tbuckley/cabot-search huggingface dataset:
Correctly diagnosing a newly characterized syndrome
Authors: Guillermo J. Ruiz‐Argüelles, Margarita Delezé, Donato Alarcón‐Segovia
Journal: American Journal of Hematology (1991)

We read with interest the paper by Iwahara, Niiya, Yamato and Miyoshi, describing a patient with autoimmune thrombocytopenic purpura, lupus anticoagulant, high titers of antiphospholipid (cardiolipin and phosphatidylinositol) antibodies, recurrent abortions and both arterial and venous thrombosis [l].In the past years there has been great interest in the literature to characterize what has been termed the "antiphospholipid syndrome" [2], associated with systemic lupus erythematosus (SLE) [3] and the primary antiphospholipid syndrome [4,5] in patients who have at least two of the clinical manifestations that have been related to antiphospholipid antibodies (venous thrombosis, arterial occlusions, thrombocytopenia, hemolytic anemia, recurrent fetal loss, leg ulcers and livedo reticularis) but had neither SLE nor other recognizable connective tissue disease.The patient described in this article fits the criteria for the diagnosis of primary antiphospholipid syndrome [4,5].The authors and reviewers seem not to be aware of this information.Our group and others have demonstrated a strong relationship between antiphospholipid antibodies and these hemocytopenias [6], recurrent fetal loss [7], venous thrombosis and arterial occlusions [3,8].Other pathogenetic mechanisms have been proposed and studied [9-111.With respect to the difficulties faced in the treatment of patients with primary antiphospholipid syndrome displaying thrombocytopenia as in the case described by Iwahara et al. [l], we have found that a small dose of aspirin (100 mg/day) may be useful to correct thrombocytopenia probably by preventing loss of platelet membrane phospholipid asymmetry with resulting exposure of anionic phospholipids [ 121.Hematologists should bear in mind this newly characterized syndrome as another cause of immune hemocytopenia.
REBECA: a phase I study of bevacizumab and whole-brain radiation therapy for the treatment of brain metastasis from solid tumours
Authors: C. Lévy, D. Allouache, J. Lacroix, A.E. Dugué, S. Supiot, M. Campone, M. Mahe, S. Kichou, M. Leheurteur, C. Hanzen, V. Dieras, Y. Kirova, F. Campana, E. Le Rhun, L. Gras, T. Bachelot, M.-P. Sunyach, I. Hrab, J. Geffrelot, K. Gunzer, J.-M. Constans, J.-M. Grellard, B. Clarisse, X. Paoletti
Journal: Annals of Oncology (2014)
Henoch-Schönlein purpura and systemic disease in children: retrospective study of clinical findings, histopathology and direct immunofluorescence in 34 paediatric patients
Authors: E.F. Johnson, J.S. Lehman, D.A. Wetter, C.M. Lohse, M.M. Tollefson
Journal: British Journal of Dermatology (2014)

Henoch-Schönlein purpura (HSP), an IgA-mediated small vessel vasculitis, is the most common form of vasculitis in children. HSP is commonly associated with systemic involvement of the gastrointestinal tract, joints and kidneys. Renal involvement is the main cause of morbidity and mortality in HSP.To characterize the clinical, histopathological and direct immunofluorescence (DIF) findings, and to correlate the findings with systemic disease in 34 children with HSP seen at our institution.This was a retrospective review of paediatric patients with HSP and with available biopsy specimens seen at our institution between 1993 and 2013.Thirty-four paediatric patients were identified (mean age 10·7 years). Renal involvement was found in 17 (50%) patients, gastrointestinal tract involvement in 22 (65%) and joint involvement in 23 (68%). Renal involvement was significantly associated with papillary dermal oedema on histopathology (P < 0·01) and the presence of perivascular C3 on DIF (P = 0·01). The presence of lesions above the waist was significantly associated with gastrointestinal involvement (P = 0·03), as was the presence of clinically apparent oedema (P = 0·01).This study suggests that in children with HSP, microscopic dermal oedema and C3 on DIF may be predictive of renal involvement. Patients with clinically apparent oedema and lesions above the waist are more likely to have gastrointestinal involvement.
Absorbable Versus Silk Sutures for Surgical Treatment of Trachomatous Trichiasis in Ethiopia: A Randomised Controlled Trial
Authors: Saul N. Rajak, Esmael Habtamu, Helen A. Weiss, Amir Bedri Kello, Teshome Gebre, Asrat Genet, Robin L. Bailey, David C. W. Mabey, Peng T. Khaw, Clare E. Gilbert, Paul M. Emerson, Matthew J. Burton
Journal: PLoS Medicine (2011)

