tbuckley/cabot-search huggingface dataset:
A 2-year randomised, double-blind, placebo-controlled, multicentre study of oral selective iNOS inhibitor, cindunistat (SD-6010), in patients with symptomatic osteoarthritis of the knee
Authors: Marie-Pierre Hellio le Graverand, Ray S Clemmer, Patricia Redifer, Robert M Brunell, Curtis W Hayes, Kenneth D Brandt, Steven B Abramson, Pamela T Manning, Colin G Miller, Eric Vignon
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Objective</h3> To determine if inhibition of inducible nitric oxide synthase (iNOS) with cindunistat hydrochloride maleate slows progression of osteoarthritis (OA) <h3>Methods</h3> This 2-year, multinational, double-blind, placebo-controlled trial enrolled patients with symptomatic knee OA (Kellgren and Lawrence Grade (KLG) 2 or 3). Standard OA therapies were permitted throughout. Patients were randomly assigned to cindunistat (50 or 200 mg/day) or placebo. Randomisation was stratified by KLG. Radiographs to assess joint space narrowing (JSN) were acquired using the modified Lyon-schuss protocol at baseline, week 48 and 96. <h3>Results</h3> Of 1457 patients (50 mg/day, n=485; 200 mg/day, n=486; placebo, n=486), 1048 (71.9%) completed the study. Patients were predominantly women; 56% had KLG3. The primary analysis did not demonstrate superiority of cindunistat versus placebo for rate of change in JSN. In KLG2 patients, JSN after 48 weeks was lower with cindunistat 50 mg/day versus placebo (p=0.032). Least-squares mean±SE JSN with cindunistat 50 mg/day ( −0.048±0.028 mm) and 200 mg/day (−0.062±0.028 mm) were 59.9% (95% CI 6.8% to 106.9%) and 48.7% (95% CI -8.4% to 93.9%) of placebo, improvement was not maintained at 96 weeks. No improvement was observed for KLG3 patients at either time-point. Cindunistat did not improve joint pain or function, but was generally well tolerated. <h3>Conclusions</h3> Cindunistat (50 or 200 mg/day) did not slow the rate of JSN versus placebo. After 48-weeks, KLG2 patients showed less JSN; however, the improvement was not sustained at 96-weeks. iNOS inhibition did not slow OA progression in KLG3 patients. <h3>Clinical trial listing</h3> NCT00565812
Epstein–Barr Virus and a Cellular Signaling Pathway in Lymphomas from Immunosuppressed Patients
Authors: David Liebowitz
Journal: New England Journal of Medicine (1998)

Epstein–Barr virus (EBV) is associated with various malignant and benign lymphoproliferative disorders. It also efficiently transforms human B lymphocytes in vitro. The latent membrane protein 1 (LMP1) of EBV-infected cells plays a central part in this process by mimicking members of the family of tumor necrosis factor (TNF) receptors, thereby transmitting growth signals from the cell membrane to the nucleus through cytoplasmic TNF-receptor–associated factors (TRAFs). I sought evidence of LMP1-mediated signal transduction through TRAFs in tumor tissue from patients with post-transplantation lymphoproliferative disease and non-Hodgkin's lymphomas related to the acquired immunodeficiency syndrome (AIDS).
Self assessment of daytime sleepiness: patient versus partner.
Authors: R N Kingshott, P J Sime, H M Engleman, N J Douglas
Journal: Thorax (1995)

We present a case of azacitidine-induced pneumonitis which is a rare adverse drug reaction and reported in less than 0.1% of cases. Common side effects of azacitidine are weakness, nausea, vomiting, constipation, injection site reactions, insomnia, among others. Our patient received azacitidine to treat her acute myeloid leukaemia and began to develop shortness of breath which progressed to dyspnoea at rest after completing a 7-day course of azacitidine and venetoclax. Initial chest X-ray revealed severe airspace disease for which the patient began receiving broad spectrum antibiotics, antifungals and antivirals therapy. Although infectious workup revealed invasive aspergillosis she did not clinically and radiologically improve despite being on isavuconazole until high-dose glucocorticoids were initiated. This case illustrates the importance of recognising and understanding the potential side effects of azacitidine and other chemotherapy agents as some adverse drug reactions can be life-threatening.
Human Papillomavirus and Prognosis of Oropharyngeal Squamous Cell Carcinoma: Implications for Clinical Research in Head and Neck Cancers
Authors: Maura L. Gillison
Journal: Journal of Clinical Oncology (2006)

