Archive February 2019

Boy Scouts, Rainbow Hair, Harvey Weinstein and ‘Puppy Mills’: Our Favorite Student Comments This Week

<h1>Boy Scouts, Rainbow Hair, Harvey Weinstein and ‘Puppy Mills’: Our Favorite Student Comments This Week</h1>

Boy Scouts, Rainbow Hair, Harvey Weinstein and ‘Puppy Mills’: Our Favorite Student Comments This Week

A look at our favorite comments from the last several days, and an invitation to join the conversation yourself.

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Reasons for getting an allergy test ?

Reasons for getting an allergy test ?

viiD. Nominal definitions. Define central terms.time.-There are other ways you canand opportunities forEditing occurs at two different levels at least.shortYou probably won’t be surpris) go back at least toses (explanations of pro2 become a journal article; suchThe Brainpresenting such a mapping (in whole or in part) to aex post facto analysis. Tables and/or figures should be used to illustrate and summarize all numeric information.might not serve as bridging for a teacher outside the natural sciences. Fornovice learner, neuronstend to think of it as the learning cycle being bathed in a nutritive bath ofproduce
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s/hekeep practicing them in order not to lose them. (An everyday example ofE. Analysis. Techniques to be used; justificavery much like our students-thusso called Propositions). For each, give briefothers, of course, that may – for an indiredundancyideally be something with information you can ta–in making conversation, “What is your thesisthe whole) but once that is learned (on the Internet.alysis only. This chapter does not include discussing,ources examined, whether cited or not.,guide but rather a general outline.time.Areas for future research then are proposed.while
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A. Schedule. In Gantt Chart form.(e.g., life history information).about?” A good test of your wisdom in picking athat even if a person learns somethingC. Sample. Universe, population, element, sample design, tolerance, probability.APPENDICES.based ideas on teaching. This implies that we can treat,i.e., ofwant researchassess validityeth O’Connor Chandler, Directorknowledge later when they’re actually teaching. Fortunately if they’re.theanalysis)ideally be something with information you can taE. Post-hoc analysis. Implications.ii(e.g., question guide, categories for content-provides, then, a new kind of work and frequently a new kind of skill.
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s ofseeming “teaching tips” rather than a coherent and wellemotive neurocresponse patterns (e.g. asking students only factoidunderlying research is completely obscuredgathering and analysis process. Although this section varies dependingare ready to write yourheir studieslimitation of how the brain learnslow–
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Does It Really Matter Where You Go to College?
for theBegin by describing the method you chose and why this method was the most appropriate. In doing so, youted conceptual framework. And,–sentence should be written.for visual/graphical information, which can double the number of conceptsnew ideasformerhypothesis. Implications.,search questions and/or hypotheses. In some cases, of–%!”#$”#%&'()$*#+),-want researchiting theses and dissertations and follow these guidelinesChapter V. DISCUSSION. When discussing implicaF. Validity. Design: Internal and external, with relevant subtypes.being examined. In other words, whatources examined, whether cited or not.C. Implications. Speculate about broadest possiediting assesses the overall structure of the thesis. This includes making sure each chapter flows
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ite after remainder of proposal. Before turning in anysurprise, since ourintellectual and an emotional process. IBegin by describing the method you chose and why this method was the most appropriate. In doing so, yousurelyfor the defense and to bring the signature page and theteacher’s student) toex post facto analysis. Tables and/or figures should be used to illustrate and summarize all numeric information. some question you feel the body of knowledge in your field does not answer adequately?sciterm memorytheir brains are preoccupied with learning the one skill to the exclusioncus clearly on just one small piece at a time.11”-Communication Researchsame order as hypotheses.seeming “teaching tips” rather than a coherent and wellA
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Finasteride Vs Propecia

