tbuckley/cabot-search huggingface dataset:
Efficacy of tocilizumab in rituximab-refractory cryoglobulinemia vasculitis
Authors: Camille Cohen, Arsene Mekinian, Nathalie Saidenberg-Kermanac'h, Jerôme Stirnemann, Pierre Fenaux, Romain Gherardi, Olivier Fain
Journal: Annals of the Rheumatic Diseases (2011)

Cryoglobulinemia vasculitis is a small-vessel systemic vasculitis.1 The most common type is mixed cryoglobulinemia (MC), which is associated with hepatitis C virus (HCV), although autoimmune disorders such as systemic lupus erythematosus, primary Sjogren's syndrome or rheumatoid arthritis have also been described with MC.

A 51-year-old man had a diagnosis of anti-cyclic citrullinated peptide antibodies (anti-CCP) positive non-erosive rheumatoid arthritis in 2006 without cryoglobulinemia, and the disease was well controlled using leflunomide. Since April 2010, asthenia, muscular pain, arthralgias and bilateral foot paresthesias occurred. There was a presence of purpura with bilateral hypoesthesia in the common fibular nerve territory (left first toe levator weakness at 2/5), but no joint swelling. C-reactive protein and fibrinogen were …
The impact of anti-endotoxin core antibodies on endotoxin and cytokine release and ventilation time after cardiac surgery
Authors: Markus Rothenburger, Rasjid Soeparwata, Mario C. Deng, Elmar Berendes, Christof Schmid, Tonny D.T. Tjan, Markus J. Wilhelm, Michael Erren, Dirk Böcker, Hans Heinrich Scheld
Journal: Journal of the American College of Cardiology (2001)
Ribavirin Treatment of the Acquired Immunodeficiency Syndrome (AIDS) and the Acquired-Immunodeficiency-Syndrome-Related Complex (ARC)
Authors: CLYDE CRUMPACKER
Journal: Annals of Internal Medicine (1987)

To assess safety, tolerance, and the clinical and laboratory effects of oral ribavirin in patients with the acquired immunodeficiency syndrome (AIDS) and the AIDS-related complex.Three uncontrolled phase I trials of increasing duration: 14 days, 8 weeks, and 12 months.Outpatient clinic of a university-referral hospital.All patients were antibody-positive for the human immunodeficiency virus (HIV) by radioimmunoprecipitation assay, all had recovered from Pneumocystis carinii pneumonia, and none had Kaposi sarcoma at entry. Nine of ten patients with AIDS had less than 100 CD4+ lymphocytes/mm3 at entry and all patients with the AIDS-related complex had fewer than 200 CD4+ lymphocytes/mm3. Five patients with AIDS and five with the AIDS-related complex entered the 14-day trial. All but two patients with AIDS went on to the 8-week trial, along with seven additional patients with AIDS. Five surviving patients with AIDS and 3 patients with the AIDS-related complex went on to the 1-year study.Oral ribavirin, 1200 mg twice daily for 3 days was given, followed by 300 mg twice daily for 11 days. During an 8-week trial, a loading dose of oral ribavirin was administered for 3 days, followed by a dose of 300 mg twice daily for 8 weeks. Prolonged regimen of a 3-day loading dose was given, followed by a dose of 300 mg twice daily for 1 year.Ribavirin treatment was well tolerated, with anemia requiring transfusion in one of the ten patients with AIDS receiving the drug for 8 weeks; no other significant toxicity occurred. Six of nine patients initially positive for HIV-1 in blood became negative during ribavirin treatment. Six of nine patients with AIDS had a twofold improvement in lymphoproliferative response to at least one lectin with ribavirin treatment. Mean survival from first episode of P. carinii pneumonia was 17.3 months in patients with AIDS receiving 8 weeks of ribavirin and 21.2 months in patients with AIDS receiving prolonged treatment.Oral ribavirin, 600 mg daily, was well tolerated and safe in the patients with severe AIDS and the AIDS-related complex. Ribavirin therapy merits extensive evaluation in a multicenter controlled trial to assess its efficacy.
Granulosa Cell Tumor of the Ovary
Authors: Susan Tinsley Schumer, Stephen A. Cannistra
Journal: Journal of Clinical Oncology (2003)