Background Trachoma causes blindness through an anatomical abnormality called trichiasis (lashes touching the eye). Trichiasis can recur after corrective surgery. We tested the hypothesis that using absorbable sutures instead of silk sutures might reduce the risk of recurrent disease among patients with major trichiasis in a randomised trial. Methods and Findings 1,300 individuals with major trichiasis from rural villages in the Amhara Region of Ethiopia were recruited and assigned (1∶1) by computer-generated randomisation sequence to receive trichiasis surgery using either an absorbable suture (polyglactin-910) or silk sutures (removed at 7–10 days) in an otherwise identical surgical technique. Participants were examined every 6 months for 2 years by clinicians masked to allocation. The primary outcome measure was recurrent trichiasis (≥one lash touching the eye) at 1 year. There was no difference in prevalence of recurrent trichiasis at 1 year (114 [18.2%] in the absorbable suture group versus 120 [19.7%] in the silk suture group; odds ratio = 0.90, 95% CI 0.68–1.20). The two groups also did not differ in terms of corneal opacification, visual acuity, conjunctival inflammation, and surgical complications. Conclusions There was no evidence that use of absorbable polyglactin-910 sutures was associated with a lower prevalence of trichiasis recurrence at 1 year postsurgery than silk sutures. However, from a programmatic perspective, polyglactin-910 offers the major advantage that patients do not have to be seen soon after surgery for suture removal. The postoperative review after surgery using absorbable polyglactin-910 sutures can be delayed for 3–6 months, which might allow us to better determine whether a patient needs additional surgery. Trial registration ClinicalTrials.gov NCT00522860 Please see later in the article for the Editors' Summary
The impact of a false-positive MRI on the choice for mastectomy in BRCA mutation carriers is limited
Authors: N. Hoogerbrugge, Y.J.L. Kamm, P. Bult, K.M. Landsbergen, E.M.H.F. Bongers, H.G. Brunner, H.J. Bonenkamp, J.A. de Hullu, M.J.L. Ligtenberg, C. Boetes
Journal: Annals of Oncology (2007)
Delayed examination of synovial fluid by ordinary and polarised light microscopy to detect and identify crystals
Authors: J Galvez
Journal: Annals of the Rheumatic Diseases (2002)

To determine the reliability of a delay in the microscopic examination of synovial fluid (SF) to detect and identify crystals.Ninety one SF samples were examined, 31 with monosodium urate (MSU) crystals, 30 with crystals of calcium pyrophosphate dihydrate (CPPD), and 30 containing no crystals. The specimens were stored with EDTA, sodium heparin, and without anticoagulant at 4 degrees C before examination at 24 and 72 hours with ordinary and polarised light microscopy. Another aliquot of the same samples was stored in a plastic container without anticoagulant at -80 degrees C and examined after two months.When the samples stored at 4 degrees C were re-examined after 24 hours, intracellular crystals of MSU were seen in 90/93 (97%) cases where they had been identified previously and 89/93 (96%) cases after 72 hours. Similarly, CPPD crystals were identified in 90/90 (100%) and 87/90 (97%) cases after 24 and 72 hours. Examination of the samples stored at -80 degrees C showed intracellular MSU crystals in 25/31 (81%) of cases and CPPD crystals in 25/30 (83%). No crystals were seen in any sample which had previously been diagnosed as crystal-free.Deferred microscopic examination of refrigerated or deep frozen SF provides a strong probability of detecting MSU or CPPD crystals if these are present initially.
Global Prevalence of Diabetes: Estimates for the Year 2000 and Projections for 2030
Authors: Sarah H. Wild, Gojka Roglic, Anders Green, Richard Sicree, Hilary King
Journal: Diabetes Care (2004)

We read the article by McCarter et al. (1) with interest. Technically, all nonanalytical variation, irrespective of its source, is biological variation. Thus, mean blood glucose (MBG)-associated changes are included in biological variation. It must also be stressed that all population regression equations have confidence limits that need to be taken into account when comparing values from individuals to the population study mean.

