tbuckley/cabot-search huggingface dataset:
Glucosamine and Chondroitin for Treatment of Osteoarthritis
Authors: Timothy E. McAlindon, Michael P. LaValley, Juan P. Gulin, David T. Felson
Journal: JAMA (2000)

ContextGlucosamine and chondroitin preparations are widely touted in the lay press as remedies for osteoarthritis (OA), but uncertainty about their efficacy exists among the medical community.ObjectiveTo evaluate benefit of glucosamine and chondroitin preparations for OA symptoms using meta-analysis combined with systematic quality assessment of clinical trials of these preparations in knee and/or hip OA.Data SourcesWe searched for human clinical trials in MEDLINE (1966 to June 1999) and the Cochrane Controlled Trials Register using the terms osteoarthritis, osteoarthrosis, degenerative arthritis, glucosamine, chondroitin, and glycosaminoglycans. We also manually searched review articles, manuscripts, and supplements from rheumatology and OA journals and sought unpublished data by contacting content experts, study authors, and manufacturers of glucosamine or chondroitin.Study SelectionStudies were included if they were published or unpublished double-blind, randomized, placebo-controlled trials of 4 or more weeks' duration that tested glucosamine or chondroitin for knee or hip OA and reported extractable data on the effect of treatment on symptoms. Fifteen of 37 studies were included in the analysis.Data ExtractionReviewers performed data extraction and scored each trial using a quality assessment instrument. We computed an effect size from the intergroup difference in mean outcome values at trial end, divided by the SD of the outcome value in the placebo group (0.2, small effect; 0.5, moderate; 0.8, large), and applied a correction factor to reduce bias. We tested for trial heterogeneity and publication bias and stratified for trial quality and size. We pooled effect sizes using a random effects model.Data SynthesisQuality scores ranged from 12.3% to 55.4% of the maximum, with a mean (SD) of 35.5% (12%). Only 1 study described adequate allocation concealment and 2 reported an intent-to-treat analysis. Most were supported or performed by a manufacturer. Funnel plots showed significant asymmetry (P≤.01) compatible with publication bias. Tests for heterogeneity were nonsignificant after removing 1 outlier trial. The aggregated effect sizes were 0.44 (95% confidence interval [CI], 0.24-0.64) for glucosamine and 0.78 (95% CI, 0.60-0.95) for chondroitin, but they were diminished when only high-quality or large trials were considered. The effect sizes were relatively consistent for pain and functional outcomes.ConclusionsTrials of glucosamine and chondroitin preparations for OA symptoms demonstrate moderate to large effects, but quality issues and likely publication bias suggest that these effects are exaggerated. Nevertheless, some degree of efficacy appears probable for these preparations.
Methotrexate and early postoperative complications in patients with rheumatoid arthritis undergoing elective orthopaedic surgery
Authors: D M Grennan
Journal: Annals of the Rheumatic Diseases (2001)

To determine whether continued methotrexate treatment increases the risk of postoperative infections or of surgical complications in patients with rheumatoid arthritis (RA) within one year of elective orthopaedic surgery.A prospective randomised study of postoperative infection or surgical complications occurring within one year of surgery in patients with RA who underwent elective orthopaedic surgery.388 patients with RA who were to undergo elective orthopaedic surgery. Patients who were receiving methotrexate were randomly allocated to groups who either continued methotrexate (group A) or who discontinued methotrexate from two weeks before surgery until two weeks after surgery (group B). Their complication rates were compared with complications occurring in 228 patients with RA (group C) who were not receiving methotrexate and who also underwent elective orthopaedic surgery.Signs of postoperative infection were recorded, including rubor, discharge, systemic infection, and frequency of wound dehiscence as well as the incidence of any surgical complication requiring a secondary revision procedure that occurred within one year of surgery. The frequencies of flare up activity of RA at six weeks and six months after surgery were also recorded. A flare of rheumatoid disease was defined as an increase in joint pain in two or more joints notified by the patient as well as by an increase in articular index of at least 25% after surgery.Signs of infection or surgical complications occurred in two of 88 procedures in group A (2%), 11 of 72 procedures in group B (15%), and 24 of 228 (10.5%) procedures in group C. The surgical complication or infection frequency in group A was less than that in either group B (p<0.003) or group C (p=0.026). At six weeks after surgery there were no flares in group A, six flares in group B (8%), and six flares in group C (2.6%). Logistic regression analysis of the overall surgical complication rate in all the patients with RA studied showed that methotrexate, whether continued or discontinued before surgery, did not increase the early complication rate in the patients with RA who underwent elective orthopaedic surgery. Other drugs-penicillamine, indometacin, cyclosporin, hydroxychloroquine, chloroquine, and prednisolone-all did significantly increase the risk of infection or surgical complication after elective orthopaedic surgery. The risk of surgery was also increased in the presence of intercurrent chronic diseases-diabetes, hypertension, bronchiectasis, psoriasis, asthma, and ischaemic heart disease.Continuation of methotrexate treatment does not increase the risk of either infections or of surgical complications occurring in patients with RA within one year of elective orthopaedic surgery. Thus methotrexate treatment should not be stopped in patients whose disease is controlled by the drug before elective orthopaedic surgery.
Effect of ultraclean air in operating rooms on deep sepsis in the joint after total hip or knee replacement: a randomised study.
Authors: O M Lidwell, E J Lowbury, W Whyte, R Blowers, S J Stanley, D Lowe
Journal: BMJ (1982)