Oropharyngeal squamous cell carcinomas are etiologically heterogeneous, with one subset attributable primarily to human papillomavirus (HPV) infection and another to alcohol and tobacco use. These subsets are clinically and molecularly distinct, and these distinctions extend to patient prognosis. 1 In this issue of the Journal of Clinical Oncology, Licitra et al 2 report that patients with HPV DNA–positive oropharyngeal cancers have an approximately 60% reduction in 5-year mortality when compared with patients with HPV-negative tumors, who have a considerably worse prognosis. These data corroborate several previous single-institutional, retrospective analyses that reported similarly improved disease
LIMD1 is more frequently altered than RB1 in head and neck squamous cell carcinoma: clinical and prognostic implications
Authors: Susmita Ghosh, Amlan Ghosh, Guru P Maiti, Nupur Mukherjee, Sankhadeep Dutta, Anup Roy, Susanta Roychoudhury, Chinmay K Panda
Journal: Molecular Cancer (2010)

Abstract Introduction To understand the role of two interacting proteins LIMD1 and pRB in development of head and neck squamous cell carcinoma (HNSCC), alterations of these genes were analyzed in 25 dysplastic head and neck lesions, 58 primary HNSCC samples and two HNSCC cell lines. Methods Deletions of LIMD1 and RB1 were analyzed along with mutation and promoter methylation analysis of LIMD1. The genotyping of LIMD1 linked microsatellite marker, hmlimD1, was done to find out any risk allele. The mRNA expression of LIMD1 and RB1 were analyzed by Q-PCR. Immunohistochemical analysis of RB1 was performed. Alterations of these genes were correlated with different clinicopathological parameters. Results High frequency [94% (78/83)] of LIMD1 alterations was observed in the samples studied. Compare to frequent deletion and methylation, mutation of LIMD1 was increased during tumor progression ( P = 0.007). Six novel mutations in exon1 and one novel intron4/exon5 splice-junction mutation were detected in LIMD1 along with a susceptible hmlimD1 (CA) 20 allele. Some of these mutations [42% (14/33)] produced non-functional proteins. RB1 deletion was infrequent (27%). Highly reduced mRNA expression of LIMD1 (25.1 ± 19.04) was seen than RB1 (3.8 ± 8.09), concordant to their molecular alterations. The pRB expression supported this data. Tumors with LIMD1 alterations in tobacco addicted patients without HPV infection showed poor prognosis. Co-alterations of these genes led the worse patients' outcome. Conclusions Our study suggests LIMD1 inactivation as primary event than inactivation of RB1 in HNSCC development.
Association of Neutrophil-To-Lymphocyte Ratio (Nlr) with Survival (Os) in Metastatic Castration-Resistant Prostate Cancer (Mcrpc) Patients Receiving Prednisone (P) Plus Cabazitaxel (Cbz) or Mitoxantrone (Mtx) in the Tropic Trial
Authors: D. Lorente, A. Templeton, O. Sartor, A. Bahl, Z. Su, J. Devin, J. de Bono
Journal: Annals of Oncology (2014)
Uric acid crystal binding to renal inner medullary collecting duct cells in primary culture.
Authors: R J Riese, J G Kleinman, J H Wiessner, G S Mandel, N S Mandel
Journal: Journal of the American Society of Nephrology (1990)

Attachment of microcrystals to cellular membranes may be an important component in the pathophysiology of urolithiasis. This study characterizes the concentration-dependent binding of uric acid crystals to rat renal inner medullary collecting duct cells in primary culture. Collecting duct cell cultures grew as monolayers with interspersed aggregates of rounded cells. Cultures were incubated with 14C-uric acid crystals, and the crystals that bound were quantitated by adherent radioactivity. Uric acid crystal adherence demonstrated concentration dependent saturation with a 1/alpha value (maximum micrograms of crystals adhering to 1 cm2 of binding area) of 645 micrograms/cm2. The beta values (fraction of cross-sectional area which bound crystals) of uric acid (mean = 0.15) and calcium oxalate monohydrate (mean = 0.13) crystals did not differ significantly. Uric acid crystal binding was inhibited by pre-bound calcium oxalate monohydrate crystals in a concentration dependent manner. These data suggest that uric acid and calcium oxalate crystals exhibit similar binding patterns to rat renal inner medullary collecting duct cells in primary culture.
STRUCTURAL UNITS OF HUMAN 7S GAMMA GLOBULIN *
Authors: Edward C. Franklin, Frances Prelli
Journal: Journal of Clinical Investigation (1960)

