tbuckley/cabot-search huggingface dataset:
Deforming arthropathy or lupus and rhupus hands in systemic lupus erythematosus
Authors: R M van Vugt, R H W M Derksen, L Kater, J W J Bijlsma
Journal: Annals of the Rheumatic Diseases (1998)

<h3>OBJECTIVE</h3> Although deforming arthropathy in systemic lupus erythematosus (SLE) is characterised by a number of manifestations, definitive criteria for the different forms have not yet been established. To define deforming arthropathy and its different types a study was undertaken of 176 SLE patients. <h3>METHODS</h3> Using as criterion any deviation from any of the metacarpus finger axes 17 patients (16 women, one man) were identified with clinical deforming arthropathy. These patients were evaluated according to a standardised protocol that covered all known characteristics of deforming arthropathy. By means of "Jaccoud's arthropathy index" three different forms were identified. <h3>RESULTS</h3> Three patients had an erosive form of deforming arthropathy (or rhupus hand) such as those seen in frank rheumatoid arthritis (RA), eight patients were identified as having Jaccoud's arthropathy (or lupus hand), and the remaining six patients had mild deforming arthropathy. Jaccoud's arthropathy is characterised by severe deformation of the hands (ulnar deviation, swan neck deformities, and Z deformity of the thumb) and feet with multiple non-erosive subluxations, mild aching and little or no evidence of synovitis. All patients, but one, fulfilled just four criteria of the ACR classification and joint symptoms were always found to precede the diagnosis of SLE. Furthermore a remarkable association of Jaccoud's arthropathy with fetal loss, thrombosis—both venous and arterial—and the presence of antiphospholipid antibodies was found. <h3>CONCLUSIONS</h3> These data suggest that Jaccoud's arthropathy represents a subset of SLE. Subdivision of deforming arthropathy into several clinical forms can facilitate the clinical management of this disorder.
Pediatricians Participating in Medicaid
Authors: E. Stephen Edwards
Journal: JAMA (1992)

To the Editor.  —The North Carolina Pediatric Society has worked for years to improve access to health care for children. We encouraged pediatricians to participate in the survey reported in Factors Associated With Pediatricians' Participation in Medicaid in North Carolina. 1 Some of the study results, however, seem inconsistent with our experience of the access problem for Medicaid children. For years we have felt that a majority of the primary care physicians restricted open access to children covered by Medicaid. Therefore, we were puzzled when the results of this survey indicated only 29% of pediatricians restricted access. If that were true, then there should be enough providers available for this population. Since we are convinced that more providers are needed, we have made efforts to determine the significant factors necessary to attract them. Our impression is that reimbursement rates are a major factor. This current study indicated that improving reimbursement
Research governance: where did it come from, what does it mean?
Authors: S. Shaw
Journal: Journal of the Royal Society of Medicine (2005)

For a variety of historical and social reasons, research has become increasingly formalized and regulated. This change has potential benefits (reduction in fraud and misconduct, protection of vulnerable groups, financial probity) but also disadvantages (increased paperwork, time delays, constraints on research freedom). The terms ‘research’ and ‘governance’ mean different things in different contexts. Even with explicit guidance, ambiguities must be resolved by human judgement. Variation in the nature and outcome of approval decisions is therefore a fact of life. The type of approval needed for a research study depends on the official remit of the approval body, the question to be addressed; the methods to be used; the context in which the work will take place; the level of analysis and interpretation; and the plans for how the findings will be presented and used.
Exact moment of tendon of pectoralis major muscle rupture captured on video: Figure 1
Authors: Alberto Castro Pochini, Benno Ejnisman, Carlos Vicente Andreoli, Gustavo Cara Monteiro, Anna Maria Fleury, Flavio Faloppa, Moises Cohen, Walter Manna Albertoni
Journal: British Journal of Sports Medicine (2007)

A powerlifting athlete ruptured his left tendon of the pectoralis major muscle while attempting to lift 160 kg in a Brazilian bench press championship. The injury seemed to occur in the concentric phase of exercise; however, the more common mechanism of rupture is during the eccentric phase. The tendon was reinserted to the humerus 3 weeks later with screws and washers. The athlete returned to competitive activities after 5 months. One year later he lifted 170 kg and won the national championship.
Diminished brain glucose metabolism is a significant determinant for falling rates of systemic glucose utilization during sleep in normal humans.
Authors: P J Boyle, J C Scott, A J Krentz, R J Nagy, E Comstock, C Hoffman
Journal: Journal of Clinical Investigation (1994)