However, such …
Strengthening governance for global health research
Authors: K. Lee
Journal: BMJ (2000)

During the international conference for health research in Bangkok it was estimated that less than 10% of the total research funds are spent on the diseases that account for 90% of the global burden of disease.  This gap which is widely quoted as epitomizing the inequitable nature of health research has profound consequences; these include the following: diseases affecting large proportions of humanity are given comparatively little attention and simple and low-cost technologies are undervalued and hence inadequately researched.  It is noted that much of the problem lies in how health research is governed. Based on the state of the global health research it is suggested that too often governance is not good.  Imbalances in financial and intellectual resources between the wealthy and poor exist. Evidence indicates that financial and technical support from donors to train and retain national researchers in developing countries and to build up research institutions that provide opportunities for researchers remains inadequate.  It is recommended that a change in approach be adopted in which developing countries are seen as partners in producing health research.  Such an approach should begin with larger-scale commitments by funding bodies investments in research capacity for the middle to long term and the need to share decision-making.
Deciding on progression of joint damage in paired films of individual patients: smallest detectable difference or change
Authors: K Bruynesteyn
Journal: Annals of the Rheumatic Diseases (2004)

Progression of radiological joint damage is usually based on the simultaneous assessment of a series of films from an individual patient ("paired", with or without known sequence). In this setting the degree of progression that can be reliably detected above the measurement error is best determined by the smallest detectable <i>change</i>, and overestimated by the traditionally calculated smallest detectable <i>difference</i>. This knowledge is important for calculation of the proportion of patients showing radiographic progression in clinical trials.
Intensive oral methotrexate protects against lymphoid marrow relapse in childhood B-precursor acute lymphoblastic leukemia.
Authors: N Winick, J J Shuster, W P Bowman, M Borowitz, A Farrow, D Jacaruso, G R Buchanan, B A Kamen
Journal: Journal of Clinical Oncology (1996)

PURPOSE To describe the use of combination chemotherapy, including divided-dose oral methotrexate (dMTX), for children with B-precursor acute lymphoblastic leukemia (ALL). dMTX produced prolonged MTX exposure on an outpatient basis. PATIENTS AND METHODS Two hundred forty-three patients were treated from January 1986 to May 1992. dMTX was given weekly during consolidation and biweekly for the first 16 months of continuation therapy with mercaptopurine (6-MP) and asparaginase (L-ASP). Initially, etoposide (VP-16) and cytarabine (Ara-C) pulses were included. Treatment continued for 30 months with single-dose weekly MTX replacing dMTX during continuation, part 2. Unexpected acute neurotoxicity was eliminated by the addition of leucovorin. VP-16 and Ara-C were omitted in the face of acute myelogenous leukemia (AML). RESULTS Two hundred thirty-nine patients entered remission: 16 had a lymphoid marrow relapse, two each with testicular or CNS relapse; 19 a CNS relapse; 16 secondary AML; three other second malignancies; two withdrew for transplant; three died in remission; 16 withdrew because of noncompliance, and nine withdrew with toxicity. Event-free survival (EFS) at 4 years was 73 +/- 4%; 81 +/- 4% for 150 patients with better risk features and 60 +/- 7% for 93 with high-risk features. Lymphoid marrow relapse-free survival in the standard- and high-risk patients was 94 +/- 3% and 86% +/- 6%, respectively. The most common adverse event was secondary AML in the standard-risk group and isolated CNS relapse in the high-risk group. CONCLUSION This therapy produced an overall EFS similar to other published regimens, but the pattern of failures is very different, with few patients having a lymphoid marrow relapse. These data suggest that highly effective therapy for children with ALL can be delivered on an outpatient basis using a regimen featuring repetitive dMTX.
Epitope spreading of the anti-citrullinated protein antibody response occurs before disease onset and is associated with the disease course of early arthritis
Authors: D. van der Woude, S. Rantapaa-Dahlqvist, A. Ioan-Facsinay, C. Onnekink, C. M. Schwarte, K. N. Verpoort, J. W. Drijfhout, T. W. J. Huizinga, R. E. M. Toes, G. J. M. Pruijn
Journal: Annals of the Rheumatic Diseases (2010)