A number of observers in the past (1-3) have successfully degraded rabbit and horse antibodies with various enzymes, thus producing fragments retaining antibody activity.More recently Porter (4, 5) has produced split products of rabbit y-glob- ulin by treatment with papain and cysteine, two of which retained antibody activity as measured by their ability to inhibit precipitation of the original antiserum with homologous antigen, while the third appeared to retain the greatest antigenic specificity.Karush (6) and Nisonoff, Woernley and Wissler (7, 8) working with antihapten antibodies have clearly shown that these fragments are univalent.Putnam, Hsiao and Tan (9), employing similar techniques, have been able to split human y-globulin and myeloma proteins into two major chro- matographically separable fractions with sedimen- tation coefficients of approximately 3.5S.A preliminary report of some physical, chemical and immunological properties of similar subunits from human y-globulins and several human antibodies has been presented (10).In the present report, results are presented which indicate that following digestion of human y-globulin there are produced at least three fragments differing from each other in chemical properties.The major part of the antibody activity against three different antigens was found to be associated with one of these frag- ments, while smaller amounts were present in a second, antigenically similar fragment.The third fragment contained virtually no antibody activity but had additional antigenic specificity. MATERIALS AND METHODSHuman 'y-globulin was obtained as Cohn fraction II (Lederle, Lot no.C576).Ultracentrifugal examination demonstrated that this preparation consisted of approxi- mately 95 per cent 7S y-globulin, and that it contained less than 5 per cent of molecules with s rates of 9 to 11S and no detectable amounts of 19S 'y-globulin.For stud-
Treatment of patients with melanoma of the extremity using hyperthermic isolated limb perfusion with melphalan, tumor necrosis factor, and interferon gamma: results of a tumor necrosis factor dose-escalation study.
Authors: D L Fraker, H R Alexander, M Andrich, S A Rosenberg
Journal: Journal of Clinical Oncology (1996)

PURPOSE To evaluate response rates and systemic and regional toxicity of hyperthermic isolated limb perfusion (ILP) for treatment of in-transit metastases of extremity melanoma using escalating-dose tumor necrosis factor (TNF) in conjunction with melphalan and interferon gamma (IFN). PATIENTS AND METHODS All patients received IFN 0.2 mg2 for 2 days followed by a 90-minute ILP with TNF and IFN (0.2 mg) given at time 0 and melphalan (10 mg/L limb volume) given at 30 minutes. Twenty-six patients were treated with 4 mg of TNF and 12 patients received 6 mg of TNF. All patients had assessable disease in the perfusion field and all but two patients were assessable for response at 1 month after treatment. RESULTS Mean peak perfusate TNF levels in the 4-mg group were 4.8 micrograms/mL, compared with 7.4 micrograms/mL for the 6-mg group (P = .03). The complete response rate in the 4-mg TNF group was 76%, with an overall objective response rate of 92%, compared with 36% and 100% for the 6-mg group. Subgroup analyses showed that the lower complete response rate in the 6-mg TNF group was not explained by differences in disease burden or prior regional therapy. Systemic drug toxicity was short-lived, easily managed, and related to perfusate leak more than to TNF perfusate dose. Regional toxicity, particularly painful myopathy and neuropathy, was greater with the 6-mg dose level and was considered dose-limiting. CONCLUSION ILP with 4 mg TNF, IFN, and melphalan can lead to complete local responses in the majority of patients with extremity melanoma. Escalating the TNF dose to 6 mg did not increase the complete response rate and increased regional toxicity.
Characterization of dermal collagen in systemic sclerosis
Authors: C.R. LOVELL, A.C. NICHOLLS, V.C. DUANCE, A.J. BAILEY
Journal: British Journal of Dermatology (1979)

The amount of dermal collagen is increased in systemic sclerosis. However, unlike certain inflammatory conditions, the relative proportions of Type I and Type III collagens are closely similar to those found in normal adult dermis. Similarly, no change in the distribution of the collagen types could be detected by immunofluorescent staining, although a considerable thickening of the epidermis was clearly evident in all the sclerotic lesions examined.
Technique-related variation in results of FANA tests.
Authors: P Chaiamnuay, C Johnston, J Maier, A S Russell
Journal: Annals of the Rheumatic Diseases (1984)