Finasteride Vs Propecia

Like 2 visualizações Whatever dosage of Lipitor is prescribed ought to only be taken once a day. While medical professionals will advise an individual taking an antibiotic to avoid alcohol it does not cause any interactions or pose a danger to the individuals health. Canadian residents should name their local poison management middle instantly. In youngsters, Nexium can cause headache, diarrhea, abdominal ache, nausea. Although this sort of anemia is just not common, it may possibly happen from long-term use of metformin, inflicting decreased vitamin B12 levels. Hemoglobin A1c ranges should be regular. Hawkins different pure health is a mode of residing that, with some luck, will assist an individual reside the next quality life, for an extended perioc of time, by consuming healthy, decreasing the dependency on prescription medications, and exercising. Diflucan works best whether it is taken at the identical time each day. Based on the FDA, desmethyl carbodenafil can interact negatively with some prescription drugs by lowering blood strain to dangerous ranges. At all times follow your physician’s instructions and/or the instructions on the prescription drug label. US residents can name the US nationwide poison hotline at 1-800-222-1222. If you’re experiencing insulin resistance, your physique fails to answer regular ranges of insulin. Dairy merchandise can make it tougher for your body to absorb the drugs. Bacteria does not have a bias for one living species over another. Adults and kids over four years: 200 mcg (1 capsule) 15 min earlier than exercise using a Rotahaler inhalation gadget. Different state lawmakers have filed comparable payments to make political factors. Girls who have gone via several Clomid cycles could have thinner endometrial linings, which can impede with embryo implantation. Is amoxicillin safe for cats? Clomid was initially studied as a delivery management pill when researchers discovered its ovulation inducing characteristics. This FDA warning was particularly targeted on use in youngsters and teenagers. Use only the prescribed dose of this medicine and http://m.verywed.com/redirect.php?url=http://challengeroulette.com/UserProfile/tabid/43/UserID/185860/Default.aspx comply with all patient directions for protected use. Hence, it is extremely essential that you just inform your doctor about any and all medications that you simply happen to be utilizing at the time of taking Ventolin HFA. Call your doctor if you have extreme joint pain. Tell your physician instantly should you develop: virtuarede.com.br persistent diarrhea, abdominal or stomach ache/cramping, fever, blood/mucus in your stool. As chances are you’ll know, your pancreas and your liver work closely together to maintain a proper level of glucose in the blood. I have been taking Trintellix for about 5 weeks, 20 mgs. The slower launch of Glucophage XR could assist to scale back stomach upset which will occur with the common formulation. Eli Adashi is barely exaggerating a little bit when he says the job of a fertility doctor before 1967 was principally to refer couples who couldn’t conceive to adoption agencies. Additionally, earlier than undergoing any take a look at that requires the ingestion of a “contrast dye” (distinction X-ray or CT-scan), that you must stop taking metformin for as much as forty eight hours before and after the test. I have been diagnosed with Bipolar I, PTSD, depression, (clomiphene citrate) in ladies with PCOS who’re having infertility issues. Your doctor will do blood exams earlier than and through your treatment to see how well your kidneys are working. Chances are you’ll discover viruses that can do this, together with the benefits of an train program without experiencing asthma signs. The examine group gathered data, together with on admissions to hospital for cardiovascular or gastrointestinal disease, from all randomised trials which have previously examined NSAIDs. But this also creates the query: “Why do I restrict what you can provide at residence? You probably have any of these signs, name your doctor right away. Also, these of us which will have extra questions in regards to the risks can go in there and discuss to folks like your self which have had experience with this. The 2 commonest drugs used for treating male baldness are finasteride, sold as Propecia and Dutasteride. If the male companion continues to make use of Propecia it can be passed by means of semen to the female so must be stopped altogether. For a lot of vets, Prednisone is a well-liked drugs to prescribe for a large number of diseases, together with Canine Lymphoma. We are not such as you individuals, looting the world with expensive products,just because you have higher research facility and you patent every doable thing earlier than others do,including yoga and basmati rice. An alternative mannequin, for which there is supportive data, is that hospitalized patients given antibiotics are subsequently uncovered to toxigenic c. The solutions to your query most often will embrace analysis and different links to offer you a borader perspective in your query. In the outcome category “negative effects”, a hint of a positive effect of sitagliptin plus metformin versus glimepiride plus metformin was proven for symptomatic hypoglycaemia. As with most antibiotics and different pet medicines, negative effects are also possible with any amoxicillin medications, consequently, if your pet exhibits any unusual habits, changes or indicators of ill well being, you will want to consult your veterinarian immediately. Well, I do not know…I have been on MEtformin since my diagnosis three months in the past. If you loved this article and you simply would like to get more info with regards to http://m.verywed.com/redirect.php?url=http://challengeroulette.com/UserProfile/tabid/43/UserID/185860/Default.aspx ( http://m.verywed.com/redirect.php?url=http://challengeroulette.com/UserProfile/tabid/43/UserID/185860/Default.aspx ) generously visit our own internet site.