<h3>Background</h3> Anti-citrullinated protein antibodies (ACPA) are the most predictive factor for the development of rheumatoid arthritis (RA). <h3>Objective</h3> To investigate whether the recognition of citrullinated epitopes changes during disease onset or progression, by studying the fine specificity of ACPA in serum samples collected throughout the disease course, from before the onset of arthritis to longstanding RA. <h3>Methods</h3> Antibodies recognising five distinct citrullinated antigens were determined by enzyme-linked immunosorbent assay. Serum samples from 36 individuals who had donated blood before and after disease manifestation were used to investigate the development of citrullinated antigen recognition before disease onset. The association of ACPA reactivities with disease outcome was studied using sera from anti-cyclic citrullinated peptide-2 (CCP2)-positive patients with undifferentiated arthritis (UA) who did or did not progress to RA (UA–RA n=81, or UA–UA n=35). To investigate the ACPA recognition profile in patients with RA over a prolonged period of time, baseline serum samples from 68 patients were compared with samples obtained 7 years later. <h3>Results</h3> The number of recognised citrullinated peptides increased in the period preceding disease onset. At the time of disease manifestation, patients with UA who later developed RA recognised significantly more peptides than UA–UA patients. At later stages of the disease course, the ACPA fine specificity did not change. <h3>Conclusion</h3> Epitope spreading with an increase in the recognition of citrullinated antigens occurs before the onset of RA. Immunological differences in ACPA fine specificity between UA–UA patients and UA–RA patients are present at baseline and are associated with the future disease course.
Reactivation of hepatitis B
Authors: Jay H. Hoofnagle
Journal: Hepatology (2009)

Reactivation of hepatitis B refers to the abrupt increase in hepatitis B virus (HBV) replication in a patient with inactive or resolved hepatitis B. Reactivation can occur spontaneously, but more typically is triggered by immunosuppressive therapy of cancer, autoimmune disease, or organ transplantation. Reactivation can be transient and clinically silent, but often causes a flare of disease that can be severe resulting in acute hepatic failure. Most instances of reactivation resolve spontaneously, but if immune suppression is continued, re-establishment of chronic hepatitis occurs which can lead to progressive liver injury and cirrhosis. The best-described instances of reactivation occur in hepatitis B surface antigen (HBsAg) carriers with inactive or minimally active disease who are given cancer chemotherapy for lymphoma or leukemia. Typically, serum HBV DNA rises during chemotherapy, followed by a disease flare and HBV DNA clearance with immune reconstitution after chemotherapy is stopped. Special forms of reactivation occur after solid organ and bone marrow transplantation in which chronic infection often results. Several randomized, placebo-controlled trials have shown that reactivation can be prevented by antiviral prophylaxis. Routine prophylaxis is therefore recommended for persons with HBsAg undergoing cancer chemotherapy or transplantation, but major questions remain. Which patients should be screened for HBsAg and should all be treated? Which antiviral should be used and for how long? Should persons with resolved hepatitis B without HBsAg receive prophylaxis? Future research should address the underlying molecular mechanisms of reactivation as well as its optimal means of diagnosis, treatment, and prevention in different patient populations. (HEPATOLOGY 2009;49:S156–S165.)
The low-penetrance R92Q mutation of the tumour necrosis factor superfamily 1A gene is neither a major risk factor for Wegener's granulomatosis nor multiple sclerosis
Authors: D. E Jenne, P. M Aries, S. Einwachter, A. D Akkad, S. Wieczorek, P. Lamprecht, W. L Gross
Journal: Annals of the Rheumatic Diseases (2007)

Inherited autosomal-dominant mutations in the tumour necrosis factor receptor superfamily 1A ( TNFRSF1A ) gene encoding the tumour necrosis factor receptor p55 (TNF-R1) are the cause of an auto-inflammatory syndrome that is characterized by periodic fever attacks, aseptic peritonitis, arthritis, meningitis, conjunctivitis, pleuritis and skin rash (OMIM #142680). The most common TNFR-associated periodic syndrome (TRAPS)-like disease that is associated with a R92Q mutation, however, occurs sporadically, with later onset (median 23 years vs 7 years with other mutations) and a milder and often oligosymptomatic course.1,2 Intriguingly, carriers of the R92Q allele bear a slightly increased risk for some other diseases, such as myocardial infarction,3 increased carotid intima-media thickness,3 thrombotic complications in Behcet’s disease4 and early synovitis.1

Due to the low …
Benefits and Risks With Glyburide and Glipizide in Elderly NIDDM Patients
Authors: Robert G Brodows
Journal: Diabetes Care (1992)