Systemic glucose utilization declines during sleep in man. We tested the hypothesis that this decline in utilization is largely accounted for by reduced brain glucose metabolism. 10 normal subjects underwent internal jugular and radial artery cannulation to determine cerebral blood flow by N2O equilibrium technique and to quantitate cross-brain glucose and oxygen differences before and every 3 h during sleep. Sleep stage was graded by continuous electroencephalogram, and systemic glucose turnover was estimated by isotope dilution. Brain glucose metabolism fell from 33.6 +/- 2.2 mumol/100 g per min (mean +/- SE) before sleep (2300 h) to a mean nadir of 24.3 +/- 1.1 mumol/100 g per min at 0300 h during sleep (P = 0.001). Corresponding rates of systemic glucose utilization fell from 13.2 +/- 0.8 to 11.0 +/- 0.5 mumol/kg per min (P = 0.003). Diminished brain glucose metabolism was the product of a reduced arteriovenous glucose difference, 0.643 +/- 0.024 to 0.546 +/- 0.020 mmol/liter (P = 0.002), and cerebral blood flow, 50.3 +/- 2.8 to 44.6 +/- 1.4 cc/100 g per min (P = 0.021). Brain oxygen metabolism fell commensurately from 153.4 +/- 11.8 to 128.0 +/- 8.4 mumol/100 g per min (P = 0.045). The observed reduction in brain metabolism occurred independent of stage of central nervous system electrical activity (electroencephalographic data), and was more closely linked to duration of sleep. We conclude that a decline in brain glucose metabolism is a significant determinant of falling rates of systemic glucose utilization during sleep.
6-Month Clinical Outcomes Following Implantation of the Bioresorbable Everolimus-Eluting Vascular Scaffold in Vessels Smaller or Larger Than 2.5 mm
Authors: Roberto Diletti, Yoshinobu Onuma, Vasim Farooq, Josep Gomez-Lara, Salvatore Brugaletta, Robert Jan van Geuns, Evelyn Regar, Bernard de Bruyne, Dariusz Dudek, Leif Thuesen, Bernard Chevalier, Dougal McClean, Stephan Windecker, Robert Whitbourn, Pieter Smits, Jacques Koolen, Ian Meredith, Dong Li, Susan Veldhof, Richard Rapoza, Hector M. Garcia-Garcia, John A. Ormiston, Patrick W. Serruys
Journal: Journal of the American College of Cardiology (2011)
P01.04 * THERAPEUTIC POTENTIAL OF TARGETING HOX PROTEIN FUNCTION IN GLIOBLASTOMA
Authors: T. Brend, Z. Kelly, M. Ajaz, R. Morgan, H. Pandha, S. C. Short
Journal: Neuro-Oncology (2014)

BACKGROUND: Resistance of glioblastoma to standard chemoradiotherapy may be mediated, at least partially, by a population of inherently resistant glioma stem cells (GSCs) which are able to survive treatment and reconstitute the tumour. HOX genes are dysregulated in various cancers and a subset of GSCs show high levels of HOX expression. In addition, a HOX gene signature has been associated with treatment resistance in glioblastoma. Our goal was to determine the potential of targeting HOX function as a novel therapy for glioblastoma. METHODS: HOX expression profiles for patient-derived GSCs and established glioma cell lines were determined by quantitative RT-PCR. In vitro, cells were treated with the HOX inhibitor peptide HXR9 (or control peptide CXR9), with or without radiation two hours later. Subsequently, cells were incubated through two doubling times and the MTS assay was used to determine cell viability. In vivo, sub-cutaneous xenografts of U87-MG cells were established in Balb/c Nude mice. Treatments (peptide and/or radiation) or controls were administered in three doses over consecutive days. RESULTS: Analysis of HOX expression in GSC lines demonstrated up-regulation of genes across all four clusters, although expression patterns varied between cell lines. In contrast, the established glioma cell lines T98G and U87-MG showed lower overall HOX expression. The HOX inhibitor peptide HXR9 had potent cytotoxic activity in a number of GSC lines, with IC50 values between 3 and 5 µM. In contrast, T98G and U87-MG were more resistant (IC50s of 70 and 35 µM, respectively), as was a normal neural progenitor cell line NP1 (IC50 65 µM). In vitro, combinations of sub-lethal doses of HXR9 with radiation demonstrated an additive cytoxic effect on GSCs. In vivo, treatment with HXR9 peptide resulted in tumour growth delay when combined with radiotherapy in a mouse xenograft model. CONCLUSIONS: Knockdown of HOX protein function reduced viability of glioma cells in vitro, with greater potency in GSCs than established cell lines. Combination of HOX-inhibition with radiation or demonstrated an additive cytoxicity in vitro and improved tumour growth delay in a preclinical mouse model. Therefore, targeting HOX proteins shows potential as an adjuvant therapy with current standard of care chemoradiotherapy for glioblastoma.
The likeness of fetal growth and newborn size across non-isolated populations in the INTERGROWTH-21st Project: the Fetal Growth Longitudinal Study and Newborn Cross-Sectional Study
Authors: José Villar, Aris T Papageorghiou, Ruyan Pang, Eric O Ohuma, Leila Cheikh Ismail, Fernando C Barros, Ann Lambert, Maria Carvalho, Yasmin A Jaffer, Enrico Bertino, Michael G Gravett, Doug G Altman, Manorama Purwar, Ihunnaya O Frederick, Julia A Noble, Cesar G Victora, Zulfiqar A Bhutta, Stephen H Kennedy
Journal: The Lancet Diabetes & Endocrinology (2014)
Molecular Pathogenesis of Hodgkin's Lymphoma: Increasing Evidence of the Importance of the Microenvironment
Authors: Christian Steidl, Joseph M. Connors, Randy D. Gascoyne
Journal: Journal of Clinical Oncology (2011)