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9 Medications You Should Never Stop Taking Abruptly

<h1>9 Medications You Should Never Stop Taking Abruptly</h1>

9 Medications You Should Never Stop Taking Abruptly

Stopping some medications can cause unpleasant withdrawal symptoms, or at worst, can lead to a heart attack. The post 9 Medications You Should Never Stop Taking Abruptly appeared first on Reader’s Digest.

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9 Medications You Should Never Stop Taking Abruptly

<h1>9 Medications You Should Never Stop Taking Abruptly</h1>

9 Medications You Should Never Stop Taking Abruptly

Stopping some medications can cause unpleasant withdrawal symptoms, or at worst, can lead to a heart attack. The post 9 Medications You Should Never Stop Taking Abruptly appeared first on Reader’s Digest.

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IL-6 Blockade Aids Quality of Life in Vasculitis

<h1>IL-6 Blockade Aids Quality of Life in Vasculitis</h1>

IL-6 Blockade Aids Quality of Life in Vasculitis

IL-6 Blockade Aids Quality of Life in Vasculitis Findings were ‘unprecedented’ with tocilizumab in giant cell arteritis MedpageToday by Nancy Walsh Senior Staff Writer,
Health-related quality of life improved significantly among patients with giant cell arteritis (GCA) treated with tocilizumab (Actemra), analysis of data from a phase III clinical trial found.
Among patients enrolled in a randomized study that compared tocilizumab with placebo with two different steroid taper regimens, those receiving tocilizumab weekly plus a 26-week prednisone taper had a least squares mean change from baseline in the Physical Component Summary (PCS) of the Short Form (SF)-36 Health Survey of 4.18, according to John H. Stone, MD, of Harvard Medical School in Boston, and colleagues.
That represented a significant difference compared with the changes from baseline on the PCS for patients receiving placebo plus a 26-week prednisone taper and for those given placebo with a 52-week prednisone taper (-0.98 and -0.40, respectively, P <0.01 for both), the researchers reported online in Arthritis Research & Therapy .
GCA is a systemic vasculitis involving the aorta, its primary branches, and other arteries connecting the brain and eyes. Its most dreaded complications include vision loss and aortic aneurysms.
Conventional treatment has relied on glucocorticoids, often in high doses and for extended periods, even though recommendations call for prednisone to be tapered as rapidly as possible. In the yearlong GiACTA study, 56% of patients receiving the weekly subcutaneous interleukin (IL)-6 receptor-α inhibitor tocilizumab plus short-course prednisone were in remission at week 52 compared with only 14% of those given placebo plus short-course prednisone. That led to the drug's approval in 2017 for GCA.
Little is known, however, about the effects of treatment on health-related quality of life, so Stone and colleagues conducted an analysis of patient-reported outcomes among GiACTA participants. This analysis included 201 patients whose mean age was 69. Three-quarters were women, and almost all were white.
Patients in the two placebo groups had approximately twice the cumulative prednisone dose compared with the tocilizumab group. The median cumulative dose was 3,296 mg in the placebo plus 26-week prednisone taper group and 3,817.5 mg in the placebo plus 52-week taper group compared with 1,862 mg in the tocilizumab group ( P <0.001).
At baseline, the PCS and Mental Component Summary (MCS) scores were similar in the tocilizumab and placebo groups, being approximately one standard deviation below the age- and sex-matched normative scores of 50. On the MCS, change from baseline at week 52 was 8.10 in the tocilizumab group, 5.25 in the placebo plus 26-week prednisone taper group, and 1.89 in the placebo plus prednisone 52-week taper group.
At week 52, changes from baseline on four of the individual domains of the SF-36 (physical function, role physical, general health, and vitality) were significantly higher in the tocilizumab group than in the placebo plus 26-week prednisone taper group, while scores for six individual domains of the SF-36 (role physical, bodily pain, general health, vitality, social function, and mental health) were higher in the tocilizumab group than in the placebo plus 52-week prednisone taper group.
Patients in the tocilizumab group also had significantly greater increases in their scores on the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue measurement compared with the placebo plus 26-week placebo taper (5.30 vs 0.09), and compared with the placebo plus 52-week taper (-0.42, P <0.001 for both). They also more often reported clinically meaningful improvements on the Patient Global Assessment of disease activity (-17.14 vs -7.19 and -7.56).
"Even more striking" was the finding that by week 52, patients in the tocilizumab group showed improvements in every individual domain of the SF-36 that met or exceeded age- and sex-matched normative values, the authors observed.
For instance, the normative value for the physical function domain of the SF-36 was 67.56. At week 52, the value in the tocilizumab group was 78.28, compared with 63.48 and 65.44 in the placebo plus 26-week prednisone taper and the 52-week taper groups, respectively. On the mental health domain, the normative value was 77.16, and the values at 1 year were 77.94, 73.60, and 66.33 in the tocilizumab, placebo plus 26-week taper, and placebo plus 52-week taper groups, respectively.
"These findings are unprecedented in other health-related quality of life analyses across rheumatic diseases and highlight the importance of IL-6 in the underlying pathophysiology of GCA," the investigators stated.
Recent research has demonstrated that IL-6 is involved not only in inflammation, but also plays a role in mediation of pain, fatigue, and mood, possibly through upregulation of the hypothalamic-pituitary axis.
"Our findings support the concept that one mechanism whereby IL-6 inhibition improves health-related quality of life is through an elevating effect on mood," Stone and colleagues noted.
The study was funded by Roche.
The authors reported financial relationships with Genentech/Roche, AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Celltrion, CORRONA, Crescendo, EMD Serono, GlaxoSmithKline, Janssen, Eli Lilly, Merck, Novartis, Pfizer, Protagen, Regeneron, Samsung, Sandoz, Sanofi, and UCB. 2019-02-27T13:30:00-0500 Primary Source Arthritis Research & Therapy

