tbuckley/cabot-search huggingface dataset:
Effect of resumption of second line drugs in patients with rheumatoid arthritis that flared up after treatment discontinuation
Authors: S. ten Wolde, J. Hermans, F. C Breedveld, B. A C Dijkmans
Journal: Annals of the Rheumatic Diseases (1997)

<h3>OBJECTIVE</h3> To assess the effect of resumption of second line drugs in patients with rheumatoid arthritis (RA) that flared after treatment discontinuation. <h3>METHODS</h3> RA patients were studied whose RA flared up after discontinuation of second line treatment while being in remission and who received a second course of the drug. Disease activity parameters were prospectively assessed at the time of treatment discontinuation, during the period when the disease flared up, and three months thereafter. Furthermore the medical charts were reviewed at 12 months after treatment resumption. <h3>RESULTS</h3> There were 51 patients included in the study: 25 patients treated with antimalarial drugs, 10 with parenteral gold, four with d-penicillamine, eight with sulphasalazine, two with azathioprine, and two with methotrexate. Disease activity parameters showed significant improvement within three months of treatment resumption, but remained significantly worse when compared with that measured before treatment discontinuation. Within three months 47% of the patients fulfilled 20% response criteria. Disease activity 12 months after treatment resumption was considered to be absent in 35%, mild in 43%, and moderate or active in 22% of the patients. In four (8%) patients the resumed treatment was stopped because of lack of efficacy. Side effects were recorded in four patients, which did not result in treatment discontinuation. <h3>CONCLUSIONS</h3> Resumption of second line drugs in RA patients whose disease flared up after discontinuation of treatment is effective and safe in most patients. Half of the patients responded within three months after resumption of the second line drug.
The behavior of asialotransferrin‐iron in the rat
Authors: Yves Beguin, Gaetano Bergamaschi, Helmut A. Huebers, Clement A. Finch
Journal: American Journal of Hematology (1988)

Abstract The effect of desialylation of rat and human transferrins on hepatocyte processing of the protein and its iron was studied in rats. No alteration in early transferrin catabolism was observed. Radioiron disappearance from the plasma and liver iron uptake were more rapid for asialotransferrins than for normal transferrins ( P &lt;.001). Furthermore, radio‐iron plasma clearance of human tri‐sialotransferrin was faster ( P &lt; .05) and liver uptake higher ( P &lt; .002) than for human pentasialotransferrin. When the asialoglycoprotein receptor was blocked by the prior injection of asialofetuin, asialotransferrin behaved like normal transferrin. When the transferrin receptor was blocked by the prior injection of 50 mg human diferric transferrin, iron uptake from all transferrins was delayed to such an extent that uptake through both receptors seemed to be affected. Approximately 90% of the hepatic radioiron from all transferrins was chelated by desferrioxamine and excreted into the bile, indicating its uptake by the hepatocyte rather than the reticulo‐endothelial (RE) cell. The rate of iron release into the plasma and its subsequent accumulation in the red cell mass over a 2‐week period was similar for human asialotransferrin, ferritin, and hemoglobin iron. This study 1) confirmed that asialotransferrin‐iron uptake by the hepatocyte is mediated by both transferrin and asialoglycoprotein receptors; 2) demonstrated that not only asialotransferrin but also transferrin of low sialic acid content will increase iron turnover and lead to excessive iron loading of the hepatocyte; 3) and showed that the intrahepatocyte metabolism of asialotransferrin‐iron did not differ from that of iron delivered by normal transferrin.
Severe atherosclerotic changes, including aortic occlusion, associated with hyperhomocysteinaemia and antiphospholipid antibodies
Authors: P E Spronk
Journal: Annals of the Rheumatic Diseases (2001)

Three patients are described with severe systemic atherosclerosis, including aortic occlusion, in the presence of a spectrum of risk factors, including hypercholesterolaemia, hypertension, a positive family history of cardiovascular problems, and hyperhomocysteinaemia. In all three patients high levels of anticardiolipin antibodies were found. The possible pathogenic role of antiphospholipid antibodies in atherosclerosis in the context of hyperhomocysteinaemia in these patients is discussed.
Sleep-disordered breathing in children: are we underestimating the problem?
Authors: R. B. Mitchell
Journal: European Respiratory Journal (2005)