Hodgkin's lymphoma (HL) represents the most common subtype of malignant lymphoma in young people in the Western world. Most patients can be cured with modern treatment strategies, although approximately 20% will die after relapse or progressive disease. The histologic hallmark of the disease is the presence of the characteristic Hodgkin Reed-Sternberg (HRS) cells in classical HL and so-called lymphocyte-predominant (LP) cells in nodular lymphocyte-predominant HL. HL is unique among all cancers because malignant cells are greatly outnumbered by reactive cells in the tumor microenvironment and make up only approximately 1% of the tumor. Expression of a variety of cytokines and chemokines by the HRS and LP cells is believed to be the driving force for an abnormal immune response, perpetuated by additional factors secreted by reactive cells in the microenvironment that help maintain the inflammatory milieu. The malignant HRS and LP cells manipulate the microenvironment, permitting them to develop their malignant phenotype fully and evade host immune attack. Gene expression signatures derived from non-neoplastic cells correlate well with response to initial and subsequent therapies, reflecting their functional relevance. Recent biomarker studies have added texture to clinical outcome predictors, and their incorporation into prognostic models may improve our understanding of the biologic correlates of treatment failure. Moreover, recent preclinical and clinical studies have demonstrated that the tumor microenvironment represents a promising therapeutic target, raising hope that novel treatment strategies focused on the interface between malignant and reactive cells will soon emerge.
Should Normothermia Be Maintained During Major Surgery?
Authors: Frederick W. Cheney
Journal: JAMA (1997)

Mild hypothermia has long been a well-known accompaniment of anesthesia and surgery. General anesthetic agents inhibit normal thermoregulatory control so that a reduction in core body temperature of 1°C to 2°C is expected in patients anesthetized for 1 to 2 hours or more. This effect is compounded during prolonged operations, especially those in which thoracic and abdominal cavities are exposed to ambient air. Another factor contributing to intraoperative hypothermia is the intravenous administration of cold (blood) or room temperature fluids. Mild hypothermia (35°C) has been accepted as an inevitable consequence of general anesthesia and surgery. See also p 1127. In this issue of<i>JAMA</i>, Frank et al<sup>1</sup>report an association between mild intraoperative hypothermia and postoperative morbid cardiac events. They prospectively studied 300 patients older than 60 years, undergoing abdominal, thoracic, or peripheral vascular surgical procedures who had documented coronary artery disease or were at high risk for coronary
Cystinosis. Intracellular cystine depletion by aminothiols in vitro and in vivo.
Authors: J G Thoene, R G Oshima, J C Crawhall, D L Olson, J A Schneider
Journal: Journal of Clinical Investigation (1976)

Certain aminothiols rapidly deplete cultured cystinotic skin fibroblasts of their abnormally high free (nonprotein) cystine pool. The free cystine content of these cells if reduced by over 90% in 1 h with 0.1 mM cysteamine. This is more rapid than previously known methods of removing free cystine from cystinotic fibroblasts. The disulfide, cystamine, is also able to deplete cystinotic cells of free cystine. A patient with nephropathic cystinosis and end-stage renal disease was treated with cysteamine, both intravenously and orally. Both methods of administration rapidly lowered the free cystine content of the patient's peripheral leukocytes. Study of the patient's urinary sulfur excretion did not conclusively determine the effect of this therapy on the total body cystine pool. Her renal status remained at end stage after 1 mo of oral cysteamine, when an episode of grand mal seizures prompted cessation of the study. Determination of the proper place of aminothiol therapy in this disease will depend upon further clinical trial with patients whose kidney function has not deteriorated to the point of irreversible change, accompanied by careful monitoring of plasma aminothiol levels.
Bone marrow cells for cardiac regeneration: the quest for the protagonist continues
Authors: B DAWN, R BOLLI
Journal: Cardiovascular Research (2004)

See also article by Hattan et al.  [11]  (pages 334-344) in this issue .