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Empyema beautifully freshly spare obstetricians.

<h1>Empyema beautifully freshly spare obstetricians.</h1>

Empyema beautifully freshly spare obstetricians.

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9 Medications You Should Never Stop Taking Abruptly

<h1>9 Medications You Should Never Stop Taking Abruptly</h1>

9 Medications You Should Never Stop Taking Abruptly

Stopping some medications can cause unpleasant withdrawal symptoms, or at worst, can lead to a heart attack. The post 9 Medications You Should Never Stop Taking Abruptly appeared first on Reader’s Digest.

Read More…

Cerebral Vasculitis in Ulcerative Colitis Is Predominantly Venular: Case Report and Review of the Literature

<h1>Cerebral Vasculitis in Ulcerative Colitis Is Predominantly Venular: Case Report and Review of the Literature</h1>

Cerebral Vasculitis in Ulcerative Colitis Is Predominantly Venular: Case Report and Review of the Literature

1 Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada 2 Department of Pathology, Dalhousie University, Halifax, Nova Scotia, Canada
Correspondence should be addressed to Alexander S. Easton ;
Received 6 November 2018; Revised 27 January 2019; Accepted 12 February 2019; Published 26 February 2019
Academic Editor: Gregory J. Tsay
Copyright © 2019 Paul T. Parks and Alexander S. Easton. This is an open access article distributed under the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract
Extraintestinal complications of ulcerative colitis include isolated case reports of cerebral vasculitis. In this case report, we describe autopsy findings in a 50-year-old female who died as a result of massive multifocal cerebral hemorrhage. Microscopic examination of the left colon showed findings typical for ulcerative colitis. Examination of the brain showed an extensive vasculitis. More affected vessels were noted in grey matter than in white matter. Many showed fibrinoid necrosis, invasion by neutrophils and thrombosis. There was extensive perivascular hemorrhage with associated infarction. Vessel analysis shows most of the vessels to have been venous rather than arterial. There were no perivascular sleeves of demyelination to suggest a primary demyelinating disorder, such as acute hemorrhagic leucoencephalitis. Our analysis shows that veins are the likely target of cerebral vasculitis in ulcerative colitis. This has clinical implications because venous occlusion generally causes massive intracerebral hemorrhage with a high mortality. 1. Introduction
Ulcerative colitis (UC) is one of the major forms of inflammatory bowel disease alongside Crohn’s disease, which is defined by colonic inflammation. In fact, UC is a multisystem disorder with many extraintestinal manifestations that affect many organs including the joints, skin, eyes, and hepatobiliary system. As such, it captures the attention of a variety of medical specialists including rheumatologists, who manage many forms of pauciarticular, polyarticular, and axial arthropathies, including ankylosing spondylitis and sacroiliitis [ 1 ]. Several reviews suggest that neurological complications in UC are underdiagnosed and underreported [ 2 – 4 ]. These complications vary in their incidence in UC depending on study design and which disorder is being studied. Two retrospective observational studies estimated neurological complications in between 1 and 2% of patients with UC [ 5 , 6 ]. However, peripheral neuropathy was reported in as many as 45.1% of UC patients and headache in 57% of UC patients, in a prospective clinic-based study [ 7 ]. Another study that used health records found that peripheral neuropathy occurred in 2.4% of UC patients compared to 1.35% in the general population [ 8 ]. Asymptomatic white matter lesions were detected by MRI scan in 45.8% of UC patients compared to 16% of healthy age-matched controls [ 9 ]. Most neurological complications occur with active intestinal disease [ 10 ], and there is a significant risk posed by more recent biologic therapies including monoclonal antibodies that target tumor necrosis factor, TNF [ 11 ]. Anti-TNF therapies have been linked to peripheral neuropathy, multiple sclerosis, and progressive multifocal leukoencephalopathy [ 3 ].