We compared the reliability and reproducibility of three tests for fluorescent antinuclear antibodies (FANA) that are routinely performed in our laboratory. Sera from 72 patients, selected according to diagnosis (SLE in 28, RA in 12, and other connective-tissue diseases in 33), and from 32 healthy controls were tested with all three assays. There were wide variations between the results obtained with these tests. The variations did not reflect sensitivity or degree of standardisation (reproducibility on retesting was greater than 95%) and appeared to be inherent in the techniques. Clinicians should be aware of the technique-related differences in FANA assays.
Elevated rheumatoid factor and long term risk of rheumatoid arthritis: a prospective cohort study
Authors: S. F. Nielsen, S. E. Bojesen, P. Schnohr, B. G. Nordestgaard
Journal: BMJ (2012)

<b>Objective</b> To test whether elevated concentration of rheumatoid factor is associated with long term development of rheumatoid arthritis. <b>Design</b> A prospective cohort study, the Copenhagen City Heart Study. Blood was drawn in 1981-83, and participants were followed until 10 August 2010. <b>Setting</b> Copenhagen general population. <b>Participants</b> 9712 white Danish individuals from the general population aged 20-100 years without rheumatoid arthritis at study entry. <b>Main outcome measures</b> Rheumatoid arthritis according to baseline plasma IgM rheumatoid factor level categories of 25-50, 50.1-100, and &gt;100, versus &lt;25 IU/mL. <b>Results</b> Rheumatoid factor levels were similar from age 20 to 100 years. During 187 659 person years, 183 individuals developed rheumatoid arthritis. In healthy individuals, a doubling in levels of rheumatoid factor was associated with a 3.3-fold (95% confidence interval 2.7 to 4.0) increased risk of developing rheumatoid arthritis, with a similar trend for most other autoimmune rheumatic diseases. The cumulative incidence of rheumatoid arthritis increased with increasing rheumatoid factor category (P<sub>trend</sub>&lt;0.0001). Multivariable adjusted hazard ratios for rheumatoid arthritis were 3.6 (95% confidence interval 1.7 to 7.3) for rheumatoid factor levels of 25-50 IU/mL, 6.0 (3.4 to 10) for 50.1-100 IU/mL, and 26 (15 to 46) for &gt;100 IU/mL, compared with &lt;25 IU/mL (P<sub>trend</sub>&lt;0.0001). The highest absolute 10 year risk of rheumatoid arthritis of 32% was observed in 50-69 years old women who smoked with rheumatoid factor levels &gt;100 IU/mL. <b>Conclusion</b> Individuals in the general population with elevated rheumatoid factor have up to 26-fold greater long term risk of rheumatoid arthritis, and up to 32% 10 year absolute risk of rheumatoid arthritis. These novel findings may lead to revision of guidelines for early referral to a rheumatologist and early arthritis clinics based on rheumatoid factor testing.
Lidocaine for the alleviation of pain associated with subcutaneous erythropoietin injection.
Authors: U S Alon, S Allen, Z Rameriz, B A Warady, R A Kaplan, D J Harris
Journal: Journal of the American Society of Nephrology (1994)

Alon, U S; Allen, S; Rameriz, Z; Warady, B A; Kaplan, R A; Harris, D J Author Information
A genome-wide association study of nonsynonymous SNPs identifies a type 1 diabetes locus in the interferon-induced helicase (IFIH1) region
Authors: Deborah J Smyth, Jason D Cooper, Rebecca Bailey, Sarah Field, Oliver Burren, Luc J Smink, Cristian Guja, Constantin Ionescu-Tirgoviste, Barry Widmer, David B Dunger, David A Savage, Neil M Walker, David G Clayton, John A Todd
Journal: Nature Genetics (2006)
Screening colonoscopy for the detection of neoplastic lesions in asymptomatic HIV-infected subjects
Authors: E. J. Bini, B. Green, M. A. Poles
Journal: Gut (2009)