The past few years have witnessed an explosion of research on methods to achieve myocardial repair via cellular transplantation or mobilization of endogenous cells [1]. Several different cell types, including skeletal myoblasts [2], c-kit+/Sca-1+/lin− bone marrow (BM) cells [3], BM mesenchymal stem cells (MSCs) [4], BM ‘side-population’ (SP) cells [5], endothelial progenitor cells (EPCs) [6], and cardiac stem cells (CSCs) [7], have been utilized in an effort to achieve cardiac reconstitution and restoration of function following myocardial infarction (MI). The evidence accumulated over the past few years indicates that left ventricular (LV) function and adverse LV remodeling can be ameliorated via cell-based therapies, and the preliminary results from several small-scale, mostly non-randomized, clinical trials have been encouraging [8–10]. However, the mechanism(s) underlying the observed functional improvement remains unclear and the debate regarding the advantages of one candidate cell versus another continues unabated.

So, what characteristics should a cell have in order to be selected for therapeutic use in humans? The answer is simple: it has to differentiate into cardiomyocytes that are connected both mechanically and electrically with native myocytes (contracting in synchrony with adjacent cells) and be able to form vascular structures in order to get blood supply in the scar. Thus far, very few cell types have been shown to do all of these things.

In this issue of the Journal, Hattan, Kawaguchi, and colleagues … 

*Corresponding author. Tel.: +1 502 852 7959; fax: +1 502 852 7147. Email address: buddha{at}louisville.edu
IL-13 Effector Functions
Authors: Thomas A. Wynn
Journal: Annual Review of Immunology (2003)

IL-13 was first recognized for its effects on B cells and monocytes, where it upregulated class II expression, promoted IgE class switching and inhibited inflammatory cytokine production. It was also thought to be functionally redundant with IL-4. However, studies conducted with knockout mice, neutralizing antibodies, and novel antagonists demonstrate that IL-13 possesses several unique effector functions that distinguish it from IL-4. Resistance to most gastrointestinal nematodes is mediated by type-2 cytokine responses, in which IL-13 plays a dominant role. By regulating cell-mediated immunity, IL-13 modulates resistance to intracellular organisms including Leishmania major, Leishmania mexicana, and Listeria monocytogenes. In the lung, IL-13 is the central mediator of allergic asthma, where it regulates eosinophilic inflammation, mucus secretion, and airway hyperresponsiveness. Manipulation of IL-13 effector function may also prove useful in the treatment of some cancers like B-cell chronic lymphocytic leukemia and Hodgkin's disease, where IL-13 modulates apoptosis or tumor cell growth. IL-13 can also inhibit tumor immunosurveillance. As such, inhibitors of IL-13 might be effective as cancer immunotherapeutics by boosting type-1-associated anti-tumor defenses. Finally, IL-13 was revealed as a potent mediator of tissue fibrosis in both schistosomiasis and asthma, which indicates that it is a key regulator of the extracellular matrix. The mechanisms that regulate IL-13 production and/or function have also been investigated, and IL-4, IL-12, IL-18, IFN-γ, IL-10, TGF-β, TNF-α, and the IL-4/IL-13 receptor complex play important roles. This review highlights the effector functions of IL-13 and describes multiple pathways for modulating its activity in vivo.
In-flight emergencies: playing The Good Samaritan
Authors: B. Shepherd, D. Macpherson, C. M. B. Edwards
Journal: Journal of the Royal Society of Medicine (2006)

On a recent holiday, one of the authors was asked to lend medical assistance to a passenger on the flight out and another on the flight back. Anecdotally, it appears that other doctors are also being asked more often than previously. This led us to investigate the area more closely. About three quarters of in-flight emergencies are managed by cabin crew but in the remaining situations it is off-duty medical professionals who offer their services as Good Samaritans.1 This review article aims to identify and clarify issues surrounding doctors who act as Good Samaritans onboard commercial airline flights. This includes discussion points ranging from common clinical scenarios to the legal protection of an intervening doctor.
Adalimumab therapy reduces hand bone loss in early rheumatoid arthritis: explorative analyses from the PREMIER study
Authors: M Hoff, T K Kvien, J Kalvesten, A Elden, G Haugeberg
Journal: Annals of the Rheumatic Diseases (2008)