In a multicentre study of sepsis after total hip or knee replacement the operations performed by each surgeon were allocated at random between control and ultraclean-air operating rooms. Records were obtained from over 8000 such operations. In the patients whose prostheses were inserted in an operating room ventilated by an ultraclean-air system the incidence of joint sepsis confirmed at reoperation within the next one to four years was about half that of patients who had had the operation in a conventionally ventilated room at the same hospital. When whole-body exhaust-ventilated suits had been worn by the operating team in a theatre ventilated by an ultraclean-air system the incidence of sepsis was about a quarter of that found after operations performed with conventional ventilation. When all groups in the trial were considered together the analysis showed deep sepsis after 63 out of 4133 operations in the control group (1.5%) and after 23 out of 3922 operations in the ultraclean-air groups (0.6%) (ratio 2.6, 95% confidence limits 1.6-4.2; p less than 0.001). The design of the study did not include a strictly controlled test of the effect of prophylactic antibiotics, but their use was associated with a lower incidence of sepsis than in patients who had received no antibiotic prophylaxis at their operations (0.6% (34/5831) v 2.3% (52/2221); ratio 4.0).
Elevated red cell distribution width is associated with advanced fibrosis in NAFLD
Authors: Hwa Mok Kim, Bum Soo Kim, Yong Kyun Cho, Byung Ik Kim, Chong Il Sohn, Woo Kyu Jeon, Hong Joo Kim, Dong Il Park, Jung Ho Park, Kwan Joong Joo, Chang Joon Kim, Yong Sung Kim, Woon Je Heo, Won Seok Choi
Journal: Clinical and Molecular Hepatology (2013)

See the commentary-article "Chasing after novel non-invasive markers to identify advanced fibrosis in NAFLD" on page 255.
Can the state of cancer chemotherapy resistance be reverted by epigenetic therapy?
Authors: Carlos Perez-Plasencia, Alfonso Duenas-Gonzalez
Journal: Molecular Cancer (2006)

Transcriptome analysis shows that the chemotherapy innate resistance state of tumors is characterized by: poorly dividing tumor cells; an increased DNA repair; an increased drug efflux potential by ABC-transporters; and a dysfunctional ECM. Because chemotherapy resistance involves multiple genes, epigenetic-mediated changes could be the main force responsible of this phenotype. Our hypothesis deals with the potential role of epigenetic therapy for affecting the chemotherapy resistant phenotype of malignant tumors. Recent studies reveal the involvement of DNA methylation and histone modifications in the reprogramming of the genome of mammalian cells in cancer. In this sense, it can be hypothesized that epigenetic reprogramming can participate in the establishment of an epigenetic mark associated with the chemotherapy resistant phenotype. If this were correct, then it could be expected that agents targeting DNA methylation and histone deacetylation would by reverting the epigenetic mark induce a global expression profile that mirror the observed in untreated resistant cells. It is proposed to perform a detailed analysis using all the available databases where the gene expression of primary tumors was analyzed and data correlated with the therapeutic outcome to determine whether a transcriptome profiling of "resistance" is observed. Assuming an epigenetic programming determines at some level the intrinsic resistant phenotype, then a similar pattern of gene expression dictated by an epigenetic mark should also be found in cell acquiring drug resistance. If these expectations are meet, then it should be further investigated at the genomic level whether these phenotypes are associated to certain patterns of DNA methylation and chromatin modification. Once confirmed the existence of an epigenetic mark associated to either the intrinsic or acquired chemotherapy resistant phenotype, then a causal association should be investigated. These preclinical findings should also be tested in a clinical setting. Our hypothesis on the ability of epigenetic therapy to revert the epigenetic changes leading to a transcritome profile that defines the resistant state will eventually be a more rational and effective way to treat malignant tumors.
Exploring systemic RNA interference in insects: a genome-wide survey for RNAi genes in Tribolium
Authors: Yoshinori Tomoyasu, Sherry C Miller, Shuichiro Tomita, Michael Schoppmeier, Daniela Grossmann, Gregor Bucher
Journal: Genome biology (2008)