Sleep-disordered breathing (SDB) is a spectrum of disorders, ranging from primary snoring to severe obstructive sleep apnoea syndrome (OSAS). Several studies have suggested that primary snoring may affect 10–25% of children aged 3–12 yrs, and 10% of these children may have OSAS 1–3. SDB is known to be associated with behavioural problems, such as aggression, hyperactivity, attention-deficit disorder and poor socialisation 4. Gozal 5 showed that SDB was 6–9-fold more common in 1st grade children (aged 6 yrs) who were in the bottom tenth percentile for academic achievement. Furthermore, neurocognitive functions, such as memory, learning and problem solving, are reduced in children with SDB 6. Therefore, it is not surprising that the overall health status and quality of life for children with SDB is reduced significantly 4, 7. Indeed, the quality of life for children with adenotonsillar disease, a group of children with SDB and/or recurrent throat infections, was shown to be similar to children with asthma or juvenile rheumatoid arthritis and, in some respects, worse 8.

A high percentage of children with SDB who undergo adenotonsillectomy experience resolution of the disorder, as documented by post-operative polysomnography (PSG) 9. However, do behavioural and neurocognitive problems also resolve …
Low levels of apoptosis and high FLIP expression in early rheumatoid arthritis synovium
Authors: A I Catrina
Journal: Annals of the Rheumatic Diseases (2002)

To define synovial apoptosis with respect to disease duration, inflammatory cell type, FLIP (FLICE-like inhibitory protein), and cytokines expression in patients with rheumatoid arthritis (RA).Synovial biopsy specimens from 11 patients with longstanding RA (median disease duration 21 years) and eight with early RA (median disease duration five months) were investigated. Apoptosis (TUNEL method combined with morphological analysis), cell surface markers (CD3, CD68), cytokines (interleukin (IL) 1alpha, IL1beta, tumour necrosis factor alpha, and IL6), and FLIP expression were evaluated. Computer assisted image analysis was used for quantification.The apoptosis level in RA synovium was significantly higher in the group of patients with longstanding RA than in the patients with early RA (8.8% v 0.6%, p=0.001), while the number of macrophages and FLIP expression were higher in the group with early disease than in the group with longstanding RA (16.2% v 8.3%, p=0.02 and 31.1% v 0.2%, p=0.001 respectively). All three markers correlated significantly with disease duration (R=-0.7, p<0.001 for FLIP, R=0.6, p=0.001 for apoptosis, and R=-0.5, p<0.05 for CD68). Cytokine expression and T cell score were not significantly different in early RA from longstanding RA. No differences were seen between patients treated or not treated with corticosteroids or between patients treated or not treated with disease modifying antirheumatic drugs.The findings suggest that RA synovial macrophages are resistant to apoptosis in early RA and express high levels of FLIP. During natural or drug modified disease progression the apoptotic mechanism may be restored with a specific increase of synovial apoptosis in patients with longstanding arthritis.
Association Between Regional Adipose Tissue Distribution and Both Type 2 Diabetes and Impaired Glucose Tolerance in Elderly Men and Women
Authors: Bret H. Goodpaster, Shanthi Krishnaswami, Helaine Resnick, David E. Kelley, Catherine Haggerty, Tamara B. Harris, Ann V. Schwartz, Steven Kritchevsky, Anne B. Newman
Journal: Diabetes Care (2003)

OBJECTIVE—We examined whether regional adipose tissue distribution, specifically that of skeletal muscle fat and visceral abdominal fat aggregation, is characteristic of elderly individuals with hyperinsulinemia, type 2 diabetes, and impaired glucose tolerance (IGT). RESEARCH DESIGN AND METHODS—A total of 2,964 elderly men and women (mean age 73.6 years) were recruited for cross-sectional comparisons of diabetes or glucose tolerance, generalized obesity with dual-energy X-ray absorptiometry, and regional body fat distribution with computed tomography. RESULTS—Approximately one-third of men with type 2 diabetes and less than half of women with type 2 diabetes were obese (BMI ≥30 kg/m2). Despite similar amounts of subcutaneous thigh fat, intermuscular fat was higher in subjects with type 2 diabetes and IGT than in subjects with normal glucose tolerance (NGT) (11.2 ± 9.4, 10.3 ± 5.8, and 9.2 ± 5.9 cm2 for men; 12.1 ± 6.1, 10.9 ± 6.5, and 9.4 ± 5.3 cm2 for women; both P &amp;lt; 0.0001). Visceral abdominal fat was also higher in men and women with type 2 diabetes and IGT than in subjects with NGT (172 ± 79, 163 ± 72, and 145 ± 66 cm2 for men; 162 ± 66, 141 ± 60, and 116 ± 54 cm2 for women; both P &amp;lt; 0.0001 across groups). Higher rates of intermuscular fat and visceral abdominal fat were associated with higher fasting insulin in normal-weight (BMI &amp;lt;25 kg/m2) men (r = 0.24 for intermuscular fat, r = 0.37 for visceral abdominal fat, both P &amp;lt; 0.0001) and women (r = 0.20 for intermuscular fat, r = 0.40 for visceral abdominal fat, both P &amp;lt; 0.0001). These associations were not found in obese subjects. CONCLUSIONS—Elderly men and women with normal body weight may be at risk for metabolic abnormalities, including type 2 diabetes, if they possess an inordinate amount of muscle fat or visceral abdominal fat.
Rapid evolution of fertilization selectivity and lysin cDNA sequences in teguline gastropods
Authors: M. E. Hellberg, V. D. Vacquier
Journal: Molecular Biology and Evolution (1999)

