tbuckley/cabot-search huggingface dataset:
Close association of HLA-B51 and B52 in Israeli patients with Behcet's syndrome.
Authors: N Arber, T Klein, Z Meiner, E Pras, A Weinberger
Journal: Annals of the Rheumatic Diseases (1991)

Epidemiological data, family history, clinical data, and HLA typing were studied in three groups of patients with Behçet's syndrome: six Israeli Ashkenazi Jews, 29 non-Ashkenazi Jews, and three Israeli Arabs. HLA-B51 and B52 were present in 24/38 (63%) and 8/38 (21%), respectively, of the patients compared with 13/151 (9%) of the control group for both cases, a relative risk of 18.2 and 2.8 respectively. The syndrome was found in six of the 34 families. Ninety five per cent of the affected family members were either B51 or B52 positive. Eleven of the 14 families (79%) chosen for study contained a close relative of the proband who had recurrent oral ulcers. All the relatives with ulcers, except for one, were B51 or B52 carriers. Recurrent oral ulcers in the patients with Behçet's syndrome began a few years before other manifestations of the syndrome occurred. Our findings suggest that (a) HLA-B51 and HLA-B52 are primarily associated with Behçet's disease of Israeli patients; (b) the familial occurrence of this syndrome is high and occurs predominantly in the B5 positive group; (c) recurrent oral ulcers may be the first symptom of Behçet's syndrome, appearing early in life; HLA analysis can provide the clue for a correct diagnosis; (d) ulcer recurrence is common among members of a family containing a patient with Behçet's syndrome.
Heberden Oration, 1956 : The Connective Tissue System
Authors: R. E. Tunbridge
Journal: Annals of the Rheumatic Diseases (1957)

<h3>Introduction</h3> NICE NG18 includes guidelines on diabetic ketoacidosis (DKA) management in children and young people up to their 18th birthday. In most hospitals, a diabetic young person in DKA is managed by adult medical teams using adult guidelines. Most in-patient medical units follow Joint British Diabetes Societies Inpatient Care Group (JBDSICG) recommendations (2013) to calculate intravenous fluid. <h3>Aim</h3> We aimed to analyse the difference in fluids given to young people if they are treated for DKA using adult guidelines and compare that with NICE NG18. <h3>Methods</h3> Since risk of cerebral oedema is highest within first 12 hours of treatment of DKA, we worked out the volume of intravenous fluids administered to a young person of different weights within first 12 hours of treatment using NICE NG 18 and JBDSICG 2013 recommendations. We used UK-WHO Growth Charts to workout average weight of boys and girls at ages 16 to 18 years. We used Microsoft Excel 2016 to plot the data to highlight difference in fluid calculation between adult and paediatric guidelines. <h3>Results</h3> In contrast to the paediatric DKA guidelines, fluid administered as per adult guidelines is not calculated based on weight of the patient. For a young person in DKA with 5% dehydration and weighing 60 kg, if no fluid bolus is given then paediatric guidelines would recommend administration of 1230 ml in contrast to 4750 ml recommended by adult guidelines in first 12 hours of treatment. If one fluid bolus is given, then this young person would have 1830 mls within first 12 hours of treatment as per paediatric guidelines in contrast to 5250 mls as per adult guidelines. The difference amounts to 65%–74% less fluid recommended by paediatric guidelines. The difference is greater if young person weights less than 60 kg. The difference is smallest but still significant for a young person weighing 100 kg. <h3>Conclusion</h3> Treating young people in DKA in adult wards using NICE NG18 will need a huge culture change. Until that happens, great care must be exercised in treating these young people with adult guidelines. Studies are needed to identify incidence of DKA associated cerebral oedema in young people.
Addressing the burden of asthma in San Francisco through the San Francisco asthma task force*1
Authors: P. Strub, B. Conner-Andersen, R. Castro, L. Kroon, M. Alioto, J. McKown, M. Hoemke, K. Cohn, D. Rossi, B. Saiki, N. Warren
Journal: Journal of Allergy and Clinical Immunology (2004)
Developing aptamer probes for acute myelogenous leukemia detection and surface protein biomarker discovery
Authors: Mingli Yang, Guohua Jiang, Wenjing Li, Kai Qiu, Min Zhang, Christopher M Carter, Samer Z Al-Quran, Ying Li
Journal: Journal of Hematology & Oncology (2014)