Abstract Background RNA interference (RNAi) is a highly conserved cellular mechanism. In some organisms, such as Caenorhabditis elegans , the RNAi response can be transmitted systemically. Some insects also exhibit a systemic RNAi response. However, Drosophila , the leading insect model organism, does not show a robust systemic RNAi response, necessitating another model system to study the molecular mechanism of systemic RNAi in insects. Results We used Tribolium , which exhibits robust systemic RNAi, as an alternative model system. We have identified the core RNAi genes, as well as genes potentially involved in systemic RNAi, from the Tribolium genome. Both phylogenetic and functional analyses suggest that Tribolium has a somewhat larger inventory of core component genes than Drosophila , perhaps allowing a more sensitive response to double-stranded RNA (dsRNA). We also identified three Tribolium homologs of C. elegans sid-1 , which encodes a possible dsRNA channel. However, detailed sequence analysis has revealed that these Tribolium homologs share more identity with another C. elegans gene, tag-130 . We analyzed tag-130 mutants, and found that this gene does not have a function in systemic RNAi in C. elegans . Likewise, the Tribolium sid- like genes do not seem to be required for systemic RNAi. These results suggest that insect sid-1 -like genes have a different function than dsRNA uptake. Moreover, Tribolium lacks homologs of several genes important for RNAi in C. elegans . Conclusion Although both Tribolium and C. elegans show a robust systemic RNAi response, our genome-wide survey reveals significant differences between the RNAi mechanisms of these organisms. Thus, insects may use an alternative mechanism for the systemic RNAi response. Understanding this process would assist with rendering other insects amenable to systemic RNAi, and may influence pest control approaches.
Role of Venous Return in the Cardiovascular Response Following Injection of Ganglion-Blocking Agents
Authors: JOSEPH H. TRAPOLD, Joan G. Sullivan, James L. Hawkins
Journal: Circulation Research (1957)

The reduction of arterial pressure in anesthetized dogs following the injection of ganglion-blocking agents is dependent primarily upon a reduction in arterial vasomotor activity and secondarily upon a reduction in venous return associated with an increase in vascular capacity. When venous return is maintained at control levels, the administration of the blocking agents of this study invariably produce a decrease in total peripheral resistance (TPR). Ordinarily in the intact animal such a decrease in TPR is not observed due to a marked reduction in cardiac output which produces a secondary increase in TPR. The results of this study further suggests that the venous and arterial systems may differ in their sensitivity to the effects of ganglion-blocking agents.
The role of the liver in the metabolism of vitamin D
Authors: G. Ponchon, H. F. Deluca
Journal: Journal of Clinical Investigation (1969)

The metabolism of vitamin D3 has been studied after intravenous injection of 10 IU of [1,2-3H]-vitamin D3 to vitamin D-deficient rats. The disappearance of the radioactivity from the plasma follows a very peculiar pattern characterized by an early rapid disappearance followed by a rebound of radioactivity before assuming still a third rather slow disappearance rate. The "rebound" phenomenon is concomitant with a rapid release of the radioactivity from the liver and is accounted for by the appearance of 25-hydroxycholecalciferol and other metabolites in the blood. It is postulated that the liver is the major site of transformation of vitamin D3 into 25-hydroxycholecalciferol.
Stillbirths: the way forward in high-income countries
Authors: Vicki Flenady, Philippa Middleton, Gordon C Smith, Wes Duke, Jan Jaap Erwich, T Yee Khong, Jim Neilson, Majid Ezzati, Laura Koopmans, David Ellwood, Ruth Fretts, J Frederik Frøen
Journal: The Lancet (2011)
ATM down-regulation is associated with poor prognosis in sporadic breast carcinomas
Authors: R.C. Bueno, R.A. Canevari, R.A.R. Villacis, M.A.C. Domingues, J.R.F. Caldeira, R.M. Rocha, S.A. Drigo, S.R. Rogatto
Journal: Annals of Oncology (2013)
Autonomic Modulation of Heart Rate during Obstructive versus Central Apneas in Patients with Sleep-disordered Breathing
Authors: Lucia Spicuzza, Luciano Bernardi, Alessandro Calciati, Giuseppe Ugo Di Maria
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

