH (OR=1.02; 95% CI: 0.94-1.10; I=0) and any ICH (OR=1.07; 95% CI: 0.96-1.18; I=25.8). Renal dysfunction does not increase the risk of poor outcome and ICH after stroke thrombolysis. Renal dysfunction should not be a contraindication for administration of intravenous thrombolysis to eligible patients. PMID:25526464

  1. Homogeneity and the outcome of clinical trials: An appraisal of the outcome of recent clinical trials on endovascular intervention in acute ischemic stroke

    PubMed Central

    Husain, Shakir; Srijithesh, PR

    2016-01-01

    Clinical trials that allow significant heterogeneity of population or interventions often result in uncertain outcomes. In this paper, we review the outcomes of five recent trials of endovascular interventions in acute ischemic stroke in the context of the neutral results of previous large clinical trials on the subject. PMID:27011623

  2. Possible involvement of ubiquitin proteasome system and other proteases in acute and delayed aspects of ischemic preconditioning of brain in mice.

    PubMed

    Rehni, Ashish Kumar; Singh, Thakur Gurjeet; Behl, Nidhi; Arora, Sandeep

    2010-01-01

    The present study has been designed to investigate the potential role of ubiquitin proteasome system and other proteases in acute as well as delayed aspects of ischemic preconditioning induced reversal of ischemia-reperfusion injury in mouse brain. Bilateral carotid artery occlusion of 17 min followed by reperfusion for 24 h was employed in present study to produce ischemia and reperfusion induced cerebral injury in mice. Cerebral infarct size was measured using triphenyltetrazolium chloride staining. Memory was evaluated using elevated plus-maze test. Rota rod test was employed to assess motor incoordination. Bilateral carotid artery occlusion followed by reperfusion produced cerebral infarction and impaired memory and motor co-ordination. Three preceding episodes of bilateral carotid artery occlusion for 1 min and reperfusion of 1 min (ischemic preconditioning) both immediately before (for acute preconditioning) and 24 h before (for delayed preconditioning) global cerebral ischemia prevented markedly ischemia-reperfusion-induced cerebral injury as measured in terms of infarct size, loss of memory and motor coordination. Z-Leu-Leu-Phe-Chinese hamster ovary (CHO) (2 mg/kg, intraperitoneally (i.p.)), an inhibitor of ubiquitin proteasome system and other proteases attenuated the neuroprotective effect of both the acute as well as delayed ischemic preconditioning. It is concluded that the neuroprotective effect of both the acute as well as delayed phases of ischemic preconditioning may be due to the activation of ubiquitin proteasome system and other proteases.

  3. Age determines the effects of blood pressure lowering during the acute phase of ischemic stroke: the TICA study.

    PubMed

    Leira, Rogelio; Millán, Mónica; Díez-Tejedor, Exuperio; Blanco, Miguel; Serena, Joaquín; Fuentes, Blanca; Rodríguez-Yáñez, Manuel; Castellanos, Mar; Lago, Aida; Dávalos, Antonio; Castillo, José

    2009-10-01

    To increase understanding of the influence of blood pressure (BP) changes on functional outcome, we designed a multicenter, prospective, observational study involving patients with ischemic stroke. We included 1092 patients with ischemic stroke. BP was measured on admission and after 8, 16, 24, 32, 40, and 48 hours, and the averages of the readings were taken every 8 hours on days 3 to 7, at the day of discharge, and at 3 months. The main study variable was modified Rankin scale at 3 months. Systolic BPs >181 mm Hg at the emergency department and after 24 hours were associated with poor prognosis (odds ratio [OR]: 2.2, 95% CI: 1.2 to 4.2 and OR: 1.3, 95% CI: 1.1 to 2.3, respectively); systolic BP <136 mm Hg at the emergency department also determined worse prognosis at 3 months (OR: 1.3; 95% CI: 1.1 to 2.9). The influence of systolic BP changes in the first hours depended on patient age. In elder patients (>70 years), reductions in systolic BP determined a significant increase in the proportion of patients with worse prognosis. In patients >80 years of age, decreases in systolic BP >27.2 mm Hg determined a worse prognosis in patients with antihypertensive treatment at the emergency department (n=91) compared with those who did not receive treatment (n=106; OR: 21.7, 95% CI: 13.6 to 33.5 versus OR: 8.5, 95% CI: 3.2 to 19.6). In summary, the effect of BP modification during the acute phase of ischemic stroke on functional outcome is strongly dependent on age.

  4. Critical Role of Interleukin-11 in Isoflurane-mediated Protection against Ischemic Acute Kidney Injury in Mice

    PubMed Central

    Ham, Ahrom; Kim, Mihwa; Kim, Joo Yun; Brown, Kevin M.; Yeh, James; D’Agati, Vivette D.; Lee, H. Thomas

    2013-01-01

    Background Isoflurane releases renal tubular transforming growth factor-beta 1 (TGF-β1) and protects against ischemic acute kidney injury (AKI). Recent studies suggest that TGF-β1 can induce a cytoprotective cytokine interleukin (IL)-11. Here, we tested the hypothesis that isoflurane protects against ischemic AKI by direct induction of renal tubular IL-11 synthesis. Methods Human kidney proximal tubule (HK-2) cells were treated with 1.25-2.5% isoflurane or carrier gas (room air+5% carbon dioxide) for 0-16 h. We also anesthetized C57BL/6 mice with 1.2% isoflurane or with equi-anesthetic dose of pentobarbital for 4 h. In addition, we subjected IL-11 receptor (IL-11R) wild type, IL-11R deficient or IL-11 neutralized mice to 30-min renal ischemia followed by reperfusion under 4 h of pentobarbital or isoflurane (1.2%) anesthesia. Results Isoflurane increased IL-11 synthesis in human (~300-500% increase, N = 6) and mouse (23 ± 4 (mean ± SD) fold over carrier gas group, N = 4) proximal tubule cells that were attenuated by a TGF-β1 neutralizing antibody. Mice anesthetized with isoflurane showed significantly increased kidney IL-11 messenger RNA (13.8 ± 2 fold over carrier gas group, N = 4) and protein (31 ± 9 vs. 18±2 pg/mg protein or ~80% increase, N = 4) expression compared to pentobarbital anesthetized mice and this increase was also attenuated by a TGF-β1 neutralizing antibody. Furthermore, isoflurane-mediated renal protection in IL-11R wild-type mice were absent in IL-11R deficient mice or in IL-11R wild-type mice treated with IL-11 neutralizing antibody (N = 4-6). Conclusions Our studies suggest that isoflurane induces renal tubular IL-11 via TGF-β1 signaling to protect against ischemic AKI. PMID:24037316

  5. EEG patterns from acute to chronic stroke phases in focal cerebral ischemic rats: correlations with functional recovery.

    PubMed

    Zhang, Shao-jie; Ke, Zheng; Li, Le; Yip, Shea-ping; Tong, Kai-yu

    2013-04-01

    Monitoring the neural activities from the ischemic penumbra provides critical information on neurological recovery after stroke. The purpose of this study is to evaluate the temporal alterations of neural activities using electroencephalography (EEG) from the acute phase to the chronic phase, and to compare EEG with the degree of post-stroke motor function recovery in a rat model of focal ischemic stroke. Male Sprague-Dawley rats were subjected to 90 min transient middle cerebral artery occlusion surgery followed by reperfusion for seven days (n = 58). The EEG signals were recorded at the pre-stroke phase (0 h), acute phase (3, 6 h), subacute phase (12, 24, 48, 72 h) and chronic phase (96, 120, 144, 168 h) (n = 8). This study analyzed post-stroke seizures and polymorphic delta activities (PDAs) and calculated quantitative EEG parameters such as the alpha-to-delta ratio (ADR). The ADR represented the ratio between alpha power and delta power, which indicated how fast the EEG activities were. Forelimb and hindlimb motor functions were measured by De Ryck's test and the beam walking test, respectively. In the acute phase, delta power increased fourfold with the occurrence of PDAs, and the histological staining showed that the infarct was limited to the striatum and secondary sensory cortex. In the subacute phase, the alpha power reduced to 50% of the baseline, and the infarct progressed to the forelimb cortical region. ADRs reduced from 0.23 ± 0.09 to 0.04 ± 0.01 at 3 h in the acute phase and gradually recovered to 0.22 ± 0.08 at 168 h in the chronic phase. In the comparison of correlations between the EEG parameters and the limb motor function from the acute phase to the chronic phase, ADRs were found to have the highest correlation coefficients with the beam walking test (r = 0.9524, p < 0.05) and De Ryck's test (r = 0.8077, p < 0.05). This study measured EEG activities after focal cerebral ischemia and showed that functional recovery was closely

  6. Alteration of Thyroid-Related Hormones within Normal Ranges and Early Functional Outcomes in Patients with Acute Ischemic Stroke.

    PubMed

    Xu, Xiao-Yan; Li, Wen-Yu; Hu, Xing-Yue

    2016-01-01

    This study evaluated the prognostic value of thyroid-related hormones within normal ranges after acute ischemic stroke. This was a retrospective study and we reviewed 1072 ischemic stroke patients consecutively admitted within 72 h after symptom onset. Total triiodothyronine (T3), total thyroxine (T4), free T3, free T4, and thyroid-stimulating hormone (TSH) were assessed to determine their values for predicting functional outcome at the first follow-up clinic visits, which usually occurred 2 to 4 weeks after discharge from the hospital. 722 patients were finally included. On univariate analysis, poor functional outcome was associated with presence of atrial fibrillation as the index event. Furthermore, score of National Institutes of Health Stroke Scale (NIHSS), total T4, free T4, and C-reactive protein at admission were significantly higher in patients with poor functional outcome, whereas free T3 and total T3 were significantly lower. On multiple logistic regression analysis, lower total T3 concentrations remained independently associated with poor functional outcome [odds ratio (OR), 0.10; 95% confidence interval (CI), 0.01-0.84; P = 0.035]. The only other variables independently associated with poor functional outcome were NIHSS scores. In sum, lower total T3 concentrations that were within the normal ranges were independently associated with poor short-term outcomes. PMID:27375741

  7. Ischemic tissue injury in the dorsal skinfold chamber of the mouse: a skin flap model to investigate acute persistent ischemia.

    PubMed

    Harder, Yves; Schmauss, Daniel; Wettstein, Reto; Egaña, José T; Weiss, Fabian; Weinzierl, Andrea; Schuldt, Anna; Machens, Hans-Günther; Menger, Michael D; Rezaeian, Farid

    2014-11-17

    Despite profound expertise and advanced surgical techniques, ischemia-induced complications ranging from wound breakdown to extensive tissue necrosis are still occurring, particularly in reconstructive flap surgery. Multiple experimental flap models have been developed to analyze underlying causes and mechanisms and to investigate treatment strategies to prevent ischemic complications. The limiting factor of most models is the lacking possibility to directly and repetitively visualize microvascular architecture and hemodynamics. The goal of the protocol was to present a well-established mouse model affiliating these before mentioned lacking elements. Harder et al. have developed a model of a musculocutaneous flap with a random perfusion pattern that undergoes acute persistent ischemia and results in ~50% necrosis after 10 days if kept untreated. With the aid of intravital epi-fluorescence microscopy, this chamber model allows repetitive visualization of morphology and hemodynamics in different regions of interest over time. Associated processes such as apoptosis, inflammation, microvascular leakage and angiogenesis can be investigated and correlated to immunohistochemical and molecular protein assays. To date, the model has proven feasibility and reproducibility in several published experimental studies investigating the effect of pre-, peri- and postconditioning of ischemically challenged tissue.

  8. Successful Intra-Arterial Thrombolysis for Acute Ischemic Stroke in the Immediate Postpartum Period: Case Report

    SciTech Connect

    Mendez, Jose C. Masjuan, J.; Garcia, N.; Lecinana, M. de

    2008-01-15

    Stroke in pregnancy and the puerperium is a rare but potentially devastating event. We present the case of a previously healthy woman who underwent a cesarean delivery and experienced a middle cerebral artery thrombosis in the immediate postpartum period that was subsequently lysed with intra-arterial urokinase. The patient made a complete neurologic recovery. To the best of our knowledge, this is the first reported case of successful intra-arterial thrombolysis for ischemic stroke in the postpartum period.

  9. Impact of baseline characteristics on outcomes of carotid artery stenting in acute ischemic stroke patients

    PubMed Central

    Yu, Cheng-Sheng; Lin, Chih-Ming; Liu, Chi-Kuang; Lu, Henry Horng-Shing

    2016-01-01

    Carotid artery stenting is an effective treatment for ischemic stroke patients with moderate-to-severe carotid artery stenosis. However, the midterm outcome for patients undergoing this procedure varies considerably with baseline characteristics. To determine the impact of baseline characteristics on outcomes following carotid artery stenting, data from 107 eligible patients with a first episode of ischemic stroke were collected by retrospective chart review. A modified Rankin Scale (mRS) was used to divide patients into two baseline groups, mRS ≤2 and mRS >2. A three-step decision-tree statistical analysis was conducted. After weighting the decision-tree parameters, the following impact hierarchy was obtained: admission low-density lipoprotein, gouty arthritis, chronic kidney disease, ipsilateral common carotid artery resistance index, contralateral ophthalmic artery resistance index, sex, and dyslipidemia. The finite-state machine model demonstrated that, in patients with baseline mRS ≤2, 46% had an improved mRS score at follow-up, whereas 54% had a stable mRS score. In patients with baseline mRS >2, a stable mRS score was observed in 75%, improved score in 23%, and a poorer score in 2%. Admission low-density lipoprotein was the strongest predictive factor influencing poststenting outcome. In addition, our study provides further evidence that carotid artery stenting can be of benefit in first-time ischemic stroke patients with baseline mRS scores >2. PMID:27099508

  10. Functional Polymorphisms in Toll-like Receptor 4 Are Associated With Worse Outcome in Acute Ischemic Stroke Patients

    PubMed Central

    Weinstein, Jonathan R.; Schulze, Juliane; Lee, Richard V.; Phillips, Hunter; Zierath, Dannielle; Tanzi, Patricia; Shibata, Dean; Cain, Kevin C.; Becker, Kyra J.

    2014-01-01

    Toll-like receptor-4 (TLR4) is important in neuroinflammation. Single nucleotide polymorphisms (SNPs) in TLR4, including 1063 A/G [Asp299Gly] and 1363 C/T [Thr399Ile], are associated with altered immune responses but their effect on acute ischemic stroke (AIS) outcome is unknown. We collected demographic, clinical, laboratory, radiologic and genotype data on 113 AIS patients and performed multivariate analyses to assess associations between TLR4 SNP haplotype and either neurological outcome, infection or inflammatory markers. In adjusted analyses, TLR4 SNPs were associated with worse outcome as well as increases in circulating leukocytes, C-reactive protein and interleukin-1 receptor antagonist. In AIS, variations in TLR4 may influence neurological outcome. PMID:24784586

  11. Automatic detection of CT perfusion datasets unsuitable for analysis due to head movement of acute ischemic stroke patients.

    PubMed

    Fahmi, Fahmi; Marquering, Henk A; Streekstra, Geert J; Beenen, Ludo F M; Janssen, Natasja N Y; Majoie, Charles B L; van Bavel, Ed

    2014-01-01

    Head movement during brain Computed Tomography Perfusion (CTP) can deteriorate perfusion analysis quality in acute ischemic stroke patients. We developed a method for automatic detection of CTP datasets with excessive head movement, based on 3D image-registration of CTP, with non-contrast CT providing transformation parameters. For parameter values exceeding predefined thresholds, the dataset was classified as 'severely moved'. Threshold values were determined by digital CTP phantom experiments. The automated selection was compared to manual screening by 2 experienced radiologists for 114 brain CTP datasets. Based on receiver operator characteristics, optimal thresholds were found of respectively 1.0°, 2.8° and 6.9° for pitch, roll and yaw, and 2.8 mm for z-axis translation. The proposed method had a sensitivity of 91.4% and a specificity of 82.3%. This method allows accurate automated detection of brain CTP datasets that are unsuitable for perfusion analysis. PMID:24691387

  12. Experimental colitis.

    PubMed

    MacPherson, B; Pfeiffer, C J

    1976-01-01

    Ulcerative colitis and Crohn's disease are complex, problematic diseases of unknown etiology in man, and appropriate experimental models would be useful in elucidating their pathogenesis and treatment. Although there have been numerous attempts to produce inflammatory ulcerative colonic disease in laboratory animals resembling those human disease forms, none has been entirely successful. Investigators have conducted experiments involving almost every etiological factor suggested for initiation of these diseases. The methods reviewed in this paper include production of experimental colitis by vascular impairment, and immunological methods such as bacterial infection, allergic reactions, direct and indirect hypersensitivity reactions, as well as autoimmune mechanisms. The results of carrageenan-induced colitis, irradiation, dietary, and drug-induced techniques are also discussed and the frequency and nature of spontaneous colonic lesions in animals is summarized.

  13. [Complex network analysis on dynamic change regularity of combining use of Chinese and western medicine in 27,678 cases with ischemic stroke in acute phase].

    PubMed

    Yang, Wei; Li, Yang; Sun, Lei-lei; Xie, Yan-ming; Guo, Chong-hui; Zhuang, Yan

    2015-12-01

    The acute phase of ischemic stroke patients are often treated with both Chinese patent medicine:and western medicine therapies in clinical practice. This research included 27,678 cases of the acute phase of ischemic stroke came from 14 3A level hospitals. We collected data from patients with ischemic stroke who used both Chinese patent medicine and western medicine and were hopitalized within 14 days from hospital information system (HIS). Constructing complex network of Chinese patent medicine and western medicine were found to show scale-free network. Hierarchical structure of the core algorithm was used to analyze the characteristics of combined core Chinese patent medicine and western medicine in admission condition of "acute", "critically", and "general" of ischemic stroke acute phase patient within one day, 2-3 days, 4-7 days and 8-14 days. We found that the core Chinese patent medicine mainly used for activate blood and resolve stasis medicine, and phlegm eliminating brain refreshing medicine in all kinds of patients, but the phlegm eliminating brain refreshing medicine were used to reduce with time elapsing. The core western medicine mainly used for anti-platelet medicine, improve circulation medicine, neuroprotective medicine, anticoagulants medicine and dehydration medicine. The dehydration medicine as the core western medicine for critically patients within 14 days, but the patients for general admission as core western medicine within 3 days. The neuroprotective medicine was used to decreases after 7 days in hospital. Combination of Chinese patent medicine and western medicine were mainly for neuroprotective medicine + activate blood and resolve stasis medicine, and anti-platelet medicine + activate blood and resolve stasis medicine, and improve circulation medicine + activate blood and resolve stasis medicine. The phlegm eliminating brain refreshing medicine was mainly combined with neuroprotective medicine by urgent and general admission condition

  14. Relationship between Blood Pressure and Outcomes in Acute Ischemic Stroke Patients Administered Lytic Medication in the TIMS-China Study

    PubMed Central

    Zhao, Xingquan; Liao, Xiaoling; Wang, Chunjuan; Pan, Yuesong; Wang, Yilong; Wang, Yongjun

    2016-01-01

    Objective Increased blood pressure (BP) management following acute ischemic stroke (AIS) remains controversial. This study aimed to identify the association between BP and clinical outcomes in AIS patients administered lytic medication in the TIMS-China (thrombolysis implementation and monitor of acute ischemic stroke in China) database. Methods The sample comprised 1128 patients hospitalized within 4.5 hours (h) of AIS for intravenous recombinant tissue plasminogen activator (i.v. rt-PA) thrombolysis. Systolic BP (SBP) and diastolic BP (DBP) at baseline, 2 h and 24 h after treatment, and changes from baseline were analyzed. The study outcomes comprised a favorable outcome (modified Rankin Scale 0–1 at 90 days) and symptomatic intracerebral hemorrhage (SICH), analyzed using logistic regression, with low BP as the reference group. Results Lower BP (baseline, 2 h, and 24 h) was beneficial in AIS patients and significantly related to a favorable outcome (P<0.05). A substantial BP decrease at 24 h after rt-PA thrombolysis was significantly associated with a favorable outcome compared with a moderate BP decrease (P = 0.0298). A SBP >160 mmHg 2 h after rt-PA thrombolysis was significantly associated with SICH compared with a SBP <140 mmHg (P = 0.0238). An increase or no change (>25 mmHg) in SBP was significantly associated with SICH (P = 0.002) compared with a small SBP decrease (1–9 mmHg). Conclusions This study provides novel evidence that lower BP within the first 24 h is associated with a more favorable outcome and less frequent SICH in AIS patients administered lytic medication. Routine BP-lowering treatment should be considered in AIS patients following lytic medication. PMID:26828609

  15. MULTIPARAMETRIC MRI AND CT MODELS OF INFARCT CORE AND FAVORABLE PENUMBRAL IMAGING PATTERNS IN ACUTE ISCHEMIC STROKE

    PubMed Central

    Kidwell, Chelsea S.; Wintermark, Max; De Silva, Deidre A.; Schaewe, Timothy J.; Jahan, Reza; Starkman, Sidney; Jovin, Tudor; Hom, Jason; Jumaa, Mouhammad; Schreier, Jeffrie; Gornbein, Jeffrey; Liebeskind, David S.; Alger, Jeffry R.; Saver, Jeffrey L.

    2013-01-01

    Background and Purpose Objective imaging methods to identify optimal candidates for late recanalization therapies are needed. The study goals were 1) to develop MRI and CT multiparametric, voxel-based predictive models of infarct core and penumbra in acute ischemic stroke patients, and 2) to develop patient-level imaging criteria for favorable penumbral pattern based on good clinical outcome in response to successful recanalization. Methods An analysis of imaging and clinical data was performed on two cohorts of patients (one screened with CT, the other with MRI) who underwent successful treatment for large vessel, anterior circulation stroke. Subjects were divided 2:1 into derivation and validation cohorts. Pretreatment imaging parameters independently predicting final tissue infarct and final clinical outcome were identified. Results The MRI and CT models were developed and validated from 34 and 32 patients, employing 943,320 and 1,236,917 voxels respectively. The derivation MRI and two-branch CT models had an overall accuracy of 74% and 80% respectively, and were independently validated with an accuracy of 71% and 79% respectively. The imaging criteria of 1) predicted infarct core ≤ 90 mL and 2) ratio of predicted infarct tissue within the at-risk region ≤ 70% identified patients as having a favorable penumbral pattern with 78–100% accuracy. Conclusions Multiparametric voxel-based MRI and CT models were developed to predict the extent of infarct core and overall penumbral pattern status in patients with acute ischemic stroke who may be candidates for late recanalization therapies. These models provide an alternative approach to mismatch in predicting ultimate tissue fate. PMID:23233383

  16. Hydrosulfide attenuates acute myocardial ischemic injury through the glycogen synthase kinase-3β/β-catenin signaling pathway.

    PubMed

    Ge, Ning; Liu, Chao; Li, Guofeng; Xie, Lijun; Zhang, Qinzeng; Li, Liping; Hao, Na; Zhang, Jianxin

    2016-05-01

    The endogenous signaling gasotransmitter, hydrosulfide (H2S), has been shown to exert cardioprotective effects against acute myocardial infarction (AMI) due to ischemic injury. However, the mechanisms responsible for these effects are not yet fully understood. In this study, we investigated whether sodium hydrogen sulfide (NaHS), an H2S donor, attenuates acute myocardial ischemic injury through glycogen synthase kinase-3β (GSK-3β)/β-catenin signaling. For this purpose, we utilized an in vivo rat model of AMI by occluding the left anterior descending coronary artery. NaHS (0.39, 0.78 or 1.56 mg/kg, intraperitoneally), the GSK-3β inhibitor, SB216763 (0.6 mg/kg, intravenously), or 1% dimethylsulfoxide (2 ml/kg, intravenously) were administered to the rats. The results demonstrated that the administration of medium- and high-dose NaHS and SB216763 significantly improved rat cardiac function, as evidenced by an increase in the mean arterial pressure, left ventricular developed pressure, contraction and relaxation rates, as well as a decrease in left ventricular end-diastolic pressure. In addition, the administration of NaHS and SB216763 attenuated myocardial injury as reflected by a decrease in apoptotic cell death and in the serum lactate dehydrogenase concentrations, and prevented myocardial structural changes. The administration of NaHS and SB216763 increased the concentrations of phosphorylated (p-)GSK-3β, the p-GSK-3β/t-GSK-3β ratio and downstream protein β-catenin. Moreover, western blot and immunohistochemical analyses of apoptotic signaling pathway proteins further established the cardioprotective potential of NaHS, as reflected by the upregulation of Bcl-2 expression, the downregulation of Bax expression, and a decrease in the number of TUNEL-positive stained cells. These findings suggest that hydrosulfide exerts cardioprotective effects against AMI-induced apoptosis through the GSK-3β/β-catenin signaling pathway.

  17. Hydrosulfide attenuates acute myocardial ischemic injury through the glycogen synthase kinase-3β/β-catenin signaling pathway

    PubMed Central

    GE, NING; LIU, CHAO; LI, GUOFENG; XIE, LIJUN; ZHANG, QINZENG; LI, LIPING; HAO, NA; ZHANG, JIANXIN

    2016-01-01

    The endogenous signaling gasotransmitter, hydrosulfide (H2S), has been shown to exert cardioprotective effects against acute myocardial infarction (AMI) due to ischemic injury. However, the mechanisms responsible for these effects are not yet fully understood. In this study, we investigated whether sodium hydrogen sulfide (NaHS), an H2S donor, attenuates acute myocardial ischemic injury through glycogen synthase kinase-3β (GSK-3β)/β-catenin signaling. For this purpose, we utilized an in vivo rat model of AMI by occluding the left anterior descending coronary artery. NaHS (0.39, 0.78 or 1.56 mg/kg, intraperitoneally), the GSK-3β inhibitor, SB216763 (0.6 mg/kg, intravenously), or 1% dimethylsulfoxide (2 ml/kg, intravenously) were administered to the rats. The results demonstrated that the administration of medium- and high-dose NaHS and SB216763 significantly improved rat cardiac function, as evidenced by an increase in the mean arterial pressure, left ventricular developed pressure, contraction and relaxation rates, as well as a decrease in left ventricular end-diastolic pressure. In addition, the administration of NaHS and SB216763 attenuated myocardial injury as reflected by a decrease in apoptotic cell death and in the serum lactate dehydrogenase concentrations, and prevented myocardial structural changes. The administration of NaHS and SB216763 increased the concentrations of phosphorylated (p-)GSK-3β, the p-GSK-3β/t-GSK-3β ratio and downstream protein β-catenin. Moreover, western blot and immunohistochemical analyses of apoptotic signaling pathway proteins further established the cardioprotective potential of NaHS, as reflected by the upregulation of Bcl-2 expression, the downregulation of Bax expression, and a decrease in the number of TUNEL-positive stained cells. These findings suggest that hydrosulfide exerts cardioprotective effects against AMI-induced apoptosis through the GSK-3β/β-catenin signaling pathway. PMID:27035393

  18. [Ulcerative colitis].

    PubMed

    Lopetuso, Loris; Gasbarrini, Antonio

    2016-06-01

    Inflammatory bowel disease (IBD), such as Crohn's disease (CD) and ulcerative colitis (UC), are chronic, relapsing inflammatory disorders of the digestive tract resulting from dysregulated immune responses toward environmental factors in genetically predisposed individuals. This review focus on what is the state of the art of UC pathophysiology, diagnosis, and treatment and how any future findings could drive our clinical practice. PMID:27362722

  19. [ROLE OF MICROFLORA OF THE ABDOMINAL CAVITY EXUDATE IN THE ENDOGENIC INTOXICATION OCCURRENCE IN PATIENTS, SUFFERING COMPLICATED ACUTE CHOLECYSTITIS WITH CONCURRENT CARDIAC INSUFFICIENCY OF ISCHEMIC GENESIS].

    PubMed

    Ivantsok, V M

    2015-05-01

    While complicated acute cholecystitis (ACH) course the focus of infection constitutes one of the main causes of the endogenic intoxication (EI) occurrence, what leads to ischemic and hypoxic myocardial damage. There were presented the treatment results analysis in 213 patients, ageing 60 years old and older, managed for an ACH, complicated by peritonitis, paravesical abscess, with concurrent cardiac insufficiency of ischemic genesis, to whom laparoscopic cholecytectomy (LCHE) was conducted. Microflora of the abdominal cavity exudates in the patients, suffering an ACH of various severity, was studied. More rapid regression of inflammatory process, the EI severity and the ischemic-hypoxic myocardial affection reduction, positive impact on hemodynamics, reduction of myocardial ischemia severity were noted while local affection, when bacteriophages for treatment were applied.

  20. A Clinical Experimental Model to Evaluate Analgesic Effect of Remote Ischemic Preconditioning in Acute Postoperative Pain

    PubMed Central

    Pereira, Francisco Elano Carvalho; Mello, Irene Lopes; Pimenta, Fernando Heladio de Oliveira Medeiros; Costa, Debora Maia; Wong, Deysi Viviana Tenazoa; Fernandes, Claudia Regina; Lima Junior, Roberto César; Gomes, Josenília M. Alves

    2016-01-01

    This study aims to evaluate the viability of a clinical model of remote ischemic preconditioning (RIPC) and its analgesic effects. It is a prospective study with twenty (20) patients randomly divided into two groups: control group and RIPC group. The opioid analgesics consumption in the postoperative period, the presence of secondary mechanical hyperalgesia, the scores of postoperative pain by visual analog scale, and the plasma levels interleukins (IL-6) were evaluated. The tourniquet applying after spinal anesthetic block was safe, producing no pain for all patients in the tourniquet group. The total dose of morphine consumption in 24 hours was significantly lower in RIPC group than in the control group (p = 0.0156). The intensity analysis of rest pain, pain during coughing and pain in deep breathing, showed that visual analogue scale (VAS) scores were significantly lower in RIPC group compared to the control group: p = 0.0087, 0.0119, and 0.0015, respectively. There were no differences between groups in the analysis of presence or absence of mechanical hyperalgesia (p = 0.0704) and in the serum levels of IL-6 dosage over time (p < 0.0001). This clinical model of remote ischemic preconditioning promoted satisfactory analgesia in patients undergoing conventional cholecystectomy, without changing serum levels of IL-6. PMID:27446611

  1. A Clinical Experimental Model to Evaluate Analgesic Effect of Remote Ischemic Preconditioning in Acute Postoperative Pain.

    PubMed

    Pereira, Francisco Elano Carvalho; Mello, Irene Lopes; Pimenta, Fernando Heladio de Oliveira Medeiros; Costa, Debora Maia; Wong, Deysi Viviana Tenazoa; Fernandes, Claudia Regina; Lima Junior, Roberto César; Gomes, Josenília M Alves

    2016-01-01

    This study aims to evaluate the viability of a clinical model of remote ischemic preconditioning (RIPC) and its analgesic effects. It is a prospective study with twenty (20) patients randomly divided into two groups: control group and RIPC group. The opioid analgesics consumption in the postoperative period, the presence of secondary mechanical hyperalgesia, the scores of postoperative pain by visual analog scale, and the plasma levels interleukins (IL-6) were evaluated. The tourniquet applying after spinal anesthetic block was safe, producing no pain for all patients in the tourniquet group. The total dose of morphine consumption in 24 hours was significantly lower in RIPC group than in the control group (p = 0.0156). The intensity analysis of rest pain, pain during coughing and pain in deep breathing, showed that visual analogue scale (VAS) scores were significantly lower in RIPC group compared to the control group: p = 0.0087, 0.0119, and 0.0015, respectively. There were no differences between groups in the analysis of presence or absence of mechanical hyperalgesia (p = 0.0704) and in the serum levels of IL-6 dosage over time (p < 0.0001). This clinical model of remote ischemic preconditioning promoted satisfactory analgesia in patients undergoing conventional cholecystectomy, without changing serum levels of IL-6. PMID:27446611

  2. Endovascular Recanalization in Acute Ischemic Stroke Using the Solitaire FR Revascularization Device with Adjunctive C-Arm CT Imaging.

    PubMed

    Mitchell, B D; Chinnadurai, P; Chintalapani, G; Morsi, H A; Shaltoni, H; Mawad, M E

    2015-07-01

    In this clinical report, we examined a single-center experience by using the Solitaire FR Revascularization Device in the treatment of acute ischemic stroke in which there was poor initial visualization of the occluded arterial branches by using biplanar cerebral angiography. In all cases, adjunctive C-arm CT was used during the deployment of the thrombectomy device to gain additional information regarding device placement and expansion. Outcome measures included the extent of reperfusion, posttreatment changes in NIHSS scores, posttreatment TICI scores, cerebral hemorrhage, and survival. Clot removal with successful arterial recanalization was achieved in 15/18 cases (83.3%) with TICI scores of 2b/3 in all patients who had initial recanalization. The NIHSS score improved, on average, from 19 pretreatment to 11 posttreatment, and 72% of patients survived. In cases of acute stroke in which there is little information available regarding the positioning and deployment of a retrievable stent during mechanical thrombectomy, the use of C-arm CT may provide more information about device placement across an area of thrombus.

  3. Optical bedside monitoring of cerebral perfusion: technological and methodological advances applied in a study on acute ischemic stroke

    NASA Astrophysics Data System (ADS)

    Steinkellner, Oliver; Gruber, Clemens; Wabnitz, Heidrun; Jelzow, Alexander; Steinbrink, Jens; Fiebach, Jochen B.; MacDonald, Rainer; Obrig, Hellmuth

    2010-11-01

    We present results of a clinical study on bedside perfusion monitoring of the human brain by optical bolus tracking. We measure the kinetics of the contrast agent indocyanine green using time-domain near-IR spectroscopy (tdNIRS) in 10 patients suffering from acute unilateral ischemic stroke. In all patients, a delay of the bolus over the affected when compared to the unaffected hemisphere is found (mean: 1.5 s, range: 0.2 s to 5.2 s). A portable time-domain near-IR reflectometer is optimized and approved for clinical studies. Data analysis based on statistical moments of time-of-flight distributions of diffusely reflected photons enables high sensitivity to intracerebral changes in bolus kinetics. Since the second centralized moment, variance, is preferentially sensitive to deep absorption changes, it provides a suitable representation of the cerebral signals relevant for perfusion monitoring in stroke. We show that variance-based bolus tracking is also less susceptible to motion artifacts, which often occur in severely affected patients. We present data that clearly manifest the applicability of the tdNIRS approach to assess cerebral perfusion in acute stroke patients at the bedside. This may be of high relevance to its introduction as a monitoring tool on stroke units.

  4. Recanalization and Mortality Rates of Thrombectomy With Stent-Retrievers in Octogenarian Patients with Acute Ischemic Stroke

    SciTech Connect

    Parrilla, G.; Carreón, E.; Zamarro, J.; Espinosa de Rueda, M.; García-Villalba, B.; Marín, F.; Hernández-Fernández, F.; Morales, A.; Fernández-Vivas, M.; Núñez, R.; Moreno, A.

    2015-04-15

    BackgroundOur objective was to evaluate the effect of treatment with stent-retrievers in octogenarians suffering an acute ischemic stroke.MethodsA total of 150 consecutive patients with acute stroke who were treated with stent-retrievers between April 2010 and June 2012 were retrospectively reviewed. Patients were divided into those <80 years old (n = 116) and those ≥80 (n = 34). Baseline characteristics, procedure data, and endpoints (postprocedural NIHSS, death, and mRS at 3 months) were compared.ResultsHigh blood pressure, atrial fibrillation, and anticoagulation were more frequent in octogenarians (p = 0.01, 0.003, and 0.04 respectively). There were no differences between both groups regarding previous intravenous thrombolysis (32.4 vs. 48.3 %, p = 0.1), preprocedural NIHSS (18.1 vs. 16.8, p = 0.3), procedure time (74.5 (40–114) min vs. 63 (38–92) min, p = 0.2), revascularization time (380.5 (298–526.3) min vs. 350 (296.3–452.8), p = 0.3), TICI ≥ 2B (88.2 vs. 93.9 %, p = 0.1), and symptomatic haemorrhage (5.9 vs. 2.6 %, p = 0.3). Discharge NIHSS was higher in octogenarians (9.7 vs. 6.5, p = 0.03). Death and 3-month mRS ≥3 were more frequent in octogenarians (35.3 vs. 17.2 %, p = 0.02 and 73.5 vs. 37.1 %, p = 0.02). ICA-involvement and prolonged revascularization involved higher mortality (66.7 vs. 27.6 %, p = 0.03) and worse mRS (50 vs. 24.4 %, p = 0.06) in octogenarians.ConclusionsIn our series, treatment with stent-retrievers in octogenarians with acute ischemic stroke achieved good rates of recanalization but with a high mortality rate. ICA involvement and revascularization times beyond 6 hours associated to a worse prognosis. These data might be of value in the design of prospective studies evaluating the clinical efficacy of the endovascular treatments in octogenarians.

  5. Application of hidden Markov random field approach for quantification of perfusion/diffusion mismatch in acute ischemic stroke.

    PubMed

    Dwyer, Michael G; Bergsland, Niels; Saluste, Erik; Sharma, Jitendra; Jaisani, Zeenat; Durfee, Jacqueline; Abdelrahman, Nadir; Minagar, Alireza; Hoque, Romy; Munschauer, Frederick E; Zivadinov, Robert

    2008-10-01

    The perfusion/diffusion 'mismatch model' in acute ischemic stroke provides the potential to more accurately understand the consequences of thrombolytic therapy on an individual patient basis. Few methods exist to quantify mismatch extent (ischemic penumbra) and none have shown a robust ability to predict infarcted tissue outcome. Hidden Markov random field (HMRF) approaches have been used successfully in many other applications. The aim of the study was to develop a method for rapid and reliable identification and quantification of perfusion/diffusion mismatch using an HMRF approach. An HMRF model was used in combination with automated contralateral identification to segment normal tissue from non-infarcted tissue with perfusion abnormality. The infarct was used as a seed point to initialize segmentation, along with the contralateral mirror tissue. The two seeds were then allowed to compete for ownership of all unclassified tissue. In addition, a novel method was presented for quantifying tissue salvageability by weighting the volume with the degree of hypoperfusion, allowing the penumbra voxels to contribute unequal potential damage estimates. Simulated and in vivo datasets were processed and compared with results from a conventional thresholding approach. Both simulated and in vivo experiments demonstrated a dramatic improvement in accuracy with the proposed technique. For the simulated dataset, the mean absolute error decreased from 171.9% with conventional thresholding to 2.9% for the delay-weighted HMRF approach. For the in vivo dataset, the mean absolute error decreased from 564.6% for thresholding to 34.2% for the delay-weighted HMRF approach. The described method represents a significant improvement over thresholding techniques.