Objective –To compare the efficacy, benefits, and risks of glyburide and glipizide in elderly patients with non-insulin-dependent diabetes mellitus (NIDDM). Research Design and Methods –Twenty-one elderly outpatients (mean age 70 yr) were treated for 8 wk, after being dose-titrated to achieve a fasting plasma glucose (FPG) concentration of &amp;lt; 7.8 mM with glyburide or glipizide in a randomized crossover trial. FPG and postprandial plasma glucose, serum C-peptide, and HbA1c levels were measured. In 13 patients, self-monitoring of blood glucose (SMBG) with a memory meter was performed seven times per week. Results –Glipizide (11.9 mg) and glyburide (8.4 mg) produced similar fasting and postprandial plasma glucose and HbA1c concentrations. No significant differences in basal or stimulated C-peptide levels were detected. Despite a few patient reports of hypoglycemia, a high incidence of SMBG readings &amp;lt; 4.5 mM was attributed to the use of both drugs. Conclusions –Both treatments proved effective for glycemic control; however, both second-generation sulfonylureas are associated with a significant risk of hypoglycemia in elderly NIDDM patients. The proper use of sulfonylureas in this population should include close surveillance of ambulatory glucose monitoring and intensive and repeated patient education about the risks of hypoglycemia.
Need for expertise based randomised controlled trials
Authors: P J Devereaux, Mohit Bhandari, Mike Clarke, Victor M Montori, Deborah J Cook, Salim Yusuf, David L Sackett, Claudio S Cinà, S D Walter, Brian Haynes, Holger J Schünemann, Geoffrey R Norman, Gordon H Guyatt
Journal: BMJ (2005)

Surgical procedures are less likely to be rigorously evidence based than drug treatments because of difficulties with randomisation. Expertise based trials could be the way forward 

Although conventional randomised controlled trials are widely recognised as the most reliable method to evaluate pharmacological interventions,1 2 scepticism about their role in nonpharmacological interventions (such as surgery) remains.3–6 Conventional randomised controlled trials typically randomise participants to one of two intervenions (A or B) and individual clinicians give intervention A to some participants and B to others. An alternative trial design, the expertise based randomised controlled trial, randomises participants to clinicians with expertise in intervention A or clinicians with expertise in intervention B, and the clinicians perform only the procedure they are expert in. We present evidence to support our argument that increased use of the expertise based design will enhance the validity, applicability, feasibility, and ethical integrity of randomised controlled trials in surgery, as well as in other areas. We focus on established surgical interventions rather than new surgical procedures in which clinicians have not established expertise.

Investigators have used the expertise based design when conventional randomised controlled trials were impossible because different specialty groups provided the interventions under evaluation—for example, percutaneous transluminal coronary angioplasty versus coronary artery bypass graft surgery.7–9 In 1980, Van der Linden suggested randomising participants to clinicians committed to performing different interventions in an area in which a conventional randomised controlled trial was possible.10 Since that time, however, the expertise based design has been little used, even in areas where it has high potential (such as, surgery, physiotherapy, and chiropractic).

### Differential expertise between procedures

Because it takes training and experience to develop expertise in surgical interventions, individual surgeons tend to solely or primarily use a single surgical approach to treat a specific problem.10 11 …
Apoptosis modulates protective immunity to the pathogenic fungus Histoplasma capsulatum
Authors: H. L. Allen
Journal: Journal of Clinical Investigation (2005)

Pathogen-induced apoptosis of lymphocytes is associated with increased susceptibility to infection. In this study, we determined whether apoptosis influenced host resistance to the fungus Histoplasma capsulatum. The level of apoptotic leukocytes progressively increased in the lungs of naive and immune mice during the course of H. capsulatum infection. T cells constituted the dominant apoptotic population. Apoptosis was diminished in H. capsulatum-infected gld/gld and TNF-alpha-deficient mice; concomitantly, the fungal burden exceeded that of controls. Treatment of naive and H. capsulatum-immune mice with caspase inhibitors decreased apoptosis but markedly enhanced the severity of infection. Administration of a proapoptotic dose of suramin diminished the fungal burden. The increased burden in recipients of a caspase inhibitor was associated with elevations in IL-4 and IL-10 levels. In the absence of either of these cytokines, caspase inhibition suppressed apoptosis but did not increase the fungal burden. Thus, apoptosis is a critical element of protective immunity to H. capsulatum. Production of IL-4 and IL-10 is markedly elevated when apoptosis is inhibited, and the release of these cytokines exacerbates the severity of infection.