Proteins mediating intercellular recognition face opposing selective forces as they evolve: purifying selection to maintain function, and diversifying selection to alter specificity. Lysin is a 16-kDa protein which enables sperm of free-spawning marine snails to make a hole in the vitelline layer (VE) surrounding conspecific eggs. Previous work on abalone (Haliotis spp.) has shown that positive selection promotes rapid interspecific divergence of lysin. Here, we present data on the specificity of VE dissolution by four species of teguline gastropods, along with lysin cDNA sequences. The teguline and abalone lineages diverged over 250 MYA. As in abalone, VE dissolution by lysin in tegulines is species-selective, and positive selection promotes rapid interspecific divergence over the entire mature protein. Nonsynonymous substitution rates, calculated using a mtCOI molecular clock calibrated by two Tegula species separated by the Isthmus of Panama, are high (> 25 substitutions per site per 10(9) years). However, the extensive replacements in teguline lysins are overwhelmingly conservative with respect to type, charge, and polarity of residues. Predictions of secondary structure suggest that the size and position of alpha-helices are also conserved, even through pairwise amino acid identities between Haliotis rufescens and the different tegulines are less than 15%.
MAST CELLS AS “TUNABLE” EFFECTOR AND IMMUNOREGULATORY CELLS: Recent Advances
Authors: Stephen J. Galli, Janet Kalesnikoff, Michele A. Grimbaldeston, Adrian M. Piliponsky, Cara M.M. Williams, Mindy Tsai
Journal: Annual Review of Immunology (2005)

▪ Abstract This review focuses on recent progress in our understanding of how mast cells can contribute to the initiation, development, expression, and regulation of acquired immune responses, both those associated with IgE and those that are apparently expressed independently of this class of Ig. We emphasize findings derived from in vivo studies in mice, particularly those employing genetic approaches to influence mast cell numbers and/or to alter or delete components of pathways that can regulate mast cell development, signaling, or function. We advance the hypothesis that mast cells not only can function as proinflammatory effector cells and drivers of tissue remodeling in established acquired immune responses, but also may contribute to the initiation and regulation of such responses. That is, we propose that mast cells can also function as immunoregulatory cells. Finally, we show that the notion that mast cells have primarily two functional configurations, off (or resting) or on (or activated for extensive mediator release), markedly oversimplifies reality. Instead, we propose that mast cells are “tunable,” by both genetic and environmental factors, such that, depending on the circumstances, the cell can be positioned phenotypically to express a wide spectrum of variation in the types, kinetics, and/or magnitude of its secretory functions.
<i>BRCA</i> Mutation Frequency and Patterns of Treatment Response in <i>BRCA</i> Mutation–Positive Women With Ovarian Cancer: A Report From the Australian Ovarian Cancer Study Group
Authors: Kathryn Alsop, Sian Fereday, Cliff Meldrum, Anna deFazio, Catherine Emmanuel, Joshy George, Alexander Dobrovic, Michael J. Birrer, Penelope M. Webb, Colin Stewart, Michael Friedlander, Stephen Fox, David Bowtell, Gillian Mitchell
Journal: Journal of Clinical Oncology (2012)