Sleep-disordered breathing is associated with an altered sympathovagal balance determined by the nocturnal cyclic alternating of apneas and hyperventilation. The aim of this study was to determine whether the autonomic modulation of heart rate during obstructive apneas (OA) and central apneas (CA) in patients with sleep-disordered breathing is different. Therefore, by using the time-varying Wigner-Ville transform spectral analysis we described, in 17 patients, the time course of the low-frequency (LF) and the high-frequency (HF) components of the interbeat interval (R-R interval) reflecting, at large, respectively, the sympathetic and the parasympathetic modulation, during OA (n = 185) and CA (n = 51) and during the postapneic hyperventilation. In both types of apneas we found cyclic lengthening/shortening in R-R interval, during apneas/postapneic hyperventilation, respectively, with more marked bradycardia during OA (R-R: 1,011 ± 23 versus 893 ± 30 ms2, p < 0.01). In OA the HF oscillations decreased from the apnea to the postapneic hyperventilation (from 1,964 ± 244 to 387 ± 98 ms2, p < 0.0001), whereas the LF oscillations increased (from 2,649 ± 230 to 9,820 ± 716 ms2, p < 0.0001). Conversely, in CA the HF oscillations increased from the apnea to the postapneic hyperventilation (from 452 ± 177 to 1,485 ± 406 ms2, p < 0.0001), whereas the LF component remained unchanged. These results show markedly different autonomic alterations during and after OA versus CA, suggesting a surge in sympathetic modulation after the obstructive episodes.
Respective role of humoral factors and blood pressure in cardiac remodeling of DOCA hypertensive rats
Authors: H. Karam, D. Heudes, P. Hess, M.-F. Gonzales, B.-M. Loffler, M. Clozel, J.-P. Clozel
Journal: Cardiovascular Research (1996)

Recent studies have shown that beside elevated arterial blood pressure, humoral factors such as angiotensin II, aldosterone, endothelin or bradykinin might play a role in the cardiac hypertrophy and fibrosis secondary to hypertension. In addition, it seems that perivascular fibrosis and interstitial fibrosis are controlled by independent mechanisms. Therefore, the goal of our study was to evaluate the respective role of the increased arterial pressure and of humoral factors on cardiac remodeling in an experimental hypertension model.Uninephrectomized rats received DOCA, a high salt diet, and when hypertension was installed, they were treated for 6 weeks with either a long-acting calcium antagonist, mibefradil (30 mg/kg day-1), an ACE inhibitor, enalapril (3 mg/kg day-1), or a mixed ETA-ETB endothelin receptor antagonist, bosentan (100 mg/kg day-1). A group of hypertensive rats was left untreated and a sham-operated group of normotensive rats was used for control. At the end of treatment, maximal coronary blood flow was measured in isolated perfused hearts. Cardiac hypertrophy and interstitial as well as perivascular fibrosis were evaluated by quantitative morphometry.DOCA-salt hypertensive rats exhibited a marked cardiac hypertrophy associated with a decrease of maximal coronary blood flow and interstitial and perivascular fibrosis. The calcium antagonist nearly normalized arterial pressure and suppressed all these changes. Enalapril had no effect on arterial pressure and perivascular fibrosis but decreased subendocardial fibrosis. Bosentan had a very small effect on arterial pressure but decreased cardiac hypertrophy and both perivascular and subendocardial fibrosis.We conclude that in DOCA salt hypertension, humoral factors such as endothelin may play a role beside high blood pressure in cardiac remodeling. In addition, the different components of this remodeling (decrease of vascular reserve, cardiac hypertrophy and cardiac fibrosis) are controlled independently.
Reflections on the Relationship Between Psychiatric Genetics and Psychiatric Nosology
Authors: Kenneth S. Kendler
Journal: American Journal of Psychiatry (2006)