The majority of patients with acute myelogenous leukemia (AML) still die of their disease. In order to improve survival rates in AML patients, new strategies are necessary to discover biomarkers for the detection and targeted therapy of AML. One of the advantages of the aptamer-based technology is the unique cell-based selection process, which allows us to efficiently select for cell-specific aptamers without knowing which target molecules are present on the cell surface. The NB4 AML cell line was used as the target cell population for selecting single stranded DNA aptamers. After determining the affinity of selected aptamers to leukocytes, the aptamers were used to phenotype human bone marrow leukocytes and AML cells in clinical specimens. Then a biotin-labelled aptamer was used to enrich and identify its target surface protein. Three new aptamers were characterized from the selected aptamer pools (JH6, JH19, and K19). All of them can selectively recognize myeloid cells with Kd in the low nanomole range (2.77 to 12.37 nM). The target of the biotin-labelled K19 aptamer probe was identified as Siglec-5, a surface membrane protein in low abundance whose expression can serve as a biomarker of granulocytic maturation and be used to phenotype AML. More importantly, Siglec-5 expression can be used to detect low concentrations of AML cells in human bone marrow specimens, and functions as a potential target for leukemic therapy. We have demonstrated a pipeline approach for developing single stranded DNA aptamer probes, phenotyping AML cells in clinical specimens, and then identifying the aptamer-recognized target protein. The developed aptamer probes and identified Siglec-5 protein may potentially be used for leukemic cell detection and therapy in our future clinical practice.
Angiotensin‐converting enzyme inhibitor‐induced angioedema: late onset, irregular course, and potential role of triggers
Authors: P. I. Schiller, S. Langauer Messmer, W. E. Haefeli, R. G. Schlienger, A. J. Bircher
Journal: Allergy (1997)

Angioedema is a rare but potentially life‐threatening adverse effect of angiotensin‐converting enzyme inhibitors (ACEI) which usually occurs within the first weeks of therapy. We report three patients in whom ACEI‐induced angioedema began with a late onset of 12‐33 months, and who had an irregular, unpredictable course under ACEI therapy. In two patients, other drugs or trauma appeared to trigger some of the episodes. After withdrawal of the ACEI, the trigger drugs were well tolerated in provocation tests and upon re‐exposure. To avoid putting some patients unnecessarily at risk for long periods, one should consider this irregular pattern of ACEI‐induced angioedema and regularly monitor patients for this adverse effect.
By Altering Ocular Immune Privilege, Bone Marrow–derived Cells Pathogenically Contribute to DBA/2J Pigmentary Glaucoma
Authors: Jun-Song Mo, Michael G. Anderson, Meredith Gregory, Richard S. Smith, Olga V. Savinova, David V. Serreze, Bruce R. Ksander, J. Wayne Streilein, Simon W.M. John
Journal: The Journal of Experimental Medicine (2003)

Pigment dispersion syndrome causes iris pigment release and often progresses to elevated intraocular pressure and pigmentary glaucoma (PG). Because melanin pigment can have adjuvant like properties and because the Gpnmb gene, which contributes to pigment dispersion in DBA/2J (D2) mice, is expressed in dendritic cells, we tested the hypothesis that ocular immune abnormalities participate in PG phenotypes. Strikingly, we show that D2 eyes exhibit defects of the normally immunosuppressive ocular microenvironment including inability of aqueous humor to inhibit T cell activation, failure to support anterior chamber (AC)-associated immune deviation, and loss of ocular immune privilege. Histologic analysis demonstrates infiltration of inflammatory leukocytes into the AC and their accumulation within the iris, whereas clinical indications of inflammation are typically very mild to undetectable. Importantly, some of these abnormalities precede clinical indications of pigment dispersal, suggesting an early role in disease etiology. Using bone marrow chimeras, we show that lymphohematopoietic cell lineages largely dictate the progression of pigment dispersion, the ability of the eye to support induction of AC-associated immune deviation, and the integrity of the blood/ocular barrier. These results suggest previously unsuspected roles for bone marrow–derived cells and ocular immune privilege in the pathogenesis of PG.
Phase I Trial of the Human Immunodeficiency Virus Protease Inhibitor Nelfinavir and Chemoradiation for Locally Advanced Pancreatic Cancer
Authors: Thomas B. Brunner, Matthias Geiger, Gerhard G. Grabenbauer, Marga Lang-Welzenbach, Tine S. Mantoni, Alexander Cavallaro, Rolf Sauer, Werner Hohenberger, W. Gillies McKenna
Journal: Journal of Clinical Oncology (2008)