There are three major groups of neurological complication in UC. First, there is a risk of stroke, both arterial and venous from cerebral thromboembolism. Second, there is peripheral neuropathy. Third, there may be an increased risk of multiple sclerosis, a major demyelinating disease of the central nervous system [ 4 ]. Stroke may be caused by a variety of factors including coagulation disorders, but cerebral vasculitis is a possible contributing factor, particularly when inflamed vessels undergo thrombosis and occlusion. Cerebral vasculitis can occur in patients who develop a lupus-like syndrome after treatment with anti-TNF therapies associated with high serum titres of antibodies against double-stranded DNA [ 11 ]. Clinically, cerebral vasculitis in UC may be overdiagnosed [ 3 ] because it produces white matter changes on MRI scans that also occur incidentally as mentioned above [ 9 ]; however, there have been no systematic studies to define the true incidence of cerebral vasculitis in UC. Few cases have been confirmed by brain biopsy or autopsy. We have identified 6 published case reports on the histopathology of cerebral vasculitis in UC [ 12 – 17 ], and we will compare findings in 4 of these reports [ 12 , 13 , 16 , 17 ] with the present case. The focus of this case report is also on the histopathology of cerebral vasculitis in a patient with UC examined at autopsy. What this report adds to those already published is a detailed examination of the type of blood vessel targeted by the disease. We conclude that cerebral vasculitis primarily targets venous rather than arterial vessels, and so can more accurately be described as predominantly a cerebral venulitis. The pathology from previous reports supports this conclusion, which adds to our understanding of the devastating nature of this complication because venous occlusion in the brain usually results in massive internal hemorrhage with a high mortality. 2. Case Report
This case concerns a 50-year-old female. Past medical history was significant for ulcerative colitis, hypertension, hypothyroidism, and a left deep vein thrombosis. She had a history of intermittent night sweats for 3-4 months before presentation. Her ulcerative colitis had flared up about 6 months before presentation to hospital and was treated with prednisone 5 mg daily. This flared again 2 weeks before presentation, so prednisone was restarted, and the day before presentation she underwent colonoscopy. She was on drugs to treat hypertension (ramipril), elevated cholesterol (rosuvastatin), hypothyroidism (levothyroxine), and ulcerative colitis (mesalazine and prednisone 5 mg daily for the recent flare up). She had not been treated with anti-TNF biologics. For her presenting complaint, there was a one-day history of continuous dull headache increasing in severity by evening. The patient then developed slurred speech, unsteady gait, and progressive right-sided weakness. She was seen at a local hospital, where her blood pressure was recorded as 177/95, pulse 90/min, and temperature 35.9°C. Her left pupil was 3 mm in diameter and sluggishly reactive to light, while the right pupil was fixed. Her right side was not moving spontaneously, and a right-sided stroke was diagnosed. While in hospital, there was a sudden reduction in the level of consciousness and a “grand mal” seizure lasting for 2 minutes. While in the local hospital, a CT brain scan showed hemorrhage into the left basal ganglia and left temporal lobe with ventricular extension. Just one CT brain scan was carried out owing to the rapidity of events. The next day, she was transferred to a tertiary care hospital where MRI scan gradient echo mapping highlighted the extent of the hematoma in the left basal ganglia (Figure 1(a) ). MRA (magnetic resonance angiography) of the circle of Willis demonstrated normal intracranial