Research advances in psychiatric genetics have raised expectations that genetic findings might lead to major breakthroughs in psychiatric nosology. The author reviews the plausibility of these claims. Four areas are addressed. First, it is argued that familial aggregation of a single putative psychiatric syndrome provides at best limited evidence for the validity of that syndrome. Second, both traditional and molecular genetic strategies can supply important insights into major diagnostic conundrums. However, evidence that one or a few individual genes impact on risk for two disorders is not likely to resolve definitively the nosologic relationship between the two syndromes. Third, while gene-based essentialist models for psychiatric disorders are conceptually appealing, they are not well supported empirically. Gene discovery in psychiatry is, on its own, unlikely to allow us to "carve nature at its joints," thereby validating categorical psychiatric diagnoses. Fourth, the project to ground "messy" psychiatric categories on the firm foundation of genes—as an archetypal natural kind—may be fundamentally flawed because the very concept of "the gene" as a discrete entity is itself increasingly in doubt. Whereas psychiatric genetics has and will continue to provide important insights into the etiology of psychiatric and substance use disorders, it is not likely alone to provide deep answers to the complex and multifaceted problems facing psychiatric nosology.
Randomised controlled trial of patient centred care of diabetes in general practice: impact on current wellbeing and future disease risk
Authors: A. L. Kinmonth, A. Woodcock, S. Griffin, N. Spiegal, M. J Campbell
Journal: BMJ (1998)

<h3>abstract</h3> <b>Objective</b> To assess the effect of additional training of practice nurses and general practitioners in patient centred care on the lifestyle and psychological and physiological status of patients with newly diagnosed type 2 diabetes. <b>Design</b> Pragmatic parallel group design, with randomisation between practice teams to routine care (comparison group) or routine care plus additional training (intervention group); analysis at one year, allowing for practice effects and stratifiers; self reporting by patients on communication with practitioners, satisfaction with treatment, style of care, and lifestyle. <b>Setting</b> 41 practices (21 in intervention group, 20 in comparison group) in a health region in southern England. <b>Subjects</b> 250/360 patients (aged 30-70 years) diagnosed with type 2 diabetes and completing follow up at one year (142 in intervention group, 108 in comparison group). <b>Intervention</b> 1.5 days9 group training for the doctors and nurses—introducing evidence for and skills of patient centred care and a patient held booklet encouraging questions. <b>Main outcome measures</b> Quality of life, wellbeing, haemoglobin A<sub>1c</sub> and lipid concentrations, blood pressure, body mass index (kg/m<sup>2</sup>). <b>Results</b> Compared with patients in the C group, those in the intervention group reported better communication with the doctors (odds ratio 2.8; 95% confidence interval 1.8 to 4.3) and greater treatment satisfaction (1.6;1.1 to 2.5) and wellbeing (difference in means (d) 2.8; 0.4 to 5.2). However, their body mass index was significantly higher (d=2.0; 0.3 to 3.8), as were triglyceride concentrations (d=0.4 mmol/l; 0.07 to 0.73 mmol/l), whereas knowledge scores were lower −2.74;−0.23 to −5.25. Differences in lifestyle and glycaemic control were not significant. <b>Conclusions</b> The findings suggest greater attention to the consultation process than to preventive care among trained practitioners; those committed to achieving the benefits of patient centred consulting should not lose the focus on disease management.
Age-Dependent Rise and Fall of Immunological Reactivity in the CBA Mouse&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Hans Wigzell, Jan Stjernswärd
Journal: JNCI Journal of the National Cancer Institute (1966)

The age-dependent rise and fall of immunological reactivity were studied in the CBA mouse. The 19S antibody synthesis was considered both at the single cell level and as serum antibody titers (7S antibody production only as serum titers). Immediately after birth a rapid exponential increase of immunological reactivity lasted for approximately 1 month, followed by a slower rise. The peak of reactivity for both 19S and 7S antibody synthesis was reached when the mice were around 7 months of age, after which it began to decline slowly during the age periods tested (36 months). No evidence was found that the single antibody-producing cell in a senile mouse differed from that of a younger animal. The data strongly suggest that the decline of immunological reactivity was due to a decrease with age in the relative and absolute numbers of potential antibody-producing cells. The relative role of the spleen as antibody producer was the same, irrespective of age. The data are discussed with regard to earlier findings, and the possible implications for the increased frequency of tumors in old ages are considered.