Preclinically, HIV protease inhibitors radiosensitize tumors with activated PI3-kinase/Akt pathway. We determined the toxicity of nelfinavir chemoradiotherapy in borderline resectable and unresectable pancreatic cancer.Oral nelfinavir (2 x 1,250 mg) was started 3 days before and continued throughout chemoradiotherapy to 50.4 Gy (boost, 59.4 Gy) in 12 patients. Two gemcitabine dose levels (DL) were tested (200 mg/m(2) and 300 mg/m(2) on days 1, 8, 22, and 29). Cisplatin was administered on the same days at 30 mg/m(2). Phospho-Akt downregulation by nelfinavir was monitored by immunoblotting in patient leukocytes. Restaging positron emission tomography (PET)/computed tomography (CT) and CA19-9 levels served to assess response, and responding tumors were resected.At each DL, five of six patients completed chemoradiotherapy, and two of 12 patients had incomplete chemoradiotherapy because of clinical depression (DL1) and peritoneal metastasis (DL2). Grade 4 toxicities were a transaminase elevation (DL2) as a result of biliary stent occlusion and acute cholecystitis as a result of peritoneal metastasis (DL2). Stent occlusions led to dose-limiting toxicities of grade 3 liver enzyme and bilirubin elevations (two patients at DL1, one patient at DL2). Grade 3 nausea and vomiting occurred in a DL2 patient, and weight loss occurred in a DL1 patient who refused supportive feeding. Secondary complete resection was possible in six of 10 patients with complete chemoradiotherapy, including one tumor with pathologic sterilization. Partial CT responses were observed in five of 10 patients who completed chemoradiotherapy. Of nine patients assessable by PET,responses were complete in five patients and partial patients, and stable disease was observed in two patients.The combination of nelfinavir and chemoradiotherapy showed acceptable toxicity and promising activity in patients with pancreatic cancer.
Comparison of soluble adhesion molecules in juvenile idiopathic arthritis between the active and remission stages
Authors: C-Y Chen, C-H Tsao, L-S Ou, M-H Yang, M-L Kuo, J-L Huang
Journal: Annals of the Rheumatic Diseases (2002)

Objective: To determine the serum levels of soluble adhesion molecules in patients with juvenile idiopathic arthritis (JIA), and to determine whether the levels of these molecules differ between active disease and remission in the same JIA subtype, and whether differences in these levels exist between controls and the three JIA subtypes. Methods: The serum levels of soluble E-selectin (sE-selectin) and soluble intercellular adhesion molecule-1 (sICAM-1) were determined by enzyme linked immunosorbent assay (ELISA) in 40 patients with JIA (12 systemic, 13 polyarticular, and 15 oligoarticular) who had active disease or were in clinical remission and 16 healthy controls. Differences in the levels of adhesion molecules of the same JIA subtype during different disease activity were determined by the paired<i>t</i> test, and differences between the disease and control groups were calculated by one way analysis of variance. A value p&lt;0.01 was considered significant. Results: During the same disease stage (active or in remission), systemic JIA was associated with a significantly higher sE-selectin level than the oligoarticular JIA subtype, whereas this was not found for sICAM-1. Although the mean levels of sE-selectin and sICAM-1 in active systemic and polyarticular JIA were higher than those in remission, this did not reach statistical significance. The levels of sE-selectin and sICAM-1 of the three JIA subtypes, in both the active stage and clinical remission, were still significantly higher than in normal controls. Conclusions: Systemic JIA is associated with a higher sE-selectin level than oligoarticular JIA both in active disease and in clinical remission. This may explain why the morbidity of systemic JIA is greater than that of oligoarticular JIA—namely, owing to increased endothelial cell activation. As significantly higher levels of sE-selectin and sICAM-1 were found in the active and remission stages of the three JIA subtypes compared with those in the control group, JIA may recur even when clinical remission has been achieved.
Clinical Value of Mitochondrial Mutations in Colorectal Cancer
Authors: Astrid Lièvre, Caroline Chapusot, Anne-Marie Bouvier, Franck Zinzindohoué, Françoise Piard, Patrick Roignot, Laurent Arnould, Philippe Beaune, Jean Faivre, Pierre Laurent-Puig
Journal: Journal of Clinical Oncology (2005)