The frequency of BRCA1 and BRCA2 germ-line mutations in women with ovarian cancer is unclear; reports vary from 3% to 27%. The impact of germ-line mutation on response requires further investigation to understand its impact on treatment planning and clinical trial design.Women with nonmucinous ovarian carcinoma (n = 1,001) enrolled onto a population-based, case-control study were screened for point mutations and large deletions in both genes. Survival outcomes and responses to multiple lines of chemotherapy were assessed.Germ-line mutations were found in 14.1% of patients overall, including 16.6% of serous cancer patients (high-gradeserous, 17.1%); [corrected] 44% had no reported family history of breast orovarian cancer.Patients carrying germ-line mutations had improved rates of progression-free and overall survival. In the relapse setting, patients carrying mutations more frequently responded to both platin- and nonplatin-based regimens than mutation-negative patients, even in patients with early relapse after primary treatment. Mutation-negative patients who responded to multiple cycles of platin-based treatment were more likely to carry somatic BRCA1/2 mutations.BRCA mutation status has a major influence on survival in ovarian cancer patients and should be an additional stratification factor in clinical trials. Treatment outcomes in BRCA1/2 carriers challenge conventional definitions of platin resistance, and mutation status may be able to contribute to decision making and systemic therapy selection in the relapse setting. Our data, together with the advent of poly(ADP-ribose) polymerase inhibitor trials, supports the recommendation that germ-line BRCA1/2 testing should be offered to all women diagnosed with nonmucinous, ovarian carcinoma, regardless of family history.
RESPONSE: Re: Multiple Births and Risk of Epithelial Ovarian Cancer
Authors: D. C. Whiteman, M. F. G. Murphy, L. S. Cook, D. W. Cramer, P. Hartge, P. A. Marchbanks, P. C. Nasca, R. B. Ness, D. M. Purdie, H. A. Risch
Journal: JNCI Journal of the National Cancer Institute (2001)
Problem Management Plus (PM+): a WHO transdiagnostic psychological intervention for common mental health problems
Authors: Katie S. Dawson, Richard A. Bryant, Melissa Harper, Alvin Kuowei Tay, Atif Rahman, Alison Schafer, Mark van Ommeren
Journal: World Psychiatry (2015)

Mental disorders are significant contributors to the global burden of disease (1). While they occur across all levels of socio-economic status, the majority of populations in low- and middle-income countries (LMICs) do not have access to effective psychological and pharmacological interventions (2). Key barriers to sustainable delivery of psychological therapies in LMICs include limited mental health funding and infrastructure, chronic shortage of mental health professionals, lack of treatments adapted to the local context, and challenges associated with training and supervision. Implementation of low-intensity psychological interventions by trained para-professionals is one potential solution to this problem (3,4) which is receiving significant attention as part of global mental health research agendas (e.g.,(5)).

A number of low-intensity interventions have demonstrated clinical benefit and utility in high-income settings. For example, early analyses of the UK’s Improving Access to Psychological Therapies programme (IAPT,(6)) found a substantial reduction in depression and anxiety in people who attended at least two sessions of low-intensity interventions. Additionally, a recent meta-analysis challenged conventional thinking and provided support for low-intensity interventions as an effective treatment even for individuals with symptoms of severe depression (7).

Evidence for the applicability of psychological interventions by non-specialists in LMICs is mounting (8,9). For instance, group interpersonal psychotherapy facilitated by local para-professionals has been shown to be effective in rural Uganda among depressed adults compared to usual care at six month follow-up (10). In rural Pakistan, Rahman et al (11) found that local community health workers could effectively deliver a locally adapted cognitive-behavioural intervention for perinatal depression. Mothers receiving the treatment demonstrated significant clinical improvement on depression symptoms, showed less disability and better overall and social functioning. Finally, a comparatively more intensive transdiagnostic intervention, the Common Elements Treatment Approach (CETA), has shown promising results for the treatment of symptoms of depression, anxiety and post-traumatic stress in Burmese refugees when delivered by para-professionals (12).

To fill the gap between mental health needs and access to quality care, and extend the current research on low-intensity interventions in LMICs, the World Health Organization (WHO) – as part of its Mental Health Gap Action Programme (mhGAP) – has begun to develop and test low-intensity psychological interventions. The current paper focuses on one such intervention, named Problem Management Plus (PM+).
Late-breaking abstract: Baseline factors and survival difference between normocapnia, compensated respiratory acidosis and decompensated respiratory acidosis in COPD exacerbation
Authors: Chung-tat Lun, Miranda Sn Tsui, Suet-lai Cheng, Pik-shan Cheung, Veronica L Chan, Wah-shing Leung, Chung-ming Chu
Journal: European Respiratory Journal (2014)

Background 

Patients experiencing acute exacerbation of chronic obstructive pulmonary disease (AE-COPD) with decompensated respiratory acidosis are known to have poor outcomes in terms of recurrent respiratory failure and death. The outcomes of AE-COPD patients with compensated respiratory acidosis are not known.