Adult granulosa cell tumor (GCT) of the ovary is oftentimes a hormonally active, stromal cell neoplasm that is distinguished by its ability to secrete sex steroids such as estrogen. Patients may present with vaginal bleeding caused by endometrial hyperplasia or uterine cancer as a result of prolonged exposure to tumor-derived estrogen. In addition, GCT is a vascular tumor that may occasionally rupture and result in abdominal pain, hemoperitoneum, and hypotension, mimicking an ectopic pregnancy in younger patients. GCT is usually associated with a mass on pelvic examination that is subsequently confirmed on ultrasonography. Surgery is required for definitive tissue diagnosis, staging, and tumor debulking. In older women, a total abdominal hysterectomy and bilateral salpingooophorectomy are typically performed. In women of childbearing age, a more conservative unilateral salpingo-oophorectomy may be performed, assuming that careful staging reveals that the disease has not extended outside of the involved ovary and that a concomitant uterine cancer has been excluded. Survival of patients with GCT is generally excellent because most patients present with early-stage disease, although certain high-risk patient groups may be identified. Stage is the most important prognostic factor, with a higher risk of relapse being associated with stages II through IV disease. In addition, patients with stage I disease associated with features such as large tumor size, high mitotic index, or tumor rupture may also be at higher risk in some series. The value of postoperative adjuvant therapy for high-risk patients has not been investigated by prospective randomized trials, which are difficult to perform because of the rarity of this tumor. Nonetheless, the use of adjuvant chemotherapy or radiation has sometimes been associated with prolonged disease-free survival in patients with high-risk features. Because of the propensity of GCT to recur years after initial diagnosis, prolonged surveillance with serial physical examination and serum tumor markers such as estradiol and inhibin is reasonable.
Advanced Glycation End Products Accumulate in Vascular Smooth Muscle and Modify Vascular but Not Ventricular Properties in Elderly Hypertensive Canines
Authors: Brian P. Shapiro, Theophilus E. Owan, Selma F. Mohammed, Donna M. Meyer, Lisa D. Mills, Casper G. Schalkwijk, Margaret M. Redfield
Journal: Circulation (2008)

Advanced glycation end products (AGEs) are believed to increase left ventricular (LV) and vascular stiffness, in part via cross-linking proteins. We determined whether and where AGEs were increased in elderly hypertensive nondiabetic dogs and whether an AGE cross-link breaker (ALT-711) improved vascular or ventricular function.
Interleukin 15 Provides Relief to CTLs from Regulatory T Cell–Mediated Inhibition: Implications for Adoptive T Cell–Based Therapies for Lymphoma
Authors: Serena K. Perna, Biagio De Angelis, Daria Pagliara, Sayyeda T. Hasan, Lan Zhang, Aruna Mahendravada, Helen E. Heslop, Malcolm K. Brenner, Cliona M. Rooney, Gianpietro Dotti, Barbara Savoldo
Journal: Clinical Cancer Research (2012)

Abstract Purpose: Systemic administration of recombinant interleukin (IL)-2 is used to support the expansion and persistence of adoptively transferred antigen-specific CTLs in patients with cancer. However, IL-2 also expands regulatory T cells (Treg) that in turn impair the antitumor activity of CTLs. As recombinant IL-15 is approaching clinical applications, we assessed the effects of this cytokine on the proliferation and antitumor activity of CTLs in the presence of Tregs. We used the model of adoptive transfer of Epstein–Barr virus (EBV)-CTLs, as these cells induce responses in patients with EBV-associated Hodgkin lymphoma, and Tregs are frequently abundant in these patients. Experimental Design: Tregs were isolated from the peripheral blood of healthy donors and patients with Hodgkin lymphoma or from Hodgkin lymphoma tumors and assessed for their ability to inhibit the proliferation and antitumor activity of EBV-CTLs in the presence of IL-15 or IL-2. Specific molecular pathways activated by IL-15 were also explored. Results: We found that in the presence of Tregs, IL-15, but not IL-2, promoted the proliferation, effector function, and resistance to apoptosis of effectors T cells and EBV-CTLs. IL-15 did not reverse or block Tregs but instead preferentially supported the proliferation of CTLs and effector T cells as compared with Tregs. Conclusions: IL-15 selectively favors the survival, proliferation, and effector function of antigen-specific CTLs in the presence of Tregs, and thus IL-15, unlike IL-2, would have a significant impact in sustaining expansion and persistence of adoptively transferred CTLs in patients with cancer, including those infused with EBV-CTLs for treatment of EBV-associated malignancies. Clin Cancer Res; 19(1); 106–17. ©2012 AACR.
DETOXICATION IN THE TREATMENT OF BURNS
Authors: W. R. Wilson
Journal: BMJ (1927)