  6. Incremental Value of Left Atrial Global Longitudinal Strain for Prediction of Post Stroke Atrial Fibrillation in Patients with Acute Ischemic Stroke

    PubMed Central

    Kim, Darae; Cho, In Jeong; Kim, Young Dae; Nam, Hyo Suk; Chang, Hyuk-Jae; Hong, Geu-Ru; Ha, Jong-Won; Heo, Ji Hoe; Chung, Namsik

    2016-01-01

    Background Atrial fibrillation (AF) is a well-established risk factor for stroke. Interestingly, ischemic stroke increases risk of incident AF in patients without prior diagnosed AF. For better risk stratification for post-stroke AF, we studied left atrial (LA) size and mechanical function using two-dimensional (2D) speckle tracking imaging in patients with acute ischemic stroke. Methods A total of 227 patients (132 males, age 67 ± 12) with acute ischemic stroke without a history of AF underwent 2D transthoracic echocardiography and speckle tracking imaging for the assessment of LA volume index and global LA longitudinal strain (LALS). From clinical variables, the CHA2DS2-VASc score and National Institute of Health Stroke Scale (NIHSS) were calculated in each patient. Post-stroke AF was defined as newly diagnosed AF during the course after ischemic stroke. Results Post-stroke AF occurred in 25 patients (11%). Patients with post-stroke AF were older and showed a higher tendency of CHA2DS2-VASc score, significantly higher log NIHSS, larger LA volume index and lower global LALS than those without. In multivariate analysis, global LALS was an independent predictor for post-stroke AF (hazard ratio 0.90, 95% confidence interval 0.83.0.97, p < 0.01) after controlling for confounding factors. Furthermore, global LALS provided incremental predictive value for post-stroke AF over the CHA2DS2-VASc score, NIHSS, and LA volume index. The global LALS < 14.5% better distinguished post-stroke AF (area under the curve 0.837, sensitivity 60%, specificity 95%, p < 0.01) than CHA2DS2-VASc score. Conclusion Global LALS as a marker of LA mechanical function has incremental predictive value for post-stroke AF in patients with acute ischemic stroke. PMID:27081440

  7. Safety and efficacy of non-vitamin K oral anticoagulant treatment compared with warfarin in patients with non-valvular atrial fibrillation who develop acute ischemic stroke or transient ischemic attack: a multicenter prospective cohort study (daVinci study).

    PubMed

    Saji, Naoki; Kimura, Kazumi; Tateishi, Yohei; Fujimoto, Shigeru; Kaneko, Nobuyuki; Urabe, Takao; Tsujino, Akira; Iguchi, Yasuyuki

    2016-11-01

    The safety and efficacy of non-vitamin K oral anticoagulant (NOAC) compared with warfarin in treating patients with non-valvular atrial fibrillation (NVAF) who developed acute ischemic stroke or transient ischemic attack (AIS/TIA), particularly those receiving tissue-plasminogen activator (tPA) therapy, remains unclear. Between April 2012 and December 2014, we conducted a multicenter prospective cohort study to assess the current clinical practice for treating such patients. We divided the patients into two groups according to the administration of oral anticoagulants (warfarin or NOACs) and tPA therapy. The risk of any hemorrhagic or ischemic event was compared within 1 month after the onset of stroke. We analyzed 235 patients with AIS/TIA including 73 who received tPA therapy. Oral anticoagulants were initiated within 2-4 inpatient days. NOACs were administered to 49.8 % of patients, who were predominantly male, younger, had small infarcts, lower NIHSS scores, and had a lower all-cause mortality rate (0 vs. 4.2 %, P = 0.06) and a lower risk of any ischemic events (6.0 vs. 7.6 %, P = 0.797) compared with warfarin users. The prevalence of all hemorrhagic events was equivalent between the two groups. Early initiation of NOACs after tPA therapy appeared to lower the risk of hemorrhagic events, although there was no significant difference (0 vs. 5.6 %, P = 0.240). Although more clinicians are apt to prescribe NOACs in minor ischemic stroke, NOAC treatment may provide a potential benefit in such cases. Early initiation of NOACs after tPA therapy may reduce the risk of hemorrhagic events compared with warfarin.

  8. Neuroinflammation and Neuroimmune Dysregulation after Acute Hypoxic-Ischemic Injury of Developing Brain

    PubMed Central

    Bhalala, Utpal S.; Koehler, Raymond C.; Kannan, Sujatha

    2015-01-01

    Hypoxic-ischemic (HI) injury to developing brain results from birth asphyxia in neonates and from cardiac arrest in infants and children. It is associated with varying degrees of neurologic sequelae, depending upon the severity and length of HI. Global HI triggers a series of cellular and biochemical pathways that lead to neuronal injury. One of the key cellular pathways of neuronal injury is inflammation. The inflammatory cascade comprises activation and migration of microglia – the so-called “brain macrophages,” infiltration of peripheral macrophages into the brain, and release of cytotoxic and proinflammatory cytokines. In this article, we review the inflammatory and immune mechanisms of secondary neuronal injury after global HI injury to developing brain. Specifically, we highlight the current literature on microglial activation in relation to neuronal injury, proinflammatory and anti-inflammatory/restorative pathways, the role of peripheral immune cells, and the potential use of immunomodulators as neuroprotective compounds. PMID:25642419

  9. Ultra-rapid manufacturing of engineered epicardial substitute to regenerate cardiac tissue following acute ischemic injury.

    PubMed

    Serpooshan, Vahid; Ruiz-Lozano, Pilar

    2014-01-01

    Considering the impaired regenerative capacity of adult mammalian heart tissue, cardiovascular tissue engineering aims to create functional substitutes that can restore the structure and function of the damaged cardiac tissue. The success of cardiac regenerative therapies has been limited mainly due to poor control on the structure and properties of the tissue substitute, lack of vascularization, and immunogenicity. In this study we introduce a new approach to rapidly engineer dense biomimetic scaffolds consisting of type I collagen, to protect the heart against severe ischemic injury. Scaffold biomechanical properties are adjusted to mimic embryonic epicardium which is shown to be optimal to support cardiomyocyte contractile work. Moreover, the designed patch can serve as a delivery device for targeted, controlled release of cells or therapeutic macromolecules into the lesion area.

  10. [The effect of nitrates on the outcome of acute experimental ischemic stroke].

    PubMed

    Kuzenkov, V S; Krushinskiĭ, A L; Reutov, V P

    2012-01-01

    Effects of nitrates NaNO(3), KNO(3), Mg(NO(3)) 2 on animals (Wistar rats) were studied on the basis of the experimental model of ischemic stroke induced by the occlusion of two carotid arteries. The animals were divided into two groups: the main group (n=60) and the control group (n=30). Three series of experiments were conducted. In each experiment, the rats of the main group were treated with one of nitrates and the control group was treated with physiological solution. It has been shown that nitrates exert either positive or negative effect depending on the cation type, nitrate concentration and the duration of their action on the dynamics of neurologic disturbances. Conditions of the development of neuroprotective effect of nitrates are discussed.

  11. Combined Neuroprotective Modalities Coupled with Thrombolysis in Acute Ischemic Stroke: A Pilot Study of Caffeinol and Mild Hypothermia

    PubMed Central

    Martin-Schild, Sheryl; Hallevi, Hen; Shaltoni, Hashem; Barreto, Andrew D.; Gonzales, Nicole R.; Aronowski, Jarek; Savitz, Sean I.; Grotta, James C.

    2009-01-01

    Background Both caffeinol and hypothermia are neuroprotective in preclinical models of transient middle cerebral artery occlusion. We tested whether combining caffeinol and hypothermia with t-PA in acute stroke patients is safe and feasible. Methods 20 patients with acute ischemic stroke were treated with caffeinol (caffeine 8-9 mg/kg + ethanol 0.4g/kg IV X 2 hours, started by 4 hrs after symptom onset) and hypothermia (started by 5 hrs and continued for 24 hrs (target temp 33-35°C) followed by 12 hrs of rewarming). IV t-PA was given to eligible patients. Meperidine and buspirone were used to suppress shivering. Results All patients received caffeinol, and most reached target blood levels. Cooling was attempted in 18 patients via endovascular (n=8) or surface (n=10) approaches. Two patients were not cooled due to catheter or machine failure. Thirteen patients reached target temperature; average time from symptom onset was 9hrs, 43min. The last 5 hypothermia patients received surface cooling with iced saline induction and larger doses of meperidine; all patients reached target temperature, on average within 2hrs 30min from induction and 6hrs 21min from symptom onset. Three patients died: one from symptomatic hemorrhage, one from malignant cerebral edema, and one from unrelated medical complications. No adverse events were attributed to caffeinol. One patient had reduced respiratory drive due to meperidine, requiring BiPAP. Discussion Combining caffeinol with hypothermia in acute stroke patients given IV t-PA is feasible. A prospective placebo-controlled randomized study is needed to further assess safety and to test the efficacy of caffeinol, hypothermia or both. PMID:19251183

  12. CMV - gastroenteritis/colitis

    MedlinePlus

    Colitis - cytomegalovirus; Gastroenteritis - cytomegalovirus; Gastrointestinal CMV disease ... or after bone marrow or organ transplant Ulcerative colitis or Crohn disease Rarely, serious CMV infection involving ...

  13. Bilirubin prevents acute DSS-induced colitis by inhibiting leukocyte infiltration and suppressing upregulation of inducible nitric oxide synthase.

    PubMed

    Zucker, Stephen D; Vogel, Megan E; Kindel, Tammy L; Smith, Darcey L H; Idelman, Gila; Avissar, Uri; Kakarlapudi, Ganesh; Masnovi, Michelle E

    2015-11-15

    Bilirubin is thought to exert anti-inflammatory effects by inhibiting vascular cell adhesion molecule-1 (VCAM-1)-dependent leukocyte migration and by suppressing the expression of inducible nitric oxide synthase (iNOS). As VCAM-1 and iNOS are important mediators of tissue injury in the dextran sodium sulfate (DSS) murine model of inflammatory colitis, we examined whether bilirubin prevents colonic injury in DSS-treated mice. Male C57BL/6 mice were administered 2.5% DSS in the drinking water for 7 days, while simultaneously receiving intraperitoneal injections of bilirubin (30 mg/kg) or potassium phosphate vehicle. Disease activity was monitored, peripheral blood counts and serum nitrate levels were determined, and intestinal specimens were analyzed for histological injury, leukocyte infiltration, and iNOS expression. The effect of bilirubin on IL-5 production by HSB-2 cells and on Jurkat cell transendothelial migration also was determined. DSS-treated mice that simultaneously received bilirubin lost less body weight, had lower serum nitrate levels, and exhibited reduced disease severity than vehicle-treated animals. Concordantly, histopathological analyses revealed that bilirubin-treated mice manifested significantly less colonic injury, including reduced infiltration of eosinophils, lymphocytes, and monocytes, and diminished iNOS expression. Bilirubin administration also was associated with decreased eosinophil and monocyte infiltration into the small intestine, with a corresponding increase in peripheral blood eosinophilia. Bilirubin prevented Jurkat migration but did not alter IL-5 production. In conclusion, bilirubin prevents DSS-induced colitis by inhibiting the migration of leukocytes across the vascular endothelium and by suppressing iNOS expression.

  14. A mismatch between the abnormalities in diffusion- and susceptibility-weighted magnetic resonance imaging may represent an acute ischemic penumbra with misery perfusion.

    PubMed

    Fujioka, Masayuki; Okuchi, Kazuo; Iwamura, Asami; Taoka, Toshiaki; Siesjö, Bo K

    2013-11-01

    Susceptibility-weighted imaging (SWI) has recently attracted attention for its ability to investigate acute stroke pathophysiology. SWI detects an increased ratio of deoxyhemoglobin to oxyhemoglobin in cerebral venous compartments, which can illustrate cerebral misery perfusion with a compensatory increase of oxygen extraction fraction in the hypoperfused brain. In this study we make the first case report of blunt cervical trauma leading to a stroke, demonstrating the disparity between diffusion-weighted imaging (DWI) and SWI changes, or DWI-SWI mismatch, in the acute ischemic brain. The area of mismatch between a smaller DWI cytotoxic edema and a larger SWI misery perfusion in our patient matured into a complete infarction with time. The DWI-SWI mismatch may signify the presence of an ischemic penumbra, and provide information about viability of the brain tissue at risk of potential infarction if without early reperfusion.

  15. Traditional Chinese Patent Medicine for Acute Ischemic Stroke: An Overview of Systematic Reviews Based on the GRADE Approach.

    PubMed

    Zhang, Xin; Liu, Xue-Ting; Kang, De-Ying

    2016-03-01

    The aim of the study is to conduct an overview of systematic reviews (SRs) to provide a contemporary review of the evidence for delivery of Traditional Chinese Patent Medicine (TCPMs) for patients with acute ischemic stroke.SRs were assessed for quality using the Assessment of Multiple Systematic Reviews (AMSTAR) tool and the Oxman-Guyatt Overview Quality Assessment Questionnaire (OQAQ). We assessed the quality of the evidence of high methodological quality (an AMSTAR score ≥9 or an OQAQ score ≥7) for reported outcomes using the GRADE (the Grading of Recommendations Assessment, Development and Evaluation) approach.(1) Dan Shen agents: tiny trends toward the improvement in different neurological outcomes (RR = 1.16, 1.10, 1.23, 1.08, 1.12); (2) Mailuoning: a tiny trend toward improvement in the neurological outcome (RR = 1.18); (3) Ginkgo biloba: tiny trends toward improvement in the neurological outcome (RR = 1.18, MD = 0.81); (4) Dengzhanhua: a tiny trend toward an improvement in neurological (RR = 1.23); (5) Acanthopanax: a small positive (RR = 1.17, 1.31) result on neurological improvement reported; (6) Chuanxiong-type preparations: neurological functional improved (MD = 2.90);(7) Puerarin: no better effect on the rate of death or disability (OR = 0.81, 95% CI 0.35-1.87); (8) Milk vetch: no better effect on the rate of death (OR = 0.66, 95% CI: 0.11-2.83);(9) Qingkailing: rate of death reduced (OR = 0.66, 95% CI: 0.11-2.83). Limitations in the methodological quality of the RCTs, inconsistency and imprecision led to downgrading of the quality of the evidence, which varied by review and by outcome. Consequently, there are currently only weak evidences to support those TCPMs.The 9 TCPMs may be effective in the treatment of acute ischemic stroke, as the GRADE approach indicated a weak recommendation for those TCPMs' usage.

  16. Immediate effects of scalp acupuncture with twirling reinforcing manipulation on hemiplegia following acute ischemic stroke: a hidden association study.

    PubMed

    Du, Xiao-Zheng; Bao, Chun-Ling; Dong, Gui-Rong; Yang, Xu-Ming

    2016-05-01

    Data mining has the potential to provide information for improving clinical acupuncture strategies by uncovering hidden rules between acupuncture manipulation and therapeutic effects in a data set. In this study, we performed acupuncture on 30 patients with hemiplegia due to acute ischemic stroke. All participants were pre-screened to ensure that they exhibited immediate responses to acupuncture. We used a twirling reinforcing acupuncture manipulation at the specific lines between the bilateral Baihui (GV20) and Taiyang (EX-HN5). We collected neurologic deficit score, simplified Fugl-Meyer assessment score, muscle strength of the proximal and distal hemiplegic limbs, ratio of the maximal H-reflex to the maximal M-wave (Hmax/Mmax), muscle tension at baseline and immediately after treatment, and the syndromes of traditional Chinese medicine at baseline. We then conducted data mining using an association algorithm and an artificial neural network backpropagation algorithm. We found that the twirling reinforcing manipulation had no obvious therapeutic difference in traditional Chinese medicine syndromes of "Deficiency and Excess". The change in the muscle strength of the upper distal and lower proximal limbs was one of the main factors affecting the immediate change in Fugl-Meyer scores. Additionally, we found a positive correlation between the muscle tension change of the upper limb and Hmax/Mmax immediate change, and both positive and negative correlations existed between the muscle tension change of the lower limb and immediate Hmax/Mmax change. Additionally, when the difference value of muscle tension for the upper and lower limbs was > 0 or < 0, the difference value of Hmax/Mmax was correspondingly positive or negative, indicating the scalp acupuncture has a bidirectional effect on muscle tension in hemiplegic limbs. Therefore, acupuncture with twirling reinforcing manipulation has distinct effects on acute ischemic stroke patients with different symptoms or

  17. Immediate effects of scalp acupuncture with twirling reinforcing manipulation on hemiplegia following acute ischemic stroke: a hidden association study.

    PubMed

    Du, Xiao-Zheng; Bao, Chun-Ling; Dong, Gui-Rong; Yang, Xu-Ming

    2016-05-01

    Data mining has the potential to provide information for improving clinical acupuncture strategies by uncovering hidden rules between acupuncture manipulation and therapeutic effects in a data set. In this study, we performed acupuncture on 30 patients with hemiplegia due to acute ischemic stroke. All participants were pre-screened to ensure that they exhibited immediate responses to acupuncture. We used a twirling reinforcing acupuncture manipulation at the specific lines between the bilateral Baihui (GV20) and Taiyang (EX-HN5). We collected neurologic deficit score, simplified Fugl-Meyer assessment score, muscle strength of the proximal and distal hemiplegic limbs, ratio of the maximal H-reflex to the maximal M-wave (Hmax/Mmax), muscle tension at baseline and immediately after treatment, and the syndromes of traditional Chinese medicine at baseline. We then conducted data mining using an association algorithm and an artificial neural network backpropagation algorithm. We found that the twirling reinforcing manipulation had no obvious therapeutic difference in traditional Chinese medicine syndromes of "Deficiency and Excess". The change in the muscle strength of the upper distal and lower proximal limbs was one of the main factors affecting the immediate change in Fugl-Meyer scores. Additionally, we found a positive correlation between the muscle tension change of the upper limb and Hmax/Mmax immediate change, and both positive and negative correlations existed between the muscle tension change of the lower limb and immediate Hmax/Mmax change. Additionally, when the difference value of muscle tension for the upper and lower limbs was > 0 or < 0, the difference value of Hmax/Mmax was correspondingly positive or negative, indicating the scalp acupuncture has a bidirectional effect on muscle tension in hemiplegic limbs. Therefore, acupuncture with twirling reinforcing manipulation has distinct effects on acute ischemic stroke patients with different symptoms or

  18. Traditional Chinese Patent Medicine for Acute Ischemic Stroke: An Overview of Systematic Reviews Based on the GRADE Approach.

    PubMed

    Zhang, Xin; Liu, Xue-Ting; Kang, De-Ying

    2016-03-01

    The aim of the study is to conduct an overview of systematic reviews (SRs) to provide a contemporary review of the evidence for delivery of Traditional Chinese Patent Medicine (TCPMs) for patients with acute ischemic stroke.SRs were assessed for quality using the Assessment of Multiple Systematic Reviews (AMSTAR) tool and the Oxman-Guyatt Overview Quality Assessment Questionnaire (OQAQ). We assessed the quality of the evidence of high methodological quality (an AMSTAR score ≥9 or an OQAQ score ≥7) for reported outcomes using the GRADE (the Grading of Recommendations Assessment, Development and Evaluation) approach.(1) Dan Shen agents: tiny trends toward the improvement in different neurological outcomes (RR = 1.16, 1.10, 1.23, 1.08, 1.12); (2) Mailuoning: a tiny trend toward improvement in the neurological outcome (RR = 1.18); (3) Ginkgo biloba: tiny trends toward improvement in the neurological outcome (RR = 1.18, MD = 0.81); (4) Dengzhanhua: a tiny trend toward an improvement in neurological (RR = 1.23); (5) Acanthopanax: a small positive (RR = 1.17, 1.31) result on neurological improvement reported; (6) Chuanxiong-type preparations: neurological functional improved (MD = 2.90);(7) Puerarin: no better effect on the rate of death or disability (OR = 0.81, 95% CI 0.35-1.87); (8) Milk vetch: no better effect on the rate of death (OR = 0.66, 95% CI: 0.11-2.83);(9) Qingkailing: rate of death reduced (OR = 0.66, 95% CI: 0.11-2.83). Limitations in the methodological quality of the RCTs, inconsistency and imprecision led to downgrading of the quality of the evidence, which varied by review and by outcome. Consequently, there are currently only weak evidences to support those TCPMs.The 9 TCPMs may be effective in the treatment of acute ischemic stroke, as the GRADE approach indicated a weak recommendation for those TCPMs' usage. PMID:27015174

  19. Immediate effects of scalp acupuncture with twirling reinforcing manipulation on hemiplegia following acute ischemic stroke: a hidden association study

    PubMed Central

    Du, Xiao-zheng; Bao, Chun-ling; Dong, Gui-rong; Yang, Xu-ming

    2016-01-01

    Data mining has the potential to provide information for improving clinical acupuncture strategies by uncovering hidden rules between acupuncture manipulation and therapeutic effects in a data set. In this study, we performed acupuncture on 30 patients with hemiplegia due to acute ischemic stroke. All participants were pre-screened to ensure that they exhibited immediate responses to acupuncture. We used a twirling reinforcing acupuncture manipulation at the specific lines between the bilateral Baihui (GV20) and Taiyang (EX-HN5). We collected neurologic deficit score, simplified Fugl-Meyer assessment score, muscle strength of the proximal and distal hemiplegic limbs, ratio of the maximal H-reflex to the maximal M-wave (Hmax/Mmax), muscle tension at baseline and immediately after treatment, and the syndromes of traditional Chinese medicine at baseline. We then conducted data mining using an association algorithm and an artificial neural network backpropagation algorithm. We found that the twirling reinforcing manipulation had no obvious therapeutic difference in traditional Chinese medicine syndromes of “Deficiency and Excess”. The change in the muscle strength of the upper distal and lower proximal limbs was one of the main factors affecting the immediate change in Fugl-Meyer scores. Additionally, we found a positive correlation between the muscle tension change of the upper limb and Hmax/Mmax immediate change, and both positive and negative correlations existed between the muscle tension change of the lower limb and immediate Hmax/Mmax change. Additionally, when the difference value of muscle tension for the upper and lower limbs was > 0 or < 0, the difference value of Hmax/Mmax was correspondingly positive or negative, indicating the scalp acupuncture has a bidirectional effect on muscle tension in hemiplegic limbs. Therefore, acupuncture with twirling reinforcing manipulation has distinct effects on acute ischemic stroke patients with different symptoms or

  20. Increased Epicardial Fat Thickness Correlates with Aortic Stiffness and N-Terminal Pro-Brain Natriuretic Peptide Levels in Acute Ischemic Stroke Patients.

    PubMed

    Altun, Ibrahim; Unal, Yasemin; Basaran, Ozcan; Akin, Fatih; Emir, Gulser Karadaban; Kutlu, Gulnihal; Biteker, Murat

    2016-06-01

    Epicardial fat, a metabolically active tissue, has emerged as a risk factor and active player in metabolic and cardiovascular diseases. We investigated epicardial fat thickness in patients who had sustained an acute ischemic stroke, and we evaluated the relationship of epicardial fat thickness with other prognostic factors. We enrolled 61 consecutive patients (age, ≥18 yr) who had sustained a first acute ischemic stroke and had been admitted to our hospital within 24 hours of the onset of stroke symptoms. The control group comprised 82 consecutive sex- and age-matched patients free of past or current stroke who had been admitted to our cardiology clinics. Blood samples were taken for measurement of N-terminal pro-brain natriuretic peptide (NT-proBNP) levels at admission. Aortic stiffness indices and epicardial fat thickness were measured by means of transthoracic echocardiography within the first 48 hours. In comparison with the control group, the patients with acute ischemic stroke had significantly higher epicardial fat thickness (4.8 ± 0.9 vs 3.8 ± 0.7 mm; P <0.001), lower aortic distensibility (2.5 ± 0.8 vs 3.4 ± 0.9 cm(2) ·dyn(-1); P <0.001) and lower aortic strain (5.5% ± 1.9% vs 6.4% ± 1.8%; P=0.003). We found a significant association between epicardial fat thickness, NT-proBNP levels, and arterial dysfunction in patients who had sustained acute ischemic stroke. Increased epicardial fat thickness might be a novel risk factor and might enable evaluation of subclinical target-organ damage in these patients.

  1. Increased Epicardial Fat Thickness Correlates with Aortic Stiffness and N-Terminal Pro-Brain Natriuretic Peptide Levels in Acute Ischemic Stroke Patients

    PubMed Central

    Unal, Yasemin; Basaran, Ozcan; Akin, Fatih; Emir, Gulser Karadaban; Kutlu, Gulnihal; Biteker, Murat

    2016-01-01

    Epicardial fat, a metabolically active tissue, has emerged as a risk factor and active player in metabolic and cardiovascular diseases. We investigated epicardial fat thickness in patients who had sustained an acute ischemic stroke, and we evaluated the relationship of epicardial fat thickness with other prognostic factors. We enrolled 61 consecutive patients (age, ≥18 yr) who had sustained a first acute ischemic stroke and had been admitted to our hospital within 24 hours of the onset of stroke symptoms. The control group comprised 82 consecutive sex- and age-matched patients free of past or current stroke who had been admitted to our cardiology clinics. Blood samples were taken for measurement of N-terminal pro-brain natriuretic peptide (NT-proBNP) levels at admission. Aortic stiffness indices and epicardial fat thickness were measured by means of transthoracic echocardiography within the first 48 hours. In comparison with the control group, the patients with acute ischemic stroke had significantly higher epicardial fat thickness (4.8 ± 0.9 vs 3.8 ± 0.7 mm; P <0.001), lower aortic distensibility (2.5 ± 0.8 vs 3.4 ± 0.9 cm2·dyn−1; P <0.001) and lower aortic strain (5.5% ± 1.9% vs 6.4% ± 1.8%; P=0.003). We found a significant association between epicardial fat thickness, NT-proBNP levels, and arterial dysfunction in patients who had sustained acute ischemic stroke. Increased epicardial fat thickness might be a novel risk factor and might enable evaluation of subclinical target-organ damage in these patients. PMID:27303237

  2. Diffusion-weighted imaging–fluid-attenuated inversion recovery mismatch is associated with better neurologic response to intravenous thrombolytic therapy in acute ischemic stroke patients

    PubMed Central

    Jeong, Jong Yeong; Han, Sang Kuk; Shin, Dong Hyuk; Na, Ji Ung; Lee, Hyun Jung; Choi, Pil Cho; Lee, Jeong Hun

    2015-01-01

    Objective To investigate differences in the effect of intravenous (IV) thrombolysis regarding the mismatch of diffusion-weighted imaging–fluid-attenuated inversion recovery (DWI-FLAIR) among acute ischemic stroke patients who visited the emergency department (ED) within 3 hours from the onset of symptoms. Methods Among ED patients presenting with an acute ischemic stroke between January 2011 and May 2013 at a tertiary hospital, those who underwent magnetic resonance imaging before IV thrombolytic therapy were included in this retrospective study. Patients were divided into DWI-FLAIR mismatch and match groups. National Institutes of Health Stroke Scale (NIHSS) scores obtained initially, 24 hours after thrombolytic therapy, and on discharge, and early neurologic improvement (ENI) and major neurologic improvement (MNI) were compared. Results During the study period, 50 of the 213 acute ischemic stroke patients who presented to the ED were included. The DWI-FLAIR mismatch group showed a statistically significantly greater reduction in NIHSS both at 24 hours after thrombolytic therapy and upon discharge than did the match group (5.5 vs. 1.2, P<0.001; 6.0 vs. 2.3, P<0.01, respectively). Moreover, ENI and MNI were significantly greater for the DWI-FLAIR mismatch group than for the match group (27/36 vs. 2/14, P<0.001; 12/36 vs. 0/14, P=0.012, respectively). Conclusion Among acute ischemic stroke patients who visited the ED within 3 hours from the onset of symptoms, patients who showed DWI-FLAIR mismatch showed a significantly better response to IV thrombolytic therapy than did the DWI-FLAIR match group in terms of neurologic outcome.

  3. Inhibition of Notch signaling by Dll4-Fc promotes reperfusion of acutely ischemic tissues

    SciTech Connect

    Liu, Ren; Trindade, Alexandre; Sun, Zhanfeng; Kumar, Ram; Weaver, Fred A.; Krasnoperov, Valery; Naga, Kranthi; Duarte, Antonio; Gill, Parkash S.

    2012-02-03

    Highlights: Black-Right-Pointing-Pointer Low dose Dll4-Fc increases vascular proliferation and overall perfusion. Black-Right-Pointing-Pointer Low dose Dll4-Fc helps vascular injury recovery in hindlimb ischemia model. Black-Right-Pointing-Pointer Low dose Dll4-Fc helps vascular injury recovery in skin flap model. Black-Right-Pointing-Pointer Dll4 heterozygous deletion promotes vascular injury recovery. Black-Right-Pointing-Pointer Dll4 overexpression delays vascular injury recovery. -- Abstract: Notch pathway regulates vessel development and maturation. Dll4, a high-affinity ligand for Notch, is expressed predominantly in the arterial endothelium and is induced by hypoxia among other factors. Inhibition of Dll4 has paradoxical effects of reducing the maturation and perfusion in newly forming vessels while increasing the density of vessels. We hypothesized that partial and/or intermittent inhibition of Dll4 may lead to increased vascular response and still allow vascular maturation to occur. Thus tissue perfusion can be restored rapidly, allowing quicker recovery from ischemia or tissue injury. Our studies in two different models (hindlimb ischemia and skin flap) show that inhibition of Dll4 at low dose allows faster recovery from vascular and tissue injury. This opens a new possibility for Dll4 blockade's therapeutic application in promoting recovery from vascular injury and restoring blood supply to ischemic tissues.

  4. Effect of Cardioembolic Etiology on Intravenous Thrombolysis Efficacy for Acute Ischemic Stroke.

    PubMed

    Anticoli, Sabrina; Bravi, Maria Cristina; Perillo, Giovanni; Siniscalchi, Antonio; Pozzessere, Claudio; Pezzella, Francesca Romana; Tanzi, Piero; Gallelli, Luca; Cartoni, Domenico

    2016-01-01

    Previous clinical studies suggest that intravenous (IV) recombinant tissue plasminogen activator (rt-PA) benefits stroke patients regardless of the underlying etiology. In this study, we assessed the possible differences in response to IV rt-PA between cardioembolic stroke and other stroke subtypes. A total of 303 consecutive stroke ischemic patients (from January 2005 to April 2014) admitted to our Stroke Unit and treated with IV rt-PA were retrospectively reviewed. All patients were classified in two groups: Cardioembolic (CE) and Non-Cardioembolic (NCE). We analyzed a total of 303 patients. Thirty patients died in the first hours after fibrinolysis and no statistically significant differences were found in two groups (14 CE vs 18 N-CE). We observed a significant differences in clinical outcome in terms of symptoms "improvement" (p< 0.01 .2) and symptoms" regression" (p<0.057 .2) even if this last result did not reach statistical significance in CE patients respect to N-CE patients. In conclusion, the intravenous fibrinolysis is more effective in CE group than in N-CE regarding symptoms "improvement" and the PFO-Stroke patients treated with fibrinolysis have better outcome than other patients and they have high rate of symptoms" regression". Moreover the main predictor of good outcomes were younger age and milder stroke severity on hospital admission. PMID:27149937

  5. Phase IIB/III Trial of Tenecteplase in Acute Ischemic Stroke: Results of a Prematurely Terminated Randomized Clinical Trial

    PubMed Central

    Haley, E. Clarke; Thompson, John L.P.; Grotta, James C.; Lyden, Patrick D.; Hemmen, Thomas G.; Brown, Devin L.; Fanale, Christopher; Libman, Richard; Kwiatkowski, Thomas G.; Llinas, Rafael H.; Levine, Steven R.; Johnston, Karen C.; Buchsbaum, Richard; Levy, Gilberto; Levin, Bruce

    2010-01-01

    Background: Intravenous alteplase (rt-PA) remains the only approved treatment for acute ischemic stroke, but its use remains limited. In a previous pilot dose-escalation study, intravenous tenecteplase showed promise as a potentially safer alternative. Therefore, a Phase IIB clinical trial was begun to a) choose a best dose of tenecteplase to carry forward, and b) to provide evidence for either promise or futility of further testing of tenecteplase versus rt-PA. If promise was established, then the trial would continue as a Phase III efficacy trial comparing the selected tenecteplase dose to standard rt-PA. Methods: The trial began as a small, multi-center, randomized, double-blind, controlled clinical trial comparing 0.1, 0.25, and 0.4 mg/kg tenecteplase with standard 0.9 mg/kg rt-PA in patients with acute stroke within 3 hours of onset. An adaptive sequential design used an early (24 hour) assessment of major neurological improvement balanced against occurrence of symptomatic intracranial hemorrhage (ICH) to choose a “best” dose of tenecteplase to carry forward. Once a “best” dose was established, the trial was to continue until at least 100 pairs of the selected tenecteplase dose versus standard rt-PA could be compared by 3 month outcome using the modified Rankin Scale in an interim analysis. Decision rules were devised to yield a clear recommendation to either stop for futility or to continue into Phase III. Results: The trial was prematurely terminated for slow enrollment after only 112 patients had been randomized at 8 clinical centers between 2006 and 2008. The 0.4 mg/kg dose was discarded as inferior after only 73 patients were randomized, but the selection procedure was still unable to distinguish between 0.1 mg/kg and 0.25 mg/kg as a propitious dose at the time the trial was stopped. There were no statistically persuasive differences in 3 month outcomes between the remaining tenecteplase groups and rt-PA. Symptomatic ICH rates were highest in the

  6. Biological Signatures of Brain Damage Associated with High Serum Ferritin Levels in Patients with Acute Ischemic Stroke and Thrombolytic Treatment

    PubMed Central

    Millán, Mónica; Sobrino, Tomás; Arenillas, Juan Francisco; Rodríguez-Yáñez, Manuel; García, María; Nombela, Florentino; Castellanos, Mar; de la Ossa, Natalia Pérez; Cuadras, Patricia; Serena, Joaquín; Castillo, José; Dávalos, Antoni

    2008-01-01

    Background and purpose: Increased body iron stores have been related to greater oxidative stress and brain injury in clinical and experimental cerebral ischemia and reperfusion. We aimed to investigate the biological signatures of excitotoxicity, inflammation and blood brain barrier disruption potentially associated with high serum ferritin levels-related damage in acute stroke patients treated with i.v. t-PA. Methods: Serum levels of ferritin (as index of increased cellular iron stores), glutamate, interleukin-6, matrix metalloproteinase-9 and cellular fibronectin were determined in 134 patients treated with i.v. t-PA within 3 hours from stroke onset in blood samples obtained before t-PA treatment, at 24 and 72 hours. Results: Serum ferritin levels before t-PA infusion correlated to glutamate (r = 0.59, p < 0.001) and interleukin-6 (r = 0.55, p <0.001) levels at baseline, and with glutamate (r = 0.57,p <0.001), interleukin-6 (r = 0.49,p <0.001), metalloproteinase-9 (r = 0.23, p = 0.007) and cellular fibronectin (r = 0.27, p = 0.002) levels measured at 24 hours and glutamate (r = 0.415, p < 0.001), interleukin-6 (r = 0.359, p < 0.001) and metalloproteinase-9 (r = 0.261, p = 0.004) at 72 hours. The association between ferritin and glutamate levels remained after adjustment for confounding factors in generalized linear models. Conclusions: Brain damage associated with increased iron stores in acute ischemic stroke patients treated with iv. tPA may be mediated by mechanisms linked to excitotoxic damage. The role of inflammation, blood brain barrier disruption and oxidative stress in this condition needs further research. PMID:19096131

  7. Improvement of the microcirculation in the acute ischemic rat limb during intravenous infusion of drag-reducing polymers.

    PubMed

    Hu, Feng; Zha, Daogang; Du, Rongsheng; Chen, Xianghui; Zhou, Bingjie; Xiu, Jiancheng; Bin, Jianping; Liu, Yili

    2011-01-01

    Drag-reducing polymers (DRPs) are blood-soluble macromolecules that can increase blood flow and reduce vascular resistance. The purpose of the present study is to examine the effects of DRPs on microcirculation in rat hind limb during acute femoral artery occlusion. Two groups of 20 male Wistar rats were subjected to either hemodynamic measurement or contrast enhanced ultrasound (CEU) imaging during peripheral ischemia. Both groups were further subdivided into a DRP-treated group or a saline-treated group. Polyethylene oxide (PEO) was chosen as the test DRP, and rats were injected with either 10 ppm PEO solution or saline through the caudal vein at a constant rate of 5 ml/h for 20 min. Abdominal aortic flow, iliac artery pressure, iliac vein pressure, heart rate, carotid artery pressure and central venous pressure (CVP) were monitored, and vascular resistance was calculated by (iliac artery pressure-iliac vein pressure)/abdominal aortic blood flow. Flow perfusion and capillary volume of skeletal muscle were measured by CEU. During PEO infusion, abdominal aortic blood flow increased (p<0.001) and vascular resistance decreased (p<0.001) compared to rats that received saline during peripheral ischemia. There was no significant change in ischemic skeletal capillary volume (A) with DRP treatment (p>0.05), but red blood cell velocity (β) and capillary blood flow (A×β) increased significantly (p<0.05) during PEO infusion. In addition, A, β and A×β all increased (p<0.05) in the contralateral hind limb muscle. In contrast, PEO had no significant influence on heart rate, mean carotid artery blood pressure or CVP. Intravenous infusion of drag reducing polymers may offer a novel hydrodynamic approach for improving microcirculation during acute peripheral ischemia.