Methods and Objective 

We performed a prospective, single-centre, cohort study in patients with AE-COPD for one year, to compare baseline factors between groups with normocapnia, compensated respiratory acidosis and decompensated respiratory acidosis. Survival analysis was done to examine time to readmissions, life-threatening events and death.

Results 

Compared with normocapnia, both compensated and decompensated respiratory acidosis are associated with lower FEV1 % , higher GOLD stage and higher BODE index and they have shorter time to life-threatening events (fig1). Comparing compensated and decompensated respiratory acidosis, there was no difference in FEV1 (% predicted), GOLD stage, BODE index, and time to life-threatening events.

PaCO2 and previous use of non-invasive ventilation (NIV) in acute setting are predictive factors of future life-threatening events by multivariate analysis.

Conclusions 

Comparing with normocapnia, both compensated and decompensated respiratory are associated with poorer lung function and at high risk of future life-threatening events. PaCO2 and past history of NIV use in acute settings were predictive factors for future life-threatening events. Compensated respiratory acidosis warrants special attention and optimisation of medical therapy as it poses risk of life-threatening events.
Demonstration of GAD-65 as the main immunogenic isoform of glutamate decarboxylase in type 1 diabetes and determination of autoantibodies using a radioligand produced by eukaryotic expression.
Authors: L A Velloso, O Kämpe, A Hallberg, L Christmanson, C Betsholtz, F A Karlsson
Journal: Journal of Clinical Investigation (1993)

Plasmids containing cDNA for the rat 67- and 65-kD isoforms of glutamate decarboxylase (GAD-67 and GAD-65) were expressed in COS-cells, and lysates of [35S]methionine-labeled cells were used for immunoprecipitations. Sera from 38 patients with type 1 (insulin-dependent) diabetes mellitus, which precipitated a 64-kD antigen from rat islets, reacted with recombinant GAD-65 in relation to their anti-64-kD titers. The eight strongest sera also precipitated recombinant GAD-67, suggesting that certain epitopes are common to both isoforms. Subsequently, [35S]methionine-labeled GAD-65 was purified from COS cell lysates and employed in a binding assay with 50 sera of patients with recent onset of type 1 diabetes mellitus. 38 sera (76%) precipitated labeled GAD-65 with titers that correlated with islet cell antibodies (ICA), determined in a standard immunofluorescence assay. 2 sera were GAD positive but ICA negative, 4 were positive only for ICA, and 6 were negative for both GAD and ICA, as were the sera of 20 controls. The data illustrate that antibodies against GAD-65 are present in a majority of patients with type 1 diabetes mellitus and that autoantibodies against other islet cell antigens also exist. The radioligand-binding assay, which is convenient and sensitive for detecting GAD antibodies, will facilitate the screening of individuals with autoimmune islet cell disease.
Republished research: Facilitated physical activity as a treatment for depressed adults: randomised controlled trial:
Authors: Melanie Chalder, Nicola J Wiles, John Campbell, Sandra P Hollinghurst, Anne M Haase, Adrian H Taylor, Kenneth R Fox, Ceire Costelloe, Aidan Searle, Helen Baxter, Rachel Winder, Christine Wright, Katrina M Turner, Michael Calnan, Deborah A Lawlor, Tim J Peters, Deborah J Sharp, Alan A Montgomery, Glyn Lewis
Journal: British Journal of Sports Medicine (2013)

Study question Does facilitated physical activity provide an effective treatment for adults with depression presenting in primary care? Summary answer Although trial participants receiving the physical activity intervention in addition to usual care reported increased physical activity compared with those receiving usual care alone, there was no evidence to suggest that the intervention brought about any improvement in depressive symptoms or reduction in antidepressant use. What is known and what this paper adds Numerous studies have reported the positive effects of physical activity, but most of the current evidence originates from small non-clinical samples using interventions that are not practicable in a healthcare setting. Our results indicate that offering patients a facilitated physical activity intervention is not an effective strategy for reducing symptoms of depression, although it increased self reported physical activity and sustained this effect over 12 months.