<h3>Background</h3> The prevalence of excessive gestation weight gain, extended postpartum weight retention and pregravid obese women is increasing and is associated with numerous adverse health outcomes. <h3>Objective</h3> To review the evidence from studies employing exercise-only interventions for weight management among pregnant and postpartum women. <h3>Search strategy</h3> Ten databases were searched for randomised controlled trials conducted during pregnancy or within the 12 months following childbirth and published between 1990 and 2013. <h3>Selection criteria</h3> There were no restrictions to the type, frequency, duration or intensity of exercise intervention. Interventions not specifically designed to target weight were excluded. The outcomes were a change in body weight (kg) or body mass index (BMI; kg/m<sup>2</sup>). <h3>Data collection and analysis</h3> All data were continuous and were reported as weighted mean differences (WMD), with 95% CIs. Data were analysed with a fixed-effect model and heterogeneity was determined using the I<sup>2</sup> statistic. <h3>Results</h3> Five studies were included in this review. Exercise significantly reduced gestational weight gain (WMD=−2.22 kg, CI −3.14 to −1.3, p≤0.00001) and had no significant effect on postpartum weight loss (WMD=−1.74 kg, CI −3.59 to 0.10, p=0.06) or BMI during pregnancy (WMD=−2.8 kg/m<sup>2</sup>, CI −5.60 to 0.00, p=0.05) or postpartum (WMD=−0.54 kg/m<sup>2</sup>, CI −1.17 to 0.08, p=0.09). <h3>Conclusions</h3> There is currently limited evidence to suggest that exercise can be used to limit maternal gestational weight gain.
THE K-CHAINS OF THE IMMUNOGLOBULIN FROM A CONTINUOUS CULTURE OF HUMAN LYMPHOCYTES (DAUDI) HAVE AN UNUSUAL MOLECULAR SIZE
Authors: Stephen J. Kennel
Journal: The Journal of Experimental Medicine (1974)

Membrane-associated immunoglobulin (M-Ig) was isolated from Daudi cells which had been radioiodinated using lactoperoxidase. This M-Ig was found to have a molecular size on SDS-PAGE of 330,000 daltons. The component protein chains (µ and K) have molecular sizes of 75,000 and 33,000 daltons, respectively. Further studies showed that [3H]galactose can be incorporated into K-chains, but that extra protein and not carbohydrate was responsible for the increased molecular size of this molecule.
Effect of acute pH change on serum anion gap.
Authors: W D Paulson
Journal: Journal of the American Society of Nephrology (1996)

The serum anion gap is decreased in hyperchloremic (HCl) acidosis and increased in diuretic-induced alkalosis. These anion gap changes have been largely attributed to titration-induced variations in the net negative charge of the serum proteins, which are the predominant non-HCO3 buffers of serum. It has recently been shown, however, that albumin has all of the net protein charge, and titration-induced changes in charge are smaller than have been widely believed. Because the non-HCO3 buffers are also titrated in acute hypocapnia and hypercapnia, these disorders were induced in 16 anesthetized dogs for 10 min in order to assess the effect of acute changes in pH on the anion gap. Although the mean arterial pH varied from 7.04 to 7.65, the calculated mean albumin charge only varied from 6.8 to 9.0 mEq/L. When the anion gap was computed with HCO3 (AGHCO3 = Na + K - Cl - HCO3), the change in AGHCO3 per 0.1 change in pH (delta AGHCO3/ delta pH) was only 0.15 mEq/L per 0.1 pH. When the anion gap was computed with total CO2 content (AGTCO2 = Na + K - Cl - TCO2), delta AGTCO2/delta pH was larger (0.51 mEq/L per 0.1 pH) because of the effect of variable PCO2 levels on TCO2. In a review of 22 previous studies in humans and dogs, similar estimates of delta AG/delta pH were obtained (after adjusting for the lower albumin level in dogs). These results show that simple titration processes that occur within 10 min of a change in pH cause minimal changes in the anion gap. Titration of the known non-HCO3 buffers of serum does not explain the much larger anion gap changes of HCl acidosis and diuretic alkalosis.
Biochemical markers of myocardial remodelling in hypertensive heart disease
Authors: A. Gonzalez, B. Lopez, S. Ravassa, J. Beaumont, T. Arias, N. Hermida, A. Zudaire, J. Diez
Journal: Cardiovascular Research (2008)