<h3>Background:</h3> Although non-AIDS defining malignancies are rapidly increasing as HIV-infected subjects live longer, little is know about the results of screening for colonic neoplasms (adenomatous polyps and adenocarcinomas) in this population. <h3>Methods:</h3> We conducted a screening colonoscopy study to determine the prevalence of colonic neoplasms in 136 asymptomatic HIV-infected subjects ⩾50 years of age and 272 asymptomatic uninfected control subjects matched for age, sex, and family history of colorectal cancer. Advanced neoplasms were defined as adenomas ⩾10 mm or any adenoma, regardless of size, with villous histology, high-grade dysplasia, or adenocarcinoma. <h3>Results:</h3> The prevalence of neoplastic lesions was significantly higher in HIV-infected subjects than in control subjects (62.5% vs 41.2%, p&lt;0.001), and remained highly significant after adjustment for potential confounding variables (odds ratio = 3.00; 95% confidence interval, 1.83 to 4.93). Among patients with colorectal adenocarcinoma, HIV-infected subjects were significantly younger (52.4 (SD 1.3) vs 60.3 (SD 4.0) years, p = 0.002) and were more likely to have advanced cancers (stage III or IV) than control subjects (60.0% vs 16.7%, p = 0.24). Of HIV-infected subjects with advanced neoplasms proximal to the splenic flexure, distal neoplastic lesions were absent in 88.9% of individuals and these would have been missed by flexible sigmoidoscopy. <h3>Conclusions:</h3> HIV-infected subjects have a higher prevalence of colonic neoplasms, and adenocarcinomas develop at a younger age and are more advanced than in uninfected subjects. Our findings suggest that screening colonoscopy should be offered to HIV-infected subjects, but the age of initiation and the optimal frequency of screening require further study.
Frobell and colleagues' NEJM paper debunks 'early reconstruction' after ACL rupture: give a piece of rehab a chance!
Authors: Karim M Khan
Journal: British Journal of Sports Medicine (2010)

<h3>ABSTRACT</h3> Polystyrene or PS is one of the plastics contributing to environmental pollution with its durability and resistance to biodegradation. Recent research has found that mealworms (<i>Tenebrio molitor</i>) and superworms (<i>Zophobas morio</i>) are able to utilize polystyrene as a carbon food source and degrade them without toxic effects. In this study, we studied food additives to augment the plastic consumption and found that small additions of sucrose and bran were able to encourage PS consumption. To close the plastic carbon cycle, we also evaluated the use of the worm frass for dragon-fruit cacti (<i>Hylocereus undatus</i>) growth and found that superworm frass supported rooting and growth better than mealworm frass and control media over a fortnight. From the results, superworms are shown to be a suitable natural solution to the PS plastic problem that can also support plant growth towards a zero-waste sustainable bioremediation cycle.
The Muscle in Dire Straits
Authors: Stephan von Haehling
Journal: Circulation (2012)

I t has been established for centuries that body wasting and changes in body composition play important roles in patients with chronic diseases.This is also true for patients with heart failure (HF). 1 For clinicians not actively involved in this area of research, however, it may be difficult to decipher the complex and sometimes confusing terminology used in this context.Cachexia, body wasting, anorexia, sarcopenia, malnutrition, or even the recent addition myopenia-do they essentially all mean the same? 2,3Is loss of fat mass commonly propagated for healthy people or patients with cardiovascular disease also beneficial once HF is present?Or is it at least preferable to muscle loss?No physician would seriously suggest to a patient with malignant cancer to start losing weight, as this is generally thought of as a signum mali ominis.Just the same may be true for HF.Current guidelines 4 for coronary artery disease, however, do not distinguish between those who do and those who do not suffer from concomitant HF, and, hence, all these patients are lumped together and provided with guidance that is everything but evidence-based. Article see p 2716To more fully understand the changes in body composition that take place over the course of HF, it is necessary to differentiate changes with versus those without weight loss.Both may be detrimental and associated with decreased exercise capacity, quality of life, or even increased mortality.Further differentiation is needed with regard to voluntary versus involuntary weight loss, and all changes in body weight that are deemed clinically relevant need to be measured in an edema-free state.According to a recent consensus definition, 5 the term cachexia describes involuntary weight loss in patients with chronic disease; the key component of the diagnostic criteria is weight loss that exceeds 5% within 12 months or less.In patients with HF, such weight loss may be the result of reduction in fat or muscle mass; however, counterintuitively the muscle compartment may be predominantly affected.
MPs criticise government for inaction since Winterbourne View scandal
Authors: I. Torjesen
Journal: BMJ (2015)

Failures to close psychiatric hospitals and to tackle the financial disincentives for re-housing patients are to blame for the government missing its target of moving most patients with a learning disability and challenging behaviour into the community, MPs have said.1

MPs on the House of Commons Public Accounts Committee examined changes to care services for people with learning disabilities and challenging behaviour since the Winterbourne View scandal in 2011, when widespread abuse of patients at the hospital was uncovered by the BBC’s Panorama programme.2

The incidents at Winterbourne View prompted the government to commit to moving any people with a learning disability and challenging behaviour out of hospital by 1 June 2014 if they would be …