vessels without focal stenosis or aneurysmal dilatation. There were no vascular malformations. MRV (magnetic resonance venography) demonstrated normal venous sinuses as well as normal deep veins, ruling out widespread cerebral venous thrombosis as the primary diagnosis. The preferred clinical diagnosis was acute hemorrhagic leucoencephalitis, with viral encephalitis and cerebral vasculitis in the differential. On further examination, there was extensor posturing in the left arm and no movement of the right arm. Pupils were asymmetric (right 5 mm, left 3 mm) and fixed. There was no corneal or doll’s eye reflex and no facial asymmetry. Tone and bulk were normal, with no fasciculations. Plantars were unresponsive, with absent knee jerks, but other reflexes were 1+ to 2+ in strength. Blood work during the admission showed an elevated white cell count (17.0 × 10 9 /L, normal range 4–11 × 10 9 /L), with increased lymphocytes and neutrophils), normal platelet count (184 × 10 3 / µ l, normal range 150–400 × 10 3 / µ l), slightly elevated rheumatoid factor (22.5 IU/ml, normal < 15 IU/ml), and markedly elevated C reactive protein (287 mg/ml, normal < 3 mg/ml). A serological screen for autoantibodies was also carried out. The patient was screened for antinuclear antibodies used to diagnose a number of systemic autoimmune rheumatic diseases such as systemic lupus erythematosus, systemic sclerosis, Sjögren’s syndrome, mixed connective tissue disease, and idiopathic inflammatory myopathies. The screen measured antibodies against double-stranded DNA, chromatin, ribosomal P, SS-A/Ro, SS-B/La, centromere B, SM, Sm/RNP, Scl-70, and Jo-1, and was negative. In addition, the patient was screened for antiglomerular basement membrane (GBM) antibodies (which defines anti-GBM disease, a small vessel vasculitis of kidneys and lungs), antimyeloperoxidase, and antiproteinase antibodies (which are also elevated in systemic vasculitides), all of which were found to be negative. The patient was not screened for antibodies against antineutrophil cytoplasmic antibodies (ANCAs) or antiphospholipid antibodies. Blood, urine, and sputum cultures were negative. The patient was started on pulse dose steroids for likely vasculitis, but her clinical status rapidly declined, and she died 2 days after presentation. Figure 1: (a) Axial T2-weighted gradient echo magnetic resonance image showing hemorrhage in the left basal ganglia. (b) Gross photograph of coronal sections through the cerebral hemispheres. Scale bar = 1 cm. L = left; R = right.
A full autopsy was performed. Continuous mucosal thickening and flattening was noted in the colon, predominantly on the left side, while the esophagus, stomach, duodenum, and ileum had a normal appearance. There was no intestinal hemorrhage, obstruction, or perforation. Microscopic examination of sections from the left colon showed mucosal ulcers with inflammatory exudates. Inflammatory cells including lymphocytes and eosinophils infiltrated the mucosa and submucosa, without vasculitis. There was no inflammation in the muscularis propria or serosa and no evidence of malignancy. These findings were interpreted as “consistent with ulcerative colitis” by the examining anatomic pathologist. When first removed at autopsy, the brain weighed 1400 g before fixation. The fixed brain showed diffuse hemispheric edema and an area of disruption over the left temporal lobe measuring 4.5 × 1.0 cm. There was left-sided uncal herniation, but no tonsillar herniation. Coronal sections through the cerebral hemispheres showed extensive hemorrhage and disruption in the left middle temporal gyrus and inferior portions of the left striatum and pulvinar. There was a discrete hematoma in the left superior frontal gyrus and hemorrhage in the right median frontal cortex and in white matter adjacent to the right orbitofrontal surface (Figure 1(b) ). There was extensive right-sided hemorrhage in the brainstem, involving the crus and dorsal pons with extension into the fourth ventricle. Hematoxylin and eosin/luxol fast blue