  8. Current perspectives on the use of intravenous recombinant tissue plasminogen activator (tPA) for treatment of acute ischemic stroke

    PubMed Central

    Chapman, Sherita N; Mehndiratta, Prachi; Johansen, Michelle C; McMurry, Timothy L; Johnston, Karen C; Southerland, Andrew M

    2014-01-01

    In 1995, the NINDS (National Institute of Neurological Disorders and Stroke) tPA (tissue plasminogen activator) Stroke Study Group published the results of a large multicenter clinical trial demonstrating efficacy of intravenous tPA by revealing a 30% relative risk reduction (absolute risk reduction 11%–15%) compared with placebo at 90 days in the likelihood of having minimal or no disability. Since approval in 1996, tPA remains the only drug treatment for acute ischemic stroke approved by the US Food and Drug Administration. Over the years, an abundance of research and clinical data has supported the safe and efficacious use of intravenous tPA in all eligible patients. Despite such supporting data, it remains substantially underutilized. Challenges to the utilization of tPA include narrow eligibility and treatment windows, risk of symptomatic intracerebral hemorrhage, perceived lack of efficacy in certain high-risk subgroups, and a limited pool of neurological and stroke expertise in the community. With recent US census data suggesting annual stroke incidence will more than double by 2050, better education and consensus among both the medical and lay public are necessary to optimize the use of tPA for all eligible stroke patients. Ongoing and future research should continue to improve upon the efficacy of tPA through more rapid stroke diagnosis and treatment, refinement of advanced neuroimaging and stroke biomarkers, and successful demonstration of alternative means of reperfusion. PMID:24591838

  9. Desmoteplase for Acute Ischemic Stroke within 3 to 9 Hours after Symptom Onset: Evidence from Randomized Controlled Trials

    PubMed Central

    Shi, Ligen; Liang, Feng; Li, Yunping; Shao, Anwen; Zhou, Keren; Yu, Jun; Zhang, Jianmin

    2016-01-01

    Recent studies have shown inconsistent results regarding the value of desmoteplase for treating acute ischemic stroke (AIS) when administered within an extended time window. We performed a meta-analysis to explore the value of desmoteplase in AIS treatment. The MEDLINE, EMBASE, and Cochrane Library databases were searched for randomized controlled trials (RCTs) that had evaluated desmoteplase versus placebo for AIS. The primary outcomes were intracranial hemorrhage (ICH) within 72 hours and favorable outcome at Day 90. We pooled 819 patients from 5 RCTs. Desmoteplase treatment showed a neutral effect on favorable outcome (P = 0.42) but a favorable safety profile in terms of ICH (P = 0.64) compared with the placebo group. In the subgroup analysis, 90 μg/kg desmoteplase, a late time to treatment (6–9 hours), and serious stroke symptoms at baseline (NIHSS > 12) subgroups showed high risks of ICH (P ≤ 0.02). A high dose of desmoteplase (125 μg/kg) showed a tendency to improve recanalization (P = 0.05), but was also associated with an increased risk of death (P = 0.04). In conclusion, desmoteplase administered over an extended time window had no significant effect on functional recovery but exhibited a favorable safety profile in patients with AIS. PMID:27671010

  10. Machine Learning for Outcome Prediction of Acute Ischemic Stroke Post Intra-Arterial Therapy

    PubMed Central

    Asadi, Hamed; Dowling, Richard; Yan, Bernard; Mitchell, Peter

    2014-01-01

    Introduction Stroke is a major cause of death and disability. Accurately predicting stroke outcome from a set of predictive variables may identify high-risk patients and guide treatment approaches, leading to decreased morbidity. Logistic regression models allow for the identification and validation of predictive variables. However, advanced machine learning algorithms offer an alternative, in particular, for large-scale multi-institutional data, with the advantage of easily incorporating newly available data to improve prediction performance. Our aim was to design and compare different machine learning methods, capable of predicting the outcome of endovascular intervention in acute anterior circulation ischaemic stroke. Method We conducted a retrospective study of a prospectively collected database of acute ischaemic stroke treated by endovascular intervention. Using SPSS®, MATLAB®, and Rapidminer®, classical statistics as well as artificial neural network and support vector algorithms were applied to design a supervised machine capable of classifying these predictors into potential good and poor outcomes. These algorithms were trained, validated and tested using randomly divided data. Results We included 107 consecutive acute anterior circulation ischaemic stroke patients treated by endovascular technique. Sixty-six were male and the mean age of 65.3. All the available demographic, procedural and clinical factors were included into the models. The final confusion matrix of the neural network, demonstrated an overall congruency of ∼80% between the target and output classes, with favourable receiving operative characteristics. However, after optimisation, the support vector machine had a relatively better performance, with a root mean squared error of 2.064 (SD: ±0.408). Discussion We showed promising accuracy of outcome prediction, using supervised machine learning algorithms, with potential for incorporation of larger multicenter datasets, likely further

  11. Thrombectomy assisted by carotid stenting in acute ischemic stroke management: benefits and harms.

    PubMed

    Steglich-Arnholm, Henrik; Holtmannspötter, Markus; Kondziella, Daniel; Wagner, Aase; Stavngaard, Trine; Cronqvist, Mats E; Hansen, Klaus; Højgaard, Joan; Taudorf, Sarah; Krieger, Derk Wolfgang

    2015-12-01

    Extracranial carotid artery occlusion or high-grade stenosis with concomitant intracranial embolism causes severe ischemic stroke and shows poor response rates to intravenous thrombolysis (IVT). Endovascular therapy (EVT) utilizing thrombectomy assisted by carotid stenting was long considered risky because of procedural complexities and necessity of potent platelet inhibition-in particular following IVT. This study assesses the benefits and harms of thrombectomy assisted by carotid stenting and identifies factors associated with clinical outcome and procedural complications. Retrospective single-center analysis of 47 consecutive stroke patients with carotid occlusion or high-grade stenosis and concomitant intracranial embolus treated between September 2011 and December 2014. Benefits included early improvement of stroke severity (NIHSS ≥ 10) or complete remission within 72 h and favorable long-term outcome (mRS ≤ 2). Harms included complications during and following EVT. Mean age was 64.3 years (standard deviation ±12.5), 40 (85%) patients received IVT initially. Median NIHSS was 16 (inter-quartile range 14-19). Mean time from stroke onset to recanalization was 311 min (standard deviation ±78.0). Early clinical improvement was detected in 22 (46%) patients. Favorable outcome at 3 months occurred in 32 (68%) patients. Expedited patient management was associated with favorable clinical outcome. Two (4%) patients experienced symptomatic hemorrhage. Eight (17%) patients experienced stent thrombosis. Four (9%) patients died. Thrombectomy assisted by carotid stenting seems beneficial and reasonably safe with a promising rate of favorable outcome. Nevertheless, adverse events and complications call for additional clinical investigations prior to recommendation as clinical standard. Expeditious patient management is central to achieve good clinical outcome. PMID:26345413

  12. Factors Associated with Early Hospital Arrival in Patients with Acute Ischemic Stroke

    PubMed Central

    Song, Dongbeom; Tanaka, Eijirou; Lee, Kijeong; Sato, Shoichiro; Koga, Masatoshi; Kim, Young Dae; Nagatsuka, Kazuyuki; Toyoda, Kazunori

    2015-01-01

    Background and Purpose Factors associated with early arrival may vary according to the characteristics of the hospital. We investigated the factors associated with early hospital arrival in two different stroke centers located in Korea and Japan. Methods Consecutive patients with ischemic stroke arrived hospital within 48 hours of onset between January 2011 and December 2012 were identified and the clinical and time variables were retrieved from the prospective stroke registries of Severance Hospital of Yonsei University Health System (YUHS; Seoul, Korea) and National Cerebral and Cardiovascular Center (NCVC; Osaka, Japan). Subjects were dichotomized into early (time from onset to arrival ≤4.5 hours) and late (>4.5 hours) arrival groups. Univariate and multivariate analyses were performed to evaluate factors associated with early hospital arrival. Results A total of 1,966 subjects (992 from YUHS; 974 from NCVC) were included in this study. The median time from onset to arrival was 6.1 hours [interquartile range, 1.7-17.8 hours]. In multivariate analysis, the factors associated with early arrival were atrial fibrillation (Odds ratio [OR], 1.505; 95% confidence interval [CI], [1.168-1.939]), higher initial National Institute of Health Stroke Scale scores (OR, 1.037; 95% CI [1.023-1.051]), onset during daytime (OR, 2.799; 95% CI [2.173-3.605]), and transport by an emergency medical service (OR, 2.127; 95% CI [1.700-2.661]). These factors were consistently associated with early arrival in both hospitals. Conclusions Despite differences between the hospitals, there were common factors related to early arrival. Efforts to identify and modify these factors may promote early hospital arrival and improve stroke outcome. PMID:26060803

  13. Factors Associated with In-Hospital Delay in Intravenous Thrombolysis for Acute Ischemic Stroke: Lessons from China.

    PubMed

    Huang, Qiang; Ma, Qing-feng; Feng, Juan; Cheng, Wei-yang; Jia, Jian-ping; Song, Hai-qing; Chang, Hong; Wu, Jian

    2015-01-01

    In-hospital delay reduces the benefit of intravenous thrombolysis (IVT) in acute ischemic stroke (AIS), while factors affecting in-hospital delay are less well known in Chinese. We are aiming at determining the specific factors associated with in-hospital delay through a hospital based cohort. In-hospital delay was defined as door-to-needle time (DTN) ≥60 min (standard delay criteria) or ≥75% percentile of all DTNs (severe delay criteria). Demographic data, time intervals [onset-to-door time (OTD), DTN, door-to-examination time (DTE), door-to-imaging time (DTI), door-to-laboratory time (DTL) and final-test-to-needle time (FTN, the time interval between the time obtaining the result of the last screening test and the needle time)], medical history and additional variables were calculated using Mann-Whitney U or Pearson Chi-Square tests for group comparison, and multivariate linear regression analysis was performed to identify independent variables of in-hospital delay. A total of 202 IVT cases were enrolled. The median age was 61 years and 25.2% were female. The cutoff points for the upper quartile of DTN (severe delay criteria) was 135 min.When compared with the reference group without in-hospital delay, older age, shorter OTD and less referral were found in the standard delay group and male sex, presence with transient ischemic attacks or rapidly improving symptom, and with multi-model CT imaging were more frequent in the severe delay group. In the multivariate linear regression analysis, FTN (P<0.001) and DTL (P = 0.002) were significantly associated with standard delay; while DTE (P = 0.005), DTI (P = 0.033), DTL (P<0.001), and FTN (P<0.001) were positively associated with severe delay. There was not a significant change in the trend of DTNs during the study period (P = 0.054). In-hospital delay was due to multifactors in China, in which time delays of decision-making process and laboratory tests contributed the most. Efforts aiming at reducing the delay

  14. Remote Ischemic Preconditioning for the Prevention of Contrast-Induced Acute Kidney Injury in Diabetics Receiving Elective Percutaneous Coronary Intervention

    PubMed Central

    Balbir Singh, Gillian; Ann, Soe Hee; Park, Jongha; Chung, Hyun Chul; Lee, Jong Soo; Kim, Eun-Sook; Choi, Jung Il; Lee, Jiho; Kim, Shin-Jae; Shin, Eun-Seok

    2016-01-01

    Objective Remote ischemic preconditioning (RIPC) induces transient episodes of ischemia by the occlusion of blood flow in non-target tissue, before a subsequent ischemia-reperfusion injury. When RIPC is applied before percutaneous coronary intervention (PCI), the kidneys may be protected against ischemia-reperfusion injury and subsequently contrast-induced acute kidney injury (CI-AKI). The aim of this study was to evaluate the efficacy of RIPC for the prevention of CI-AKI in patients with diabetes with pre-existing chronic kidney disease (CKD) undergoing elective PCI. Methods This randomized, double-blind, sham-controlled study enrolled patients with diabetes scheduled for elective PCI with eGFR ≤60 ml/min/1.73 m2 or urinary albumin creatinine ratio of >300 mg/g to receive either RIPC or the sham ischemic preconditioning. Results One hundred and two patients (68.9 ± 8.2 years old, 47.1% men) were included. Baseline eGFR, creatinine and serum NGAL was similar between RIPC and control groups (48.5 ± 12 ml/min vs. 46.6 ± 10 ml/min, p = 0.391; 1.42 ± 0.58 mg/dl vs. 1.41 ± 0.34 mg/dl, p = 0.924; and 136.0 ± 45.0 ng/ml vs. 137.6 ± 43.3 ng/ml, p = 0.961, respectively). CI-AKI occurred in 13.7% (14/102) of the total subjects, with both RIPC and control groups having an equal incidence of 13.7% (7/51). No significant differences were seen in creatinine, NGAL, cardiac enzymes (troponin T, CKMB) and hs-CRP between the groups post-procedure. Conclusions In this study, RIPC applied prior to elective PCI was not effective in preventing CI-AKI in patients with diabetes with pre-existing CKD. Trial Registration ClinicalTrials.gov NCT02329444 PMID:27723839

  15. Short Door-to-Needle Times in Acute Ischemic Stroke and Prospective Identification of Its Delaying Factors

    PubMed Central

    Van Schaik, Sander M.; Scott, Saskia; de Lau, Lonneke M.L.; Van den Berg-Vos, Renske M.; Kruyt, Nyika D.

    2015-01-01

    Background The clinical benefit of intravenous thrombolysis (IVT) in acute ischemic stroke is time dependent. Several studies report a short median door-to-needle time (DNT; 20 min), mainly in large tertiary referral hospitals equipped with a level 1 emergency department, a dedicated stroke team available 24/7, and on-site neuroimaging facilities. Meanwhile, in daily practice, the majority of stroke patients are admitted to secondary care hospitals, and in practice, even the generous benchmark of the American Heart Association (a DNT of 60 min in >80% of the cases) is met for a minority of patients treated with IVT. The first objective of our study was to investigate if, in a secondary care teaching hospital rather than a tertiary referral hospital, similar short DNTs can be accomplished with an optimized IVT protocol. Our second objective was to prospectively identify factors that delay the DNT in this setting. Methods A multicenter, consecutive cohort study of patients treated with IVT in one of two secondary care teaching hospitals. In both hospitals, data of consecutive stroke patients as well as median DNTs and factors delaying this were prospectively assessed for each patient. Multivariable logistic regression analysis was used to evaluate associations between patient-related and logistic factors with a delayed (i.e. exceeding 30 min) DNT. Results In total, 1,756 patients were admitted for ischemic stroke during the study period. Out of these, 334 (19.0%) patients were treated with IVT. The median DNT was 25 min (interquartile range: 20-35). A total of 71% (n = 238) had a DNT below 30 min. In 63% of the patients treated with IVT the DNT was delayed by at least one factor. Patients without any delaying factor had a 10 min shorter median DNT compared to patients with at least one delaying factor (p < 0.001). The following factors were independently associated with a delayed DNT: uncertainty about symptom onset, uncontrolled blood pressure, fluctuating

  16. Transient ischemic cerebral lesions during induction chemotherapy for acute lymphoblastic leukemia.

    PubMed

    Pihko, H; Tyni, T; Virkola, K; Valanne, L; Sainio, K; Hovi, L; Saarinen, U M

    1993-11-01

    Ninety children were treated for acute lymphoblastic leukemia or non-Hodgkin lymphoma during 1986 through 1992 in the Children's Hospital, University of Helsinki, in Finland. During induction chemotherapy, nine of the children had visual hallucinations progressing to confusion and seizure. The symptoms were often preceded by severe constipation and significantly elevated blood pressure. Neuroradiologic examinations showed bilateral cortical or subcortical white matter lesions. Despite the stroke like manifestations, the lesions were reversible. The triangular shape and location of the lesions in the watershed areas between the major cerebral arteries suggest vascular ischemia as the cause.

  17. Anomalous equivalent potential temperature: an atmospheric feature predicting days with higher risk for fatal outcome in acute ischemic stroke-a preliminary study.

    PubMed

    Folyovich, András; Biczó, Dávid; Al-Muhanna, Nadim; Béres-Molnár, Anna K; Fejős, Ádám; Pintér, Ádám; Bereczki, Dániel; Fischer, Antal; Vadasdi, Károly; Pintér, Ferenc

    2015-09-01

    Acute stroke is a life-threatening condition. Fatal outcome is related to risk factors, some of these affected by climatic changes. Forecasting potentially harmful atmospheric processes may therefore be of practical importance in the acute care of stroke patients. We analyzed the history of all patients with acute ischemic stroke (N = 184) confirmed by neuroimaging including those who died (N = 35, 15 males) at our hospital department in the winter months of 2009. Patient data were anonymized, and the human meteorologists were only aware of patients' age, gender, and exact time of death. Of the meteorological parameters, equivalent potential temperature (EPT) has been chosen for analysis. EPT is generally used for forecasting thunderstorms, but in the case of synoptic scale airflow (10(6) m), it is suitable for characterizing the air mass inflowing from different regions. The behavior of measured EPT values was compared to the climatic (30 years) averages. We developed meteorological criteria for anomalous periods of EPT and tested if such periods are associated with higher rate of fatal outcome. The duration of anomalous and non-anomalous periods was nearly equal during the studied 3 months. Stroke onset distributed similarly between anomalous and non-anomalous days; however, of the 35 deaths, 27 occurred during anomalous periods: on average, 0.56 deaths occurred on anomalous days and 0.19 on non-anomalous days. Winter periods meeting the criteria of anomalous EPT may have a significant adverse human-meteorological impact on the outcome in acute ischemic stroke.

  18. MDCT in ischaemic colitis: how to define the aetiology and acute, subacute and chronic phase of damage in the emergency setting.

    PubMed

    Berritto, Daniela; Iacobellis, Francesca; Mazzei, Maria Antonietta; Volterrani, Luca; Guglielmi, Giuseppe; Brunese, Luca; Grassi, Roberto

    2016-01-01

    Ischemic colitis (IC) is the most common vascular disorder of the gastrointestinal tract with a reported incidence of 6.1-44 cases/100,000 person years with confirmatory histopathology. However, the true incidence of IC poses some difficulty, and even vigilant clinicians with patients at high risk often miss the diagnosis, since clinical presentation is non-specific or could have a mild transient nature. Detection of IC results is crucial to plan the correct therapeutic approach and reduce the reported mortality rate (4-12%). Diagnosis of IC is based on a combination of clinical suspicion, radiological, endoscopic and histological findings. Some consider colonoscopy as a diagnostic test of choice; however, preparation is required and it is not without risk, above all in patients who are severely ill. There are two manifestations of vascular colonic insult: ischaemic and reperfusive. The first one occurs above all during ischaemic/non-occlusive mesenteric ischaemia; in this case, the colonic wall appears thinned with dilated lumen and fluid appears in the paracolic space. When reperfusion occurs, the large bowel wall appears thickened and stratified, because of subepithelial oedema and/or haemorrhage, with consequent lumen calibre reduction. Shaggy contour of the involved intestine and misty mesentery are associated with the pericolic fluid. The pericolic fluid results are a crucial finding for IC diagnosis since its evidence suggests the presence of an ongoing damage thus focusing the attention on other pathological aspects which could be otherwise misdiagnosed, such as thinned or thickened colonic wall. Moreover, the pericolic fluid may increase or decrease, depending on the evolution of the ischaemic damage, suggesting the decision of medical or surgical treatment. Radiologists should not forget the hypothesis of IC, being aware that multidetector CT could be sufficient to suggest the diagnosis of IC, allowing for early identification and grading definition, and

  19. [Cognitive disorders and its correction in the acute period of ischemic stroke].

    PubMed

    Prokopenko, S V; Mozheĭko, E Iu; Levin, O S; Koriagina, T D; Chernykh, T V; Berezovskaia, M A

    2012-01-01

    The efficiency of using of original stimulating programs for correction of memory decline, attention impairment and optical-spatial gnosis disorders was evaluated in 100 post stroke patients with the degree of cognitive decline from mild cognitive impairment to mild dementia in the acute period of stroke. In addition to traditional methods of treatment, we applied training using computer programs within 20-30 minutes daily 5 times a week during 14 days. Efficiency of treatment was measured by the MMSE, the FAB, the Clock drawing test, Shulte's tables and a letter correction test. After the treatment, the statistically significant improvement of cognitive functions was found in the group of patients receiving the correction with computer programs. PMID:23390653

  20. Mechanical thrombectomy with ‘ADAPT’ technique by transcervical access in acute ischemic stroke

    PubMed Central

    Remollo, Sebastian; García, Maria Rosa; Hidalgo, Cristina; Hernández-Perez, Maria; Ciorba, Mihaela

    2015-01-01

    Background The mechanical thrombectomy (MT) for endovascular clot retrieval has dramatically improved successful revascularization and clinical outcome in selected acute stroke patients. MT is typically performed via a transfemoral approach, but catheterization of the occluded vessel can be problematic in cases of extensive vessel tortuosity. We describe a case of MT with the ‘ADAPT’ technique by direct carotid access due to an inability to catheterize the ICA by a transfemoral approach for acute cerebral ischemia in the setting of left MCA occlusion. Excellent angiographic and good clinical results were obtained without any complications. Case report An 80-year-old woman was admitted with a stroke by occlusion of the left MCA, with an NIHSS: 11, and an ASPECT: 7 in the CT. Under sedation a transfemoral angiography was performed, but after multiple attempts, it was impossible to make a stable catheterization of the left CCA. A transcervical approach was pursued. With ultrasound guidance the CCA was catheterized. Using the ‘ADAPT’ technique, we performed a successful MT. Post-procedure angiography (at 14 minutes) demonstrated recanalization of the entire left MCA (TICI: 3), without complications. The carotid access point was closed with a percutaneous closure. Control TC at 24 h showed a slight hypodensity in the left lenticular nucleus, and loss of gray-white matter differentiation in the adjacent cortex. Neurologically, the patient presented with progressive improvement. At discharge, she had an NIHSS: 0, mRS: 0 and Barthel: 100. Conclusions MT by direct carotid access is an effective alternative technique in those cases where it is not accessible by a transfemoral approach. PMID:26443297

  1. Simulation training for emergency teams to manage acute ischemic stroke by telemedicine.

    PubMed

    Richard, Sébastien; Mione, Gioia; Varoqui, Claude; Vezain, Arnaud; Brunner, Arielle; Bracard, Serge; Debouverie, Marc; Braun, Marc

    2016-06-01

    Telemedicine contributes to initiating early intravenous recombinant tissue plasminogen activator (rt-PA) treatment for patients with acute cerebral infarction in areas without a stroke unit. However, the experience and skills of the emergency teams in the spokes to prepare patients and administer rt-PA treatment are ill-defined. Improving these skills could vastly improve management of acute stroke by telemedicine. We developed a medical simulation training model for emergency teams to perform intravenous rt-PA treatment in a telestroke system.From February 2013 to May 2015, 225 learners from 6 emergency teams included in the telestroke system "Virtuall"-in Lorrain (northeastern France)-received a standardized medical simulation training module to perform rt-PA treatment. All learners were assessed with the same pretraining and posttraining test consisting of 52 items. The percentage of right answers was determined for every learner before and after training.Median percentages of right answers were significantly higher in the posttraining test overall (82 ± 10 vs. 59 ± 13% pretraining; P < 0.001), but also in all professional subgroups: physicians (88 ± 8 vs. 67 ± 12%; P < 0.001), paramedical staff (80 ± 9 vs. 54 ± 12%; P < 0.001), nurses (80 ± 8 vs. 54 ± 12%; P < 0.001), and auxiliary nurses (76 ± 17 vs. 37 ± 15%; P = 0.002).We describe for the first time a training model for emergency teams in a telestroke system. We demonstrate significant gain in knowledge for all groups of healthcare professionals. This simulation model could be applied in any medical simulation center and form the basis of a standardized training program of spokes in a telestroke system. PMID:27311003

  2. Cardiac progenitor-derived exosomes protect ischemic myocardium from acute ischemia/reperfusion injury

    SciTech Connect

    Chen, Lijuan; Wang, Yingjie; Pan, Yaohua; Zhang, Lan; Shen, Chengxing; Qin, Gangjian; Ashraf, Muhammad; Weintraub, Neal; Ma, Genshan; Tang, Yaoliang

    2013-02-15

    Highlights: ► Cardiac progenitor-derived (CPC) Exosomes protect H9C2 from apoptosis in vitro. ► CPC-exosomes protect cardiomyoyctes from MI/R induced apoptosis in vivo. ► CPC-exosomes were taken up by H9C2 with high efficiency using PKH26 labeling. ► miR-451, one of GATA4-responsive miRNA cluster, is enriched in CPC-exosomes. -- Abstract: Background: Cardiac progenitors (CPC) mediate cardioprotection via paracrine effects. To date, most of studies focused on secreted paracrine proteins. Here we investigated the CPC-derived-exosomes on protecting myocardium from acute ischemia/reperfusion (MI/R) injury. Methods and results: CPC were isolated from mouse heart using two-step protocol. Exosomes were purified from conditional medium, and confirmed by electron micrograph and Western blot using CD63 as a marker. qRT-PCR shows that CPC-exosomes have high level expression of GATA4-responsive-miR-451. Exosomes were ex vivo labeled with PKH26, We observed exosomes can be uptaken by H9C2 cardiomyoblasts with high efficiency after 12 h incubation. CPC-exosomes protect H9C2 from oxidative stress by inhibiting caspase 3/7 activation invitro. In vivo delivery of CPC-exosomes in an acute mouse myocardial ischemia/reperfusion model inhibited cardiomyocyte apoptosis by about 53% in comparison with PBS control (p < 0.05). Conclusion: Our results suggest, for the first time, the CPC-exosomes can be used as a therapeutic vehicle for cardioprotection, and highlights a new perspective for using non-cell exosomes for cardiac disease.

  3. Mechanical Revascularization for Acute Ischemic Stroke: A Single-Center, Retrospective Analysis

    SciTech Connect

    Jeromel, Miran Milosevic, Z. V. Kocijancic, I. J. Lovric, D.; Svigelj, V. Zvan, B.

    2013-04-15

    BackgroundEndovascular mechanical revascularization (thrombectomy) is an increasingly used method for intracranial large vessel recanalization in acute stroke. The purpose of the study was to analyze the recanalization rate, clinical outcome, and complication rate in our stroke patients treated with mechanical revascularization. A total of 57 patients with large vessel stroke (within 3 h for anterior and 12 h for posterior circulation) were treated with mechanical revascularization at a single center during 24 months. The primary goal of endovascular treatment using different mechanical devices was recanalization of the occluded vessel. Recanalization rate (reported as thrombolysis in cerebral infarction [TICI] score), clinical outcome (reported as National Institutes of Health Stroke Scale [NIHSS] score and modified Rankin scale [mRS] score), as well as periprocedural complications were analyzed. The mean age of the patients was 63.1 {+-} 12.9 years, with baseline median NIHSS score of 14 (interquartile range, 9.5-19). Successful recanalization (TICI 2b or 3) was achieved in 41 (72 %) patients. Twenty patients (35 %) presented with favorable outcome (mRS {<=}2) 30 days after stroke. Overall, significant neurological improvement ({>=}4 NIHSS point reduction) occurred in 36 (63 %) patients. A clinically significant procedure-related adverse events (vessel disruption, peri/postprocedural intracranial bleeding) defined with decline in NIHSS of {>=}4 or death occurred in three (5 %) patients. The study showed a high recanalization rate with improved clinical outcome and a low rate of periprocedural complications in our stroke patients treated with mechanical revascularization. Therefore, we could conclude that endovascular revascularization (primary or in combination with a bridging thrombolysis) was an effective and safe procedure for intracranial large vessel recanalization in acute stroke.

  4. Simulation training for emergency teams to manage acute ischemic stroke by telemedicine

    PubMed Central

    Richard, Sébastien; Mione, Gioia; Varoqui, Claude; Vezain, Arnaud; Brunner, Arielle; Bracard, Serge; Debouverie, Marc; Braun, Marc

    2016-01-01

    Abstract Telemedicine contributes to initiating early intravenous recombinant tissue plasminogen activator (rt-PA) treatment for patients with acute cerebral infarction in areas without a stroke unit. However, the experience and skills of the emergency teams in the spokes to prepare patients and administer rt-PA treatment are ill-defined. Improving these skills could vastly improve management of acute stroke by telemedicine. We developed a medical simulation training model for emergency teams to perform intravenous rt-PA treatment in a telestroke system. From February 2013 to May 2015, 225 learners from 6 emergency teams included in the telestroke system “Virtuall”—in Lorrain (northeastern France)—received a standardized medical simulation training module to perform rt-PA treatment. All learners were assessed with the same pretraining and posttraining test consisting of 52 items. The percentage of right answers was determined for every learner before and after training. Median percentages of right answers were significantly higher in the posttraining test overall (82 ± 10 vs. 59 ± 13% pretraining; P < 0.001), but also in all professional subgroups: physicians (88 ± 8 vs. 67 ± 12%; P < 0.001), paramedical staff (80 ± 9 vs. 54 ± 12%; P < 0.001), nurses (80 ± 8 vs. 54 ± 12%; P < 0.001), and auxiliary nurses (76 ± 17 vs. 37 ± 15%; P = 0.002). We describe for the first time a training model for emergency teams in a telestroke system. We demonstrate significant gain in knowledge for all groups of healthcare professionals. This simulation model could be applied in any medical simulation center and form the basis of a standardized training program of spokes in a telestroke system. PMID:27311003

  5. Platelet aggregation but not activation and degranulation during the acute post-ischemic reperfusion phase in livers with no underlying disease

    PubMed Central

    van Golen, Rowan F.; Stevens, Katarzyna M.; Colarusso, Pina; Jaeschke, Hartmut; Heger, Michal

    2016-01-01

    Background Platelets and P-selectin (CD62P) play an unequivocal role in the pathology of hepatic ischemia/reperfusion (I/R) injury. Inhibition or knock-out of P-selectin or immunodepletion of platelets results in amelioration of post-ischemic inflammation, reduced hepatocellular damage, and improved survival. However, P-selectin expression on platelets and endothelial cells, which concurs with platelet activation, has never been clearly demonstrated in I/R-subjected livers. Aims To determine whether platelets become activated and degranulate in the acute phase of liver I/R and whether the platelets interact with neutrophils. Methods Hepatic I/R was induced in male C57BL/6J mice (N = 12) using 37.5-min ischemia time. Platelets, endothelial cells, and neutrophils were fluorescently labeled by systemic administration of non-blocking antibodies. Cell kinetics were monitored by intravital spinning disk confocal microscopy during 90 min of reperfusion. Image analysis and quantification was performed with dedicated software. Results Platelets adhered to sinusoids more extensively in post-ischemic livers compared to livers not subjected to I/R and formed aggregates, which occurred directly after ischemia. Platelets and endothelial cells did not express P-selectin in post-ischemic livers. There was no interaction between platelets and neutrophils. Conclusions Platelets aggregate but do not become activated and do not degranulate in post-ischemic livers. There is no platelet-neutrophil interplay during the early reperfusion phase in a moderate model of hepatic I/R injury. The mechanisms underlying the biological effects of platelets and P-selectin in this setting warrant further investigation. Relevance for patients I/R in surgical liver patients may compromise outcome due to post-ischemic oxidative stress and sterile inflammation. Both processes are mediated in part by platelets. Understanding platelet function during I/R is key to developing effective interventions for I

  6. Multimodal magnetic resonance imaging for assessing evolution of ischemic penumbra: a key translational medicine strategy to manage the risk of developing novel therapies for acute ischemic stroke.

    PubMed

    Chavez, Juan C; Zaleska, Margaret M; Wang, Xinkang; Wood, Andrew; Hurko, Orest; Pangalos, Menelas N; Feuerstein, Giora Z

    2009-01-01

    The implicit aim of neuroprotection is to rescue neurons within distressed but still viable tissue, thereby promoting functional recovery upon neuronal salvage. The clinical failure of this approach suggests that previous efforts to develop stroke therapies lacked means to predict success or futility in pre-clinical and early clinical studies. A key translational medicine strategy that can improve predictability relies on imaging methodologies to map the spatiotemporal evolution of the ischemic penumbra. This could serve as a biomarker indicative of neuroprotective potential and could increase likelihood of success in clinical studies by allowing selection of patients who are most likely to respond to therapy. PMID:18766199

  7. Acute Pre-operative Infarcts and Poor Cerebrovascular Reserve are Independent Risk Factors for Severe Ischemic Complications Following Direct Extracranial-Intracranial Bypass for Moyamoya Disease

    PubMed Central

    Pulling, T. Michael; Rosenberg, Jarrett; Marks, Michael P.; Steinberg, Gary K.; Zaharchuk, Greg

    2015-01-01

    Background and Purpose Severe ischemic changes are a rare but devastating complication following direct superficial temporal artery to middle cerebral artery (STA MCA) bypass in Moyamoya patients. This study was undertaken to determine whether pre-operative MR imaging and/or cerebrovascular reserve (CVR) assessment using reference standard stable xenon enhanced computed tomography (xeCT) could predict such complications. Materials and Methods Among all adult patients receiving direct bypass at our institution between 2005 and 2010 who received a clinically interpretable xeCT examination, we identified index cases (patients with >15 ml post-operative infarcts) and control cases (patients without post-operative infarcts and without transient or permanent ischemic symptoms). Differences between groups were evaluated using the Mann Whitney test. Univariate and multivariate generalized linear model regression were employed to test predictors of post-operative infarct. Results Six index cases were identified and compared with 25 controls. Infarct size in the index cases was 95±55 ml. Four of six index cases (67%), but no control patients, had pre-operative acute infarcts. Baseline CBF was similar, but CVR was significantly lower in the index cases compared with control cases. For example, in the anterior circulation, median CVR was 0.4% (range: −38.0% to 16.6%) in index vs. 26.3% (range: −8.2% to 60.5%) in control patients (p=0.003). Multivariate analysis demonstrated that the presence of a small pre-operative infarct (regardless of location) and impaired CVR were independent, significant predictors of severe post-operative ischemic injury. Conclusion Acute infarcts and impaired CVR on pre operative imaging are independent risk factors for severe ischemic complications following STA MCA bypass in Moyamoya disease. PMID:26564435

  8. Low ficolin-3 levels in early follow-up serum samples are associated with the severity and unfavorable outcome of acute ischemic stroke

    PubMed Central

    2011-01-01

    Background A number of data indicate that the lectin pathway of complement activation contributes to the pathophysiology of ischemic stroke. The lectin pathway may be triggered by the binding of mannose-binding lectin (MBL), ficolin-2 or ficolin-3 to different ligands. Although several papers demonstrated the significance of MBL in ischemic stroke, the role of ficolins has not been examined. Methods Sera were obtained within 12 hours after the onset of ischemic stroke (admission samples) and 3-4 days later (follow-up samples) from 65 patients. The control group comprised 100 healthy individuals and 135 patients with significant carotid stenosis (patient controls). The concentrations of ficolin-2 and ficolin-3, initiator molecules of the lectin complement pathway, were measured by ELISA methods. Concentration of C-reactive protein (CRP) was also determined by a particle-enhanced immunturbidimetric assay. Results Concentrations of both ficolin-2 and ficolin-3 were significantly (p < 0.001) decreased in both the admission and in the follow-up samples of patients with definite ischemic stroke as compared to healthy subjects. Concentrations of ficolin-2 and ficolin-3 were even higher in patient controls than in healthy subjects, indicating that the decreased levels in sera during the acute phase of stroke are related to the acute ischemic event. Ficolin-3 levels in the follow-up samples inversely correlated with the severity of stroke indicated by NIH scale on admission. In follow-up samples an inverse correlation was observed between ficolin-3 levels and concentration of S100β, an indicator of the size of cerebral infarct. Patients with low ficolin-3 levels and high CRP levels in the follow up samples had a significantly worse outcome (adjusted ORs 5.6 and 3.9, respectively) as measured by the modified Rankin scale compared to patients with higher ficolin-3 and lower CRP concentrations. High CRP concentrations were similarly predictive for worse outcome, and the

  9. Hepatic Sulfotransferase as a Nephropreventing Target by Suppression of the Uremic Toxin Indoxyl Sulfate Accumulation in Ischemic Acute Kidney Injury

    PubMed Central

    Saito, Hideyuki; Yoshimura, Misato; Saigo, Chika; Komori, Megumi; Nomura, Yui; Yamamoto, Yuko; Sagata, Masataka; Wakida, Ayaka; Chuman, Erina; Nishi, Kazuhiko; Jono, Hirofumi

    2014-01-01

    Ischemia/reperfusion (I/R)-induced acute kidney injury (AKI) is evoked by diverse pathophysiological conditions and/or surgical procedures. Here, we evaluated the nephropreventive effect of sulfotransferase (SULT) inhibitors, quercetin, and resveratrol, which hamper hepatic indoxyl sulfate (IS) production. I/R of the kidney caused severe renal injury with marked accumulation of serum and renal IS and urinary excretion of kidney injury molecule-1. Oral administration of AST-120 resulted in a significant restoration of kidney injury, suggesting that uremic toxins, which can be suppressed or adsorbed by AST-120 in the intestine, contribute to the progression or development of I/R-induced AKI. Oral administration of resveratrol or quercetin, SULT inhibitors, suppressed IS accumulation, accompanied by significant amelioration of renal dysfunction. The expression of nuclear factor E2-related factor 2 (Nrf2) in the renal nuclear fractions was markedly elevated by renal I/R, but suppressed by treatment with SULT inhibitors. IS is primarily taken up by HK-2 cells derived from human proximal tubular cells via organic anion transporters, which then evokes activation of Nrf2, most likely due to intracellular oxidative stress. Renal basolateral organic anion transporters OAT1 and OAT3, which mediate renal tubular uptake of IS in basolateral membrane, were markedly downregulated by renal I/R, but restored by SULT inhibitors. Our results suggest that renal accumulation of IS in ischemic AKI induces oxidative stress and downregulation of organic anion transporters resulting in kidney damage, which could be restored to some extent by inhibiting hepatic SULT activity as a nephropreventive target. PMID:24958931

  10. Presenting symptoms and onset-to-arrival time in patients with acute stroke and transient ischemic attack.

    PubMed

    Gargano, Julia Warner; Wehner, Susan; Reeves, Mathew J

    2011-11-01

    Delayed arrival to the emergency department (ED) precludes most stroke patients from receiving thrombolytic treatment. Our objective in this study was to examine the association between presenting symptoms and onset-to-arrival time (ie, time between onset of symptoms to arrival at the ED) in a statewide stroke registry. Demographics, clinical data, and presenting symptoms were collected for patients with acute stroke or symptomatic transient ischemic attack (TIA) admitted to 15 Michigan hospitals (n = 1922). Polytomous logistic regression models were developed to test the association between presenting symptoms and onset-to-arrival time (classified as <2 hours, 2-6 hours, or >6 hours/unknown). Onset-to-arrival time was <2 hours in 19% of the patients, 2-6 hours in 22%, and >6 hours/unknown in 59%. Unilateral symptoms (reported by 40%) and speech difficulties (reported by 22%) were associated with increased likelihood of arriving within 2 hours (unilateral: adjusted odds ratio [aOR], 1.5; 95% confidence interval [CI], 1.1-1.9; speech: aOR, 1.6; 95% CI, 1.2-2.2). Difficulty with walking, balance, or dizziness (12%), confusion (9%), loss of consciousness (6.7%) and falls (3.4%) were associated with lower likelihood of arriving within 2 hours (walking: aOR, 0.7; 95% CI, 0.4-1.0; confusion: aOR, 0.5; 95% CI, 0.3-0.8; consciousness: aOR, 0.5; 95% CI, 0.1-0.9; falls: aOR, 0.4; 95% CI, 0.3-0.9). Presenting symptoms were strongly associated with time of arrival; patients with unilateral symptoms and speech difficulties were more likely to seek care early. Future studies should consider including more specific patient-level data to identify psychosocial and behavioral aspects of recognition and action to stroke symptoms. PMID:20719538

  11. Association between i.v. thrombolysis volume and door-to-needle times in acute ischemic stroke.

    PubMed

    Groot, Adrien E; van Schaik, Ivo N; Visser, Marieke C; Nederkoorn, Paul J; Limburg, Martien; Aramideh, Majid; de Beer, Frank; Zwetsloot, Caspar P; Halkes, Patricia; de Kruijk, Jelle; Kruyt, Nyika D; van der Meulen, Willem; Spaander, Fianne; van der Ree, Taco; Kwa, Vincent I H; Van den Berg-Vos, Renske M; Roos, Yvo B; Coutinho, Jonathan M

    2016-04-01

    Centralization of intravenous thrombolysis (IVT) for acute ischemic stroke in high-volume centers is believed to improve the door-to-needle times (DNT), but limited data support this assumption. We examined the association between DNT and IVT volume in a large Dutch province. We identified consecutive patients treated with IVT between January 2009 and 2013. Based on annualized IVT volume, hospitals were categorized as low-volume (≤ 24), medium-volume (25-49) or high-volume (≥ 50). In logistic regression analysis, low-volume hospitals were used as reference category. Of 17,332 stroke patients from 11 participating hospitals, 1962 received IVT (11.3 %). We excluded 140 patients because of unknown DNT (n = 86) or in-hospital stroke (n = 54). There were two low-volume (total 101 patients), five medium-volume (747 patients) and four high-volume hospitals (974 patients). Median DNT was shorter in high-volume hospitals (30 min) than in medium-volume (42 min, p < 0.001) and low-volume hospitals (38 min, p < 0.001). Patients admitted to high-volume hospitals had a higher chance of DNT < 30 min (adjusted OR 3.13, 95 % CI 1.70-5.75), lower risk of symptomatic intracerebral hemorrhage (adjusted OR 0.39, 95 % CI 0.16-0.92), and a lower mortality risk (adjusted OR 0.45, 95 % CI 0.21-1.01), compared to low-volume centers. There was no difference in DNT between low- and medium-volume hospitals. Onset-to-needle times (ONT) did not differ between the groups. Hospitals in this Dutch province generally achieved short DNTs. Despite this overall good performance, higher IVT volumes were associated with shorter DNTs and lower complication risks. The ONT was not associated with IVT volume. PMID:26946499

  12. Automated Entire Thrombus Density Measurements for Robust and Comprehensive Thrombus Characterization in Patients with Acute Ischemic Stroke

    PubMed Central

    Santos, Emilie M. M.; Niessen, Wiro J.; Yoo, Albert J.; Berkhemer, Olvert A.; Beenen, Ludo F.