Purpose Prognostic factors that could select high-risk recurrence colorectal cancer patients and predict chemosensitivity are needed. Since mutations of mitochondrial DNA (mtDNA) have been described in different types of cancers and since they may play a role in response to anticancer agents, we investigated in a population-based series of colorectal cancer patients the clinical value of mtDNA mutations. Patients and Methods The displacement loop (D-loop) region of mtDNA was sequenced on a series of 365 patients recorded in the Digestive Cancer Registry of Côte-d'Or (France) between 1998 and 2000. Clinicopathologic characteristics were correlated to the presence of a D-loop mutation. Survival rates were compared with the log-rank test. A multivariate survival analysis was performed. Results D-loop mutations were found in 38.3% of the tumors. The 3-year survival rate was 53.5% in patients with D-loop mutation versus 62.1% in patients without (P = .05). After adjustment for age, stage, and microsatellite instability status, the relative risk of death in patients with D-loop mutation was 1.40 (95% CI, 1.02 to 1.93; P = .034) as compared with those without. In stage III colon cancers, adjuvant chemotherapy was beneficial only for patients without D-loop mutation (3-year survival, 78.3% v 45.4%, P &lt; .02). In those with D-loop mutation who received adjuvant chemotherapy, the relative risk of death was 4.30 (95% CI, 1.23 to 15.00; P &lt; .02). Conclusion The D-loop region is a hotspot for somatic mutations in colorectal tumors. Moreover, presence of tumor D-loop mutation appears to be a factor of poor prognosis in colorectal patients and a factor of resistance to fluorouracil-based adjuvant chemotherapy in stage III colon cancers.
Psychological Impact of Genetic Testing for Hereditary Nonpolyposis Colorectal Cancer
Authors: Ellen R. Gritz, Susan K. Peterson, Sally W. Vernon, Salma K. Marani, Walter F. Baile, Beatty G. Watts, Christopher I. Amos, Marsha L. Frazier, Patrick M. Lynch
Journal: Journal of Clinical Oncology (2005)

This study examines the impact of hereditary nonpolyposis colorectal cancer (HNPCC) genetic test results on psychological outcomes among cancer-affected and -unaffected participants up to 1 year after results disclosure.A total of 155 persons completed study measures before HNPCC genetic testing, and at 2 weeks and 6 and 12 months after disclosure of test results.Mean scores on all outcome measures remained stable and within normal limits for cancer-affected participants, regardless of mutation status. Among unaffected carriers of HNPCC-predisposing mutations, mean depression, state anxiety, and cancer worries scores increased from baseline to 2 weeks postdisclosure and decreased from 2 weeks to 6 months postdisclosure. Among unaffected noncarriers, mean depression and anxiety scores did not differ, but cancer worries scores decreased during the same time period. Affected and unaffected carriers had higher mean test-specific distress scores at 2 weeks postdisclosure compared with noncarriers in their respective groups; scores decreased for affected carriers and all unaffected participants from 2 weeks to 12 months postdisclosure. Classification of participants into high- versus low-distress clusters using mean scores on baseline psychological measures predicted significantly higher or lower follow-up scores, respectively, on depression, state anxiety, quality of life, and test-specific distress measures, regardless of mutation status.Although HNPCC genetic testing does not result in long-term adverse psychological outcomes, unaffected mutation carriers may experience increased distress during the immediate postdisclosure time period. Furthermore, those with higher levels of baseline mood disturbance, lower quality of life, and lower social support may be at risk for both short- and long-term increased distress.
T Cell Receptor (TCR) Engagement Leads to Activation-induced Splicing of Tumor Necrosis Factor (TNF) Nuclear Pre-mRNA
Authors: Yang Yang, Ju-Fay Chang, Jane R. Parnes, C. Garrison Fathman
Journal: The Journal of Experimental Medicine (1998)