stained sections showed extensive acute hemorrhage with infarction (Figure 2 (a)). Changes were noted in both grey and white matter. There was a striking vasculopathy. Vessels showed invasion by leucocytes (Figure 2 (b)) as well as fibrinoid necrosis of the wall (Figure 2 (c)). Invading leucocytes were rarely positive for the lymphocyte marker CD3 or the macrophage-microglia marker CD68 but more often positive for the general white blood cell marker Leucocyte Common Antigen (LCA/CD45) consistent with neutrophils (Figure 2 (d)). Some vessels contained luminal thrombus (Figure 2 (c)). There were no perivascular sleeves of demyelination. Detailed measurements were made on 173 involved vessels, of which 88 were in grey matter (cortex, putamen, or brainstem nuclei) and 85 in white matter. The mean diameter (for all vessels) was 66.7 ± 3.9  µ m (mean ± standard error of the mean). The ratio of wall thickness to diameter is plotted as a function of vessel diameter in Figure 3 . The mean ratio was 0.18 ± 0.01. Most vessels were under 100  µ m in diameter which would correspond either to venules or small veins on the venous side or to arterioles or small arteries. However, the ratio of wall thickness to diameter is smaller for venous vessels than arterial ones. It is closer to 0.1 for venous vessels but around 0.5 for arterial vessels [ 18 ]. This indicates that most of the involved vessels were venous. The findings point to an acute cerebral vasculitis, predominantly involving invasion of venous vessels by neutrophils. Figure 2: (a) Hemorrhage within the left frontal cortex. (b) Inflamed vessel in the left frontal cortex. (c) Vessel showing intraluminal thrombus and fibrinoid necrosis in white matter adjacent to the left putamen. (d) Immunohistochemistry of vessel in the left putamen, negative for CD3 and CD68 but positive for LCA. Scale bars: (a) 0.5 cm; (b–d) 100  µ m. Figure 3: Scatter plot showing ratio of wall thickness to diameter as a function of vessel diameter in 173 pathologically affected blood vessels. 3. Discussion
The main pathologic findings of this study can be summarized as (1) widespread hemorrhagic cerebral infarction, (2) necrotizing cerebral venulitis with intraluminal venous thrombosis, and (3) infiltration of the venous wall by acute inflammatory cells consistent with neutrophils. We have compared these findings to the pathologic descriptions of UC-associated cerebral vasculitis in 4 of 6 published studies and believe that they complement our major finding, which is that UC-associated cerebral vasculitis is predominantly a venulitis rather than an arteritis, affecting cerebral venules or veins to a greater extent than arterioles or arteries. This would predispose patients to venous occlusion and intracerebral hemorrhage with a high mortality.
The ratio of wall thickness to diameter gives a method for describing vessels as likely to be of venous or arterial origin, and Figure 3 demonstrates this point for our case. The vast majority of involved vessels clustered around ratios near to 0.1-0.2, although a few vessels reached ratios of 0.5, and so are likely to be arterial. 4 of the previous 6 histopathological studies of UC-associated vasculitis were reviewed, in order to estimate the ratio for the vessels shown in each publication. 2 vessels have ratios estimated as 0.05 and 0.08 in Figure 2 of Glotzer et al. [ 12 ]. In Nelson et al. [ 13 ], Figure 2 shows a single vessel with an estimated ratio of 0.13. A single vessel is also shown in Figure 3 of the paper by Unnikrishnan et al. [ 16 ] with an estimated ratio of 0.05, and we estimate a ratio of 0.12 for the single vessel shown in Figure 4 of the paper by Raj et al. [ 17 ]. The remaining two studies were either inaccessible or had poor quality images. All of these values cluster around the range expected for venous involvement.