    2016-01-01

    Background and Purpose In acute ischemic stroke (AIS) management, CT-based thrombus density has been associated with treatment success. However, currently used thrombus measurements are prone to inter-observer variability and oversimplify the heterogeneous thrombus composition. Our aim was first to introduce an automated method to assess the entire thrombus density and then to compare the measured entire thrombus density with respect to current standard manual measurements. Materials and Method In 135 AIS patients, the density distribution of the entire thrombus was determined. Density distributions were described using medians, interquartile ranges (IQR), kurtosis, and skewedness. Differences between the median of entire thrombus measurements and commonly applied manual measurements using 3 regions of interest were determined using linear regression. Results Density distributions varied considerably with medians ranging from 20.0 to 62.8 HU and IQRs ranging from 9.3 to 55.8 HU. The average median of the thrombus density distributions (43.5 ± 10.2 HU) was lower than the manual assessment (49.6 ± 8.0 HU) (p<0.05). The difference between manual measurements and median density of entire thrombus decreased with increasing density (r = 0.64; p<0.05), revealing relatively higher manual measurements for low density thrombi such that manual density measurement tend overestimates the real thrombus density. Conclusions Automatic measurements of the full thrombus expose a wide variety of thrombi density distribution, which is not grasped with currently used manual measurement. Furthermore, discrimination of low and high density thrombi is improved with the automated method. PMID:26765847

  13. Drug-Like Property Profiling of Novel Neuroprotective Compounds to Treat Acute Ischemic Stroke: Guidelines to Develop Pleiotropic Molecules

    PubMed Central

    Lapchak, Paul A.

    2012-01-01

    The development of novel neuroprotective compounds to treat acute ischemic stroke (AIS) has been problematic and quite complicated, since many candidates that have been tested clinically lacked significant pleiotropic activity, were unable to effectively cross the blood brain barrier (BBB), had poor bioavailability or were toxic. Moreover, the compounds did not confer significant neuroprotection or clinical efficacy measured using standard behavioral endpoints, when studied in clinical trials in a heterogeneous population of stroke patients. To circumvent some of the drug development problems describe above, we have used a rational funnel approach to identify and develop promising candidates. Using a step-wise approach, we have identified a series of compounds based upon two different neuroprotection assays. We have then taken the candidates and determined their “drug-like” properties. This guidelines article details in vitro screening assays used to show pleiotropic activity of a series of novel compounds; including enhanced neuroprotective activity compared to the parent compound fisetin. Moreover, for preliminary drug de-risking or risk reduction during development, we used compound assessment in the CeeTox assay, ADME toxicity using the AMES test for genotoxicity and interaction with Cytochrome P450 using CYP450 inhibition analysis against a spectrum of CYP450 enzymes (CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A4) as a measure of drug interaction. Moreover, the compounds have been studied using a transfected Madin Darby canine kidney (MDCK) cell assay to assess blood brain barrier penetration (BBB). Using this series of assays, we have identified 4 novel molecules to be developed as an AIS treatment. PMID:23687519

  14. Dual isotope thallium and indium antimyosin SPECT imaging to identify acute infarct patients at further ischemic risk

    SciTech Connect

    Johnson, L.L.; Seldin, D.W.; Keller, A.M.; Wall, R.M.; Bhatia, K.; Bingham, C.O. III; Tresgallo, M.E. )

    1990-01-01

    Forty-two patients (28 men and 14 women) with acute myocardial infarction (35 Q, seven non-Q wave) were injected with 2.0 mCi indium 111-labeled antimyosin (AM) monoclonal antibody (111In AM) within 48 hours of the onset of chest pain. Forty-eight hours later (72-96 hours after onset of chest pain), patients were injected with 2.2 mCi thallium 201, and two sets of single-photon emission computed tomography (SPECT) images were obtained simultaneously using dual energy windows set for the 247 keV indium photopeak and the 70 keV thallium peak. Seventeen patients had repeat scans at 4 hours. 111In AM uptake and 201Tl defects were localized to one or more of 24 coronal and sagittal segments. Scans with only 201Tl defects and corresponding 111In AM uptake were classified as matches; scans with unmatched 201Tl defects in addition to matching regions corresponding to electrocardiographic infarct location were classified as mismatches; and scans with 201Tl and 111In AM uptake in the same segments were classified as overlap. Scan patterns were correlated with clinical evidence for residual ischemia occurring within 6 weeks of infarct and including infarct extension, recurrent angina, and positive predischarge low-level or 6-week symptom-limited stress tests and with coronary anatomy. Fourteen patients had only matching patterns (group 1), 23 had mismatches (group 2), and five had 201Tl-111In overlap as the predominant pattern. None of the patients in group 1 had previous myocardial infarction; in each, the matched area corresponded to the Q wave location on electrocardiogram, and none had further in-hospital ischemic events or positive stress tests.

  15. Methylene Blue Reduces Acute Cerebral Ischemic Injury via the Induction of Mitophagy.

    PubMed

    Di, Yao; He, Yun-Ling; Zhao, Tong; Huang, Xin; Wu, Kui-Wu; Liu, Shu-Hong; Zhao, Yong-Qi; Fan, Ming; Wu, Li-Ying; Zhu, Ling-Ling

    2015-05-19

    The treatment of stroke is limited by a short therapeutic window and a lack of effective clinical drugs. Methylene blue (MB) has been used in laboratories and clinics since the 1890s. Few studies have reported the neuroprotective role of MB in cerebral ischemia-reperfusion injury. However, whether and how MB protects against acute cerebral ischemia (ACI) injury was unclear. In this study, we investigated the effect of MB on this injury and revealed that MB protected against ACI injury by augmenting mitophagy. Using a rat middle cerebral artery occlusion (MCAO) model, we demonstrated that MB improved neurological function and reduced the infarct volume and necrosis after ACI injury. These improvements depended on the effect of MB on mitochondrial structure and function. ACI caused the disorder and disintegration of mitochondrial structure, while MB ameliorated the destruction of mitochondria. In addition, mitophagy was inhibited at 24 h after stroke and MB augmented mitophagy. In an oxygen-glucose deprivation (OGD) model in vitro, we further revealed that the elevation of mitochondrial membrane potential (MMP) by MB under OGD conditions mediated the augmented mitophagy. In contrast, exacerbating the decline of MMP during OGD abolished the MB-induced activation of mitophagy. Taken together, MB promotes mitophagy by maintaining the MMP at a relatively high level, which contributes to a decrease in necrosis and an improvement in neurological function, thereby protecting against ACI injury.

  16. Mortality, Recurrence, and Dependency Rates Are Higher after Acute Ischemic Stroke in Elderly Patients with Diabetes Compared to Younger Patients.

    PubMed

    Long, Xue; Lou, Yongzhong; Gu, Hongfei; Guo, Xiaofei; Wang, Tao; Zhu, Yanxia; Zhao, Wenjuan; Ning, Xianjia; Li, Bin; Wang, Jinghua; An, Zhongping

    2016-01-01

    Stroke has a greater effect on the elderly than on younger patients. However, the long-term outcomes associated with stroke among elderly patients with diabetes are unknown. We aimed to assess the differences in long-term outcomes between young and elderly stroke patients with diabetes. A total of 3,615 acute ischemic stroke patients with diabetes were recruited for this study between 2006 and 2014. Outcomes at 12 and 36 months after stroke (including mortality, recurrence, and dependency) were compared between younger (age <75 years) and elderly (age ≥75 years) patients. The elderly group included 692 patients (19.1%) overall. Elderly patients were more likely than younger patients to have a Trial of Org 10172 in Acute Stroke Treatment classification of stroke due to cardioembolism, moderate and severe stroke, and atrial fibrillation, but less likely to have hypertension and dyslipidemia, current smokers, and alcohol consumers. Mortality, dependency, and recurrence rates at 12 months after stroke were 19.0, 48.5, and 20.9% in the elderly group and 7.4, 30.9, and 15.4% in the younger group, respectively (all P < 0.05). Corresponding rates at 36 months after stroke were 35.4, 78.7, and 53.8% in the elderly group and 13.7, 61.7, and 43.0% in the younger group, respectively (all P < 0.001). The mortality, dependency, and recurrence rates at 12 and 36 months after stroke were significantly higher in the elderly group than in the younger group after adjusting for stroke subtypes, stroke severity, and risk factors. Odds ratios (95% confidence interval) at 12 and 36 months after stroke were 2.18 (1.64-2.89) and 3.10 (2.35-4.08), respectively, for mortality, all P < 0.001; 1.81 (1.49-2.20) and 2.04 (1.57-2.34), respectively, for dependency, all P < 0.001; and 1.37 (1.06-1.76) and 1.40 (1.07-1.85), respectively, for recurrence, P = 0.016. The findings from this study suggest that management and secondary prevention should be emphasized in elderly patients with diabetes in

  17. Mortality, Recurrence, and Dependency Rates Are Higher after Acute Ischemic Stroke in Elderly Patients with Diabetes Compared to Younger Patients

    PubMed Central

    Long, Xue; Lou, Yongzhong; Gu, Hongfei; Guo, Xiaofei; Wang, Tao; Zhu, Yanxia; Zhao, Wenjuan; Ning, Xianjia; Li, Bin; Wang, Jinghua; An, Zhongping

    2016-01-01

    Stroke has a greater effect on the elderly than on younger patients. However, the long-term outcomes associated with stroke among elderly patients with diabetes are unknown. We aimed to assess the differences in long-term outcomes between young and elderly stroke patients with diabetes. A total of 3,615 acute ischemic stroke patients with diabetes were recruited for this study between 2006 and 2014. Outcomes at 12 and 36 months after stroke (including mortality, recurrence, and dependency) were compared between younger (age <75 years) and elderly (age ≥75 years) patients. The elderly group included 692 patients (19.1%) overall. Elderly patients were more likely than younger patients to have a Trial of Org 10172 in Acute Stroke Treatment classification of stroke due to cardioembolism, moderate and severe stroke, and atrial fibrillation, but less likely to have hypertension and dyslipidemia, current smokers, and alcohol consumers. Mortality, dependency, and recurrence rates at 12 months after stroke were 19.0, 48.5, and 20.9% in the elderly group and 7.4, 30.9, and 15.4% in the younger group, respectively (all P < 0.05). Corresponding rates at 36 months after stroke were 35.4, 78.7, and 53.8% in the elderly group and 13.7, 61.7, and 43.0% in the younger group, respectively (all P < 0.001). The mortality, dependency, and recurrence rates at 12 and 36 months after stroke were significantly higher in the elderly group than in the younger group after adjusting for stroke subtypes, stroke severity, and risk factors. Odds ratios (95% confidence interval) at 12 and 36 months after stroke were 2.18 (1.64–2.89) and 3.10 (2.35–4.08), respectively, for mortality, all P < 0.001; 1.81 (1.49–2.20) and 2.04 (1.57–2.34), respectively, for dependency, all P < 0.001; and 1.37 (1.06–1.76) and 1.40 (1.07–1.85), respectively, for recurrence, P = 0.016. The findings from this study suggest that management and secondary prevention should be emphasized in elderly patients with

  18. Mortality, Recurrence, and Dependency Rates Are Higher after Acute Ischemic Stroke in Elderly Patients with Diabetes Compared to Younger Patients.

    PubMed

    Long, Xue; Lou, Yongzhong; Gu, Hongfei; Guo, Xiaofei; Wang, Tao; Zhu, Yanxia; Zhao, Wenjuan; Ning, Xianjia; Li, Bin; Wang, Jinghua; An, Zhongping

    2016-01-01

    Stroke has a greater effect on the elderly than on younger patients. However, the long-term outcomes associated with stroke among elderly patients with diabetes are unknown. We aimed to assess the differences in long-term outcomes between young and elderly stroke patients with diabetes. A total of 3,615 acute ischemic stroke patients with diabetes were recruited for this study between 2006 and 2014. Outcomes at 12 and 36 months after stroke (including mortality, recurrence, and dependency) were compared between younger (age <75 years) and elderly (age ≥75 years) patients. The elderly group included 692 patients (19.1%) overall. Elderly patients were more likely than younger patients to have a Trial of Org 10172 in Acute Stroke Treatment classification of stroke due to cardioembolism, moderate and severe stroke, and atrial fibrillation, but less likely to have hypertension and dyslipidemia, current smokers, and alcohol consumers. Mortality, dependency, and recurrence rates at 12 months after stroke were 19.0, 48.5, and 20.9% in the elderly group and 7.4, 30.9, and 15.4% in the younger group, respectively (all P < 0.05). Corresponding rates at 36 months after stroke were 35.4, 78.7, and 53.8% in the elderly group and 13.7, 61.7, and 43.0% in the younger group, respectively (all P < 0.001). The mortality, dependency, and recurrence rates at 12 and 36 months after stroke were significantly higher in the elderly group than in the younger group after adjusting for stroke subtypes, stroke severity, and risk factors. Odds ratios (95% confidence interval) at 12 and 36 months after stroke were 2.18 (1.64-2.89) and 3.10 (2.35-4.08), respectively, for mortality, all P < 0.001; 1.81 (1.49-2.20) and 2.04 (1.57-2.34), respectively, for dependency, all P < 0.001; and 1.37 (1.06-1.76) and 1.40 (1.07-1.85), respectively, for recurrence, P = 0.016. The findings from this study suggest that management and secondary prevention should be emphasized in elderly patients with diabetes in

  19. Oral administration of fermented wild ginseng ameliorates DSS-induced acute colitis by inhibiting NF-κB signaling and protects intestinal epithelial barrier.

    PubMed

    Seong, Myeong A; Woo, Jong Kyu; Kang, Ju-Hee; Jang, Yeong Su; Choi, Seungho; Jang, Young Saeng; Lee, Taek Hwan; Jung, Kyung Hoon; Kang, Dong Kyu; Hurh, Byung Seok; Kim, Dae Eung; Kim, Sun Yeou; Oh, Seung Hyun

    2015-07-01

    Ginseng has been widely used for therapeutic and preventive purposes for thousands of years. However, orally administered ginseng has very low bioavailability and absorption in the intestine. Therefore, fermented ginseng was developed to enhance the beneficial effects of ginseng in the intestine. In this study, we investigated the molecular mechanisms underlying the anti-inflammatory activity of fermented wild ginseng (FWG). We found that FWG significantly alleviated the severity of colitis in a dextran sodium sulfate (DSS)-induced colitis mouse model, and decreased expression level of pro-inflammatory cytokines in colonic tissue. Moreover, we observed that FWG suppressed the infiltration of macrophages in DSS-induced colitis. FWG also attenuated the transcriptional activity of nuclear factor-κB (NF-κB) by reducing the translocation of NF-κB into the nucleus. Our data indicate that FWG contains anti-inflammatory activity via NF-κB inactivation and could be useful for treating colitis.

  20. The cost-effectiveness of telestroke in the treatment of acute ischemic stroke

    PubMed Central

    Nelson, R.E.; Saltzman, G.M.; Skalabrin, E.J.; Demaerschalk, B.M.

    2011-01-01

    Objective: To conduct a cost-effectiveness analysis of telestroke—a 2-way, audiovisual technology that links stroke specialists to remote emergency department physicians and their stroke patients—compared to usual care (i.e., remote emergency departments without telestroke consultation or stroke experts). Methods: A decision-analytic model was developed for both 90-day and lifetime horizons. Model inputs were taken from published literature where available and supplemented with western states' telestroke experiences. Costs were gathered using a societal perspective and converted to 2008 US dollars. Quality-adjusted life-years (QALYs) gained were combined with costs to generate incremental cost-effectiveness ratios (ICERs). In the lifetime horizon model, both costs and QALYs were discounted at 3% annually. Both one-way sensitivity analyses and Monte Carlo simulations were performed. Results: In the base case analysis, compared to usual care, telestroke results in an ICER of $108,363/QALY in the 90-day horizon and $2,449/QALY in the lifetime horizon. For the 90-day and lifetime horizons, 37.5% and 99.7% of 10,000 Monte Carlo simulations yielded ICERs <$50,000/QALY, a ratio commonly considered acceptable in the United States. Conclusion: When a lifetime perspective is taken, telestroke appears cost-effective compared to usual care, since telestroke costs are upfront but benefits of improved stroke care are lifelong. If barriers to use such as low reimbursement rates and high equipment costs are reduced, telestroke has the potential to diminish the striking geographic disparities of acute stroke care in the United States. PMID:21917781

  1. Vitamin D deficiency contributes to vascular damage in sustained ischemic acute kidney injury.

    PubMed

    de Bragança, Ana C; Volpini, Rildo A; Mehrotra, Purvi; Andrade, Lúcia; Basile, David P

    2016-07-01

    Reductions in renal microvasculature density and increased lymphocyte activity may play critical roles in the progression of chronic kidney disease (CKD) following acute kidney injury (AKI) induced by ischemia/reperfusion injury (IRI). Vitamin D deficiency is associated with tubulointerstitial damage and fibrosis progression following IRI-AKI We evaluated the effect of vitamin D deficiency in sustained IRI-AKI, hypothesizing that such deficiency contributes to the early reduction in renal capillary density or alters the lymphocyte response to IRI Wistar rats were fed vitamin D-free or standard diets for 35 days. On day 28, rats were randomized into four groups: control, vitamin D deficient (VDD), bilateral IRI, and VDD+IRI Indices of renal injury and recovery were evaluated for up to 7 days following the surgical procedures. VDD rats showed reduced capillary density (by cablin staining), even in the absence of renal I/R. In comparison with VDD and IRI rats, VDD+IRI rats manifested a significant exacerbation of capillary rarefaction as well as higher urinary volume, kidney weight/body weight ratio, tissue injury scores, fibroblast-specific protein-1, and alpha-smooth muscle actin. VDD+IRI rats also had higher numbers of infiltrating activated CD4(+) and CD8(+) cells staining for interferon gamma and interleukin-17, with a significant elevation in the Th17/T-regulatory cell ratio. These data suggest that vitamin D deficiency impairs renal repair responses to I/R injury, exacerbates changes in renal capillary density, as well as promoting fibrosis and inflammation, which may contribute to the transition from AKI to CKD.

  2. Myocardial perfusion and contraction in acute ischemia and chronic ischemic heart disease.

    PubMed

    Canty, John M; Suzuki, Gen

    2012-04-01

    A large body of evidence has demonstrated that there is a close coupling between regional myocardial perfusion and contractile function. When ischemia is mild, this can result in the development of a new balance between supply and energy utilization that allows the heart to adapt for a period of hours over which myocardial viability can be maintained, a phenomenon known as "short-term hibernation". Upon reperfusion after reversible ischemia, regional myocardial function remains depressed. The "stunned myocardium" recovers spontaneously over a period of hours to days. The situation in myocardium subjected to chronic repetitive ischemia is more complex. Chronic dysfunction can initially reflect repetitive stunning with insufficient time for the heart to recover between episodes of spontaneous ischemia. As the frequency and/or severity of ischemia increases, the heart undergoes a series of adaptations which downregulate metabolism to maintain myocyte viability at the expense of contractile function. The resulting "hibernating myocardium" develops regional myocyte cellular hypertrophy as a compensatory response to ischemia-induced apoptosis along with a series of molecular adaptations that while regional, are similar to global changes found in advanced heart failure. As a result, flow-function relations become independently affected by tissue remodeling and interventions that stimulate myocyte regeneration. Similarly, chronic vascular remodeling may alter flow regulation in a fashion that increases myocardial vulnerability to ischemia. Here we review our current understanding of myocardial flow-function relations during acute ischemia in normal myocardium and highlight newly identified complexities in their interpretation in viable chronically dysfunctional myocardium with myocyte cellular and molecular remodeling. This article is part of a Special Issue entitled "Coronary Blood Flow".

  3. Primary Angioplasty Versus Stenting for Endovascular Management of Intracranial Atherosclerotic Disease Following Acute Ischemic Stroke

    PubMed Central

    Villwock, Mark R.; Padalino, David J.; Ramaswamy, Raghu; Deshaies, Eric M.

    2016-01-01

    Background The future of neuroendovascular treatment for intracranial atherosclerotic disease (ICAD) has been debated since the results of SAMMPRIS reflected poor outcomes following endovascular therapy. There is currently a large spectrum of current management strategies. We compared historical outcomes of patients with ICAD and stroke that were treated with angioplasty-alone versus stent placement. Methods We extracted a population from the Nationwide Inpatient Sample (NIS) (2005–2011) and the National Inpatient Sample (NIS) (2012) composed of patients with ICAD and infarction that were admitted nonelectively and received endovascular revascularization. Patients treated with thrombectomy or thrombolysis were excluded. Categorical variables were compared with Chi-squared tests. Binary logistic regression was performed to evaluate mortality while controlling for age, sex, severity, and comorbidities. Results About 2059 admissions met our criteria. A majority were treated via stent placement (71%). Angioplasty-alone had significantly higher mortality (17.6% vs. 8.4%, P<0.001), but no difference in iatrogenic stroke rate (3.4% vs. 3.6%, P=0.826), compared to stent placement. The adjusted odds ratio of mortality for stented patients was 0.536 (95% CI: 0.381–0.753, P<0.001) in comparison to patients treated with angioplasty alone. Conclusions This study found the risk of mortality to be elevated following angioplasty alone in comparison to revascularization with stent placement, without a corresponding significant difference in iatrogenic stroke rate. This may represent selection bias due to patient characteristics not defined in the database, but it also may indicate that patients with ICAD and acute stroke have increased odds of stenosis that is refractory to angioplasty alone and have a high risk of mortality without revascularization. PMID:27403216

  4. First report of Entamoeba histolytica infection from Timor-Leste--acute amoebic colitis and concurrent late development of amoebic liver abscess in returned travellers to Australia.

    PubMed

    Nourse, Clare B; Robson, Jennifer M; Whitby, Michael R; Francis, Josh R

    2016-02-01

    This communication reports invasive amoebic colitis and late onset amoebic liver abscess in three members of a group of 12 Australian travellers to Timor-Leste (TL). This is the first report of Entamoeba histolytica infection from TL. Clinicians in Australia need to consider amoebiasis in the differential diagnosis in travellers returning with colitis, abdominal pain and fever. Presentation with amoebic liver abscess months after exposure is rare but should be suspected in symptomatic individuals with a relevant history of travel. PMID:26858275

  5. First report of Entamoeba histolytica infection from Timor-Leste--acute amoebic colitis and concurrent late development of amoebic liver abscess in returned travellers to Australia.

    PubMed

    Nourse, Clare B; Robson, Jennifer M; Whitby, Michael R; Francis, Josh R

    2016-02-01

    This communication reports invasive amoebic colitis and late onset amoebic liver abscess in three members of a group of 12 Australian travellers to Timor-Leste (TL). This is the first report of Entamoeba histolytica infection from TL. Clinicians in Australia need to consider amoebiasis in the differential diagnosis in travellers returning with colitis, abdominal pain and fever. Presentation with amoebic liver abscess months after exposure is rare but should be suspected in symptomatic individuals with a relevant history of travel.

  6. Increased Expression of mir-34a-5p and Clinical Association in Acute Ischemic Stroke Patients and in a Rat Model.

    PubMed

    Liang, Ting-Ying; Lou, Ji-Yu

    2016-01-01

    BACKGROUND MiRNA is widely recognized as the most important regulator in various diseases. However, there has been little research regarding miRNA expression and its involvement in ischemic stroke. MATERIAL AND METHODS In this study, we investigated the pattern of miRNA-34a-5p expression along with its clinical application in human ischemic stroke and in an in vivo rat model. We recruited 102 cerebral ischemia patients and 97 health controls for this study. Clinical data were gathered and recorded with the help of questionnaires. Blood samples were obtained from patients within 72 h after cerebral ischemia. National Institutes of Health Stroke Scale (NIHSS), Acute Stroke Treatment (TOAST), and infarct volume were used to analyze the correlation of miRNA-34a-5p expression and clinical information. In addition, blood samples and brain tissues were collected from an established middle cerebral artery occlusion (MCAO) model consisting of 20 adult male mice at 24 h after the MCAO. Expression level of miRNA-34a-5p was detected by real-time polymerase chain reactions. RESULTS Results showed overexpression of miRNA-34a-5p in acute ischemic stroke patients blood samples compared to the controls (p<0.05). Also, large and small arterial strokes types demonstrated elevated miRNA-34a-5p expression levels. Further correlation analysis revealed a negative association between miRNA-34a-5p and NIHSS scores (r=-0.692 p<0.05) and infarct volume (r=-0.719, p<0.05). Moreover, in vivo experiment results showed significant up-regulated expression of miRNA-34a-5p in middle cerebral artery occlusion compared to controls, along with a positive correlation between miRNA-34a-5p in blood and brain (r=0.742, p<0.05). CONCLUSIONS Our results suggest there is a potential regulatory role of miRNA-34a-5p in acute ischemic stroke, which could serve as a therapeutic target or biomarker in stroke prognosis. PMID:27545688

  7. Increased Expression of mir-34a-5p and Clinical Association in Acute Ischemic Stroke Patients and in a Rat Model

    PubMed Central

    Liang, Ting-ying; Lou, Ji-yu

    2016-01-01

    Background MiRNA is widely recognized as the most important regulator in various diseases. However, there has been little research regarding miRNA expression and its involvement in ischemic stroke. Material/Methods In this study, we investigated the pattern of miRNA-34a-5p expression along with its clinical application in human ischemic stroke and in an in vivo rat model. We recruited 102 cerebral ischemia patients and 97 health controls for this study. Clinical data were gathered and recorded with the help of questionnaires. Blood samples were obtained from patients within 72 h after cerebral ischemia. National Institutes of Health Stroke Scale (NIHSS), Acute Stroke Treatment (TOAST), and infarct volume were used to analyze the correlation of miRNA-34a-5p expression and clinical information. In addition, blood samples and brain tissues were collected from an established middle cerebral artery occlusion (MCAO) model consisting of 20 adult male mice at 24 h after the MCAO. Expression level of miRNA-34a-5p was detected by real-time polymerase chain reactions. Results Results showed overexpression of miRNA-34a-5p in acute ischemic stroke patients blood samples compared to the controls (p<0.05). Also, large and small arterial strokes types demonstrated elevated miRNA-34a-5p expression levels. Further correlation analysis revealed a negative association between miRNA-34a-5p and NIHSS scores (r=−0.692 p<0.05) and infarct volume (r=−0.719, p<0.05). Moreover, in vivo experiment results showed significant up-regulated expression of miRNA-34a-5p in middle cerebral artery occlusion compared to controls, along with a positive correlation between miRNA-34a-5p in blood and brain (r=0.742, p<0.05). Conclusions Our results suggest there is a potential regulatory role of miRNA-34a-5p in acute ischemic stroke, which could serve as a therapeutic target or biomarker in stroke prognosis. PMID:27545688

  8. Change in myocardial oxygen consumption employing continuous-flow LVAD with cardiac beat synchronizing system, in acute ischemic heart failure models.

    PubMed

    Umeki, Akihide; Nishimura, Takashi; Takewa, Yoshiaki; Ando, Masahiko; Arakawa, Mamoru; Kishimoto, Yuichiro; Tsukiya, Tomonori; Mizuno, Toshihide; Kyo, Shunei; Ono, Minoru; Taenaka, Yoshiyuki; Tatsumi, Eisuke

    2013-06-01

    Aiming the 'Bridge to Recovery' course, we have developed a novel left ventricular assist device (LVAD) controlling system. It can change the rotational speed of the continuous flow LVAD, EVAHEART, synchronized with the cardiac beat. Employing this system, we have already demonstrated that myocardial oxygen consumption (MVO2), which is considered to be equivalent to native heart load, changes in the hearts of normal goats. Herein, we examined changes in goats with acute ischemic heart failure. We studied 14 goats (56.1 ± 6.9 kg) with acute ischemic heart failure due to coronary microsphere embolization. We installed the EVAHEART and drive in four modes: "circuit-clamp", "continuous support", "counter-pulse", and "co-pulse", with 50 and 100 % bypass. In comparison to the circuit-clamp mode, MVO2 was reduced to 70.4 ± 17.9 % in the counter-pulse mode and increased to 90.3 ± 14.5 % in the co-pulse mode, whereas it was 80.0 ± 14.5 % in the continuous mode, with 100 % bypass (p < 0.05). The same difference was confirmed with 50 % bypass. This means that we may have a chance to change the native heart load by controlling the LVAD rotation in synchrony with the cardiac rhythm, so we named our controller as the Native Heart Load Control System (NHLCS). Employing changeable MVO2 with NHLCS according to the patient's condition may provide more opportunity for native heart recovery with LVAD, especially for patients with ischemic heart diseases.

  9. Anomalous equivalent potential temperature: an atmospheric feature predicting days with higher risk for fatal outcome in acute ischemic stroke-a preliminary study.

    PubMed

    Folyovich, András; Biczó, Dávid; Al-Muhanna, Nadim; Béres-Molnár, Anna K; Fejős, Ádám; Pintér, Ádám; Bereczki, Dániel; Fischer, Antal; Vadasdi, Károly; Pintér, Ferenc

    2015-09-01

    Acute stroke is a life-threatening condition. Fatal outcome is related to risk factors, some of these affected by climatic changes. Forecasting potentially harmful atmospheric processes may therefore be of practical importance in the acute care of stroke patients. We analyzed the history of all patients with acute ischemic stroke (N = 184) confirmed by neuroimaging including those who died (N = 35, 15 males) at our hospital department in the winter months of 2009. Patient data were anonymized, and the human meteorologists were only aware of patients' age, gender, and exact time of death. Of the meteorological parameters, equivalent potential temperature (EPT) has been chosen for analysis. EPT is generally used for forecasting thunderstorms, but in the case of synoptic scale airflow (10(6) m), it is suitable for characterizing the air mass inflowing from different regions. The behavior of measured EPT values was compared to the climatic (30 years) averages. We developed meteorological criteria for anomalous periods of EPT and tested if such periods are associated with higher rate of fatal outcome. The duration of anomalous and non-anomalous periods was nearly equal during the studied 3 months. Stroke onset distributed similarly between anomalous and non-anomalous days; however, of the 35 deaths, 27 occurred during anomalous periods: on average, 0.56 deaths occurred on anomalous days and 0.19 on non-anomalous days. Winter periods meeting the criteria of anomalous EPT may have a significant adverse human-meteorological impact on the outcome in acute ischemic stroke. PMID:26233665

  10. Clinical efficacy and safety of hypernormal shortened door to needle time (DNT) plus individualized low-dose alteplase therapy in treating acute ischemic stroke

    PubMed Central

    Zheng, Mei; Lei, Hongyan; Cui, Yansen; Yang, Daiqun; Wang, Liquang; Wang, Ziran

    2016-01-01

    Objective: This study aims to observe the clinical efficacies of hyper-early low-dose alteplase thrombolysis in treating acute ischemic stroke (AIS). Methods: Two hundred twenty AIS patients were randomly divided into group A (90 cases), group B (90 cases), and group C (40 cases). The National Institutes of Health Stroke Scale (NIHSS) scores, mRS score-evaluated prognosis, intracranial hemorrhage, and mortality of the three groups were observed before and after the treatment. Results: The NIHSS scores of the three groups were significantly reduced after the treatment (P<0.05), among which the NIHSS score of group A was the lowest (P<0.05); and the difference between group B and C was not significant (P>0.05). The incidence of such complications as cerebral hemorrhage in the three groups was low, and there was no significant difference among the groups (P>0.05). The modified Rankin Scale (mRS)scores of the three groups showed that group A had much better prognosis than group B and C, while the difference between group B and group C was not significant. Conclusions: The hyper-early low-dose alteplase thrombolysis was safe and effective in Acute ischemic stroke (AIS). PMID:27648019

  11. Crystal-Associated Colitis with Ulceration Leading to Hematochezia and Abdominal Pain.

    PubMed

    Desai, Meeta; Reiprich, Aaron; Khov, Nancy; Yang, Zhaohai; Mathew, Abraham; Levenick, John

    2016-01-01

    Lower GI bleeding is a common cause for hospitalization in adults. Medication-associated mucosal injury is an important clinical entity that can result in significant morbidity and mortality. We present the case of a 45-year-old woman with a 3-month history of intermittent abdominal cramping and rectal bleeding. Her medical history was extensive and included end-stage renal disease and a remote history of endometrial carcinoma that was treated with radiation. Initial workup was concerning for ischemic and radiation colitis, however, histology was most consistent with acute inflammation and ulceration associated with crystal fragments. Sevelamer and cholestyramine are commonly used ion-exchange resins that have been associated with mucosal damage. Both medications were discontinued and her symptoms resolved. Our case highlights an underrecognized but important cause of hematochezia. PMID:27482192

  12. Crystal-Associated Colitis with Ulceration Leading to Hematochezia and Abdominal Pain

    PubMed Central

    Desai, Meeta; Reiprich, Aaron; Khov, Nancy; Yang, Zhaohai; Mathew, Abraham; Levenick, John

    2016-01-01

    Lower GI bleeding is a common cause for hospitalization in adults. Medication-associated mucosal injury is an important clinical entity that can result in significant morbidity and mortality. We present the case of a 45-year-old woman with a 3-month history of intermittent abdominal cramping and rectal bleeding. Her medical history was extensive and included end-stage renal disease and a remote history of endometrial carcinoma that was treated with radiation. Initial workup was concerning for ischemic and radiation colitis, however, histology was most consistent with acute inflammation and ulceration associated with crystal fragments. Sevelamer and cholestyramine are commonly used ion-exchange resins that have been associated with mucosal damage. Both medications were discontinued and her symptoms resolved. Our case highlights an underrecognized but important cause of hematochezia. PMID:27482192

  13. Ischemic Stroke

    MedlinePlus

    A stroke is a medical emergency. There are two types - ischemic and hemorrhagic. Ischemic stroke is the most common type. It is usually ... are at risk for having a more serious stroke. Symptoms of stroke are Sudden numbness or weakness ...

  14. Medical image analysis methods in MR/CT-imaged acute-subacute ischemic stroke lesion: Segmentation, prediction and insights into dynamic evolution simulation models. A critical appraisal☆

    PubMed Central

    Rekik, Islem; Allassonnière, Stéphanie; Carpenter, Trevor K.; Wardlaw, Joanna M.

    2012-01-01

    Over the last 15 years, basic thresholding techniques in combination with standard statistical correlation-based data analysis tools have been widely used to investigate different aspects of evolution of acute or subacute to late stage ischemic stroke in both human and animal data. Yet, a wave of biology-dependent and imaging-dependent issues is still untackled pointing towards the key question: “how does an ischemic stroke evolve?” Paving the way for potential answers to this question, both magnetic resonance (MRI) and CT (computed tomography) images have been used to visualize the lesion extent, either with or without spatial distinction between dead and salvageable tissue. Combining diffusion and perfusion imaging modalities may provide the possibility of predicting further tissue recovery or eventual necrosis. Going beyond these basic thresholding techniques, in this critical appraisal, we explore different semi-automatic or fully automatic 2D/3D medical image analysis methods and mathematical models applied to human, animal (rats/rodents) and/or synthetic ischemic stroke to tackle one of the following three problems: (1) segmentation of infarcted and/or salvageable (also called penumbral) tissue, (2) prediction of final ischemic tissue fate (death or recovery) and (3) dynamic simulation of the lesion core and/or penumbra evolution. To highlight the key features in the reviewed segmentation and prediction methods, we propose a common categorization pattern. We also emphasize some key aspects of the methods such as the imaging modalities required to build and test the presented approach, the number of patients/animals or synthetic samples, the use of external user interaction and the methods of assessment (clinical or imaging-based). Furthermore, we investigate how any key difficulties, posed by the evolution of stroke such as swelling or reperfusion, were detected (or not) by each method. In the absence of any imaging-based macroscopic dynamic model

  15. Oral administration of fermented wild ginseng ameliorates DSS-induced acute colitis by inhibiting NF-κB signaling and protects intestinal epithelial barrier

    PubMed Central

    Seong, Myeong A; Woo, Jong Kyu; Kang, Ju-Hee; Jang, Yeong Su; Choi, Seungho; Jang, Young Saeng; Lee, Taek Hwan; Jung, Kyung Hoon; Kang, Dong Kyu; Hurh, Byung Seok; Kim, Dae Eung; Kim, Sun Yeou; Oh, Seung Hyun

    2015-01-01

    Ginseng has been widely used for therapeutic and preventive purposes for thousands of years. However, orally administered ginseng has very low bioavailability and absorption in the intestine. Therefore, fermented ginseng was developed to enhance the beneficial effects of ginseng in the intestine. In this study, we investigated the molecular mechanisms underlying the anti-inflammatory activity of fermented wild ginseng (FWG). We found that FWG significantly alleviated the severity of colitis in a dextran sodium sulfate (DSS)-induced colitis mouse model, and decreased expression level of pro-inflammatory cytokines in colonic tissue. Moreover, we observed that FWG suppressed the infiltration of macrophages in DSS-induced colitis. FWG also attenuated the transcriptional activity of nuclear factor-κB (NF-κB) by reducing the translocation of NF-κB into the nucleus. Our data indicate that FWG contains anti-inflammatory activity via NF-κB inactivation and could be useful for treating colitis. [BMB Reports 2015; 48(7): 419-425] PMID:25936779

  16. Is indeterminate colitis determinable?

    PubMed

    Tremaine, William J

    2012-04-01

    About 10% of patients with colitis due to inflammatory bowel disease have indeterminate colitis. Despite newer diagnostic tools, the frequency has not diminished over the past 33 years. The current preferred term among academicians is colonic inflammatory bowel disease unclassified(IBDU), although indeterminate colitis is the term endorsed for inclusion in the ICD-10 coding system. Indeterminate colitis is more frequent among children. Theanti-Saccharomyces cerevisiae (ASCA) and perinuclear anti-cytoplasmic antibody (pANCA) are useful in distinguishing IBDU from ulcerative colitis and Crohn’s disease. However, current serologic and genetic studies, as well as endoscopic and imaging studies lack sufficient positive predictive values to make a definite diagnosis of Crohn’s colitis or ulcerative colitis. Patients with IBDU who undergo proctocolectomy with ileal pouch-anal anastomosis have more complications than patients with ulcerative colitis. Although some patients with indeterminate colitis eventually develop characteristic ulcerative colitis or Crohn’s disease, a subgroup are durably indeterminate. PMID:22314810

  17. Imaging recommendations for acute stroke and transient ischemic attack patients: a joint statement by the American Society of Neuroradiology, the American College of Radiology and the Society of NeuroInterventional Surgery.