Inducible gene expression is primarily regulated at the level of transcription. Additional steps of "processing" pre-mRNA, involved in the regulation of induced gene expression, have not been previously reported. Here we report a novel mechanism of "activation-induced splicing" of preexisting tumor necrosis factor (TNF) message (pre-mRNA) in naive T lymphocytes after engagement of the T cell receptor (TCR), which still occurs after inhibition of transcription. Expression of TNF has been previously demonstrated to be regulated at both the transcriptional and translational levels. However, neither the large pool of TNF mRNA observed in activated T cells nor TNF protein production, which peaks very shortly after activation, can be solely attributed to increased transcription. Evidence is presented that activation-induced splicing of TNF pre-mRNA plays a significant role in the rapid production of TNF seen in activated T cells. Activation triggers processing of TNF pre-mRNA that has accumulated in naive T cells (before activation-induced transcription), and the mature TNF mRNA is translocated to the cytoplasm for rapid translation and protein production. This novel form of activation-induced splicing of TNF may allow T cells to mount an immediate response to activation stimuli under physiological conditions.
Hospitalization Before and After Gastric Bypass Surgery
Authors: David S. Zingmond
Journal: JAMA (2005)

The use of Roux-en-Y gastric bypass (RYGB) has been reported to be effective in the treatment of obesity and its related comorbidities. Utilization of inpatient services after RYGB is less well understood.To determine the rates and indications for inpatient hospital use before and after RYGB.Retrospective study of Californians receiving RYGB in California hospitals from 1995 to 2004.Hospitalization in the 1 to 3 years after RYGB.In California from 1995 to 2004, 60,077 patients underwent RYGB-11,659 in 2004 alone. The rate of hospitalization in the year following RYGB was more than double the rate in the year preceding RYGB (19.3% vs 7.9%, P<.001). Furthermore, in the subset of patients (n = 24,678) with full 3-year follow-up, a mean of 8.4% were admitted a year before RYGB while 20.2% were readmitted in the year after RYGB, 18.4% in the second year after RYGB, and 14.9% in the third year after RYGB. The most common reasons for admission prior to RYGB were obesity-related problems (eg, osteoarthritis, lower extremity cellulitis), and elective operation (eg, hysterectomy), while the most common reasons for admission after RYGB were complications often thought to be procedure related, such as ventral hernia repair and gastric revision. In multivariate logistic regression models predicting 1-year readmission after RYGB, increasing Charlson Comorbidity Index score, and hospitalization in the 3-year period prior to RYGB were significantly associated with readmission within a year.Increases in hospital use after surgery appear to be related to RYGB. Payers, clinicians, and patients must consider the not-inconsequential rate of rehospitalization after this type of surgery.
Long term outcomes of inversion ankle injuries
Authors: A Anandacoomarasamy, L Barnsley
Journal: British Journal of Sports Medicine (2005)

Ankle sprains are common sporting injuries generally believed to be benign and self limiting. However, some studies report a significant proportion of patients with ankle sprains having persistent symptoms for months or even years.To determine the proportion of patients presenting to an Australian sports medicine clinic who had long term symptoms after a sports related inversion ankle sprain.Consecutive patients referred to the NSW Institute of Sports Medicine from August 1999 to August 2002 with inversion ankle sprain were included. Exclusion criteria were fracture, ankle surgery, or concurrent lower limb problems. A control group, matched for age and sex, was recruited from patients attending the clinic for upper limb injuries in the same time period. Current ankle symptoms, ankle related disability, and current health status were ascertained through a structured telephone interview.Nineteen patients and matched controls were recruited and interviewed. The mean age in the ankle group was 20 (range 13-28). Twelve patients (63%) were male. Average follow up was 29 months. Only five (26%) ankle injured patients had recovered fully, with no pain, swelling, giving way, or weakness at follow up. None of the control group reported these symptoms (p<0.0001). Assessments of quality of life using short form-36 questionnaires (SF36) revealed a difference in the general health subscale between the two groups, favouring the control arm (p<0.05). There were no significant differences in the other SF36 subscales between the two groups.Most patients who sustained an inversion ankle injury at sport and who were subsequently referred to a sports medicine clinic had persistent symptoms for at least two years after their injury. This reinforces the importance of prevention and early effective treatment.