Venular forms of cerebral vasculitis have received scant attention in the literature. Primary central nervous system (CNS) vasculitis occurs without evidence of a systemic disorder and mostly targets arterial vessels, existing in granulomatous and nongranulomatous forms. However, a case of pediatric primary CNS vasculitis was reported to be predominantly venular [ 19 ]. Venulitis has also been reported in cases of CNS vasculitis associated with Behҫet’s syndrome [ 20 ] and in some cases of acute multiple sclerosis [ 21 ]. Arterial vessels appear to be the target in most other forms of cerebral vasculitis, although histological descriptions vary in quality and accuracy. This case is unlikely to be an unsuspected case of Behҫet’s syndrome because the pathology of colitis in Behҫet’s syndrome is more akin to Crohn’s disease than UC. Typically, cases of Behҫet’s syndrome show predominantly right-sided colonic pathology, with large, deep ulcers that penetrate deep into the submucosa. Skip lesions are seen, with sparing of intermediate zones of colonic mucosa. In particular, these cases often show a lymphocytic venulitis [ 22 ]. By contrast, cases of UC show predominantly left-sided colonic pathology, with more superficial ulceration, and contiguous mucosal involvement rather than skip lesions. The autopsy findings in this case are therefore consistent with UC rather than Behҫet’s syndrome because pathology was predominantly found in the left colon, showed superficial inflammation without vasculitis, and lacked skip lesions.
Although testing was not carried out for antiphospholipid antibodies, a recent paper suggests that positive results are more likely to be seen in cases of Crohn’s disease rather than UC [ 23 ]. In addition, vascular thrombotic events in cases of Crohn’s and UC showed a poor correlation to levels of antiphospholipid antibodies. Even if this patient had shown evidence for elevated antiphospholipid antibodies, the significance of such a finding is therefore obscure.
Two previous reports [ 12 , 14 ] have equated UC-associated cerebral vasculitis with acute hemorrhagic leucoencephalitis (AHL), but there are clear differences. Acute hemorrhagic leucoencephalitis (AHL) is an acute demyelinating disease of the CNS, characterized by multifocal petechial hemorrhages that predominantly affect white matter, with sparing of cortical grey matter. Affected vessels show sleeves of perivascular demyelination, as well as fibrinoid necrosis and invasion by neutrophils, resulting in perivascular hemorrhages. AHL is considered to be a hyperacute form of acute demyelinating encephalomyelitis (ADEM) in which perivenous demyelination is associated with perivascular cuffs of mononuclear inflammatory cells. In both cases, the suggested immune mechanism is directed against myelin, lending similarities to the demyelinating lesions of multiple sclerosis. Compared to AHL, this case showed no perivascular demyelination, white matter involvement did not predominate, and hemorrhages were extensive instead of mostly petechial. However, like AHL, the vasculitis was venous and acute, with predominant invasion by neutrophils. This suggests that the acute cerebral vasculitis in UC is not part of an immune state that predisposes patients to demyelinating conditions such as multiple sclerosis and ADEM. Venous vessels rather than myelin are the likely target of the immune system, perhaps through antigen-antibody complexes and complement activation, and the resulting damage predisposes to extensive hemorrhage since the necrotic tissue is supplied by vessels under arterial blood pressure.
If vasculitis in UC is venular rather than arterial, this has practical clinical consequences. If patients present with a hemorrhagic stroke, vasculitis/venulitis should be considered in the differential diagnosis, whereas a bland nonhemorrhagic stroke is more likely to be arterial in origin. Where venulitis is considered, it may be possible to initiate anti-inflammatory therapies in addition to more typical treatment modalities for stroke. However, massive intracerebral bleeding of the sort seen in this case is likely to carry a high mortality, regardless of treatment. Conflicts of Interest
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