    PubMed

    Wintermark, Max; Sanelli, Pina C; Albers, Gregory W; Bello, Jacqueline A; Derdeyn, Colin P; Hetts, Steven W; Johnson, Michele H; Kidwell, Chelsea S; Lev, Michael H; Liebeskind, David S; Rowley, Howard A; Schaefer, Pamela W; Sunshine, Jeffrey L; Zaharchuk, Greg; Meltzer, Carolyn C

    2013-11-01

    In the article entitled "Imaging Recommendations for Acute Stroke and Transient Ischemic Attack Patients: A Joint Statement by the American Society of Neuroradiology, the American College of Radiology and the Society of NeuroInterventional Surgery", we are proposing a simple, pragmatic approach that will allow the reader to develop an optimal imaging algorithm for stroke patients at their institution. PMID:23948676

  18. Crohn's & Colitis Foundation of America

    MedlinePlus

    ... enabled to enjoy the full interactive experience. Crohn's & Colitis Foundation of America Find a Doctor Find a ... Local Chapters News Events Search: What are Crohn's & Colitis? What is Crohn's Disease What is Ulcerative Colitis ...

  19. Functional Contrast-Enhanced CT For Evaluation of Acute Ischemic Stroke Does Not Increase the Risk of Contrast-Induced Nephropathy

    PubMed Central

    Lima, F.O.; Lev, M.H.; Levy, R.A.; Silva, G.S.; Ebril, M.; de Camargo, É.C.; Pomerantz, S.; Singhal, A.B.; Greer, D.M.; Ay, H.; González, R. Gilberto; Koroshetz, W.J.; Smith, W.S.; Furie, K.L.

    2010-01-01

    BACKGROUND AND PURPOSE Concerns have recently grown regarding the safety of iodinated contrast agents used for CTA and CTP imaging. We tested whether the incidence of AN, defined by a ≥25% increase in the post–contrast scan creatinine level, was higher among patients with ischemic stroke who underwent a functional contrast-enhanced CT protocol compared with those who had no iodinated contrast administration. MATERIALS AND METHODS The contrast-exposed group consisted of 575 patients with acute ischemic stroke who underwent CTA (n = 313), CTA/CTP (n = 224), or CTA/CTP followed by conventional angiography (n = 38) within 24 hours of stroke onset and were consecutively enrolled in a prospective cohort study. The nonexposed group consisted of 343 patients with ischemic stroke, consecutively admitted to the same institution, who did not receive iodinated contrast material. Patients were stratified by baseline eGFR. In the primary analysis, the Fisher exact test was used to compare the incidence of AN between the contrast-exposed and the nonexposed patients at 24, 48, and 72 hours and on a cumulative basis. A secondary analysis compared the incidence of AN in patients who underwent conventional angiography following CTA/CTP versus patients who underwent CTA/CTP only. RESULTS The incidence of AN was 5% in the exposed and 10% in the nonexposed group (P = .003). Patients who underwent conventional angiography after contrast CT were at no greater risk of AN than patients who underwent CTA/CTP alone (26 patients, 5%; and 2 patients, 5%, respectively; P = .7). CONCLUSIONS Administration of a contrast-enhanced CT protocol involving CTA/CTP and conventional angiography in selected patients does not appear to increase the incidence of CIN. PMID:20044502

  20. Solitaire™ with the Intention for Thrombectomy as Primary Endovascular Treatment for Acute Ischemic Stroke (SWIFT PRIME) trial: protocol for a randomized, controlled, multicenter study comparing the Solitaire revascularization device with IV tPA with IV tPA alone in acute ischemic stroke

    PubMed Central

    Saver, Jeffrey L; Goyal, Mayank; Bonafe, Alain; Diener, Hans-Christoph; Levy, Elad I; Pereira, Vitor M; Albers, Gregory W; Cognard, Christophe; Cohen, David J; Hacke, Werner; Jansen, Olav; Jovin, Tudor G; Mattle, Heinrich P; Nogueira, Raul G; Siddiqui, Adnan H; Yavagal, Dileep R; Devlin, Thomas G; Lopes, Demetrius K; Reddy, Vivek; du Mesnil de Rochemont, Richard; Jahan, Reza

    2015-01-01

    Rationale Early reperfusion in patients experiencing acute ischemic stroke is critical, especially for patients with large vessel occlusion who have poor prognosis without revascularization. Solitaire™ stent retriever devices have been shown to immediately restore vascular perfusion safely, rapidly, and effectively in acute ischemic stroke patients with large vessel occlusions. Aim The aim of the study was to demonstrate that, among patients with large vessel, anterior circulation occlusion who have received intravenous tissue plasminogen activator, treatment with Solitaire revascularization devices reduces degree of disability 3 months post stroke. Design The study is a global multicenter, two-arm, prospective, randomized, open, blinded end-point trial comparing functional outcomes in acute ischemic stroke patients who are treated with either intravenous tissue plasminogen activator alone or intravenous tissue plasminogen activator in combination with the Solitaire device. Up to 833 patients will be enrolled. Procedures Patients who have received intravenous tissue plasminogen activator are randomized to either continue with intravenous tissue plasminogen activator alone or additionally proceed to neurothrombectomy using the Solitaire device within six-hours of symptom onset. Study Outcomes The primary end-point is 90-day global disability, assessed with the modified Rankin Scale (mRS). Secondary outcomes include mortality at 90 days, functional independence (mRS ≤ 2) at 90 days, change in National Institutes of Health Stroke Scale at 27 h, reperfusion at 27 h, and thrombolysis in cerebral infarction 2b/3 flow at the end of the procedure. Analysis Statistical analysis will be conducted using simultaneous success criteria on the overall distribution of modified Rankin Scale (Rankin shift) and proportions of subjects achieving functional independence (mRS 0–2). PMID:25777831

  1. In vivo imaging of hemodynamics and oxygen metabolism in acute focal cerebral ischemic rats with laser speckle imaging and functional photoacoustic microscopy

    NASA Astrophysics Data System (ADS)

    Deng, Zilin; Wang, Zhen; Yang, Xiaoquan; Luo, Qingming; Gong, Hui

    2012-08-01

    Stroke is a devastating disease. The changes in cerebral hemodynamics and oxygen metabolism associated with stroke play an important role in pathophysiology study. But the changes were difficult to describe with a single imaging modality. Here the changes in cerebral blood flow (CBF), cerebral blood volume (CBV), and oxygen saturation (SO2) were yielded with laser speckle imaging (LSI) and photoacoustic microscopy (PAM) during and after 3-h acute focal ischemic rats. These hemodynamic measures were further synthesized to deduce the changes in oxygen extraction fraction (OEF). The results indicate that all the hemodynamics except CBV had rapid declines within 40-min occlusion of middle cerebral artery (MCAO). CBV in arteries and veins first increased to the maximum value of 112.42±36.69% and 130.58±31.01% by 15 min MCAO; then all the hemodynamics had a persistent reduction with small fluctuations during the ischemic. When ischemia lasted for 3 h, CBF in arteries, veins decreased to 17±14.65%, 24.52±20.66%, respectively, CBV dropped to 62±18.56% and 59±18.48%. And the absolute SO2 decreased by 40.52±22.42% and 54.24±11.77%. After 180-min MCAO, the changes in hemodynamics and oxygen metabolism were also quantified. The study suggested that combining LSI and PAM provides an attractive approach for stroke detection in small animal studies.

  2. Mismatch of Low Perfusion and High Permeability Predicts Hemorrhagic Transformation Region in Acute Ischemic Stroke Patients Treated with Intra-arterial Thrombolysis

    PubMed Central

    Chen, Hui; Liu, Nan; Li, Ying; Wintermark, Max; Jackson, Alan; Wu, Bing; Su, Zihua; Chen, Fei; Hu, Jun; Zhang, Yongwei; Zhu, Guangming

    2016-01-01

    This study sought to determine whether the permeability related parameter Ktrans, derived from computed tomography perfusion (CTP) imaging, can predict hemorrhagic transformation (HT) in patients with acute ischemic stroke who receive intra-arterial thrombolysis. Data from patients meeting the criterion were examined. CTP was performed and Ktrans maps were used to assess the permeability values in HT and non-HT regions. A receiver operating characteristic (ROC) curve was calculated, showing the sensitivity and specificity of Ktrans for predicting HT risk. Composite images were produced to illustrate the spatial correlations among perfusion, permeability changes and HT. This study examined 41 patients. Twenty-six patients had hemorrhagic infarction and 15 had parenchymal hemorrhage. The mean Ktrans value in HT regions was significantly lower than that in the non-HT regions (0.26 ± 0.21/min vs. 0.78 ± 0.64/min; P < 0.001). The ROC curve analysis identified an optimal cutoff value of 0.334/min for Ktrans to predict HT risk. Composite images suggested ischemic regions with low permeability, or the mismatch area of low perfusion and high permeability, more likely have HT. HT regions after intra-arterial thrombolysis had lower permeability values on Ktrans maps. The mismatch area of lower perfusion and higher permeability are more likely to develop HT. PMID:27302077

  3. Intravenous Administration of Cilostazol Nanoparticles Ameliorates Acute Ischemic Stroke in a Cerebral Ischemia/Reperfusion-Induced Injury Model.

    PubMed

    Nagai, Noriaki; Yoshioka, Chiaki; Ito, Yoshimasa; Funakami, Yoshinori; Nishikawa, Hiroyuki; Kawabata, Atsufumi

    2015-01-01

    It was reported that cilostazol (CLZ) suppressed disruption of the microvasculature in ischemic areas. In this study, we have designed novel injection formulations containing CLZ nanoparticles using 0.5% methylcellulose, 0.2% docusate sodium salt, and mill methods (CLZnano dispersion; particle size 81 ± 59 nm, mean ± S.D.), and investigated their toxicity and usefulness in a cerebral ischemia/reperfusion-induced injury model (MCAO/reperfusion mice). The pharmacokinetics of injections of CLZnano dispersions is similar to that of CLZ solutions prepared with 2-hydroxypropyl-β-cyclodextrin, and no changes in the rate of hemolysis of rabbit red blood cells, a model of cell injury, were observed with CLZnano dispersions. In addition, the intravenous injection of 0.6 mg/kg CLZnano dispersions does not affect the blood pressure and blood flow, and the 0.6 mg/kg CLZnano dispersions ameliorate neurological deficits and ischemic stroke in MCAO/reperfusion mice. It is possible that the CLZnano dispersions will provide effective therapy for ischemic stroke patients, and that injection preparations of lipophilic drugs containing drug nanoparticles expand their therapeutic usage. PMID:26690139

  4. DIGE Proteome Analysis Reveals Suitability of Ischemic Cardiac In Vitro Model for Studying Cellular Response to Acute Ischemia and Regeneration

    PubMed Central

    Haas, Sina; Jahnke, Heinz-Georg; Moerbt, Nora; von Bergen, Martin; Aharinejad, Seyedhossein; Andrukhova, Olena; Robitzki, Andrea A.

    2012-01-01

    Proteomic analysis of myocardial tissue from patient population is suited to yield insights into cellular and molecular mechanisms taking place in cardiovascular diseases. However, it has been limited by small sized biopsies and complicated by high variances between patients. Therefore, there is a high demand for suitable model systems with the capability to simulate ischemic and cardiotoxic effects in vitro, under defined conditions. In this context, we established an in vitro ischemia/reperfusion cardiac disease model based on the contractile HL-1 cell line. To identify pathways involved in the cellular alterations induced by ischemia and thereby defining disease-specific biomarkers and potential target structures for new drug candidates we used fluorescence 2D-difference gel electrophoresis. By comparing spot density changes in ischemic and reperfusion samples we detected several protein spots that were differentially abundant. Using MALDI-TOF/TOF-MS and ESI-MS the proteins were identified and subsequently grouped by functionality. Most prominent were changes in apoptosis signalling, cell structure and energy-metabolism. Alterations were confirmed by analysis of human biopsies from patients with ischemic cardiomyopathy. With the establishment of our in vitro disease model for ischemia injury target identification via proteomic research becomes independent from rare human material and will create new possibilities in cardiac research. PMID:22384053

  5. C1q/TNF-related protein-1 functions to protect against acute ischemic injury in the heart.

    PubMed

    Yuasa, Daisuke; Ohashi, Koji; Shibata, Rei; Mizutani, Naoki; Kataoka, Yoshiyuki; Kambara, Takahiro; Uemura, Yusuke; Matsuo, Kazuhiro; Kanemura, Noriyoshi; Hayakawa, Satoko; Hiramatsu-Ito, Mizuho; Ito, Masanori; Ogawa, Hayato; Murate, Takashi; Murohara, Toyoaki; Ouchi, Noriyuki

    2016-03-01

    Obesity is associated with an increased risk of cardiovascular disease. C1q/TNF-related protein (CTRP)-1 is a poorly characterized adipokine that is up-regulated in association with ischemic heart disease. We investigated the role of CTRP1 in myocardial ischemia injury. CTRP1-knockout mice showed increased myocardial infarct size, cardiomyocyte apoptosis, and proinflammatory gene expression after I/R compared with wild-type (WT) mice. In contrast, systemic delivery of CTRP1 attenuated myocardial damage after I/R in WT mice. Treatment of cardiomyocytes with CTRP1 led to reduction of hypoxia-reoxygenation-induced apoptosis and lipopolysaccharide-stimulated expression of proinflammatory cytokines, which was reversed by inhibition of sphingosine-1-phosphate (S1P) signaling. Treatment of cardiomyocytes with CTRP1 also resulted in the increased production of cAMP, which was blocked by suppression of S1P signaling. The antiapoptotic and anti-inflammatory actions of CTRP1 were cancelled by inhibition of adenylyl cyclase or knockdown of adiponectin receptor 1. Furthermore, blockade of S1P signaling reversed CTRP1-mediated inhibition of myocardial infarct size, apoptosis, and inflammation after I/R in vivo. These data indicate that CTRP1 protects against myocardial ischemic injury by reducing apoptosis and inflammatory response through activation of the S1P/cAMP signaling pathways in cardiomyocytes, suggesting that CTRP1 plays a crucial role in the pathogenesis of ischemic heart disease.

  6. Intravenous Administration of Cilostazol Nanoparticles Ameliorates Acute Ischemic Stroke in a Cerebral Ischemia/Reperfusion-Induced Injury Model

    PubMed Central

    Nagai, Noriaki; Yoshioka, Chiaki; Ito, Yoshimasa; Funakami, Yoshinori; Nishikawa, Hiroyuki; Kawabata, Atsufumi

    2015-01-01

    It was reported that cilostazol (CLZ) suppressed disruption of the microvasculature in ischemic areas. In this study, we have designed novel injection formulations containing CLZ nanoparticles using 0.5% methylcellulose, 0.2% docusate sodium salt, and mill methods (CLZnano dispersion; particle size 81 ± 59 nm, mean ± S.D.), and investigated their toxicity and usefulness in a cerebral ischemia/reperfusion-induced injury model (MCAO/reperfusion mice). The pharmacokinetics of injections of CLZnano dispersions is similar to that of CLZ solutions prepared with 2-hydroxypropyl-β-cyclodextrin, and no changes in the rate of hemolysis of rabbit red blood cells, a model of cell injury, were observed with CLZnano dispersions. In addition, the intravenous injection of 0.6 mg/kg CLZnano dispersions does not affect the blood pressure and blood flow, and the 0.6 mg/kg CLZnano dispersions ameliorate neurological deficits and ischemic stroke in MCAO/reperfusion mice. It is possible that the CLZnano dispersions will provide effective therapy for ischemic stroke patients, and that injection preparations of lipophilic drugs containing drug nanoparticles expand their therapeutic usage. PMID:26690139

  7. Interleukin 6 promoter 174 G/C polymorphisms in acute ischemic stroke: G allele is protective but not associated with IL-6 levels or stroke outcome.

    PubMed

    Yan, J; J M, Greer; P A, McCombe

    2016-04-15

    Our study investigated the frequency of interleukin-6 (IL-6) promoter polymorphism rs1800795 (-174 G>C), possible association of this polymorphism with IL-6 levels and the outcome after stroke in 95 patients with acute ischemic stroke and 268 healthy subjects. It shows a significant reduction in the frequency of G alleles in stroke patients compared to healthy controls. Carriage of G allele is not associated with stroke subtypes, the initial severity or the outcome after stroke. The -174 polymorphisms were not associated with variation in IL-6 levels post-stroke. Our results indicate that IL-6 promoter -174 polymorphisms may play a role in susceptibility to stroke, but not stroke outcome.

  8. Utilization of a New Intracranial Support Catheter as an Intermediate Aspiration Catheter in the Treatment of Acute Ischemic Stroke: Technical Report on Initial Experience

    PubMed Central

    Lozano, J. Diego; Massari, Francesco; Howk, Mary C; de Macedo Rodrigues, Katyucia; Brooks, Christopher; Perras, Mary; Rex, David E; Wakhloo, Ajay K; Kühn, Anna Luisa

    2016-01-01

    The endovascular management of acute ischemic stroke (AIS) due to emergency large vessel occlusion (ELVO) has become the standard of care after the recent publication of landmark randomized, controlled trials. Mechanical thrombectomy, in addition to intravenous thrombolysis (within 4.5 hours when eligible), is now part of the algorithm of the standard of care when treating AIS in patients with ELVO in the anterior circulation up to six hours after symptom onset. A newly introduced device, the Arc™ intracranial support catheter (Medtronic, Irvine, USA), is specifically designed for the introduction of neurointerventional devices into the cerebral vasculature and facilitates the delivery of microcatheters into smaller, more distal intracranial vessels. This technical report describes the use of the Arc™ intracranial support catheter in the setting of AIS. PMID:27382525

  9. Prevalence, causes and risk factors of hospital readmissions after acute stroke and transient ischemic attack: a systematic review and meta-analysis.

    PubMed

    Zhong, Weibin; Geng, Na; Wang, Pengfei; Li, Zhenguang; Cao, Lili

    2016-08-01

    Acute stroke and transient ischemic attack (TIA) is a great burden not only during hospitalization but also after hospital discharge. The objective of this meta-analysis was to evaluate the hospital readmissions, causes and risk factors after survival of acute stroke and TIA. Pubmed, Web of Science, Cochrane Library, OVID and EMBASE databases were searched to identify studies reporting hospital readmissions after acute stroke and TIA. The primary outcomes were hospital readmission rates during 30 days and 1 year after discharge. The primary causes and risk factors of hospital readmissions were also identified. Ten studies with 253,680 patients were eligible for inclusion. The pooled 30-day and 1-year hospital readmission rates were 17.4 % (95 % CI, 12.7-23.5 %) and 42.5 % (95 % CI, 34.1-51.3 %), respectively. The three major causes of 30-day hospital readmissions were infection (19.9 %), coronary artery disease (CAD) (17.8 %) and recurrent stroke (16.0 %) successively, while the three major causes were recurrent stroke (19.4 %), infection (19.3 %) and CAD (16.3 %) during 1 year's follow-up. There were more patients with CAD in readmits group than that in control group (p = 0.030). The length of index admission, defined as any eligible admission to an acute care hospital assessed in the measure for the outcome, was longer (p = 0.000) and admission National Institutes of Health Stroke Score (NIHSS) was higher (p = 0.002) in readmits group than these in control group. In conclusion, there is high risk of early and long-term hospital readmissions after survival of acute stroke and TIA. These patients with coronary artery disease, longer length of index admission and higher NIHSS deserve deep attention after hospital discharge.

  10. Prevalence, causes and risk factors of hospital readmissions after acute stroke and transient ischemic attack: a systematic review and meta-analysis.

    PubMed

    Zhong, Weibin; Geng, Na; Wang, Pengfei; Li, Zhenguang; Cao, Lili

    2016-08-01

    Acute stroke and transient ischemic attack (TIA) is a great burden not only during hospitalization but also after hospital discharge. The objective of this meta-analysis was to evaluate the hospital readmissions, causes and risk factors after survival of acute stroke and TIA. Pubmed, Web of Science, Cochrane Library, OVID and EMBASE databases were searched to identify studies reporting hospital readmissions after acute stroke and TIA. The primary outcomes were hospital readmission rates during 30 days and 1 year after discharge. The primary causes and risk factors of hospital readmissions were also identified. Ten studies with 253,680 patients were eligible for inclusion. The pooled 30-day and 1-year hospital readmission rates were 17.4 % (95 % CI, 12.7-23.5 %) and 42.5 % (95 % CI, 34.1-51.3 %), respectively. The three major causes of 30-day hospital readmissions were infection (19.9 %), coronary artery disease (CAD) (17.8 %) and recurrent stroke (16.0 %) successively, while the three major causes were recurrent stroke (19.4 %), infection (19.3 %) and CAD (16.3 %) during 1 year's follow-up. There were more patients with CAD in readmits group than that in control group (p = 0.030). The length of index admission, defined as any eligible admission to an acute care hospital assessed in the measure for the outcome, was longer (p = 0.000) and admission National Institutes of Health Stroke Score (NIHSS) was higher (p = 0.002) in readmits group than these in control group. In conclusion, there is high risk of early and long-term hospital readmissions after survival of acute stroke and TIA. These patients with coronary artery disease, longer length of index admission and higher NIHSS deserve deep attention after hospital discharge. PMID:27129874

  11. A polymorphism in the promoter region of the survivin gene is related to hemorrhagic transformation in patients with acute ischemic stroke.

    PubMed

    Mallolas, Judith; Rodríguez, Rocío; Gubern, Carme; Camós, Susanna; Serena, Joaquín; Castellanos, Mar

    2014-12-01

    Hemorrhagic transformation (HT) of cerebral infarction is a common and serious occurrence following acute ischemic stroke. The expression of survivin, a member of the inhibitor of apoptosis protein family, has been shown to increase after cerebral ischemia. This protein has been mainly located at the microvasculature within the infarcted and peri-infarcted area, so we aimed to investigate whether survivin gene polymorphisms, also known as BIRC5 gene, were associated with HT of cerebral infarction. Polymorphism screening of the BIRC5 gene was performed in 107 patients with a hemispheric ischemic stroke and 93 controls by polymerase chain reaction, single-strand conformation polymorphism and sequencing analysis. Genotype-phenotype correlation was performed in patients. MRI was carried out within 12 h of symptoms onset and at 72 ± 12 h. The presence of HT was determined on the second DWI sequence and classified according to ECASS II criteria. MMP-9 levels were analyzed at admission. Forty-nine patients (45.8%) had HT. The -241 C/T (rs17878467) polymorphism was identified in the promoter region of the survivin gene. The prevalence of the mutant allele (T) was similar in patients and controls (14 vs. 16%, respectively; P = 0.37). However, 9 (29%) patients with allele T had HT compared to 40 (52.6%) of wild-type (P = 0.021). Logistic regression analysis showed that the polymorphism was associated with a lower risk of HT (OR 0.16; 95% CI 0.04-0.65; P = 0.01). The -241 C/T polymorphism in the promoter region of the survivin gene is associated with a lower risk of HT in patients with ischemic stroke. It has recently been reported that the -241 C/T polymorphism increases survivin promoter activity, reinforcing the hypothesis that patients with the mutant allele may have increased survivin expression in the brain. Different mechanisms, including BBB protection by the inhibition or activation of different angiogenic growth factors and the inhibition of apoptosis during

  12. Bifidobacterium longum CCM 7952 Promotes Epithelial Barrier Function and Prevents Acute DSS-Induced Colitis in Strictly Strain-Specific Manner

    PubMed Central

    Srutkova, Dagmar; Schwarzer, Martin; Hudcovic, Tomas; Zakostelska, Zuzana; Drab, Vladimir; Spanova, Alena; Rittich, Bohuslav; Kozakova, Hana; Schabussova, Irma

    2015-01-01

    Background Reduced microbial diversity has been associated with inflammatory bowel disease (IBD) and probiotic bacteria have been proposed for its prevention and/or treatment. Nevertheless, comparative studies of strains of the same subspecies for specific health benefits are scarce. Here we compared two Bifidobacterium longum ssp. longum strains for their capacity to prevent experimental colitis. Methods Immunomodulatory properties of nine probiotic bifidobacteria were assessed by stimulation of murine splenocytes. The immune responses to B. longum ssp. longum CCM 7952 (Bl 7952) and CCDM 372 (Bl 372) were further characterized by stimulation of bone marrow-derived dendritic cell, HEK293/TLR2 or HEK293/NOD2 cells. A mouse model of dextran sulphate sodium (DSS)-induced colitis was used to compare their beneficial effects in vivo. Results The nine bifidobacteria exhibited strain-specific abilities to induce cytokine production. Bl 372 induced higher levels of both pro- and anti-inflammatory cytokines in spleen and dendritic cell cultures compared to Bl 7952. Both strains engaged TLR2 and contain ligands for NOD2. In a mouse model of DSS-induced colitis, Bl 7952, but not Bl 372, reduced clinical symptoms and preserved expression of tight junction proteins. Importantly, Bl 7952 improved intestinal barrier function as demonstrated by reduced FITC-dextran levels in serum. Conclusions We have shown that Bl 7952, but not Bl 372, protected mice from the development of experimental colitis. Our data suggest that although some immunomodulatory properties might be widespread among the genus Bifidobacterium, others may be rare and characteristic only for a specific strain. Therefore, careful selection might be crucial in providing beneficial outcome in clinical trials with probiotics in IBD. PMID:26218526

  13. [Intravenous administration of a tissue plasminogen activator beyond 3 hours of the onset of acute ischemic stroke--MRI-based decision making].

    PubMed

    Kakuda, Wataru; Abo, Masahiro

    2008-10-01

    After large CT-based clinical trials have failed to prove the benefits of intravenous tissue plasminogen activator (tPA) administration for ischemic stroke patients beyond 3 hours of the onset of the concept of PWI/DWI mismatch which is the volume difference between a PWI lesion and DWI lesion on MRI scans, has been proposed to facilitate the selection of patients with a salvageable area. PWI/DWI mismatch is considered to represent the tissue that is not irreversibly injured and can respond to early reperfusion therapy. When an ischemic lesion is divided into 4 regions, namely, ischemic core, reversible DWI lesion, penumbra and benign oligemia, both the reversible DWI lesion and penumbra are considered to be an optimal targets for thrombolysis. In order to clarify the clinical significance of PWI/DWI mismatch in the selection of candidates for tPA therapy, some multicenter trials were performed. The results of DIAS (desmoteplase in acute ischemic stroke)/DEDAS (dose escalation of desmoteplase for acute ischemic stroke)/DIAS-2 did not difinitly demonstrate the clinical benefits of desmoteplase administration in patients with PWI/DWI mismatch between 3 to 9 hours of onset; in fact, DIAS-2 could not prove any effect of the drug. DEFUSE (diffusion and perfusion imaging evaluation for understanding stroke evolution), in which tPA was administered to all participants between 3 to 6 hours of stroke onset, showed that the occurrence of early reperfusion led to a favorable clinical response in patients with PWI/DWI mismatch. In contrast, early reperfusion was not beneficial in patients without PWI/DWI mismatch. In EPITHET (echoplanar imaging thrombolysis evaluation trial), stroke patients who showed PWI/DWI mismatch after 3 to 6 hours of the onset were assigned to receive either alteplase or placebo administration: lesion growth was lesser in patients with alteplase than in those who received placebo, although the difference was not statistically significant because of a

  14. Rosmarinus officinalis L. extract ameliorates intestinal inflammation through MAPKs/NF-κB signaling in a murine model of acute experimental colitis.

    PubMed

    Medicherla, Kanakaraju; Ketkar, Avanee; Sahu, Bidya Dhar; Sudhakar, Godi; Sistla, Ramakrishna

    2016-07-13

    We investigated the anti-inflammatory and anti-colitis effects of Rosmarinus officinalis L. extract (RE) by using both in vitro LPS-activated mouse RAW 264.7 macrophages and in vivo dextran sulfate sodium (DSS)-induced experimental murine colitis and suggested the underlying possible mechanisms. Liquid Chromatography-Mass Spectrometry (LC-MS) analysis was performed to identify the major components present in the RE. The clinical signs, biochemistry, immunoblot, ELISA and histology in colon tissues were assessed in order to elucidate the beneficial effect of RE. RE suppressed the LPS-induced pro-inflammatory cytokine production and the expressions of inflammatory proteins in macrophages. Administration of RE (50 and 100 mg kg(-1)) also significantly reduced the severity of DSS-induced murine colitis, as assessed by the clinical symptoms, colon length and histology. RE administration prevented the DSS-induced activation of p38, ERK and JNK MAPKs, attenuated IκBα phosphorylation and subsequent nuclear translocation and DNA binding of NF-κB (p65). RE also suppressed the COX-2 and iNOS expressions, decreased the levels of TNF-α and IL-6 cytokines and the myeloperoxidase activity in the colon tissue. Histological observation revealed that RE administration alleviated mucosal damage and inflammatory cell infiltration induced by DSS in the colon tissue. Hence, RE could be used as a new preventive and therapeutic food ingredient or as a dietary supplement for inflammatory bowel disease. PMID:27349640

  15. Acute ischemic stroke in a 19 month old following minor head trauma: case report and review of the literature.

    PubMed

    Garla, Vishnu; Pino, Eduardo; Coulon, Richard; Wolfer, Rebecca

    2014-01-01

    Minor head trauma is a very rare cause of ischemic stroke in the pediatric population. We describe a nineteen month old patient who developed left hemiparesis and subsequently left facial palsy after a fall. MRI of the brain showed hypodensities in the basal ganglia, internal capsule and caudate nucleus consistent with stroke. Echocardiogram and MRA were normal. Hypercoaguable work up showed that the patient was a carrier for a single MTHFR gene. The patient was treated conservatively. On follow up two weeks later his facial palsy had resolved and strength in the extremities improved. Although a rare condition awareness about this is necessary as there can be considerable delay in its recognition.

  16. Complications of collagenous colitis.

    PubMed

    Freeman, Hugh-James

    2008-03-21

    Microscopic forms of colitis have been described, including collagenous colitis. This disorder generally has an apparently benign clinical course. However, a number of gastric and intestinal complications, possibly coincidental, may develop with collagenous colitis. Distinctive inflammatory disorders of the gastric mucosa have been described, including lymphocytic gastritis and collagenous gastritis. Celiac disease and collagenous sprue (or collagenous enteritis) may occur. Colonic ulceration has been associated with use of nonsteroidal anti-inflammatory drugs, while other forms of inflammatory bowel disease, including ulcerative colitis and Crohn's disease, may evolve from collagenous colitis. Submucosal "dissection", colonic fractures or mucosal tears and perforation from air insufflation during colonoscopy may occur and has been hypothesized to be due to compromise of the colonic wall from submucosal collagen deposition. Similar changes may result from increased intraluminal pressure during barium enema contrast studies. Finally, malignant disorders have also been reported, including carcinoma and lymphoproliferative disease. PMID:18350593

  17. Successful outcome after endovascular thrombolysis for acute ischemic stroke with basis on perfusion-diffusion mismatch after 24 h of symptoms onset

    PubMed Central

    Mattei, Tobias A.; Rehman, Azeem A.; Goulart, Carlos R.; Sória, Marília G.; Rizelio, Vanessa; Meneses, Murilo S.

    2016-01-01

    Background: Although intravenous thrombolysis is the Food and Drug Administration-approved treatment for acute ischemic stroke (AIS) within 3 h, combined intravenous and intra-arterial thrombolysis with endovascular techniques may be able to extend this traditional time window. Case Description: We present the clinical evolution of a 45-year-old male presenting with acute left hemiparesis. Magnetic resonance imaging revealed a small diffusion restriction at the right basal ganglia with perfusion compromise in the entire right middle cerebral artery (MCA) territory. Angiography revealed a complete occlusion of MCA at its M1 segment. The patient underwent endovascular mechanical thrombectomy with additional intra-arterial thrombolysis more than 24 hours after the onset of the initial symptoms and experienced complete vessel recanalization. At 1 year, the patient had global independence with minor residual motor impairment in the left arm. Conclusions: We report the case of a successful thrombolytic therapy following AIS performed more than 24 h after the initial symptoms based on the presence of a perfusion-diffusion mismatch. This report is expected to stimulate the development of future prospective studies with special focus on the role of perfusion-diffusion mismatch in patient selection for treatment of AIS, especially in those presenting outside the traditional time window. PMID:27313971

  18. Is there more valuable information in PWI datasets for a voxel-wise acute ischemic stroke tissue outcome prediction than what is represented by typical perfusion maps?

    NASA Astrophysics Data System (ADS)

    Forkert, Nils Daniel; Siemonsen, Susanne; Dalski, Michael; Verleger, Tobias; Kemmling, Andre; Fiehler, Jens

    2014-03-01

    The acute ischemic stroke is a leading cause for death and disability in the industry nations. In case of a present acute ischemic stroke, the prediction of the future tissue outcome is of high interest for the clinicians as it can be used to support therapy decision making. Within this context, it has already been shown that the voxel-wise multi-parametric tissue outcome prediction leads to more promising results compared to single channel perfusion map thresholding. Most previously published multi-parametric predictions employ information from perfusion maps derived from perfusion-weighted MRI together with other image sequences such as diffusion-weighted MRI. However, it remains unclear if the typically calculated perfusion maps used for this purpose really include all valuable information from the PWI dataset for an optimal tissue outcome prediction. To investigate this problem in more detail, two different methods to predict tissue outcome using a k-nearest-neighbor approach were developed in this work and evaluated based on 18 datasets of acute stroke patients with known tissue outcome. The first method integrates apparent diffusion coefficient and perfusion parameter (Tmax, MTT, CBV, CBF) information for the voxel-wise prediction, while the second method employs also apparent diffusion coefficient information but the complete perfusion information in terms of the voxel-wise residue functions instead of the perfusion parameter maps for the voxel-wise prediction. Overall, the comparison of the results of the two prediction methods for the 18 patients using a leave-one-out cross validation revealed no considerable differences. Quantitatively, the parameter-based prediction of tissue outcome led to a mean Dice coefficient of 0.474, while the prediction using the residue functions led to a mean Dice coefficient of 0.461. Thus, it may be concluded from the results of this study that the perfusion parameter maps typically derived from PWI datasets include all

  19. Analysis of Workflow and Time to Treatment and the Effects on Outcome in Endovascular Treatment of Acute Ischemic Stroke: Results from the SWIFT PRIME Randomized Controlled Trial.

    PubMed

    Goyal, Mayank; Jadhav, Ashutosh P; Bonafe, Alain; Diener, Hans; Mendes Pereira, Vitor; Levy, Elad; Baxter, Blaise; Jovin, Tudor; Jahan, Reza; Menon, Bijoy K; Saver, Jeffrey L

    2016-06-01

    Purpose To study the relationship between functional independence and time to reperfusion in the Solitaire with the Intention for Thrombectomy as Primary Endovascular Treatment for Acute Ischemic Stroke (SWIFT PRIME) trial in patients with disabling acute ischemic stroke who underwent endovascular therapy plus intravenous tissue plasminogen activator (tPA) administration versus tPA administration alone and to investigate variables that affect time spent during discrete steps. Materials and Methods Data were analyzed from the SWIFT PRIME trial, a global, multicenter, prospective study in which outcomes were compared in patients treated with intravenous tPA alone or in combination with the Solitaire device (Covidien, Irvine, Calif). Between December 2012 and November 2014, 196 patients were enrolled. The relation between time from (a) symptom onset to reperfusion and (b) imaging to reperfusion and clinical outcome was analyzed, along with patient and health system characteristics that affect discrete steps in patient workflow. Multivariable logistic regression was used to assess relationships between time and outcome; negative binomial regression was used to evaluate effects on workflow. The institutional review board at each site approved the trial. Patients provided written informed consent, or, at select sites, there was an exception from having to acquire explicit informed consent in emergency circumstances. Results In the stent retriever arm of the study, symptom onset to reperfusion time of 150 minutes led to 91% estimated probability of functional independence, which decreased by 10% over the next hour and by 20% with every subsequent hour of delay. Time from arrival at the emergency department to arterial access was 90 minutes (interquartile range, 69-120 minutes), and time to reperfusion was 129 minutes (interquartile range, 108-169 minutes). Patients who initially arrived at a referring facility had longer symptom onset to groin puncture times compared with

  20. Effects of Dietary Glutamine on the Homeostasis of CD4+ T Cells in Mice with Dextran Sulfate Sodium-Induced Acute Colitis

    PubMed Central

    Hsiung, Yuan-Chin; Liu, Jun-Jen; Hou, Yu-Chen; Yeh, Chiu-Li; Yeh, Sung-Ling

    2014-01-01

    This study investigated the effects of dietary glutamine (Gln) on T-helper (Th) and T regulatory (Treg) cell homeostasis and colonic inflammatory mediator expression in mice with dextran sulfate sodium (DSS)-induced colitis. Mice were randomly assigned to 4 groups with 2 normal control (C and G) and 2 DSS-treated groups (DC and DG). The C and DC groups were fed a common semipurified diet, while the G and DG groups received an identical diet except that part of the casein was replaced by Gln, which provided 25% of the total amino acid nitrogen. Mice were fed the diets for 10 days. On day 6, mice in the normal control groups were given distilled water, while those in the DSS groups were given distilled water containing 1.5% DSS for 5 d. At the end of the experiment, the mice were sacrificed for further examination. Results showed that DC group had higher plasma haptoglobin, colonic weight, immunoglobulin G, inflammatory cytokine and nuclear factor (NF)-κB protein levels. Gln administration lowered inflammatory mediators and NF-κB/IκBα ratio in colitis. Compared with the DC group, the percentages of interleukin-17F and interferon-γ in blood and transcription factors, T-bet and RAR-related orphan receptor-γt, gene expressions in mesenteric lymph nodes were lower, whereas blood Foxp3 was higher in the DG group. Also, DG group had lower colon injury score. These results suggest that Gln administration suppressed Th1/Th17 and Th-associated cytokine expressions and upregulated the expression of Tregs, which may modulate the balance of Th/Treg and reduce inflammatory reactions in DSS-induced colitis. PMID:24416230

  1. Clinical factors associated with statins prescription in acute ischemic stroke patients: findings from the Lombardia Stroke Registry

    PubMed Central

    2014-01-01

    Background Statins, due to their well-established pleiotropic effects, have noteworthy benefits in stroke prevention. Despite this, a significant proportion of high-risk patients still do not receive the recommended therapeutic regimens, and many others discontinue treatment after being started on them. The causes of non-adherence to current guidelines are multifactorial, and depend on both physicians and patients. The aim of this study is to identify the factors influencing statin prescription at Stroke Unit (SU) discharge. Methods This study included 12,750 patients enrolled on the web-based Lombardia Stroke Registry (LRS) from July 2009 to April 2012 and discharged alive, with a diagnosis of ischemic stroke or transient ischemic attack (TIA) and without contra-indication to statin therapy. By logistic regression analysis and classification trees, we evaluated the impact of demographic data, risk factors, tPA treatment, in-hospital procedures and complications on statin prescription rate at discharge. Results We observed a slight increase in statins prescription during the study period (from 39.1 to 43.9%). Lower age, lower stroke severity and prestroke disability, the presence of atherothrombotic/lacunar risk factors, a diagnosis of non-cardioembolic stroke, tPA treatment, the absence of in-hospital complications, with the sole exception of hypertensive fits and hyperglycemia, were the patient-related predictors of adherence to guidelines by physicians. Overall, dyslipidemia appears as the leading factor, while TOAST classification does not reach statistical significance. Conclusions In our region, Lombardia, adherence to guidelines in statin prescription at Stroke Unit discharge is very different from international goals. The presence of dyslipidemia remains the main factor influencing statin prescription, while the presence of well-defined atherosclerotic etiopathogenesis of stroke does not enhance statin prescription. Some uncertainties about the risk

  2. Current treatment of ST elevation acute myocardial infarction in Japan: door-to-balloon time and total ischemic time from the J-AMI registry.