The effect of adalimumab on hand osteoporosis was examined and related to radiographic joint damage in the three treatment arms of the PREMIER study: adalimumab plus methotrexate, adalimumab and methotrexate monotherapy. Predictors of hand bone loss were also searched for.768 patients (537 fulfilled 2 years) with rheumatoid arthritis (RA) for less than 3 years, never treated with methotrexate, were included. Hand bone loss was assessed by digital x ray radiogrammetry (DXR) on the same hand radiographs scored with modified Sharp score at baseline, 26, 52 and 104 weeks. For DXR, metacarpal cortical index (MCI) was the primary bone measure.At all time points the rate of percentage DXR-MCI loss was lowest in the combination group (-1.15; -2.16; -3.03) and greatest in the methotrexate monotherapy group (-1.42; -2.87; -4.62), with figures in between for the adalimumab monotherapy group (-1.33; -2.45; -4.03). Significant differences between the combination group and the methotrexate group were seen at 52 (p = 0.009) and 104 weeks (p<0.001). The order of hand bone loss across the three treatment arms was similar to the order of radiographic progression. Older age, elevated C-reactive protein and non-use of adalimumab were predictors of hand bone loss.This study supports a similar pathogenic mechanism for hand bone loss and erosions in RA. The combination of adalimumab and methotrexate seems to arrest hand bone loss less effectively than radiographic joint damage. Quantitative measures of osteoporosis may thus be a more sensitive tool for assessment of inflammatory bone involvement in RA.
EFFECTS OF ETHANOL ADMINISTRATION ON URINARY EXCRETION OF MAGNESIUM AND OTHER ELECTROLYTES IN ALCOHOLIC AND NORMAL SUBJECTS*
Authors: John M. Kalbfleisch, Robert D. Lindeman, H. Earl Ginn, William O. Smith
Journal: Journal of Clinical Investigation (1963)

Although clinical magnesium deficiency is now recognized frequently in chronic alcoholics, its cause or causes are not clear.A poor dietary intake is undoubtedly important, but it is unlikely that magnesium deficiency results from dietary depletion alone, since it has been quite difficult to produce experimental dietary magnesium defi- ciency in man (2).Earlier workers have shown that the kidneys are reasonably efficient in con- serving magnesium (2, 3).Thus, it is likely that some additional mechanism may be respon- sible for magnesium deficiency associated with chronic alcoholism.Recent studies have indicated that ethanol may induce increased urinary ex- cretion of magnesium (4, 5).The purpose of the present study was to determine the effect of an acute ethanol load on urinary excretion of mag- nesium and other electrolytes, and to make pre- liminary observations on the mechanism respon- sible for an observed increase in urinary excretion of magnesium.
The genetic spectrum of familial hypercholesterolemia in south-eastern Poland
Authors: Mahtab Sharifi, Małgorzata Walus-Miarka, Barbara Idzior-Waluś, Maciej T. Malecki, Marek Sanak, Ros Whittall, Ka Wah Li, Marta Futema, Steve E. Humphries
Journal: Metabolism (2015)

BackgroundFamilial hypercholesterolemia (FH) is a common autosomal dominant disorder with a frequency of 1 in 200 to 500 in most European populations. Mutations in LDLR, APOB and PCSK9 genes are known to cause FH. In this study, we analyzed the genetic spectrum of the disease in the understudied Polish population.Materials and methods161 unrelated subjects with a clinical diagnosis of FH from the south-eastern region of Poland were recruited. High resolution melt and direct sequencing of PCR products were used to screen 18 exons of LDLR, a region of exon 26 in the APOB gene and exon 7 of PCSK9. Multiplex ligation-dependent probe amplification (MLPA) was performed to detect gross deletions and insertions in LDLR. Genotypes of six LDL-C raising SNPs were used for a polygenic gene score calculation.ResultsWe found 39 different pathogenic mutations in the LDLR gene with 10 of them being novel. 13 (8%) individuals carried the p.Arg3527Gln mutation in APOB, and overall the detection rate was 43.4%. Of the patients where no mutation could be found, 53 (84.1%) had a gene score in the top three quartiles of the healthy comparison group suggesting that they have a polygenic cause for their high cholesterol.ConclusionsThese results confirm the genetic heterogeneity of FH in Poland, which should be considered when designing a diagnostic strategy in the country. As in the UK, in the majority of patients where no mutation can be found, there is likely to be a polygenic cause of their high cholesterol level.