The intricate mechanisms responsible for the structural remodelling of the myocardium that facilitates the evolution to heart failure in hypertensive patients, namely in those with left ventricular hypertrophy, requires from clinicians the utilization of a multibiomarker approach for short-term and long-term stratification as well as prognostication of patients. Biochemical markers may also help to identify patients with no clinical evidence of hypertensive heart disease, and provide information about the need for more aggressive therapy during different stages of the disease, and potentially provide valuable biochemical data for the specialist. Although there is a continuous and complex interplay between biochemical and imaging markers, perhaps their use will also have the potential to modify the medical management of patients with hypertensive heart disease and therapeutic decision-making by tailoring a targeted therapy according to the predominant mechanism of myocardial remodelling. This article will review in brief the most relevant information on a panel of circulating molecules that may accomplish the criteria required to be considered as biochemical markers of the cardiomyocyte and non-cardiomyocyte structural changes that occur in the hypertensive myocardium.
Sudden Death: Perforation of the Superior Vena Cava
Authors: R. E. Power
Journal: BMJ (1876)

plained of pain in the abdomen.On examining the abdomen, a distinct, hard, oblong tumour, about two inches and a half long and an inch and a quarter wide, and painful on palpation, was discovered in the right iliac region, about the situation of the ileo-coecal valve.A second smaller tumour was also present, about one inch to the left of the umbilicus.He was ordered milk and lime-water, hot fomenta- tions to the abdomen, and an enema of soap and water.The enema was soon returned, mixed with blood and mucus, and smelling very feculent; but there was no feculent matter.My suspicions were now confirmed that this was a case of intussusception at the ileo-caecal valve.He was ordered four minims of tincture of opium every four hours while in pain.July 15th.The tongue was coated; vomiting was incessant; there
Survival Comparison between Hemodialysis and Peritoneal Dialysis Based on Matched Doses of Delivered Therapy
Authors: Prakash Keshaviah, Allan J. Collins, Jennie Z. Ma, David N. Churchill, Kevin E. Thorpe
Journal: Journal of the American Society of Nephrology (2002)

Several studies have recently confirmed that hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD) survival is highly associated with delivered therapy Kt/V(urea). A direct comparison of equivalently dosed CAPD and HD has not previously been performed. A total of 968 incident HD patients at the Regional Kidney Disease Program from 1987 to June 1995 were studied, and these results were compared with those of the Canadian-United States prospective trial (CANUSA) consisting of 680 incident CAPD patients from September 1990 to December 31, 1992, with follow-up through December 31, 1993. All patients had quantitation of urea nitrogen for a total delivered dialysis session. On HD, in vivo, 2-pool, pre- and post-blood urea nitrogen kinetic modeling was performed with residual renal function determined every 6 mo. Patients were characterized by age, gender, race, renal diagnosis, and comorbid conditions. A Cox proportional hazards model was used to evaluate the effect of the individual comorbid conditions and the effect of dialysis therapy in the time-dependent method. The mean total Kt/V, both residual renal function and dialytic therapy in the HD patients, was 1.59. The CANUSA-delivered weekly Kt/V was 2.38 at the beginning of the baseline period and 1.99 after 24 mo of follow-up. When the peak concentration hypothesis was used, a Kt/V of 1.59 on HD was equivalent to a weekly CAPD dose of 2.1 to 2.2. A 1-unit increase in Kt/V was associated with 7% lower risk of death on HD and with a similar 8% lower risk of death while on CAPD. Patients with diabetes aged 46 to 60 yr had virtually identical 2-yr survival estimates on HD (83 to 90%), compared with CAPD (83 to 89%), with Kt/V ranges from 0.84 to 1.70 in HD and from 1.6 to 2.2 weekly Kt/V on peritoneal dialysis. Comparisons between HD and CAPD in older patients with diabetes yielded comparable results. Patient survival is highly influenced by delivered dialysis in both HD and peritoneal dialysis. Carefully matching of the therapies with delivered Kt/V demonstrates little differences in the survival outcome of HD and peritoneal dialysis patients, in contrast to some previous reports.
Antisense oligonucleotide mediated exon skipping as a potential strategy for the treatment of a variety of inflammatory diseases such as rheumatoid arthritis
Authors: Seda Yilmaz-Elis, Annemieke Aartsma-Rus, Anne Vroon, Judith van Deutekom, Sjef de Kimpe, Peter A C 't Hoen, Gert-Jan van Ommen, J Sjef Verbeek
Journal: Annals of the Rheumatic Diseases (2012)