    PubMed

    Nakamura, Masato; Yamagishi, Masakazu; Ueno, Takafumi; Hara, Kazuhiro; Ishiwata, Sugao; Itoh, Tomonori; Hamanaka, Ichiro; Wakatsuki, Tetsuzo; Wakatsuki, Tetuszo; Sugano, Teruyasu; Kawai, Kazuya; Kimura, Takeshi

    2013-01-01

    The door-to-balloon time and total ischemic time are important predictors of the outcome in patients with ST elevation myocardial infarction (STEMI) receiving primary angioplasty, but the current situation in Japan is unknown. The Japan Acute Myocardial Infarction registry is a prospective observational study of 2,030 consecutive STEMI patients admitted to 213 Japanese institutions. The time from symptom onset to hospital arrival, door-to-balloon time, and in-hospital outcome were assessed. Data were compared between patients treated during regular hours or after hours. Percutaneous coronary angioplasty was done in 97.2 % of the patients, using drug-eluting stents in 30 % and bare metal stents in 63 % of the treated cases. The median symptom onset-to-door time (25th and 75th percentiles) was 135 min (64-305 min), median door-to-balloon time was 42 min (28-66 min), and mean procedural time was 98 ± 51 min. The on-call catheterization team performed 48.5 % of the procedures. There was no significant difference of door-to-balloon time between the patients treated after hours and those treated during regular hours. The cardiac mortality rate was 3.2 %, and it increased with longer door-to-balloon times (P = 0.03). The relationship between total ischemic time and cardiac mortality showed 2 peaks, with a trough at 5 h. Median door-to-balloon time was <90 min and was not longer in after hours cases. These findings suggest that Japanese institutions can provide primary angioplasty within an acceptable time frame. PMID:22983884

  3. Remote Ischemic Conditioning: Its Benefits and Limitations.

    PubMed

    Kloner, Robert A

    2016-03-01

    This editorial describes benefits and limitations of remote ischemic conditioning. Remote ischemic conditioning was shown to reduce myocardial intact size in at least 4 sizeable clinical trials of acute myocardial infarction. It was not effective in recent studies of cardiac surgery. Reasons for these differences are discussed.

  4. Effect of sample size on multi-parametric prediction of tissue outcome in acute ischemic stroke using a random forest classifier

    NASA Astrophysics Data System (ADS)

    Forkert, Nils Daniel; Fiehler, Jens

    2015-03-01

    The tissue outcome prediction in acute ischemic stroke patients is highly relevant for clinical and research purposes. It has been shown that the combined analysis of diffusion and perfusion MRI datasets using high-level machine learning techniques leads to an improved prediction of final infarction compared to single perfusion parameter thresholding. However, most high-level classifiers require a previous training and, until now, it is ambiguous how many subjects are required for this, which is the focus of this work. 23 MRI datasets of acute stroke patients with known tissue outcome were used in this work. Relative values of diffusion and perfusion parameters as well as the binary tissue outcome were extracted on a voxel-by- voxel level for all patients and used for training of a random forest classifier. The number of patients used for training set definition was iteratively and randomly reduced from using all 22 other patients to only one other patient. Thus, 22 tissue outcome predictions were generated for each patient using the trained random forest classifiers and compared to the known tissue outcome using the Dice coefficient. Overall, a logarithmic relation between the number of patients used for training set definition and tissue outcome prediction accuracy was found. Quantitatively, a mean Dice coefficient of 0.45 was found for the prediction using the training set consisting of the voxel information from only one other patient, which increases to 0.53 if using all other patients (n=22). Based on extrapolation, 50-100 patients appear to be a reasonable tradeoff between tissue outcome prediction accuracy and effort required for data acquisition and preparation.

  5. Lebetin 2, a Snake Venom-Derived Natriuretic Peptide, Attenuates Acute Myocardial Ischemic Injury through the Modulation of Mitochondrial Permeability Transition Pore at the Time of Reperfusion

    PubMed Central

    Tourki, Bochra; Matéo, Philippe; Morand, Jessica; Elayeb, Mohamed; Godin-Ribuot, Diane; Marrakchi, Naziha; Belaidi, Elise; Messadi, Erij

    2016-01-01

    Cardiac ischemia is one of the leading causes of death worldwide. It is now well established that natriuretic peptides can attenuate the development of irreversible ischemic injury during myocardial infarction. Lebetin 2 (L2) is a new discovered peptide isolated from Macrovipera lebetina venom with structural similarity to B-type natriuretic peptide (BNP). Our objectives were to define the acute cardioprotective actions of L2 in isolated Langendorff-perfused rat hearts after regional or global ischemia-reperfusion (IR). We studied infarct size, left ventricular contractile recovery, survival protein kinases and mitochondrial permeability transition pore (mPTP) opening in injured myocardium. L2 dosage was determined by preliminary experiments at its ability to induce cyclic guanosine monophosphate (cGMP) release without changing hemodynamic effects in normoxic hearts. L2 was found to be as effective as BNP in reducing infarct size after the induction of either regional or global IR. Both peptides equally improved contractile recovery after regional IR, but only L2 increased coronary flow and reduced severe contractile dysfunction after global ischemia. Cardioprotection afforded by L2 was abolished after isatin or 5-hydroxydecanote pretreatment suggesting the involvement of natriuretic peptide receptors and mitochondrial KATP (mitoKATP) channels in the L2-induced effects. L2 also increased survival protein expression in the reperfused myocardium as evidenced by phosphorylation of signaling pathways PKCε/ERK/GSK3β and PI3K/Akt/eNOS. IR induced mitochondrial pore opening, but this effect was markedly prevented by L2 treatment. These data show that L2 has strong cardioprotective effect in acute ischemia through stimulation of natriuretic peptide receptors. These beneficial effects are mediated, at least in part, by mitoKATP channel opening and downstream activated survival kinases, thus delaying mPTP opening and improving IR-induced mitochondrial dysfunction. PMID

  6. Lebetin 2, a Snake Venom-Derived Natriuretic Peptide, Attenuates Acute Myocardial Ischemic Injury through the Modulation of Mitochondrial Permeability Transition Pore at the Time of Reperfusion.

    PubMed

    Tourki, Bochra; Matéo, Philippe; Morand, Jessica; Elayeb, Mohamed; Godin-Ribuot, Diane; Marrakchi, Naziha; Belaidi, Elise; Messadi, Erij

    2016-01-01

    Cardiac ischemia is one of the leading causes of death worldwide. It is now well established that natriuretic peptides can attenuate the development of irreversible ischemic injury during myocardial infarction. Lebetin 2 (L2) is a new discovered peptide isolated from Macrovipera lebetina venom with structural similarity to B-type natriuretic peptide (BNP). Our objectives were to define the acute cardioprotective actions of L2 in isolated Langendorff-perfused rat hearts after regional or global ischemia-reperfusion (IR). We studied infarct size, left ventricular contractile recovery, survival protein kinases and mitochondrial permeability transition pore (mPTP) opening in injured myocardium. L2 dosage was determined by preliminary experiments at its ability to induce cyclic guanosine monophosphate (cGMP) release without changing hemodynamic effects in normoxic hearts. L2 was found to be as effective as BNP in reducing infarct size after the induction of either regional or global IR. Both peptides equally improved contractile recovery after regional IR, but only L2 increased coronary flow and reduced severe contractile dysfunction after global ischemia. Cardioprotection afforded by L2 was abolished after isatin or 5-hydroxydecanote pretreatment suggesting the involvement of natriuretic peptide receptors and mitochondrial KATP (mitoKATP) channels in the L2-induced effects. L2 also increased survival protein expression in the reperfused myocardium as evidenced by phosphorylation of signaling pathways PKCε/ERK/GSK3β and PI3K/Akt/eNOS. IR induced mitochondrial pore opening, but this effect was markedly prevented by L2 treatment. These data show that L2 has strong cardioprotective effect in acute ischemia through stimulation of natriuretic peptide receptors. These beneficial effects are mediated, at least in part, by mitoKATP channel opening and downstream activated survival kinases, thus delaying mPTP opening and improving IR-induced mitochondrial dysfunction. PMID

  7. Development of Computerized Scheme for Adjustment of Display Grayscale in Brain Diffusion-Weighted Magnetic Resonance Images with Acute Ischemic Stroke

    NASA Astrophysics Data System (ADS)

    Nagashima, Hiroyuki; Harakawa, Tetsumi; Doi, Kunio

    We developed a computerized scheme for proper adjustment of display grayscale in brain diffusion-weighted magnetic resonance images (DWI) with acute ischemic stroke by using thalamic signal intensity on concurrent images (b0 image). In our computerized scheme, the gray level of b0 image was first normalized, and the brain region was segmented using thresholding and labeling techniques. The lateral inclination in b0 image was then corrected semi-automatically by rotating and shifting. Each of the thalamic positions was determined by using the coordinate information in the brain region. The average signal intensity of the thalamus was measured on the region of interest (ROI) selected, and the thalamus in one side with the low signal intensity was selected. The display grayscale in DWI was finally adjusted by using the signal intensity of the selected thalamus. The thalamus positions in all cases were confirmed to be included in the thalamic outline. In 30 training cases, the average error between the thalamic signal intensity obtained from the manual selection and the computerized scheme were 1.8%±1.5, and in 30 testing cases, 1.3%±1.2. Our computerized scheme has a potential in the determination of the display grayscale of brain DWI, and would be useful to radiologists in decision-making for radiological diagnosis.

  8. Resolving Thrombus in the Left Atrial Appendage by Edoxaban Treatment after Acute Ischemic Stroke: Report of 2 Cases.

    PubMed

    Saito, Shin; Shindo, Seigo; Tsudaka, Shun; Uchida, Kazutaka; Shirakawa, Manabu; Yoshimura, Shinichi

    2016-10-01

    Here we report first 2 cases of patients with nonvalvular atrial fibrillation with acute cardioembolic stroke in whom thrombi in the left atrial appendage (LAA) were resolved by edoxaban administration. Case 1 reports an 86-year-old woman who suddenly showed right hemiparesis and aphasia due to occlusion of the left middle cerebral artery. She received mechanical thrombectomy and recovered neurologically. Transesophageal echocardiography (TEE) performed on day 1 demonstrated thrombus in the LAA. The thrombus was resolved on day 13 after initiation of edoxaban (30 mg once daily) instead of warfarin, which was administered before stroke onset. Case 2 reports a 49-year-old man who was admitted because of the sudden onset of left hemiparesis and aphasia. TEE demonstrated thrombus in the LAA on day 4, and edoxaban therapy (60 mg once daily) was initiated. The thrombus resolution was observed on day 16, and no embolic stroke occurred. PMID:27562709

  9. Emodin-mediated protection from acute myocardial infarction via inhibition of inflammation and apoptosis in local ischemic myocardium.

    PubMed

    Wu, Yanxia; Tu, Xin; Lin, Guosheng; Xia, Hao; Huang, Hao; Wan, Jing; Cheng, Zhide; Liu, Mengyuan; Chen, Gao; Zhang, Haimou; Fu, Jinrong; Liu, Qian; Liu, Dong-Xu

    2007-10-13

    Acute myocardial infarction (AMI) is associated with inflammation and apoptosis. Emodin plays an anti-inflammatory role in several inflammatory diseases. Recent studies have demonstrated that emodin protects against myocardial ischemia/reperfusion injury. However, its mechanism underlying its effects remains unknown. In a murine model of AMI, based on ligation of the left coronary artery, administration of emodin reduced myocardial infarct size (MIS) in a dose-dependent manner. Emodin significantly suppressed TNF-alpha expression and NF-kappaB activation in the local myocardial infarction area. Treatment with emodin inhibited myocardial cell apoptosis by inhibiting caspase-3 activation. Therefore, these studies demonstrate that emodin protects against myocardial cell injury via suppression of local inflammation and apoptosis.

  10. Ulcerative Colitis in Infancy

    PubMed Central

    Rukunuzzaman, Md; Karim, A. S. M. Bazlul

    2011-01-01

    Ulcerative colitis (UC) is a chronic idiopathic inflammatory disorder of colon. Frequency of UC is gradually increasing over few years worldwide. Prevalence is 35 to 100/100 000 people in USA, 1% of them are infants. UC develops in a genetically predisposed individual with altered intestinal immune response. An eight-month-old girl presented with loose bloody stool, growth failure, and moderate pallor. The girl was diagnosed as a case of UC by colonoscopy and biopsy. Treatment was thereafter started with immunosuppressive drugs. After initial induction therapy with parenteral steroid and infliximab, the patient is now on remission with azathioprine and mesalamine. UC is rare in Bangladesh, especially in children, and it is rarer during infancy. Several conditions like infective colitis, allergic colitis, Meckel's diverticulitis, Crohn's disease, etc. may mimic the features of UC. So, if a child presents with recurrent bloody diarrhea, UC should be considered as differential diagnosis. PMID:22064342

  11. Long-term prognosis of children with ulcerative colitis

    PubMed Central

    Goel, K. M.; Shanks, Robert A.

    1973-01-01

    The subsequent course of ulcerative colitis in 25 children admitted to hospital during the period 1931 to 1971 is reviewed. The period of observation averaged 24 years, ranging from 1 to 41 years. 19 patients showed extracolonic manifestations. 4 patients had a single attack of colitis, and in 19 the disease was of the chronic intermittent type. There was one case each of the acute fulminating and chronic continuous types. Three of 8 patients who had colectomy died postoperatively. One further patient died later of carcinoma of the rectal stump. At follow-up 5 patients (20%) had died and the remaining 20 (80%) were in remission. Although the case for surgery in the treatment of acute fulminating or resistant ulcerative colitis may be clear, that for prophylactic panproctocolectomy while the disease is in remission requires further study. PMID:4703063

  12. Efficacy and safety comparison of DL-3-n-butylphthalide and Cerebrolysin: Effects on neurological and behavioral outcomes in acute ischemic stroke

    PubMed Central

    XUE, LI-XIA; ZHANG, TING; ZHAO, YU-WU; GENG, ZHI; CHEN, JING-JIONG; CHEN, HAO

    2016-01-01

    Cerebrolysin and DL-3-n-butylphthalide (NBP) have each shown neuroprotective efficacy in preclinical models of acute ischemic stroke (AIS) and passed clinical trials as therapeutic drugs for AIS. The present study was a clinical trial to assess and compare the efficacy and safety of NBP and Cerebrolysin in the reduction of neurological and behavioral disability following AIS. A randomized, double-blind trial was conducted with enrolment of 60 patients within 12 h of AIS. In addition to routine treatment, patients were randomly assigned to receive a 10-day intravenous administration of NBP, Cerebrolysin or placebo. National Institutes of Health Stroke Scale (NIHSS) and Barthel Index (BI) scores were used to evaluate the efficacy of the treatment in the patients with AIS at 11 and 21 days after the initiation of therapy. Adverse events were also analyzed among the three groups. After 10 days of treatment with NBP or Cerebrolysin, the NIHSS and BI scores at day 21 showed statistical differences compared with those in the placebo group (P<0.05). The improvements of NIHSS and BI scores in the NBP and Cerebrolysin groups were higher than those in the placebo group at days 11 and 21 (P<0.05). A statistically significant difference in the improvement of 21-day NIHSS scores was observed between the two treatment groups (P<0.05). No significant difference was found among the three groups with regard to the rate of adverse events. Favorable outcomes and good safety were observed in the patients with moderate AIS treated with NBP or Cerebrolysin. The results indicate that NBP may be more effective than Cerebrolysin in improving short-term outcomes following AIS. This trial is registered at ClinicalTrials.gov with clinical trial identifier number NCT02149875. PMID:27168844

  13. The Prognostic Value of a Four-Dimensional CT Angiography-Based Collateral Grading Scale for Reperfusion Therapy in Acute Ischemic Stroke Patients

    PubMed Central

    Zhang, Sheng; Chen, Weili; Tang, Huan; Han, Quan; Yan, Shenqiang; Zhang, Xiaocheng; Chen, Qingmeng; Parsons, Mark; Wang, Shaoshi; Lou, Min

    2016-01-01

    Objective Leptomeningeal collaterals, which affects tissue fate, are still challenging to assess. Four-dimensional CT angiography (4D CTA) originated from CT perfusion (CTP) provides the possibility of non-invasive and time-resolved assessment of leptomeningeal collateral flow. We sought to develop a comprehensive rating system to integrate the speed and extent of collateral flow on 4D CTA, and investigate its prognostic value for reperfusion therapy in acute ischemic stroke (AIS) patients. Methods We retrospectively studied 80 patients with M1 ± internal carotid artery (ICA) occlusion who had baseline CTP before intravenous thrombolysis. The velocity and extent of collaterals were evaluated by regional leptomeningeal collateral score on peak phase (rLMC-P) and temporally fused intensity projections (tMIP) (rLMC-M) on 4D CTA, respectively. The cutoffs of rLMC-P and rLMC-M score for predicting good outcome (mRS score ≤ 2) were integrated to develop the collateral grading scale (CGS) (rating from 0–2). Results The CGS score was correlated with 3-months mRS score (non-recanalizers: ρ = -0.495, p = 0.01; recanalizers: ρ = -0.671, p < 0.001). Patients with intermediate or good collaterals (CGS score of 1 and 2) who recanalized were more likely to have good outcome than those without recanalization (p = 0.038, p = 0.018), while there was no significant difference in outcome in patients with poor collaterals (CGS score of 0) stratified by recanalization (p = 0.227). Conclusions Identification of collaterals based on CGS may help to select good responders to reperfusion therapy in patients with large artery occlusion. PMID:27505435

  14. Sex Differences in Outcomes and Associated Risk Factors After Acute Ischemic Stroke in Elderly Patients: A Prospective Follow-up Study.

    PubMed

    Li, Bin; Wang, Tao; Lou, Yongzhong; Guo, Xiaofei; Gu, Hongfei; Zhu, Yanxia; Ning, Xianjia; Wang, Jinghua; Tu, Jun

    2015-10-01

    Stroke has a greater effect on women. However, sex differences in outcome and factors associated with outcome among elderly patients are unknown. From January 2009 to December 2011, 810 patients with acute ischemic stroke aged 75 years or older were recruited in China. Clinical profile and risk factors were recorded. Outcomes and associated risk factors at 12 and 36 months after stroke were assessed by sex. Hypertension, diabetes mellitus, dyslipidemias, and obesity prevalence rates were higher in women than in men; opposite trends were found for smoking and alcohol consumption. The mortality rate at 12 months after stroke was significantly greater in men than in women (23.3% versus 16.6%, P = .015). Large-artery atherothrombotic and cardioembolic stroke subtypes were risk factors for mortality, recurrence, and dependency in both sexes. In men, atrial fibrillation was a risk factor of mortality at 12 months after stroke (relative ratio [RR], 2.12; 95% confidence interval [CI], 1.38-3.27), but obesity was a protective factor of mortality at 36 months after stroke (RR, .30; 95% CI, .10-.94). However, in women, atrial fibrillation was a risk factor of recurrence at 12 months (RR, 2.32; 95% CI, 1.31-4.12) and dependency at 36 months after stroke (RR, 7.68; 95% CI, 1.60-36.82). We assessed sex differences in stroke outcomes and associated risk factors at 12 and 36 months after stroke in a large hospital-based stroke registry of elderly patients from Northern China. Thus, it is crucial to emphasize risk management to elderly patients to reduce mortality, recurrence, and dependency after stroke.

  15. Fetal Kidney Cells Can Ameliorate Ischemic Acute Renal Failure in Rats through Their Anti-Inflammatory, Anti-Apoptotic and Anti-Oxidative Effects.

    PubMed

    Gupta, Ashwani Kumar; Jadhav, Sachin H; Tripathy, Naresh Kumar; Nityanand, Soniya

    2015-01-01

    Fetal kidney cells may contain multiple populations of kidney stem cells and thus appear to be a suitable cellular therapy for the treatment of acute renal failure (ARF) but their biological characteristics and therapeutic potential have not been adequately explored. We have culture expanded fetal kidney cells derived from rat fetal kidneys, characterized them and evaluated their therapeutic effect in an ischemia reperfusion (IR) induced rat model of ARF. The fetal kidney cells grew in culture as adherent spindle shaped/polygonal cells and expressed CD29, CD44, CD73, CD90, CD105, CD24 and CD133 markers. Administration of PKH26 labeled fetal kidney cells in ARF rats resulted in a significant decrease in the levels of blood urea nitrogen, creatinine, and neutrophil gelatinase-associated lipocalin and decreased tubular necrosis in the kidney tissues (p<0.05 for all). The injected fetal kidney cells were observed to engraft around injured tubular cells, and there was increased proliferation and decreased apoptosis of tubular cells in the kidneys (p<0.05 for both). In addition, the kidney tissues of ARF rats treated with fetal kidney cells had a higher gene expression of renotropic growth factors (VEGF-A, IGF-1, BMP-7 and bFGF) and anti-inflammatory cytokine (IL10); up regulation of anti-oxidative markers (HO-1 and NQO-1); and a lower Bax/Bcl2 ratio as compared to saline treated rats (p<0.05 for all). Our data shows that culture expanded fetal kidney cells express mesenchymal and renal progenitor markers, and ameliorate ischemic ARF predominantly by their anti-apoptotic, anti-inflammatory and anti-oxidative effects.

  16. Tissue plasminogen activator for acute ischemic stroke: calculation of dose based on estimated patient weight can increase the risk of cerebral bleeding.

    PubMed

    García-Pastor, Andrés; Díaz-Otero, Fernando; Funes-Molina, Carmen; Benito-Conde, Beatriz; Grandes-Velasco, Sandra; Sobrino-García, Pilar; Vázquez-Alén, Pilar; Fernández-Bullido, Yolanda; Villanueva-Osorio, Jose Antonio; Gil-Núñez, Antonio

    2015-10-01

    A dose of 0.9 mg/kg of intravenous tissue plasminogen activator (t-PA) has proven to be beneficial in the treatment of acute ischemic stroke (AIS). Dosing of t-PA based on estimated patient weight (PW) increases the likelihood of errors. Our objectives were to evaluate the accuracy of estimated PW and assess the effectiveness and safety of the actual applied dose (AAD) of t-PA. We performed a prospective single-center study of AIS patients treated with t-PA from May 2010 to December 2011. Dose was calculated according to estimated PW. Patients were weighed during the 24 h following treatment with t-PA. Estimation errors and AAD were calculated. Actual PW was measured in 97 of the 108 included patients. PW estimation errors were recorded in 22.7 % and were more frequent when weight was estimated by stroke unit staff (44 %). Only 11 % of patients misreported their own weight. Mean AAD was significantly higher in patients who had intracerebral hemorrhage (ICH) after t-PA than in patients who did not (0.96 vs. 0.92 mg/kg; p = 0.02). Multivariate analysis showed an increased risk of ICH for each 10 % increase in t-PA dose above the optimal dose of 0.90 mg/kg (OR 3.10; 95 % CI 1.14-8.39; p = 0.026). No effects of t-PA misdosing were observed on symptomatic ICH, functional outcome or mortality. Estimated PW is frequently inaccurate and leads to t-PA dosing errors. Increasing doses of t-PA above 0.90 mg/kg may increase the risk of ICH. Standardized weighing methods before t-PA is administered should be considered.

  17. Cost-Effectiveness of Intraarterial Treatment as an Adjunct to Intravenous Tissue Plasminogen Activator for Acute Ischemic Stroke

    PubMed Central

    Leppert, Michelle H; Campbell, Jonathan D; Simpson, Jennifer R; Burke, James F

    2015-01-01

    Background and Purpose The objective of this study was to determine the cost-effectiveness of intraarterial treatment within the 0- to 6- hour window after intravenous (IV) tissue plasminogen activator (tPA) within 0- to 4.5-hours compared to IV tPA alone, in the US setting and from a social perspective. Methods A decision analytic model estimated the lifetime costs and outcomes associated with the additional benefit of intraarterial therapy compared to standard treatment with IV tPA alone. Model inputs were obtained from published literature, the MR CLEAN study, and claims databases in the United States. Health outcomes were measured in quality adjusted life years (QALYs). Treatment benefit was assessed by calculating the cost per QALY gained. One-way and probabilistic sensitivity analyses were performed to estimate the overall uncertainty of model results. Results The addition of intraarterial therapy compared with standard treatment alone yielded a lifetime gain of 0.7 QALY for an additional cost of $9,911, which resulted in a cost of $14,137 per QALY. Multivariable sensitivity analysis predicted cost-effectiveness (≤$50,000 per QALY) in 97.6% of simulation runs. Conclusion Intraarterial treatment after IV tPA for patients with anterior circulation strokes within the 6 hour window is likely cost effective. From a societal perspective, increased investment in access to intraarterial treatment for acute stroke may be justified. PMID:26012639

  18. Constitutive activation of epithelial TLR4 augments inflammatory responses to mucosal injury and drives colitis-associated tumorigenesis

    PubMed Central

    Fukata, Masayuki; Shang, Limin; Santaolalla, Rebeca; Sotolongo, John; Pastorini, Cristhine; España, Cecilia; Ungaro, Ryan; Harpaz, Noam; Cooper, Harry S.; Elson, Greg; Kosco-Vilbois, Marie; Zaias, Julia; Perez, Maria T.; Mayer, Lloyd; Vamadevan, Arunan S.; Lira, Sergio A.; Abreu, Maria T.

    2010-01-01

    Chronic intestinal inflammation culminates in cancer and a link to TLR4 has been suggested by our observation that TLR4 deficiency prevents colitis-associated neoplasia. In the current study, we address the effect of the aberrant activation of epithelial TLR4 on induction of colitis and colitis-associated tumor development. We take a translational approach to address the consequences of increased TLR signaling in the intestinal mucosa. Mice transgenic for a constitutively-active TLR4 under the intestine-specific villin promoter (villin-TLR4 mice) were treated with DSS for acute colitis and azoxymethane-dextran sulfate sodium. TLR4 expression was analyzed by immunohistochemistry in colonic tissue from patients with ulcerative colitis and ulcerative colitis associated cancer. The effect of an antagonist TLR4 Ab was tested in prevention of colitis-associated neoplasia in the AOM-DSS model. Villin-TLR4 mice were highly susceptible to both acute colitis and colitis-associated neoplasia. Villin-TLR4 mice had increased epithelial expression of COX-2 and mucosal PGE2 production at baseline. Increased severity of colitis in villin-TLR4 mice was characterized by enhanced expression of inflammatory mediators and increased neutrophilic infiltration. In human UC samples, TLR4 expression was upregulated in almost all CAC and progressively increases with grade of dysplasia. As a proof of principle, a TLR4/MD-2 antagonist antibody inhibited colitis-associated neoplasia in the mouse model. Our results show that regulation of TLR's can affect the outcome of both acute colitis and its consequences—cancer. Targeting TLR4 and other TLR's may ultimately play a role in prevention or treatment of colitis-associated cancer. PMID:21674704

  19. Current concepts: management of diarrhea in acute care.

    PubMed

    Fruto, L V

    1994-09-01

    Diarrhea is common in the acute care setting, particularly among critically ill patients. Factors that cause diarrhea are usually multifactorial; some of the most common include medications, hyperosmolar or rapidly delivered tube feedings, atrophy of intestinal epithelium or ischemic bowel, short bowel syndrome, pseudomembranous colitis, infection (Salmonella and Shigella species), opportunistic infections in patients with acquired immunodeficiency syndrome and severe hypoproteinemia. This article reviews different types and mechanisms of diarrhea commonly encountered in acute care. It includes current concepts of managing diarrhea, such as calculation of stool osmotic gap, identification of medications that cause diarrhea, modification of enteral therapy, and the use of antisecretory agents. Nursing responsibilities and contributions in the collaborative assessment and clinical management of diarrhea are also explored. PMID:7704125

  20. Perception Versus Actual Performance in Timely Tissue Plasminogen Activation Administration in the Management of Acute Ischemic Stroke

    PubMed Central

    Lin, Cheryl B; Cox, Margueritte; Olson, DaiWai M; Britz, Gavin W; Constable, Mark; Fonarow, Gregg C; Schwamm, Lee; Peterson, Eric D; Shah, Bimal R

    2015-01-01

    Background Timely thrombolytic therapy can improve stroke outcomes. Nevertheless, the ability of US hospitals to meet guidelines for intravenous tissue plasminogen activator (tPA) remains suboptimal. What is unclear is whether hospitals accurately perceive their rate of tPA “door-to-needle” (DTN) time within 60 minutes and how DTN rates compare across different hospitals. Methods and Results DTN performance was defined by the percentage of treated patients who received tPA within 60 minutes of arrival. Telephone surveys were obtained from staff at 141 Get With The Guidelines hospitals, representing top, middle, and lowDTN performance. Less than one-third (29.1%) of staff accurately identified their DTN performance. Among middle- and low-performing hospitals (n=92), 56 sites (60.9%) overestimated their performance; 42% of middle performers and 85% of low performers overestimated their performance. Sites that overestimated tended to have lower annual volumes of tPA administration (median 8.4 patients [25th to 75th percentile 5.9 to 11.8] versus 10.2 patients [25th to 75th percentile 8.2 to 17.3], P=0.047), smaller percentages of eligible patients receiving tPA (84.7% versus 89.8%, P=0.008), and smaller percentages of DTN ≤60 minutes among treated patients (10.6% versus 16.6%, P=0.002). Conclusions Hospitals often overestimate their ability to deliver timely tPA to treated patients. Our findings indicate the need to routinely provide comparative provider performance rates as a key step to improving the quality of acute stroke care. PMID:26201547

  1. Internal Carotid Artery S-Shaped Curve as a Marker of Fibromuscular Dysplasia in Dissection-Related Acute Ischemic Stroke

    PubMed Central

    Haussen, Diogo C.; Jadhav, Ashutosh; Rebello, Leticia C.; Belagaje, Samir; Anderson, Aaron; Jovin, Tudor; Aghaebrahim, Amin; Gulati, Deepak; Wells, Bryan; Frankel, Michael; Nogueira, Raul G.

    2016-01-01

    Background and Purpose Craniocervical fibromuscular dysplasia (FMD) is associated with dissections and with S-shaped curves in the internal carotid artery (ICA). We evaluated the occurrence of S-curves in patients presenting with acute strokes due to ICA steno-occlusive dissections. Methods This was a retrospective review of the interventional databases of two academic tertiary-care institutions. The presence of ICA S-shaped curves, C-shaped curves, 360-degree loops, as well as classic FMD and atherosclerotic changes at the ICA bulb and curve/loop was determined. Cases of carotid dissections were compared with a control group (consecutive non-tandem anterior circulation strokes). Results Twenty-four patients with carotid dissections were compared to 92 controls. Baseline characteristics and procedural variables were similar, with the exception of younger age, less frequent history of hypertension, diabetes, atrial fibrillation and stent retriever use in patients with dissections. The rates of mTICI2b-3 reperfusion, parenchymal hematoma, good outcome and mortality were similar amongst groups. The frequency of S-curves (any side without superimposed atherosclerosis) was 29% in the dissection group versus 7% in controls (p < 0.01). S-curves were typically mirror images within the dissection group (85% had bilateral occurrence). The frequency of C-shaped and 360-degree curves was similar between groups. FMD changes within the craniocervical arteries were statistically more common in dissection patients. Ten patients (41%) of the dissection group had S-curves or classic FMD changes. Multivariate analysis indicated that S-curves were independently associated with the presence of dissections. Conclusion S-shaped ICA curves are predictably bilateral, highly associated with carotid dissections in patients with moderate to severe strokes, and may suggest an underlying presence of FMD. PMID:27781048

  2. Acute inflammatory reaction after myocardial ischemic injury and reperfusion. Development and use of a neutrophil-specific antibody.

    PubMed Central

    Hawkins, H. K.; Entman, M. L.; Zhu, J. Y.; Youker, K. A.; Berens, K.; Doré, M.; Smith, C. W.

    1996-01-01

    Reperfusion of the infarcted canine myocardium after 1 hour of ischemia is associated with an acute inflammatory infiltrate at the border of the infarct. In this paper, we demonstrate that early margination and emigration of neutrophils originate in thin-walled (approximately 5 micrometers) venous cisterns that average 200 micrometers in length and vary from 10 to 70 micrometers in width and show strong constitutive expression of both ICAM-1 and P-selectin; this class of vessels (venous cisterns) appears to be a unique feature in heart. A monoclonal antibody (SG8H6) with specificity for canine neutrophils was developed that allowed much more sensitive immunohistochemical detection of neutrophils in tissue and allowed us to follow tissue infiltration with time. Samples from 1 hour of reperfusion revealed dense margination and substantial emigration of neutrophils associated with the venous cisterns and collecting venules. By 2 hours, there was intense local emigration to the extravascular space between cardiac myocytes. By 3 hours, the infiltrate extended deeper into the infarct, and there was a continuous border zone of neutrophil infiltration that overlapped a region where intact cardiac myocytes strongly expressed ICAM-1 mRNA and extended into the necrotic tissue. At later times, neutrophil migration into infarcted tissue continued to progress. Neutrophil transmigration into reperfused myocardium is more extensive than previously described, and its extravascular distribution during early reperfusion is primarily in the viable border zone of the myocardium where myocyte ICAM-1 mRNA is found. These data are compatible with the hypothesis that extravascular neutrophils may participate in reperfusion injury. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:8669481

  3. Critical early thrombolytic and endovascular reperfusion therapy for acute ischemic stroke victims: a call for adjunct neuroprotection.

    PubMed

    Lapchak, Paul A

    2015-10-01

    Today, there is an enormous amount of excitement in the field of stroke victim care due to the recent success of MR. CLEAN, SWIFT PRIME, ESCAPE, EXTEND-IA, and REVASCAT endovascular trials. Successful intravenous (IV) recombinant tissue plasminogen activator (rt-PA) clinical trials [i.e., National Institute of Neurological Disorders and Stroke (NINDS) rt-PA trial, Third European Cooperative Acute Stroke Study (ECASSIII), and Third International Stroke study (IST-3)] also need to be emphasized. In the recent endovascular and thrombolytic trials, there is statistically significant improvement using both the National Institutes of Health Stroke Scale (NIHSS) and the modified Rankin Score (mRS) scale, but neither approach promotes complete recovery in patients enrolled within any particular NIHSS or mRS score tier. Absolute improvement (mRS 0-2 at 90 days) with endovascular therapy is 13.5-31 %, whereas thrombolytics alone also significantly improve patient functional independence, but to a lesser degree (NINDS rt-PA trial 13 %). This article has 3 main goals: (1) first to emphasize the utility and cost-effectiveness of rt-PA to treat stroke; (2) second to review the recent endovascular trials with respect to efficacy, safety, and cost-effectiveness as a stroke treatment; and (3) to further consider and evaluate strategies to develop novel neuroprotective drugs. A thesis will be put forth so that future stroke trials and therapy development can optimally promote recovery so that stroke victims can return to "normal" life. PMID:26314402

  4. Alteration of Isocitrate Dehydrogenase Following Acute Ischemic Injury as a Means to Improve Cellular Energetic Status in Neuroadaptation

    PubMed Central

    Grelli, Kimberly N.; Palubinsky, Amy M.; Kale, A. Cozette; Lizama-Manibusan, Britney N.; Stankowski, Jeannette N.; Milne, Ginger L.; Singer, Robert; McLaughlin, BethAnn

    2013-01-01

    The isocitrate dehydrogenase (IDH) enzymes were initially identified as essential components of the Krebs cycle. IDH mutations were thought to be incompatible with cell survival. However, 90% of glioblastomas were recently shown to be associated with somatic mutations in these enzymes, indicating a possible role for IDH in promoting cellular survival in hypoxic environments. Our proteomic analysis of rats given 10 minutes of middle cerebral artery occlusion to induce transient ischemia demonstrates a significant decrease in IDH expression. We have recapitulated this decrease in an in vitro model using primary cortical neurons exposed to acute oxygen and glucose deprivation. Given the role of IDHs in energy metabolism and antioxidant production, we hypothesize that the IDHs may serve as first-line, rapid-response enzymes that regulate survival in environments of energetic or oxidative stress. In order to identify the specific events that regulate IDH enzymes, HT-22 neural cells were subjected to either a selective energetic challenge or a pure oxidative stress. In response to the non-lethal energetic challenge induced by substituting galactose for glucose, we observed increased IDH1, 2, and 3 expression and cessation of cellular proliferation. No change in expression of any IDH isoform was observed when neural cells were subjected to subtoxic oxidative stress via glutathione depletion. Taken together, these data imply that IDH expression rapidly responds to changes in energetic status, but not to oxidative stress. These data also suggest that IDH enzymes respond not only to allosteric modulation, but can also change patterns of expression in response to moderate stress in an effort to maximize ATP production and survival. PMID:23469839

  5. Optimizing Mouse Surgery with Online Rectal Temperature Monitoring and Preoperative Heat Supply. Effects on Post-Ischemic Acute Kidney Injury.

    PubMed

    Marschner, Julian A; Schäfer, Hannah; Holderied, Alexander; Anders, Hans-Joachim

    2016-01-01

    Body temperature affects outcomes of tissue injury. We hypothesized that online body core temperature recording and selective interventions help to standardize peri-interventional temperature control and the reliability of outcomes in experimental renal ischemia reperfusion injury (IRI). We recorded core temperature in up to seven mice in parallel using a Thermes USB recorder and ret-3-iso rectal probes with three different protocols. Setup A: Heating pad during ischemia time; Setup B: Heating pad from incision to wound closure; Setup C: A ventilated heating chamber before surgery and during ischemia time with surgeries performed on a heating pad. Temperature profile recording displayed significant declines upon installing anesthesia. The profile of the baseline experimental setup A revealed that <1% of the temperature readings were within the target range of 36.5 to 38.5°C. Setup B and C increased the target range readings to 34.6 ± 28.0% and 99.3 ± 1.5%, respectively. Setup C significantly increased S3 tubular necrosis, neutrophil influx, and mRNA expression of kidney injury markers. In addition, using setup C different ischemia times generated a linear correlation with acute tubular necrosis parameters at a low variability, which further correlated with the degree of kidney atrophy 5 weeks after surgery. Changing temperature control setup A to C was equivalent to 10 minutes more ischemia time. We conclude that body temperature drops quickly in mice upon initiating anesthesia. Immediate heat supply, e.g. in a ventilated heating chamber, and online core temperature monitoring can help to standardize and optimize experimental outcomes.

  6. [Rest gated-SPECT myocardial perfusion post (99m)Tc-MIBI injection in a patient with acute chest pain and with no medical history of ischemic heart disease].

    PubMed

    Negre-Busó, M; Muntaner-Muñoz, L; Rubió-Rodríguez, A; Marin-Buriticá, A; Ferran-Sureda, N; Bassaganyas-Vilarrasa, J

    2015-01-01

    Gated-SPECT myocardial perfusion imaging is a widely used technique indicated for assessment of patients with no clear diagnosis of ischemic heart disease. Early rest gated-SPECT myocardial perfusion study in patients with acute chest pain has high sensitivity and high negative predictive value for ruling out coronary disease. We report a case of a patient admitted for the study of her chest pain. She underwent a myocardial perfusion stress-rest whose interpretation could have been equivocal due to the clinical status of the patient during the injection of the radiotracer. PMID:25759109

  7. Multiplex immunoassay characterization and species comparison of inflammation in acute and non-acute ischemic infarcts in human and mouse brain tissue.

    PubMed

    Nguyen, Thuy-Vi V; Frye, Jennifer B; Zbesko, Jacob C; Stepanovic, Kristina; Hayes, Megan; Urzua, Alex; Serrano, Geidy; Beach, Thomas G; Doyle, Kristian P

    2016-01-01

    This study provides a parallel characterization of the cytokine and chemokine response to stroke in the human and mouse brain at different stages of infarct resolution. The study goal was to address the hypothesis that chronic inflammation may contribute to stroke-related dementia. We used C57BL/6 and BALB/c mice to control for strain related differences in the mouse immune response. Our data indicate that in both mouse strains, and humans, there is increased granulocyte macrophage colony-stimulating factor (GM-CSF), interleukin-6 (IL-6), interleukin-12 p70 (IL-12p70), interferon gamma-induced protein-10 (IP-10), keratinocyte chemoattractant/interleukin-8 (KC/IL-8), monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1α (MIP-1α), macrophage inflammatory protein-1β (MIP-1β), regulated on activation, normal T cell expressed and secreted (RANTES), and Tumor necrosis factor-α (TNF-α) in the infarct core during the acute time period. Nevertheless, correlation and two-way ANOVA analyses reveal that despite this substantial overlap between species, there are still significant differences, particularly in the regulation of granulocyte colony-stimulating factor (G-CSF), which is increased in mice but not in humans. In the weeks after stroke, during the stage of liquefactive necrosis, there is significant resolution of the inflammatory response to stroke within the infarct. However, CD68+ macrophages remain present, and levels of IL-6 and MCP-1 remain chronically elevated in infarcts from both mice and humans. Furthermore, there is a chronic T cell response within the infarct in both species. This response is differentially polarized towards a T helper 1 (Th1) response in C57BL/6 mice, and a T helper 2 (Th2) response in BALB/c mice, suggesting that the chronic inflammatory response to stroke may follow a different trajectory in different patients. To control for the fact that the average age of the patients used in this study was 80 years, they

  8. Bowel obsession syndrome in a patient with ulcerative colitis.

    PubMed

    Porcelli, Piero; Leandro, Gioacchino

    2007-01-01

    Gastroenterologists are often faced with the diagnostic problem of differentiating acute symptoms of ulcerative colitis from functional intestinal disorders. Bowel obsession syndrome (BOS) is an OCD-like, functional syndrome characterized by fear of fecal incontinence and compulsive behaviors of evacuation-checking. Only sparse case studies on treatment of BOS with antidepressants have been published. This is the first study on successful psychotherapy of a male patient with ulcerative colitis overlapping functional bowel symptoms and marked symptoms of BOS. Clinical recognition of BOS may help clinicians in differential diagnosis, prevent unnecessary investigations, and give patients the most appropriate treatment.

  9. Selection of Patients and Anesthetic Types for Endovascular Treatment in Acute Ischemic Stroke: A Meta-Analysis of Randomized Controlled Trials

    PubMed Central

    Ouyang, Fubing; Chen, Yicong; Zhao, Yuhui; Dang, Ge; Liang, Jiahui; Zeng, Jinsheng

    2016-01-01

    Background and Purpose Recent randomized controlled trials have demonstrated consistent effectiveness of endovascular treatment (EVT) for acute ischemic stroke, leading to update on stroke management guidelines. We conducted this meta-analysis to assess the efficacy and safety of EVT overall and in subgroups stratified by age, baseline stroke severity, brain imaging feature, and anesthetic type. Methods Published randomized controlled trials comparing EVT and standard medical care alone were evaluated. The measured outcomes were 90-day functional independence (modified Rankin Scale ≤2), all-cause mortality, and symptomatic intracranial hemorrhage. Results Nine trials enrolling 2476 patients were included (1338 EVT, 1138 standard medical care alone). For patients with large vessel occlusions confirmed by noninvasive vessel imaging, EVT yielded improved functional outcome (pooled odds ratio [OR], 2.02; 95% confidence interval [CI], 1.64–2.50), lower mortality (OR, 0.75; 95% CI, 0.58–0.97), and similar symptomatic intracranial hemorrhage rate (OR, 1.12; 95% CI, 0.72–1.76) compared with standard medical care. A higher proportion of functional independence was seen in patients with terminus intracranial artery occlusion (±M1) (OR, 3.16; 95% CI, 1.64–6.06), baseline Alberta Stroke Program Early CT score of 8–10 (OR, 2.11; 95% CI, 1.25–3.57) and age ≤70 years (OR, 3.01; 95% CI, 1.73–5.24). EVT performed under conscious sedation had better functional outcomes (OR, 2.08; 95% CI, 1.47–2.96) without increased risk of symptomatic intracranial hemorrhage or short-term mortality compared with general anesthesia. Conclusions Vessel-imaging proven large vessel occlusion, a favorable scan, and younger age are useful predictors to identify anterior circulation stroke patients who may benefit from EVT. Conscious sedation is feasible and safe in EVT based on available data. However, firm conclusion on the choice of anesthetic types should be drawn from more

  10. Remote Ischemic Preconditioning for Prevention of Acute Kidney Injury in Patients Undergoing On-Pump Cardiac Surgery: A Systematic Review and Meta-Analysis.

    PubMed

    Zhang, Yabing; Zhang, Xiyang; Chi, Dongmei; Wang, Siyang; Wei, Hua; Yu, Hong; Li, Qian; Liu, Bin

    2016-09-01

    Remote ischemic preconditioning (RIPC) may attenuate acute kidney injury (AKI). However, results of studies evaluating the effect of RIPC on AKI after cardiac surgery have been controversial and contradictory.The aim of this meta-analysis is to examine the association between RIPC and AKI after on-pump cardiac surgery.The authors searched relevant studies in PubMed, EMBASE, and the Cochrane Library through December 2015.We considered for inclusion all randomized controlled trials that the role of RIPC in reducing AKI and renal replacement therapy (RRT) among patients underwent on-pump cardiac surgical procedures.We collected the data on AKI, initiation of RRT, serum creatinine (sCr) levels, and in-hospital mortality. Random- and fixed-effect models were used for pooling data.Nineteen trials including 5100 patients were included. The results of this meta-analysis showed a significant benefit of RIPC for reducing the incidence of AKI after cardiac interventions (odds ratio [OR] = 0.84; 95% confidence interval [CI], 0.73-0.98; P = 0.02). No significant difference was found in the incidence of RRT between RIPC and control (OR, 0.76, 95% CI, 0.46-1.24; P = 0.36). In addition, compared with standard medical care, RIPC showed no significant difference in postoperative sCr (IV 0.07; 95% CI, -0.03 to 0.16; P = 0.20; postoperative day 1; IV 0.00; 95% CI, -0.08 to 0.09; P = 0.92; postoperative day 2; IV 0.04; 95% CI, -0.05 to 0.12; P = 0.39; postoperative day 3), and in-hospital mortality (OR, 1.21, 95% CI, 0.64-2.30; P = 0.56).According to the results from present meta-analysis, RIPC was associated with a significant reduction AKI after on-pump cardiac surgery but incidence of RRT, postoperative sCr, and in-hospital mortality. Further high-quality randomized controlled trials and experimental researches comparing RIPC are desirable. PMID:27631199

  11. Effect of coronary artery revascularization on in-hospital outcomes and long-term prognoses in acute myocardial infarction patients with prior ischemic stroke

    PubMed Central

    Li, Bo-Yu; Li, Xiao-Ming; Zhang, Yan; Wei, Zhan-Yun; Li, Jing; Hua, Qi

    2016-01-01

    Objective To investigate whether coronary artery revascularization therapies (CART), including percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG), can improve the in-hospital and long-term outcomes for acute myocardial infarction (AMI) patients with prior ischemic stroke (IS). Methods A total of 387 AMI patients with prior IS were enrolled consecutively from January 15, 2005 to December 24, 2011 in this cohort study. All patients were categorized into the CART group (n = 204) or the conservative medications (CM) group (n = 183). In-hospital cardiocerebral events and long-term mortality of the two groups after an average follow-up of 36 months were recorded by Kaplan-Meier survival curves and compared by Logistic regression and the Cox regression model. Results The CART patients were younger (66.5 ± 9.7 years vs. 71.7 ± 9.7 years, P < 0.01), had less non-ST segment elevation myocardial infarction (11.8% vs. 20.8%, P = 0.016) and more multiple-vascular coronary lesions (50% vs. 69.4%, P = 0.031). The hospitalization incidence of cardiocerebral events in the CART group was 9.3% while 26.2% in the CM group (P < 0.01). CART significantly reduced the risk of in-hospital cardiocerebral events by 65% [adjusted odds ratio (OR) = 0.35, 95% CI: 0.13–0.92]. By the end of follow-up, 57 cases (41.6%) died in CM group (n = 137) and 24 cases (12.2%) died in CART group (n = 197). Cox regression indicated that CART decreased the long-term mortality by 72% [adjusted hazard ratio (HR) = 0.28, 95% CI: 0.06–0.46], while categorical analysis indicated no significant difference between PCI and CABG. Conclusions CART has a significant effect on improving the in-hospital and long-term prognoses for AMI patients with prior IS. PMID:27168740

  12. A pilot study: portable out-of-center sleep testing as an early sleep apnea screening tool in acute ischemic stroke

    PubMed Central

    Chernyshev, Oleg Y; McCarty, David E; Moul, Douglas E; Liendo, Cesar; Caldito, Gloria C; Munjampalli, Sai K; Kelley, Roger E; Chesson, Andrew L

    2015-01-01

    Introduction Prompt diagnosis of obstructive sleep apnea (OSA) after acute ischemic stroke (AIS) is critical for optimal clinical outcomes, but in-laboratory conventional polysomnograms (PSG) are not routinely practical. Though portable out-of-center type III cardiopulmonary sleep studies (out-of-center cardiopulmonary sleep testing [OCST]) are widely available, these studies have not been validated in patients who have recently suffered from AIS. We hypothesized that OCST in patients with AIS would yield similar results when compared to conventional PSG. Methods Patients with AIS had simultaneous type III OCST and PSG studies performed within 72 hours from symptom onset. The accuracy of OCST was compared to PSG using: chi-square tests, receiver operatory characteristic curves, Bland–Altman plot, paired Student’s t-test/Wilcoxon signed-rank test, and calculation of sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Results Twenty-one out of 23 subjects with AIS (age 61±9.4 years; 52% male; 58% African-American) successfully completed both studies (9% technical failure). Nearly all (95%) had Mallampati IV posterior oropharynx; the mean neck circumference was 16.8±1.6 in. and the mean body mass index (BMI) was 30±7 kg/m2. The apnea hypopnea index (AHI) provided by OCST was similar to that provided by PSG (19.8±18.0 vs 22.0±22.7, respectively; P=0.49). On identifying subjects by OCST with an AHI ≥5 on PSG, OCST had the following parameters: sensitivity 100%, specificity 85.7%, PPV 93%, and NPV 100%. On identifying subjects with an AHI ≥15 on PSG, OCST parameters were as follows: sensitivity 100%, specificity 83.3%, PPV 81.8%, and NPV 100%. Bland–Altman plotting showed an overall diagnostic agreement between OCST and PSG modalities for an AHI cutoff >5, despite fine-grained differences in estimated AHIs. Conclusion Compared with PSG, OCST provides similar diagnostic information when run simultaneously in AIS

  13. Endovascular treatment for acute ischemic stroke patients: implications and interpretation of IMS III, MR RESCUE, and SYNTHESIS EXPANSION trials: A report from the Working Group of International Congress of Interventional Neurology

    PubMed Central

    Qureshi, Adnan I.; Abd-Allah, Foad; Aleu, Aitziber; Connors, John J.; Hanel, Ricardo A.; Hassan, Ameer E.; Hussein, Haitham M.; Janjua, Nazli A.; Khatri, Rakesh; Kirmani, Jawad F.; Mazighi, Mikael; Mattle, Heinrich P.; Miley, Jefferson T.; Nguyen, Thanh N.; Rodriguez, Gustavo J.; Shah, Qaisar A.; Siddiqui, Adnan H.; Suarez, Jose I.; Suri, M. Fareed K.; Tolun, Reha

    2014-01-01

    Objective: The results of Interventional Management of Stroke (IMS) III, Magnetic Resonance and REcanalization of Stroke Clots Using Embolectomy (MR RESCUE), and SYNTHESIS EXPANSION trials are expected to affect the practice of endovascular treatment for acute ischemic stroke. The purpose of this report is to review the components of the designs and methods of these trials and to describe the influence of those components on the interpretation of trial results. Methods: A critical review of trial design and conduct of IMS III, MR RESCUE, and SYNTHESIS EXPANSION is performed with emphasis on patient selection, shortcomings in procedural aspects, and methodology of data ascertainment and analysis. The influence of each component is estimated based on published literature including multicenter clinical trials reporting on endovascular treatment for acute ischemic stroke and myocardial infarction. Results: We critically examined the time interval between symptom onset and treatment and rates of angiographic recanalization to differentiate between “endovascular treatment” and “parameter optimized endovascular treatment” as it relates to the IMS III, MR RESCUE, and SYNTHESIS EXPANSION trials. All the three trials failed to effectively test “parameter optimized endovascular treatment” due to the delay between symptom onset and treatment and less than optimal rates of recanalization. In all the three trials, the magnitude of benefit with endovascular treatment required to reject the null hypothesis was larger than could be expected based on previous studies. The IMS III and SYNTHESIS EXPANSION trials demonstrated that rates of symptomatic intracerebral hemorrhages subsequent to treatment are similar between IV thrombolytics and endovascular treatment in matched acute ischemic stroke patients. The trials also indirectly validated the superiority/equivalence of IV thrombolytics (compared with endovascular treatment) in patients with minor neurological deficits

  14. Management of ulcerative colitis

    PubMed Central

    Fell, John M; Muhammed, Rafeeq; Spray, Chris; Crook, Kay; Russell, Richard K

    2016-01-01

    Ulcerative colitis (UC) in children is increasing. The range of treatments available has also increased too but around 1 in 4 children still require surgery to control their disease. An up-to-date understanding of treatments is essential for all clinicians involved in the care of UC patients to ensure appropriate and timely treatment while minimising the risk of complications and side effects. PMID:26553909

  15. [Ulcerative colitis? Guidelines 2004].

    PubMed

    Siegmund, B; Zeitz, M

    2005-10-12

    Ulcerative colitis was first described in 1859 from Samuel Wilks, a physician at Guy's hospital in London. The prevalence in the high incidence areas ranges from 80 to 120/100.000/year. Ulcerative colitis is a chronic relapsing or chronic active disease which starts at the rectum and presents with a continuous inflammation. Primarily young adults are affected (20 to 40 years of age) but the disease may present at all ages, from younger than 1 year of life to the 80s. Many series show a secondary peak in incidence in the elderly. In the present review we will focus on the basic principles of the therapy with regard to the variety of disease manifestations. The therapeutic algorithms will be described separately for the induction of remission and the maintenance of remission. The localization of inflammation and disease activity represent crucial factors which have to be considered. With regard to these factors, the therapeutic regimens range from simple local therapy with aminosalicylates to systemic immunosuppressive therapy, which will in extreme cases require the administration of ciclosporin. Since ulcerative colitis is associated with an increased risk in developing colon carcinoma, medical therapy as well as endoscopic surveillance are fundamental in the prevention of carcinoma. In the end an outlook to future therapeutic targets and strategies will be provided. PMID:16245638

  16. Angelica acutiloba Kitagawa Extract Attenuates DSS-Induced Murine Colitis

    PubMed Central

    Jang, Jong-Chan; Lee, Kang Min

    2016-01-01

    We examined the protective effects of Angelica acutiloba Kitagawa (AAK) extract on a murine model of acute experimental colitis. Colitis was induced by 4% dextran sulfate sodium (DSS) in the drinking water of male C57BL/6 mice, for 7 consecutive days. Oral administration of AAK extract (500 mg/kg/day) significantly alleviated DSS-induced symptoms such as anorexia, weight loss, events of diarrhea or bloody stools, and colon shortening. Histological damage was also ameliorated, as evidenced by the architectural preservation and suppression of inflammatory cell infiltration in colonic samples. Treatment improved the colonic mRNA expression of different inflammatory markers: cytokines, inducible enzymes, matrix metalloproteinases, and tight junction-related proteins. In the isolated serum, IgE levels were downregulated. Collectively, these findings indicate the therapeutic potentials of AAK as an effective complementary or alternative modality for the treatment of ulcerative colitis. PMID:27293323

  17. Angelica acutiloba Kitagawa Extract Attenuates DSS-Induced Murine Colitis.

    PubMed

    Jang, Jong-Chan; Lee, Kang Min; Ko, Seong-Gyu

    2016-01-01

    We examined the protective effects of Angelica acutiloba Kitagawa (AAK) extract on a murine model of acute experimental colitis. Colitis was induced by 4% dextran sulfate sodium (DSS) in the drinking water of male C57BL/6 mice, for 7 consecutive days. Oral administration of AAK extract (500 mg/kg/day) significantly alleviated DSS-induced symptoms such as anorexia, weight loss, events of diarrhea or bloody stools, and colon shortening. Histological damage was also ameliorated, as evidenced by the architectural preservation and suppression of inflammatory cell infiltration in colonic samples. Treatment improved the colonic mRNA expression of different inflammatory markers: cytokines, inducible enzymes, matrix metalloproteinases, and tight junction-related proteins. In the isolated serum, IgE levels were downregulated. Collectively, these findings indicate the therapeutic potentials of AAK as an effective complementary or alternative modality for the treatment of ulcerative colitis.

  18. Recent advances in the management of radiation colitis

    PubMed Central

    Kountouras, Jannis; Zavos, Christos

    2008-01-01

    Radiation colitis, an insidious, progressive disease of increasing frequency, develops 6 mo to 5 years after regional radiotherapy for malignancy, owing to the deleterious effects of the latter on the colon and the small intestine. When dealing with radiation colitis and its complications, the most conservative modality should be employed because the areas of intestinal injury do not tend to heal. Acute radiation colitis is mostly self-limited, and usually, only supportive management is required. Chronic radiation colitis, a poorly predictable progressive disease, is considered as a precancerous lesion; radiation-associated malignancy has a tendency to be diagnosed at an advanced stage and to bear a dismal prognosis. Therefore, management of chronic radiation colitis remains a major challenge owing to the progressive evolution of the disease, including development of fibrosis, endarteritis, edema, fragility, perforation, partial obstruction, and cancer. Patients are commonly managed conservatively. Surgical intervention is difficult to perform because of the extension of fibrosis and alterations in the gut and mesentery, and should be reserved for intestinal obstruction, perforation, fistulas, and severe bleeding. Owing to the difficulty in managing the complications of acute and chronic radiation colitis, particular attention should be focused onto the prevention strategies. Uncovering the fibrosis mechanisms and the molecular events underlying radiation bowel disease could lead to the introduction of new therapeutic and/or preventive approaches. A variety of novel, mostly experimental, agents have been used mainly as a prophylaxis, and improvements have been made in radiotherapy delivery, including techniques to reduce the amount of exposed intestine in the radiation field, as a critical strategy for prevention. PMID:19109862

  19. Interleukin 19 reduces inflammation in chemically induced experimental colitis.

    PubMed

    Matsuo, Yukiko; Azuma, Yasu-Taka; Kuwamura, Mitsuru; Kuramoto, Nobuyuki; Nishiyama, Kazuhiro; Yoshida, Natsuho; Ikeda, Yoshihito; Fujimoto, Yasuyuki; Nakajima, Hidemitsu; Takeuchi, Tadayoshi

    2015-12-01

    Inflammatory bowel disease results from chronic dysregulation of the mucosal immune system and aberrant activation of both the innate and adaptive immune responses. Interleukin (IL)-19, a member of the IL-10 family, functions as an anti-inflammatory cytokine. Here, we investigated the contribution of IL-19 to intestinal inflammation in a model of T cell-mediated colitis in mice. Inflammatory responses in IL-19-deficient mice were assessed using the 2,4,6-trinitrobenzene sulfonic acid (TNBS) model of acute colitis. IL-19 deficiency aggravated TNBS-induced colitis and compromised intestinal recovery in mice. Additionally, the exacerbation of TNBS-induced colonic inflammation following genetic ablation of IL-19 was accompanied by increased production of interferon-gamma, IL-12 (p40), IL-17, IL-22, and IL-33, and decreased production of IL-4. Moreover, the exacerbation of colitis following IL-19 knockout was also accompanied by increased production of CXCL1, G-CSF and CCL5. Using this model of induced colitis, our results revealed the immunopathological relevance of IL-19 as an anti-inflammatory cytokine in intestinal inflammation in mice.

  20. Hyperacute management of ischemic stroke.

    PubMed

    Song, Sarah

    2013-11-01

    Stroke is a devastating disease and currently the fourth leading cause of death in this country. Acute ischemic stroke is an emergency and requires effective triage, diagnosis, and critical management. The hyperacute management of ischemic stroke begins in the field, with recognition of stroke symptoms by emergency medical systems (EMS) personnel. The EMS is an important component to an effective stroke system of care, which also includes primary stroke centers, routing protocols for acute ischemic stroke, and telemedicine. Following the arrival of a potential stroke patient to the emergency room setting, patients should be stabilized and undergo assessment for potential intravenous alteplase (IV tPA) treatment. Assessments include diagnostic tests, neuroimaging, and standardized stroke evaluations. After these assessments have been performed, IV tPA, the only medication for acute stroke approved by the U.S. Food and Drug Administration, can be considered using a variety of inclusion and exclusion criteria. Previously time restrictions limited the usage of IV tPA to 3 hours, but this time window has now been extended for eligible candidates to 4.5 hours. The administration of IV tPA has specific requirements for monitoring and should be standardized via protocol across hospitals.

  1. Protective effect of Clostridium tyrobutyricum in acute dextran sodium sulphate-induced colitis: differential regulation of tumour necrosis factor-α and interleukin-18 in BALB/c and severe combined immunodeficiency mice

    PubMed Central

    Hudcovic, T; Kolinska, J; Klepetar, J; Stepankova, R; Rezanka, T; Srutkova, D; Schwarzer, M; Erban, V; Du, Z; Wells, J M; Hrncir, T; Tlaskalova-Hogenova, H; Kozakova, H

    2012-01-01

    One of the promising approaches in the therapy of ulcerative colitis is administration of butyrate, an energy source for colonocytes, into the lumen of the colon. This study investigates the effect of butyrate producing bacterium Clostridium tyrobutyricum on dextran sodium sulphate (DSS)-induced colitis in mice. Immunocompetent BALB/c and immunodeficient severe combined immunodeficiency (SCID) mice reared in specific-pathogen-free (SPF) conditions were treated intrarectally with C. tyrobutyricum 1 week prior to the induction of DSS colitis and during oral DSS treatment. Administration of DSS without C. tyrobutyricum treatment led to an appearance of clinical symptoms – bleeding, rectal prolapses and colitis-induced increase in the antigen CD11b, a marker of infiltrating inflammatory cells in the lamina propria. The severity of colitis was similar in BALB/c and SCID mice as judged by the histological damage score and colon shortening after 7 days of DSS treatment. Both strains of mice also showed a similar reduction in tight junction (TJ) protein zonula occludens (ZO)-1 expression and of MUC-2 mucin depression. Highly elevated levels of cytokine tumour necrosis factor (TNF)-α in the colon of SCID mice and of interleukin (IL)-18 in BALB/c mice were observed. Intrarectal administration of C. tyrobutyricum prevented appearance of clinical symptoms of DSS-colitis, restored normal MUC-2 production, unaltered expression of TJ protein ZO-1 and decreased levels of TNF-α and IL-18 in the descending colon of SCID and BALB/c mice, respectively. Some of these features can be ascribed to the increased production of butyrate in the lumen of the colon and its role in protection of barrier functions and regulation of IL-18 expression. PMID:22236013

  2. Protective effect of Clostridium tyrobutyricum in acute dextran sodium sulphate-induced colitis: differential regulation of tumour necrosis factor-α and interleukin-18 in BALB/c and severe combined immunodeficiency mice.

    PubMed

    Hudcovic, T; Kolinska, J; Klepetar, J; Stepankova, R; Rezanka, T; Srutkova, D; Schwarzer, M; Erban, V; Du, Z; Wells, J M; Hrncir, T; Tlaskalova-Hogenova, H; Kozakova, H

    2012-02-01

    One of the promising approaches in the therapy of ulcerative colitis is administration of butyrate, an energy source for colonocytes, into the lumen of the colon. This study investigates the effect of butyrate producing bacterium Clostridium tyrobutyricum on dextran sodium sulphate (DSS)-induced colitis in mice. Immunocompetent BALB/c and immunodeficient severe combined immunodeficiency (SCID) mice reared in specific-pathogen-free (SPF) conditions were treated intrarectally with C. tyrobutyricum 1 week prior to the induction of DSS colitis and during oral DSS treatment. Administration of DSS without C. tyrobutyricum treatment led to an appearance of clinical symptoms - bleeding, rectal prolapses and colitis-induced increase in the antigen CD11b, a marker of infiltrating inflammatory cells in the lamina propria. The severity of colitis was similar in BALB/c and SCID mice as judged by the histological damage score and colon shortening after 7 days of DSS treatment. Both strains of mice also showed a similar reduction in tight junction (TJ) protein zonula occludens (ZO)-1 expression and of MUC-2 mucin depression. Highly elevated levels of cytokine tumour necrosis factor (TNF)-α in the colon of SCID mice and of interleukin (IL)-18 in BALB/c mice were observed. Intrarectal administration of C. tyrobutyricum prevented appearance of clinical symptoms of DSS-colitis, restored normal MUC-2 production, unaltered expression of TJ protein ZO-1 and decreased levels of TNF-α and IL-18 in the descending colon of SCID and BALB/c mice, respectively. Some of these features can be ascribed to the increased production of butyrate in the lumen of the colon and its role in protection of barrier functions and regulation of IL-18 expression.

  3. White Matter Ischemic Changes in Hyperacute Ischemic Stroke

    PubMed Central

    Trouard, Theodore P; Lafleur, Scott R.; Krupinski, Elizabeth A.; Salamon, Noriko; Kidwell, Chelsea S.

    2015-01-01

    Background and Purpose— The purpose of this study was to evaluate changes in fractional anisotropy (FA), as measured by diffusion tensor imaging, of white matter (WM) infarction and hypoperfusion in patients with acute ischemic stroke using a quantitative voxel-based analysis. Methods— In this prospective study, diffusion tensor imaging and dynamic susceptibility contrast perfusion sequences were acquired in 21 patients with acute ischemic stroke who presented within 6 hours of symptom onset. The coregistered FA, apparent diffusion coefficient, and dynamic susceptibility contrast time to maximum (Tmax) maps were used for voxel-based quantification using a region of interest approach in the ipsilateral affected side and in the homologous contralateral WM. The regions of WM infarction versus hypoperfusion were segmented using a threshold method. Data were analyzed by regression and ANOVA. Results— There was an overall significant mean difference (P<0.001) for the apparent diffusion coefficient, Tmax, and FA values between the normal, hypoperfused, and infarcted WM. The mean±SD of FA was significantly higher (P<0.001) in hypoperfused WM (0.397±0.019) and lower (P<0.001) in infarcted WM (0.313±0.037) when compared with normal WM (0.360±0.020). Regression tree analysis of hypoperfused WM showed the largest mean FA difference at Tmax above versus below 5.4 s with a mean difference of 0.033 (P=0.0096). Conclusions— Diffusion tensor imaging-FA was decreased in regions of WM infarction and increased in hypoperfused WM in patients with hyperacute acute ischemic stroke. The significantly increased FA values in the hypoperfused WM with Tmax≥5.4 s are suggestive of early ischemic microstructural changes. PMID:25523053

  4. Minocycline attenuates experimental colitis in mice by blocking expression of inducible nitric oxide synthase and matrix metalloproteinases

    SciTech Connect

    Huang, T.-Y.; Chu, H.-C.; Lin, Y.-L.; Lin, C.-K.; Hsieh, T.-Y.; Chang, W.-K.; Chao, Y.-C.; Liao, C.-L.

    2009-05-15

    In addition to its antimicrobial activity, minocycline exerts anti-inflammatory effects in several disease models. However, whether minocycline affects the pathogenesis of inflammatory bowel disease has not been determined. We investigated the effects of minocycline on experimental colitis and its underlying mechanisms. Acute and chronic colitis were induced in mice by treatment with dextran sulfate sodium (DSS) or trinitrobenzene sulfonic acid (TNBS), and the effect of minocycline on colonic injury was assessed clinically and histologically. Prophylactic and therapeutic treatment of mice with minocycline significantly diminished mortality rate and attenuated the severity of DSS-induced acute colitis. Mechanistically, minocycline administration suppressed inducible nitric oxide synthase (iNOS) expression and nitrotyrosine production, inhibited proinflammatory cytokine expression, repressed the elevated mRNA expression of matrix metalloproteinases (MMPs) 2, 3, 9, and 13, diminished the apoptotic index in colonic tissues, and inhibited nitric oxide production in the serum of mice with DSS-induced acute colitis. In DSS-induced chronic colitis, minocycline treatment also reduced body weight loss, improved colonic histology, and blocked expression of iNOS, proinflammatory cytokines, and MMPs from colonic tissues. Similarly, minocycline could ameliorate the severity of TNBS-induced acute colitis in mice by decreasing mortality rate and inhibiting proinflammatory cytokine expression in colonic tissues. These results demonstrate that minocycline protects mice against DSS- and TNBS-induced colitis, probably via inhibition of iNOS and MMP expression in intestinal tissues. Therefore, minocycline is a potential remedy for human inflammatory bowel diseases.

  5. Changes in the composition of intestinal fungi and their role in mice with dextran sulfate sodium-induced colitis.

    PubMed

    Qiu, Xinyun; Zhang, Feng; Yang, Xi; Wu, Na; Jiang, Weiwei; Li, Xia; Li, Xiaoxue; Liu, Yulan

    2015-05-27

    Intestinal fungi are increasingly believed to greatly influence gut health. However, the effects of fungi on intestinal inflammation and on gut bacterial constitution are not clear. Here, based on pyrosequencing method, we reveal that fungal compositions vary in different intestinal segments (ileum, cecum, and colon), prefer different colonization locations (mucosa and feces), and are remarkably changed during intestinal inflammation in dextran sulfate sodium (DSS)-colitis mouse models compare to normal controls: Penicillium, Wickerhamomyces, Alternaria, and Candida are increased while Cryptococcus, Phialemonium, Wallemia and an unidentified Saccharomycetales genus are decreased in the guts of DSS-colitis mice. Fungi-depleted mice exhibited aggravated acute DSS-colitis associated with gain of Hallella, Barnesiella, Bacteroides, Alistipes, and Lactobacillus and loss of butyrate-producing Clostridium XIVa, and Anaerostipes compare with normal control. In contrast, bacteria-depleted mice show attenuated acute DSS-colitis. Mice with severely chronic recurrent DSS-colitis show increased plasma (1,3)-β-D-glucan level and fungal translocation into the colonic mucosa, mesenteric lymph nodes and spleen. This work demonstrate the different roles of fungi in acute and chronic recurrent colitis: They are important counterbalance to bacteria in maintaining intestinal micro-ecological homeostasis and health in acutely inflamed intestines, but can harmfully translocate into abnormal sites and could aggravate disease severity in chronic recurrent colitis.

  6. Remote Ischemic Conditioning

    PubMed Central

    Heusch, Gerd; Bøtker, Hans Erik; Przyklenk, Karin; Redington, Andrew; Yellon, Derek

    2014-01-01

    In remote ischemic conditioning (RIC) brief, reversible episodes of ischemia with reperfusion in one vascular bed, tissue or organ confer a global protective phenotype and render remote tissues and organs resistant to ischemia/reperfusion injury. The peripheral stimulus can be chemical, mechanical or electrical and involves activation of peripheral sensory nerves. The signal transfer to the heart or other organs is through neuronal and humoral communications. Protection can be transferred, even across species, with plasma-derived dialysate and involves nitric oxide, stromal derived factor-1α, microRNA-144, but also other, not yet identified factors. Intracardiac signal transduction involves: adenosine, bradykinin, cytokines, and chemokines, which activate specific receptors; intracellular kinases; and mitochondrial function. RIC by repeated brief inflation/deflation of a blood pressure cuff protects against endothelial dysfunction and myocardial injury in percutaneous coronary interventions, coronary artery bypass grafting and reperfused acute myocardial infarction. RIC is safe and effective, noninvasive, easily feasible and inexpensive. PMID:25593060

  7. Ischemic Stroke.

    PubMed

    Capriotti, Teri; Murphy, Teresa

    2016-05-01

    Each year, more than 795,000 people in the United States suffer a stroke and by 2030, it is estimated that 4% of the U.S. population will have had a stroke. Home healthcare clinicians will be increasingly called upon to assist stroke survivors and their caregivers adjust to disability and assist the survivor during their reintegration into the community. Therapeutic modalities are changing with advanced technology. Great strides are being made in the treatment of acute stroke; particularly endovascular interventions. More patients are surviving the acute stroke event and therefore will need to learn how to live with various degrees of disability. It is important for home healthcare clinicians to understand the process from acute event to medical stabilization, and from rehabilitation to long-term adaptation.

  8. Ischemic Stroke.

    PubMed

    Capriotti, Teri; Murphy, Teresa

    2016-05-01

    Each year, more than 795,000 people in the United States suffer a stroke and by 2030, it is estimated that 4% of the U.S. population will have had a stroke. Home healthcare clinicians will be increasingly called upon to assist stroke survivors and their caregivers adjust to disability and assist the survivor during their reintegration into the community. Therapeutic modalities are changing with advanced technology. Great strides are being made in the treatment of acute stroke; particularly endovascular interventions. More patients are surviving the acute stroke event and therefore will need to learn how to live with various degrees of disability. It is important for home healthcare clinicians to understand the process from acute event to medical stabilization, and from rehabilitation to long-term adaptation. PMID:27145407

  9. Ischemic preconditioning protects against ischemic brain injury

    PubMed Central

    Ma, Xiao-meng; Liu, Mei; Liu, Ying-ying; Ma, Li-li; Jiang, Ying; Chen, Xiao-hong

    2016-01-01

    In this study, we hypothesized that an increase in integrin αvβ3 and its co-activator vascular endothelial growth factor play important neuroprotective roles in ischemic injury. We performed ischemic preconditioning with bilateral common carotid artery occlusion for 5 minutes in C57BL/6J mice. This was followed by ischemic injury with bilateral common carotid artery occlusion for 30 minutes. The time interval between ischemic preconditioning and lethal ischemia was 48 hours. Histopathological analysis showed that ischemic preconditioning substantially diminished damage to neurons in the hippocampus 7 days after ischemia. Evans Blue dye assay showed that ischemic preconditioning reduced damage to the blood-brain barrier 24 hours after ischemia. This demonstrates the neuroprotective effect of ischemic preconditioning. Western blot assay revealed a significant reduction in protein levels of integrin αvβ3, vascular endothelial growth factor and its receptor in mice given ischemic preconditioning compared with mice not given ischemic preconditioning 24 hours after ischemia. These findings suggest that the neuroprotective effect of ischemic preconditioning is associated with lower integrin αvβ3 and vascular endothelial growth factor levels in the brain following ischemia. PMID:27335560

  10. Clostridium difficile colitis.

    PubMed

    Trnka, Y M; Lamont, J T

    1984-01-01

    Clostridium difficile has become one of the commonest pathogens of the lower intestinal tract. This organism appears unique in that infection almost always occurs during or after antibiotic therapy, suggesting that some component of the normal microflora prevents colonization by C. difficile. Once it has overgrown in the colon, C. difficile releases several toxins which cause tissue damage and diarrhea. Infection can range from a simple self-limited diarrheal illness to fulminant colitis with perforation and megacolon. Assay of stool filtrates reveals the presence of cytotoxin in nearly all patients with antibiotic-associated pseudomembranous colitis, and in approximately one third to one half of those with less severe infections. Effective therapy is available in the form of oral vancomycin, although the expense of this antibiotic has led to the use of oral metronidazole or bacitracin, which appear to be equally efficacious and considerably cheaper. Although we have learned a great deal about C. difficile in the past decade, a number of fascinating puzzles remain. We know very little about the immune response to this organism or its toxin, or whether a vaccine might someday be feasible. Similarly, we have very little insight into what effects antibodies exert on the normal colonic flora and how these effects allow C. difficile infection in a small percentage of patients. Studies of this pathogen will undoubtedly lead to a fuller understanding of the enormously complex and still mysterious microbial ferment which lives within our gastrointestinal tract. PMID:6369936

  11. [Golimumab Therapy in Ulcerative Colitis].

    PubMed

    Moon, Won

    2016-02-01

    Ulcerative colitis is a chronic inflammatory condition of the colon, characterized by diffuse mucosal inflammation and blood-mixed diarrhea. The main treatment has been 5-aminosalicylic acid, steroid, thiopurine, and anti-tumor necrosis factor alpha (TNF-α) antibodies including infliximab, adalimumab, and golimumab. Golimumab, a new anti-TNF-α agent has been recently approved for patients with moderate to severe ulcerative colitis. Its efficacy and safety has been demonstrated in line with infliximab and adalimumab in preclinical and clinical studies. This review will focus on golimumab therapy in ulcerative colitis.