Arthritis is an autoantibody-driven disease. Anti-CD20 treatment, removing B cells, treats the disease but introduces a new problem. This treatment removes B cells irrespective of their specificity, and thus attenuates the humoral response which might result in impaired immunity. Since it is impossible to specifically target the autoantigen-specific B cells, therapeutic strategies are generally directed to downstream targets such as the effector cytokines interleukin 1 (IL-1) and tumour necrosis factor α (TNFα). It has already been shown that blocking these cytokines using specific antibodies (anti-TNF), antagonists (IL-1 receptor (IL-1R) antagonist) or soluble receptors (TNFR) decreases disease severity. To date, interference with the TNF pathway has been shown to be very effective and is used successfully in the clinic. However, the development and production of large amounts of specific antibodies and inhibiting proteins such as antagonists or soluble receptors for clinical use is complex and very expensive. In addition, induction of antibody responses against several of these artificial proteins reduces their efficacy. There is therefore still a need for alternative therapeutics directed more specifically at these effector cytokines and other targets that can be used individually or in combination with other therapeutics. Although the strong therapeutic effect of inhibiting the IL-1 pathway shown in mice has not so far been confirmed in humans, it cannot be excluded that inhibition of the IL-1 signaling pathway will be effective in combination therapy including other targets. Moreover, IL-1 inhibition might be an effective therapy in the many other inflammatory and autoimmune diseases in which this cytokine is known to play an important role.

IL-1 receptor accessory protein (IL-1RAcP) is a subunit of the IL-1R complex required for the stabilisation of the IL-1 and …
Intake of Vitamins B6 and C and the Risk of Kidney Stones in Women
Authors: GARY C. CURHAN, WALTER C. WILLETT, FRANK E. SPEIZER, MEIR J. STAMPFER
Journal: Journal of the American Society of Nephrology (1999)

Urinary oxalate is an important determinant of calcium oxalate kidney stone formation. High doses of vitamin B6 may decrease oxalate production, whereas vitamin C can be metabolized to oxalate. This study was conducted to examine the association between the intakes of vitamins B6 and C and risk of kidney stone formation in women. The relation between the intake of vitamins B6 and C and the risk of symptomatic kidney stones were prospectively studied in a cohort of 85,557 women with no history of kidney stones. Semiquantitative food-frequency questionnaires were used to assess vitamin consumption from both foods and supplements. A total of 1078 incident cases of kidney stones was documented during the 14-yr follow-up period. A high intake of vitamin B6 was inversely associated with risk of stone formation. After adjusting for other dietary factors, the relative risk of incident stone formation for women in the highest category of B6 intake (> or =40 mg/d) compared with the lowest category (<3 mg/d) was 0.66 (95% confidence interval, 0.44 to 0.98). In contrast, vitamin C intake was not associated with risk. The multivariate relative risk for women in the highest category of vitamin C intake (> or =1500 mg/d) compared with the lowest category (<250 mg/d) was 1.06 (95% confidence interval, 0.69 to 1.64). Large doses of vitamin B6 may reduce the risk of kidney stone formation in women. Routine restriction of vitamin C to prevent stone formation appears unwarranted.
European collaboration at its best: 23rd European Workshop for Rheumatology Research
Authors: F A Wollheim
Journal: Annals of the Rheumatic Diseases (2003)

Professor Jean Roudier hosted this workshop in Marseilles (fig 1) on the 27 February to 2 March 2003. The European Workshop for Rheumatology Research (EWRR) series of annual meetings was started in 1981 at Guy’s hospital in London, UK, by Gabriel Panayi and Peter M Johnson as a forum for scientific exchange between active investigators. In part it was intended as an alternative to the big, expensive, and industry dependent international congresses. Not least, it was a reaction to the style of the EULAR congresses of the time. The lecture hall in building 4 at Guy’s hospital was filled with about 75 participants, the registration fee was £5, and the abstracts were probably only distributed among the attendees.



 Figure 1  
Marseilles.



The success led to a second meeting which was arranged in 1982 by Arnold Cats outside Leiden, followed by the third in 1983, organised by Jochen Kalden in Mainz. Later convenors have included a large number of the scientific leaders in Europe. A scientific poster is the admission ticket to these workshops, the number of posters is 150 at most, and it is the privilege of the convenor(s) to invite a number of speakers of their own choice. The country and convenor changes every year. This has proved very fruitful and a particularly stimulating concept for the younger investigators.

EULAR now supports the meeting with a number of bursaries and the standing committees of EULAR have meetings in connection with the workshop. Some highlights from the most recent meetings are presented below. They are meant to give the readership a flavour of these open, but not heavily advertised, gatherings. Next spring the venue will be Berlin with the convenor Gerd Burmester.

Martin Lotz, La Jolla, CA, USA, dealt with differences between aging and OA in cartilage and the general problem of …