  12. Matrine ameliorates spontaneously developed colitis in interleukin-10-deficient mice.

    PubMed

    Wu, Cong; Xu, Zheng; Gai, Renhua; Huang, Kehe

    2016-07-01

    Interleukin-10 (IL-10)-deficient mice spontaneously develop T cell-mediated colitis. Previous reports have shown that Matrine may reduce the symptoms of acute colitis induced by trinitrobenzene sulfonic acid (TNBS). However, whether Matrine impacts chronic colitis remains unknown. In this study, we investigated whether Matrine could limit the symptoms of spontaneously developed colitis and its potential molecular mechanisms. IL-10 deficient mice were given Matrine or a PBS control by oral gavage daily for 4weeks and were euthanized at week 2 or week 4. We measured body weight, colon length and weight, and histological scores. We also evaluated the spontaneous secretion of IL-12/23p40, IFN-γ and IL-17 in colon explant cultures as well as IFN-γ and IL-17 secretion in unseparated mesenteric lymph node (MLN) cells, and assessed IFN-γ, IL-17, IL-1β and IL-6 mRNA expression in colon tissue. In addition, we analyzed the proportions of CD4-positive and CD8-positive cells in unseparated MLN cells. Our results show that Matrine-treated mice exhibited better body weight recovery than controls and that histological scores and spontaneously secreted IL-12/23p40, IFN-γ and IL-17 in colon tissue were significantly decreased in treated mice compared with controls. The proportion of CD4-positive cells of MLNs in treated mice was significantly smaller than that in controls at week 4. Both cytokine production and mRNA expression of IFN-γ and IL-17 were significantly reduced in treated mice compared with controls. Taken together, our results indicate that Matrine may ameliorate spontaneously developed chronic colitis and could be considered as a therapeutic alternative for chronic colitis.

  13. Matrine ameliorates spontaneously developed colitis in interleukin-10-deficient mice.

    PubMed

    Wu, Cong; Xu, Zheng; Gai, Renhua; Huang, Kehe

    2016-07-01

    Interleukin-10 (IL-10)-deficient mice spontaneously develop T cell-mediated colitis. Previous reports have shown that Matrine may reduce the symptoms of acute colitis induced by trinitrobenzene sulfonic acid (TNBS). However, whether Matrine impacts chronic colitis remains unknown. In this study, we investigated whether Matrine could limit the symptoms of spontaneously developed colitis and its potential molecular mechanisms. IL-10 deficient mice were given Matrine or a PBS control by oral gavage daily for 4weeks and were euthanized at week 2 or week 4. We measured body weight, colon length and weight, and histological scores. We also evaluated the spontaneous secretion of IL-12/23p40, IFN-γ and IL-17 in colon explant cultures as well as IFN-γ and IL-17 secretion in unseparated mesenteric lymph node (MLN) cells, and assessed IFN-γ, IL-17, IL-1β and IL-6 mRNA expression in colon tissue. In addition, we analyzed the proportions of CD4-positive and CD8-positive cells in unseparated MLN cells. Our results show that Matrine-treated mice exhibited better body weight recovery than controls and that histological scores and spontaneously secreted IL-12/23p40, IFN-γ and IL-17 in colon tissue were significantly decreased in treated mice compared with controls. The proportion of CD4-positive cells of MLNs in treated mice was significantly smaller than that in controls at week 4. Both cytokine production and mRNA expression of IFN-γ and IL-17 were significantly reduced in treated mice compared with controls. Taken together, our results indicate that Matrine may ameliorate spontaneously developed chronic colitis and could be considered as a therapeutic alternative for chronic colitis. PMID:27179305

  14. Microscopic colitis: pathologic considerations, changing dogma.

    PubMed

    Robert, Marie E

    2004-01-01

    Microscopic colitis as an entity was first recognized in 1976, and has become one of the most frequent diseases to exclude on colonic mucosal biopsies. In some pathology practices, up to 30% of colonic biopsies received are from patients in whom microscopic colitis is the clinical question. In this review, the evolution of the terminology and early studies describing the pathology of microscopic colitis are discussed. The pathology of lymphocytic and collagenous colitis is reviewed in detail, including common diagnostic pitfalls, and what is currently known about the pathogenesis of these diseases. The differential diagnosis of microscopic colitis includes other idiopathic inflammatory bowel diseases (Crohn's and ulcerative colitis), infections, and drug reactions. The distinction between these entities and microscopic colitis is discussed in detail. Finally, recent studies have revealed new histopathologic changes in microscopic colitis that challenge the currently held concepts of how microscopic colitis fits into the spectrum of inflammatory bowel diseases.

  15. Molecular Mechanisms of Renal Ischemic Conditioning Strategies.

    PubMed

    Kierulf-Lassen, Casper; Nieuwenhuijs-Moeke, Gertrude J; Krogstrup, Nicoline V; Oltean, Mihai; Jespersen, Bente; Dor, Frank J M F

    2015-01-01

    Ischemia-reperfusion injury is the leading cause of acute kidney injury in a variety of clinical settings such as renal transplantation and hypovolemic and/or septic shock. Strategies to reduce ischemia-reperfusion injury are obviously clinically relevant. Ischemic conditioning is an inherent part of the renal defense mechanism against ischemia and can be triggered by short periods of intermittent ischemia and reperfusion. Understanding the signaling transduction pathways of renal ischemic conditioning can promote further clinical translation and pharmacological advancements in this era. This review summarizes research on the molecular mechanisms underlying both local and remote ischemic pre-, per- and postconditioning of the kidney. The different types of conditioning strategies in the kidney recruit similar powerful pro-survival mechanisms. Likewise, renal ischemic conditioning mobilizes many of the same protective signaling pathways as in other organs, but differences are recognized. PMID:26330099

  16. Genetics Home Reference: ulcerative colitis

    MedlinePlus

    ... colitis is unknown because many genetic and environmental factors are likely to be involved. Even though the ... Parkes M, Annese V, Hakonarson H, Radford-Smith G, Duerr RH, Vermeire S, Weersma RK, Rioux JD. Meta-analysis identifies ...

  17. Lymphocytic and Collagenous Colitis.

    PubMed

    Cruz-Correa; Giardiello

    2000-06-01

    Patients with symptomatic collagenous-lymphocytic colitis should eliminate dietary secretagogues such as caffeine- or lactose-containing food from their diet. When possible, use of nonsteroidal anti-inflammatory drugs should be discontinued. If steatorrhea is documented, a low-fat diet may be helpful. In the presence of bile salt malabsorption, binding resins such as cholestyramine might be useful. Nonspecific diarrheal agents such as loperamide hydrochloride, diphenoxylate hydrochloride and atropine, deodorized tincture of opium, or codeine might prove effective in some patients. Antibacterial agents such as bismuth subsalicylate (8 chewable 262-mg tablets daily) have been effective in symptom control. Metronidazole and erythromycin achieve response rates of 60%. Sulfasalazine, at the usual dose of 2 to 4 g daily, used in collagenous-lymphocytic colitis, demonstrated cessation of diarrhea in 1 to 2 weeks for 50% of patients. Other 5-aminosalicylic (5-ASA) compounds are preferred for patients with a history of sulfa allergy, and those who experience adverse reactions to sulfasalazine. Adrenocorticoid medication is reserved for patients whose conventional treatment with sulfasalazine or 5-ASA has failed. Resolution of diarrhea has been documented in 80% to 90% of patients within 1 week of treatment, however, in most patients, long-term therapy is required. Surgical management is reserved for those patients with disease refractory to medical therapy. Colectomy with ileostomy resulted in clinical and histologic resolution in small case series. If there is no abatement of symptoms, rule out other etiologies of diarrhea such as thyroid dysfunction, celiac disease, or bacterial overgrowth. PMID:11097741

  18. Spontaneous laser doppler flux distribution in ischemic ulcers and the effect of prostanoids: a crossover study comparing the acute action of prostaglandin E1 and iloprost vs saline.

    PubMed

    Gschwandtner, M E; Koppensteiner, R; Maca, T; Minar, E; Schneider, B; Schnürer, G; Ehringer, H

    1996-01-01

    The flux distribution within ischemic ulcers and adjacent skin and its change by prostanoids was investigated using laser Doppler flux scanning. A prostanoid-induced increase in ulcer flux could be a rationale for the improved wound healing. In a single-blind prospective study 18 patients received prostaglandin E1 (PGE1) (333.3 ng/min.), iloprost (41.7 ng/min final dose), and 0.9% saline in a randomized order. The average laser Doppler flux within the ulcer (LFU, x +/- SEM, arbitrary units) or in the adjacent skin (LFS) was evaluated before and 30, 60, 90, and 120 min after prostanoid/saline infusion. LFU increased with PGE1 from 2.30 +/- 0.27 to 3.08 +/- 0.31 (+33.9%; P < 0.001) and with iloprost from 2.37 +/- 0.26 to 3.03 +/- 0.27 (+27.8%; P < 0.001) after 120 min, respectively. Saline did not change LFU significantly: 2.19 +/- 0.18 vs 2.55 +/- 0.26 (+16.4%; P > 0.05). Simultaneously, LFS was not significantly changed when pretreatment values were compared with mean flux at 120 min: PGE1 2.13 +/- 0.27 vs 2.54 +/- 0.34, iloprost 2.03 +/- 0.26 vs 1.94 +/- 0.21, and saline 1.74 +/- 0.27 vs 1.92 +/- 0.30 (P > 0.05, each), respectively. The laser Doppler flux scanning technique might be a tool to study the distribution of laser Doppler flux within ischemic ulcers. This might be useful to study the physiological or pathophysiological control of flux within ischemic ulcers as well as possible therapeutic approaches. PMID:8812752

  19. Still cooling after all these years: Meta-analysis of pre-clinical trials of therapeutic hypothermia for acute ischemic stroke.

    PubMed

    Dumitrascu, Oana M; Lamb, Jessica; Lyden, Patrick D

    2016-07-01

    Therapeutic hypothermia is the most potent neuroprotectant for experimental cerebral ischemia, illustrated in a 2007 meta-analysis published in this journal. To address recent therapeutic nihilism, we systematically reviewed recent experimental literature. Quality scoring showed considerable improvement in study design. Using several outcome measures in a variety of models and species, therapeutic hypothermia was protective compared with normothermia, with powerful and statistically significant normalized treatment effect sizes, in 60 papers comprising 216 comparisons. In the past 5 years, preclinical studies of ischemic stroke re-emphasize that therapeutic hypothermia is potently effective, justifying further development in larger human clinical trials. PMID:27089911

  20. Intestinal Microbiota Signatures Associated with Inflammation History in Mice Experiencing Recurring Colitis

    PubMed Central

    Berry, David; Kuzyk, Orest; Rauch, Isabella; Heider, Susanne; Schwab, Clarissa; Hainzl, Eva; Decker, Thomas; Müller, Mathias; Strobl, Birgit; Schleper, Christa; Urich, Tim; Wagner, Michael; Kenner, Lukas; Loy, Alexander

    2015-01-01

    Acute colitis causes alterations in the intestinal microbiota, but the microbiota is thought to recover after such events. Extreme microbiota alterations are characteristic of human chronic inflammatory bowel diseases, although alterations reported in different studies are divergent and sometimes even contradictory. To better understand the impact of periodic disturbances on the intestinal microbiota and its compositional difference between acute and relapsing colitis, we investigated the beginnings of recurrent inflammation using the dextran sodium sulfate (DSS) mouse model of chemically induced colitis. Using bacterial 16S rRNA gene-targeted pyrosequencing as well as quantitative fluorescence in situ hybridization, we profiled the intestinal and stool microbiota of mice over the course of three rounds of DSS-induced colitis and recovery. We found that characteristic inflammation-associated microbiota could be detected in recovery-phase mice. Successive inflammation episodes further drove the microbiota into an increasingly altered composition post-inflammation, and signatures of colitis history were detectable in the microbiota more sensitively than by pathology analysis. Bacterial indicators of murine colitis history were identified in intestinal and stool samples, with a high degree of consistency between both sample types. Stool may therefore be a promising non-invasive source of bacterial biomarkers that are highly sensitive to inflammation state and history. PMID:26697002

  1. Paternal chronic colitis causes epigenetic inheritance of susceptibility to colitis

    PubMed Central

    Tschurtschenthaler, Markus; Kachroo, Priyadarshini; Heinsen, Femke-Anouska; Adolph, Timon Erik; Rühlemann, Malte Christoph; Klughammer, Johanna; Offner, Felix Albert; Ammerpohl, Ole; Krueger, Felix; Smallwood, Sébastien; Szymczak, Silke; Kaser, Arthur; Franke, Andre

    2016-01-01

    Inflammatory bowel disease (IBD) arises by unknown environmental triggers in genetically susceptible individuals. Epigenetic regulation of gene expression may integrate internal and external influences and may thereby modulate disease susceptibility. Epigenetic modification may also affect the germ-line and in certain contexts can be inherited to offspring. This study investigates epigenetic alterations consequent to experimental murine colitis induced by dextran sodium sulphate (DSS), and their paternal transmission to offspring. Genome-wide methylome- and transcriptome-profiling of intestinal epithelial cells (IECs) and sperm cells of males of the F0 generation, which received either DSS and consequently developed colitis (F0DSS), or non-supplemented tap water (F0Ctrl) and hence remained healthy, and of their F1 offspring was performed using reduced representation bisulfite sequencing (RRBS) and RNA-sequencing (RNA-Seq), respectively. Offspring of F0DSS males exhibited aberrant methylation and expression patterns of multiple genes, including Igf1r and Nr4a2, which are involved in energy metabolism. Importantly, DSS colitis in F0DSS mice was associated with decreased body weight at baseline of their F1 offspring, and these F1 mice exhibited increased susceptibility to DSS-induced colitis compared to offspring from F0Ctrl males. This study hence demonstrates epigenetic transmissibility of metabolic and inflammatory traits resulting from experimental colitis. PMID:27538787

  2. Paternal chronic colitis causes epigenetic inheritance of susceptibility to colitis.

    PubMed

    Tschurtschenthaler, Markus; Kachroo, Priyadarshini; Heinsen, Femke-Anouska; Adolph, Timon Erik; Rühlemann, Malte Christoph; Klughammer, Johanna; Offner, Felix Albert; Ammerpohl, Ole; Krueger, Felix; Smallwood, Sébastien; Szymczak, Silke; Kaser, Arthur; Franke, Andre

    2016-01-01

    Inflammatory bowel disease (IBD) arises by unknown environmental triggers in genetically susceptible individuals. Epigenetic regulation of gene expression may integrate internal and external influences and may thereby modulate disease susceptibility. Epigenetic modification may also affect the germ-line and in certain contexts can be inherited to offspring. This study investigates epigenetic alterations consequent to experimental murine colitis induced by dextran sodium sulphate (DSS), and their paternal transmission to offspring. Genome-wide methylome- and transcriptome-profiling of intestinal epithelial cells (IECs) and sperm cells of males of the F0 generation, which received either DSS and consequently developed colitis (F0(DSS)), or non-supplemented tap water (F0(Ctrl)) and hence remained healthy, and of their F1 offspring was performed using reduced representation bisulfite sequencing (RRBS) and RNA-sequencing (RNA-Seq), respectively. Offspring of F0(DSS) males exhibited aberrant methylation and expression patterns of multiple genes, including Igf1r and Nr4a2, which are involved in energy metabolism. Importantly, DSS colitis in F0(DSS) mice was associated with decreased body weight at baseline of their F1 offspring, and these F1 mice exhibited increased susceptibility to DSS-induced colitis compared to offspring from F0(Ctrl) males. This study hence demonstrates epigenetic transmissibility of metabolic and inflammatory traits resulting from experimental colitis. PMID:27538787

  3. Retraction statement: Dynamics of Cytochrome C Oxidase Activity in Acute Ischemic Stroke' by Selaković, V.M., Jovanović, M.D., Mihajlović, R.R. and Radenović, L.L.J.

    PubMed

    2016-10-01

    The above article from Acta Neurologica Scandinavica, published online on 7 April 2005 in Wiley Online Library (wileyonlinelibrary.com) and in Volume 111, pp. 329-332, has been retracted by agreement between the journal Editor in Chief, Professor Elinor Ben-Menachem, and John Wiley & Sons Ltd. The article has been retracted because a similar article had previously been published in the Jugoslovenska medicinska biohemija in 2003. The authors presumed that since the journal was no longer existing, they felt the need to re-publish their work in Acta Neuorologica Scandinavica. However, in the consideration of the Journal, this constitutes dual publication. References SelakovićVM, JovanovićMD, MihajlovićR, RadenovićLLJ. Cytochrome c oxidase in patients with acute ischaemic brain disease. Jugoslovenska medicinska biohemija. 2003;22:329-334. SelakovićVM, JovanovićMD, MihajlovićRR, RadenovićLLJ. Dynamics of cytochrome c oxidase activity in acute ischemic stroke. Acta Neurol Scand. 2005;111:329-332.

  4. Retraction statement: Dynamics of Cytochrome C Oxidase Activity in Acute Ischemic Stroke' by Selaković, V.M., Jovanović, M.D., Mihajlović, R.R. and Radenović, L.L.J.

    PubMed

    2016-10-01

    The above article from Acta Neurologica Scandinavica, published online on 7 April 2005 in Wiley Online Library (wileyonlinelibrary.com) and in Volume 111, pp. 329-332, has been retracted by agreement between the journal Editor in Chief, Professor Elinor Ben-Menachem, and John Wiley & Sons Ltd. The article has been retracted because a similar article had previously been published in the Jugoslovenska medicinska biohemija in 2003. The authors presumed that since the journal was no longer existing, they felt the need to re-publish their work in Acta Neuorologica Scandinavica. However, in the consideration of the Journal, this constitutes dual publication. References SelakovićVM, JovanovićMD, MihajlovićR, RadenovićLLJ. Cytochrome c oxidase in patients with acute ischaemic brain disease. Jugoslovenska medicinska biohemija. 2003;22:329-334. SelakovićVM, JovanovićMD, MihajlovićRR, RadenovićLLJ. Dynamics of cytochrome c oxidase activity in acute ischemic stroke. Acta Neurol Scand. 2005;111:329-332. PMID:27592845

  5. Investigation of pulmonary involvement in inflammatory bowel disease in an experimental model of colitis

    PubMed Central

    Aydin, Bunyamin; Songur, Yıldıran; Songur, Necla; Aksu, Oğuzhan; Senol, Altug; Ciris, I. Metin; Sutcu, Recep

    2016-01-01

    Background/Aims: Inflammatory bowel disease (IBD) may also involve various extra-intestinal organs. Clinical studies have found asymptomatic/symptomatic pulmonary involvement in 1% to 6% of patients with IBD. The present study histopathologically investigated pulmonary involvement in an experimental model of colitis in order to demonstrate pulmonary tissue involvement in IBD and to expose potential etiological factors. It also explored the relation between inflammation and tissue concentrations of vascular endothelial growth factor (VEGF) and tumor necrosis factor α (TNF-α). Methods: The study comprised 24 male Wistar albino rats. The rats were divided into four groups of six rats each. Acute colitis was induced in two separate groups using either the dextran sulphate sodium (DSS) or trinitrobenzene sulfonic acid (TNBS) method, while the other two groups were used as controls for each model of colitis. Wallace scoring was used for macroscopic assessment of colitis, and the lungs were histopathologically examined. Concentrations of VEGF and TNF-α in pulmonary tissue were measured by the enzyme-linked immunosorbent assay method. Results: The number of animals that had alveolar hemorrhage was significantly higher in the TNBS-induced colitis and DSS-induced colitis groups compared to their own control groups (p = 0.015 and p = 0.015, respectively). VEGF and TNF-α concentrations in pulmonary tissues were significantly increased in both the TNBS colitis and DSS colitis groups compared to their own control groups (p = 0.002 and p = 0.004, respectively; and p = 0.002 and p = 0.002, respectively). Conclusions: The present study demonstrated that significant and serious histopathological changes directly associated with colitis occur in the lungs in IBD. PMID:27539446

  6. Microscopic Colitis (Lymphocytic and Collagenous), Eosinophilic Colitis, and Celiac Disease

    PubMed Central

    Villanueva, M. Sophia; Alimi, Yewande

    2015-01-01

    Multiple tests are needed to diagnose a patient with noninfectious diarrhea. Some patients will be mistakenly labeled as diarrhea-predominant irritable bowel syndrome (IBS-D) because of nonspecific computed tomographic scans and grossly normal endoscopic findings. It is crucial to understand other less common pathologies to avoid these instances of misdiagnosis. This article focuses on microscopic colitis (MC), eosinophilic colitis (EC), and celiac disease. MC is an inflammatory condition of the colon that presents with two subtypes, only to be differentiated by histology. EC is a rare chronic inflammatory process. Depending on the extent of the disease, it can present with mild diarrhea, malabsorption, or at its worst, cause obstruction and perforation. Celiac disease affects the small bowel, but interestingly can present similarly to colitis. Both MC and EC respond to oral budesonide. Patients with celiac disease improve on gluten-free diets. These treatments are distinctly different from typical IBS-D care plans. PMID:26034409

  7. Acute myocardial infarction associated with single vessel coronary artery disease: an analysis of clinical outcome and the prognostic importance of vessel patency and residual ischemic myocardium

    SciTech Connect

    Wilson, W.W.; Gibson, R.S.; Nygaard, T.W.; Craddock, G.B. Jr.; Watson, D.D.; Crampton, R.S.; Beller, G.A.

    1988-02-01

    The long-term outcome and the significance of residual ischemic myocardium, as assessed by predischarge exercise thallium scintigraphy and vessel patency, were studied in 97 patients with single vessel coronary artery disease by angiography 12 +/- 4 days after uncomplicated myocardial infarction. During a mean follow-up period of 39 +/- 17 months, no patients died, 6 (6%) had a recurrent nonfatal infarction and 25 (26%) experienced rapidly progressive angina requiring hospitalization. Although neither exercise-induced angina nor ST segment depression was predictive of a recurrent cardiac event, the mean number of infarct zone scan segments showing thallium redistribution (1.0 +/- 1.0 versus 0.5 +/- 0.8, p = 0.01) and the percent of patients with infarct zone redistribution (61 versus 39%, p = 0.05) were greater in those patients who experienced a late ischemic event. Kaplan-Meier analysis demonstrated a lower event-free survival rate in patients with redistribution (n = 45) than in those without redistribution (n = 52) (p = 0.019). Although no patient received immediate thrombolytic therapy, the infarct-related vessel was angiographically patent in 40 patients (41%). Vessel patency did not influence event-free survival, although a patent vessel, as compared with an occluded vessel, was associated with a greater prevalence of non-Q wave infarction (58 versus 21%, p less than 0.001), fewer persistent infarct zone thallium defects (1.2 +/- 1.1 versus 2.0 +/- 1.2, p = 0.001), more reversible infarct zone thallium defects (1.0 +/- 1.0 versus 0.5 +/- 0.9, p = 0.02) and a trend toward a higher left ventricular ejection fraction (53 +/- 10% versus 49 +/- 12%, p = 0.07).

  8. [Ischemic cerebrovascular accidents in childhood].

    PubMed

    Pascual Pascual, S I; Pascual Castroviejo, I; Vélez, A

    1988-04-01

    Authors review 53 children, aged 0 to 14 years, affected with cerebrovascular ischemic strokes. Largest aetiological groups were: a) congenital heart disease, 16 patients; b) arteritis of unknown cause, 11; c) idiopathic arterial occlusion without arteritis images on angiography, 7; d) moyamoya disease, 6; and d) local or systemic infections, 5. The mode of onset was as completed stroke in 72% and stroke in evolution in 24%. After acute stage 17.6% of patients presented other definitive strokes, 11.7% suffered only transient ischemic strokes (TIA), and 4% reversible ischemic neurologic deficits (RIND). Mean follow-up was 4.36 years, 9.8% of patients died, 11.8% recovered completely and 52.9% improved after initial stroke. Poor global evolution was associated with heart disease (p less than 0.05) and with onset of strokes before age 2 (p less than 0.05). Most important sequelae, besides motor impairment, were epilepsy (49%) and mental retardation (50% got less than IQ 80). Late epilepsy was associated with seizures at onset (p less than 0.05). Clinical factors of adverse mental development were: a) seizures at onset, b) late epilepsy and c) stroke before age 2. 66% of cases had two or more arterial lesions in the same or in different arterial trees. Therefore, embolic and arteritic factors probably play an important role in infancy and childhood stroke. PMID:3400936

  9. The effect of chemically induced colitis, psychological stress and their combination on visceral pain in female Wistar rats.

    PubMed

    Deiteren, Annemie; Vermeulen, Wim; Moreels, Tom G; Pelckmans, Paul A; De Man, Joris G; De Winter, Benedicte Y

    2014-09-01

    Visceral sensitivity is of pathophysiological importance in abdominal pain disorders and can be modulated by inflammation and stress. However, it is unclear whether inflammation and stress alter visceral perception independently of each other or in conjunction through neuroendocrine interactions. Therefore, we compared the short- and long-term effects of experimental colitis and water avoidance stress (WAS), alone or in combination, on visceral sensitivity in female Wistar rats. Colitis was induced by trinitrobenzene sulfonic acid (TNBS) and colonoscopically confirmed. During WAS, rats were placed on a platform surrounded by water for 1 h. Visceral sensitivity was assessed by quantifying the visceromotor responses (VMRs) to colorectal distension. Activation of the hypothalamic-pituitary-adrenal axis was determined by measuring serum corticosterone in a separate protocol. TNBS instillation resulted in overt colitis, associated with significant visceral hypersensitivity during the acute inflammatory phase (3 days post-TNBS; n = 8/group); after colitis had subsided (28 days post-TNBS), hypersensitivity was resolved (n = 4-8/group). Single WAS was associated with increased VMRs of a magnitude comparable to acute TNBS-induced hypersensitivity (n = 8/group). However, after repetitive WAS no significant hypersensitivity was present (n = 8/group). No additive effect of colitis and stress was seen on visceral pain perception (n = 6-8/group). Corticosterone levels were only increased in acute TNBS-colitis, acute WAS and their combination. To conclude, both colitis and stress successfully induced short-term visceral hypersensitivity and activated the hypothalamic-pituitary-adrenal axis, but long-term effects were absent. In addition, our current findings do not support an additive effect of colitis and stress on visceral sensitivity in female Wistar rats.

  10. Systematic Review and Pooled Analyses of Recent Neurointerventional Randomized Controlled Trials: Setting a New Standard of Care for Acute Ischemic Stroke Treatment after 20 Years

    PubMed Central

    Hussain, Mohammed; Moussavi, Mohammad; Korya, Daniel; Mehta, Siddhart; Brar, Jaskiran; Chahal, Harina; Qureshi, Ihtesham; Mehta, Tapan; Ahmad, Javaad; Zaidat, Osama O.; Kirmani, Jawad F.

    2016-01-01

    Background Recent advances in the treatment of ischemic stroke have focused on revascularization and led to better clinical and functional outcomes. A systematic review and pooled analyses of 6 recent multicentered prospective randomized controlled trials (MPRCT) were performed to compare intravenous tissue plasminogen activator (IV tPA) and endovascular therapy (intervention) with IV tPA alone (control) for anterior circulation ischemic stroke (AIS) secondary to large vessel occlusion (LVO). Objectives Six MPRCTs (MR CLEAN, ESCAPE, EXTEND IA, SWIFT PRIME, REVASCAT and THERAPY) incorporating image-based LVO AIS were selected for assessing the following: (1) prespecified primary clinical outcomes of AIS patients in intervention and control arms: good outcomes were defined by a modified Rankin Scale score of 0-2 at 90 days; (2) secondary clinical outcomes were: (a) revascularization rates [favorable outcomes defined as modified Thrombolysis in Cerebral Infarction scale (mTICI) score of 2b/3]; (b) symptomatic intracranial hemorrhage (sICH) rates and mortality; (c) derivation of number needed to harm (NNH), number needed to treat (NNT), and relative percent difference (RPD) between intervention and control groups, and (d) random effects model to determine overall significance (forest and funnel plots). Results A total of 1,386 patients were included. Good outcomes at 90 days were seen in 46% of patients in the intervention (p < 0.00001) and in 27% of patients in the control groups (p < 0.00002). An mTICI score of 2b/3 was achieved in 70.2% of patients in the intervention arm. The sICH and mortality in the intervention arm compared with the control arm were 4.7 and 14.3% versus 7.9 and 17.8%, respectively. The NNT and NNH in the intervention and control groups were 5.3 and 9.1, respectively. Patients in the intervention arm had a 50.1% (RPD) better chance of achieving a good 90-day outcome as compared to controls. Conclusions Endovascular therapy combined with IV t

  11. Systematic Review and Pooled Analyses of Recent Neurointerventional Randomized Controlled Trials: Setting a New Standard of Care for Acute Ischemic Stroke Treatment after 20 Years

    PubMed Central

    Hussain, Mohammed; Moussavi, Mohammad; Korya, Daniel; Mehta, Siddhart; Brar, Jaskiran; Chahal, Harina; Qureshi, Ihtesham; Mehta, Tapan; Ahmad, Javaad; Zaidat, Osama O.; Kirmani, Jawad F.

    2016-01-01

    Background Recent advances in the treatment of ischemic stroke have focused on revascularization and led to better clinical and functional outcomes. A systematic review and pooled analyses of 6 recent multicentered prospective randomized controlled trials (MPRCT) were performed to compare intravenous tissue plasminogen activator (IV tPA) and endovascular therapy (intervention) with IV tPA alone (control) for anterior circulation ischemic stroke (AIS) secondary to large vessel occlusion (LVO). Objectives Six MPRCTs (MR CLEAN, ESCAPE, EXTEND IA, SWIFT PRIME, REVASCAT and THERAPY) incorporating image-based LVO AIS were selected for assessing the following: (1) prespecified primary clinical outcomes of AIS patients in intervention and control arms: good outcomes were defined by a modified Rankin Scale score of 0-2 at 90 days; (2) secondary clinical outcomes were: (a) revascularization rates [favorable outcomes defined as modified Thrombolysis in Cerebral Infarction scale (mTICI) score of 2b/3]; (b) symptomatic intracranial hemorrhage (sICH) rates and mortality; (c) derivation of number needed to harm (NNH), number needed to treat (NNT), and relative percent difference (RPD) between intervention and control groups, and (d) random effects model to determine overall significance (forest and funnel plots). Results A total of 1,386 patients were included. Good outcomes at 90 days were seen in 46% of patients in the intervention (p < 0.00001) and in 27% of patients in the control groups (p < 0.00002). An mTICI score of 2b/3 was achieved in 70.2% of patients in the intervention arm. The sICH and mortality in the intervention arm compared with the control arm were 4.7 and 14.3% versus 7.9 and 17.8%, respectively. The NNT and NNH in the intervention and control groups were 5.3 and 9.1, respectively. Patients in the intervention arm had a 50.1% (RPD) better chance of achieving a good 90-day outcome as compared to controls. Conclusions Endovascular therapy combined with IV t

  12. Alterations of testosterone metabolism in microsomes from rats with experimental colitis induced by dextran sulfate sodium.

    PubMed

    Huang, Yanjuan; Hu, Nan; Gao, Xuejiao; Yan, Zhixiang; Li, Sai; Jing, Wanghui; Yan, Ru

    2015-05-01

    Down-regulation of some hepatic cytochrome P450s (CYP450s) was observed in patients and animals with ulcerative colitis (UC). This study examined changes of CYP450s activities in microsomes of liver (RLMs), intestine (RIMs) and kidney (RRMs) from rats with experimental acute colitis induced by 5% dextran sulfate sodium (DSS) for 7days and those receiving DSS treatment followed by 7-d cessation through measuring 6α-(CYP1A1), 7α-(CYP2A1), 16α-(CYP2C11) and 2β-/6β-(CYP3A2) hydroxytestosterone (OHT) formed from testosterone. Both pro-(IL-1β, IL-6, TNF-α) and anti-(IL-4, IL-10) inflammatory cytokines were elevated in acute colitis, while the production of the former was enhanced and that of the latter declined by DSS withdrawal. In RLMs, the CYP2A1 activity was significantly increased at DSS stimulation and partially returned to normal level when DSS treatment was terminated. Activity of other CYP450s were decreased by acute colitis and remained after DSS withdrawal. In RRMs, formations of 6α-, 16α- and 2β-OHT significantly declined in acute colitis and DSS termination further potentiated the down-regulation, while 7α-OHT formation was suppressed at DSS stimulation and remained after DSS withdrawal. The formation of 6β-OHT only showed significant decrease after DSS withdrawal. Two metabolites (6α- and 6β-OHT) formed in RIMs and 6β-OHT formation was significantly decreased by DSS stimulation and continued after DSS treatment halted. These findings indicate that the alterations of CYP450s activities vary with organ, CYP isoforms and colitis status, which arouse cautions on efficacy and toxicity of drug therapy during disease progression.

  13. Ischemic optic neuropathy.

    PubMed

    Athappilly, Geetha; Pelak, Victoria S; Mandava, Naresh; Bennett, Jeffrey L

    2008-10-01

    Ischemic optic neuropathy is the most frequent cause of vision loss in middle age. Clinical and laboratory research studies have begun to clarify the natural history, clinical presentation, diagnostic criteria and pathogenesis of various ischemic nerve injuries. As a result, physicians are acquiring new tools to aid in the diagnosis and potential treatment of ischemic nerve injury. The aim of this review is to examine recent data on anterior and posterior ischemic optic neuropathy and to provide a framework for physicians to manage and counsel affected individuals. PMID:18826805

  14. Behavioral Treatment of Mucous Colitis

    ERIC Educational Resources Information Center

    Youell, Katherine J.; McCullough, James P.

    1975-01-01

    A 22-year-old female graduate student who suffered colitis attacks at the onset of therapy was apparently successfully treated by a procedure in which the therapist labeled antecedent stress events that appeared to be precipitating the attacks. The client was then taught a behavioral coping strategy to counter the stress events. (Author)

  15. Resilience in Patients with Ischemic Heart Disease

    PubMed Central

    de Lemos, Conceição Maria Martins; Moraes, David William; Pellanda, Lucia Campos

    2016-01-01

    Background Resilience is a psychosocial factor associated with clinical outcomes in chronic diseases. The relationship between this protective factor and certain diseases, such heart diseases, is still under-explored. Objective The present study sought to investigate the frequency of resilience in individuals with ischemic heart disease. Method This was a cross-sectional study with 133 patients of both genders, aged between 35 and 65 years, treated at Rio Grande do Sul Cardiology Institute - Cardiology University Foundation, with a diagnosis of ischemic heart disease during the study period. Sixty-seven patients had a history of acute myocardial infarction. The individuals were interviewed and evaluated by the Wagnild & Young resilience scale and a sociodemographic questionnaire. Results Eighty-one percent of patients were classified as resilient according to the scale. Conclusion In the sample studied, resilience was identified in high proportion among patients with ischemic heart disease. PMID:26815312

  16. Complement component 6 deficiency increases susceptibility to dextran sulfate sodium-induced murine colitis.

    PubMed

    Ding, Peipei; Li, Ling; Huang, Tianbao; Yang, Chaoqun; Xu, Enjie; Wang, Na; Zhang, Long; Gu, Hongyu; Yao, Xudong; Zhou, Xuhui; Hu, Weiguo

    2016-11-01

    As a potent effector of innate immunity, the complement system has been shown to be involved in the pathogenesis of inflammatory bowel disease (IBD). However, the role of the membrane attack complex (MAC) in the development of IBD is still largely unknown. Here, we used C6-deficient mice in which MAC formation was blocked due to the absence of C6 to develop an acute colitis model by the administration of dextran sulfate sodium (DSS). The results showed that DSS-induced colitis was aggravated in C6-deficient mice compared with wild-type (WT) mice, as represented by the markedly greater weight loss, higher disease activity index (DAI), shortened colon length, more severe histological injury with increased epithelial ulcerations, and massively increased infiltration of leukocytes accompanied by much higher myeloperoxidase (MPO) levels in local inflammatory colonic sites. In addition, the DSS-induced colitis in C6-deficient mice could be significantly ameliorated by the exogenous C6 from WT sera. Furthermore, the significantly enhanced production of pro-inflammatory mediators, including IL-1β, IL-6, CXCL-1, CCL-3, TGF-β1 and IL-17F, was also observed in C6-deficient mice. Unexpectedly, the aggravated colitis in C6-deficient mice may be not due to the increase of lipopolysaccharide (LPS) levels in serum. Overall, we demonstrated that MAC exerts a protective role in acute colitis, strongly highlighting the host defense function of the complement system. PMID:27316715

  17. Induction of ulcerative colitis in mice influences the course of infection with the nematode Trichuris muris.

    PubMed

    Vegas-Sánchez, M C; Rollán-Landeras, E; García-Rodríguez, J J; Bolás-Fernández, F

    2015-09-01

    The aim of this study was to assess the effect of infection with the nematode whipworm Trichuris muris on the course of chemically induced acute ulcerative colitis in CBA/J mice, a strain proven to be highly resistant to infection with T. muris. Each mouse was infected with 50 embryonated eggs of T. muris by oral gavage. Acute colitis was triggered by administering 4% dextran sulphate sodium (DSS) in the drinking water for nine consecutive days at different times after infection. Concurrent infection and DSS administration exacerbate the severity of the colitis while favouring the permanence of parasites in the intestine. The induction of ulcerative colitis from days 54 to 62 post-infection (p.i.), when all worms had been expelled, ameliorated the course of the inflammatory disease. When ulcerative colitis was triggered earlier on, from days 27 to 35 p.i., the beneficial effects on inflammatory events were clearly shown with signs of mucosal epithelization and regeneration as early as day 1 after DSS administration. Previous infections by T. muris therefore accelerate recovery from subsequently induced inflammatory bowel disease and such an effect assists the nematode to persist in the intestinal niche.

  18. Determination of the Role of Oxygen in Suspected Acute Myocardial Infarction by Biomarkers

    ClinicalTrials.gov

    2016-01-25

    Acute Myocardial Infarction (AMI); Acute Coronary Syndrome (ACS); ST Elevation (STEMI) Myocardial Infarction; Ischemic Reperfusion Injury; Non-ST Elevation (NSTEMI) Myocardial Infarction; Angina, Unstable

  19. Clusterin: a protective mediator for ischemic cardiomyocytes?

    PubMed

    Krijnen, P A J; Cillessen, S A G M; Manoe, R; Muller, A; Visser, C A; Meijer, C J L M; Musters, R J P; Hack, C E; Aarden, L A; Niessen, H W M

    2005-11-01

    We examined the relationship between clusterin and activated complement in human heart infarction and evaluated the effect of this protein on ischemic rat neonatal cardiomyoblasts (H9c2) and isolated adult ventricular rat cardiomyocytes as in vitro models of acute myocardial infarction. Clusterin protects cells by inhibiting complement and colocalizes with complement on jeopardized human cardiomyocytes after infarction. The distribution of clusterin and complement factor C3d was evaluated in the infarcted human heart. We also analyzed the protein expression of clusterin in ischemic H9c2 cells. The binding of endogenous and