tbuckley/cabot-search huggingface dataset:
Biomarker-guided clinical decisions: for patients, health economists or neither?
Authors: Jens-Ulrik Jensen
Journal: European Respiratory Journal (2013)

In this issue of the European Respiratory Journal , Albrich et al. [1] report on a randomised trial. Their hypothesis is that triage decisions in patients with respiratory infections, guided by adding measurements of the calcitonin-superfamily gene derived peptide, mid-regional proadrenomedullin, are more effective than if guided according to clinical assessment alone. Length of hospital stay is, amongst other end-points, compared between the groups.

The authors should be commended for their effort in conducting a randomised trial with a biomarker-strategy; this implies a much increased workload when compared to epidemiological studies.

Adrenomedullin is a 52 amino acid polypeptide. It is formed by amino acids 95–146 of “pre-proadrenomedullin” and is involved in multiple effects, which include vasodilation [2, 3], osteoblast activity [4], renoprotection [5] and angiogenesis [6]. Mid-regional proadrenomedullin (amino acids 45–92 of “pre-proadrenomedullin”) is produced in 1:1 ratio with adrenomedullin and is not a pro-hormone of adrenomedullin. The physiological role, if any, of mid-regional proadrenomedullin is largely unknown.

Mid-regional proadrenomedullin levels in blood have been shown to be related to the prognosis of the patient. In a study of 228 patients with community acquired pneumonia, a high ability to predict a Pneumonia Severity Index score of 4–5 ( versus 1–3), was reported (area under the curve of the receiver operating characteristic curve: mid-regional proadrenomedullin 0.81, procalcitonin 0.62, C-reactive protein 0.59) [7]. However, knowledge of prognosis indicated by a biomarker is not always translated into …
Treatment with calcitonin for osteoporosis
Authors: M. AZRIA;, S. PATEL
Journal: Annals of the Rheumatic Diseases (1997)

I would like the opportunity to correct, or possibly update, a number of the facts concerning calcitonin contained in Dr Patel’s comprehensive review article on drug treatments for osteoporosis.1 

He states that nasal preparations of calcitonin are licensed for use in osteoporosis in ‘some European countries and Japan’, whereas in fact the nasal spray formulation of salmon calcitonin developed at Sandoz (now Novartis) is currently approved in more than 70 countries worldwide, including the USA and almost all the countries of Europe. Japan, …
Loss of epidermal Evi/Wls results in a phenotype resembling psoriasiform dermatitis
Authors: Iris Augustin, Julia Gross, Daniel Baumann, Claudia Korn, Grainne Kerr, Tamara Grigoryan, Cornelia Mauch, Walter Birchmeier, Michael Boutros
Journal: The Journal of Experimental Medicine (2013)

Cells of the epidermis renew constantly from germinal layer stem cells. Although epithelial cell differentiation has been studied in great detail and the role of Wnt signaling in this process is well described, the contribution of epidermal Wnt secretion in epithelial cell homeostasis remains poorly understood. To analyze the role of Wnt proteins in this process, we created a conditional knockout allele of the Wnt cargo receptor Evi/Gpr177/Wntless and studied mice that lacked Evi expression in the epidermis. We found that K14-Cre, Evi-LOF mice lost their hair during the first hair cycle, showing a reddish skin with impaired skin barrier function. Expression profiling of mutant and wild-type skin revealed up-regulation of inflammation-associated genes. Furthermore, we found that Evi expression in psoriatic skin biopsies is down-regulated, suggesting that Evi-deficient mice developed skin lesions that resemble human psoriasis. Immune cell infiltration was detected in Evi-LOF skin. Interestingly, an age-dependent depletion of dendritic epidermal T cells (DETCs) and an infiltration of γδlow T cells in Evi mutant epidermis was observed. Collectively, the described inflammatory skin phenotype in Evi-deficient mice revealed an essential role of Wnt secretion in maintaining normal skin homeostasis by enabling a balanced epidermal-dermal cross talk, which affects immune cell recruitment and DETC survival.
Evaluating bone marrow oedema patterns in musculoskeletal injury
Authors: Michael Gregory Kozoriz, Julia Grebenyuk, Gordon Andrews, Bruce B Forster
Journal: British Journal of Sports Medicine (2012)

MRI is a common tool in the evaluation of musculoskeletal injury that allows the clinician to pinpoint specific pathologies. The patient's history and physical exam play a critical role in the diagnosis of sports injuries, however, complementary imaging can play an important role in determining the nature and extent of injury. With the widespread use of MRI, attention has focused on the signals generated following injury. In particular, bone marrow oedema (BME) patterns can be used to aid in the diagnosis of musculoskeletal injury. In this pictorial essay, the authors will demonstrate common patterns of BME that accompany a wide range of musculoskeletal injuries. It is expected that by the end of this article, the reader will be able to (1) recognise BME is a phenomenon observed on MRI following sports injury; (2) recognise typical patterns of BME; (3) understand the relationship of oedema to the type of injury and (4) in the presence of oedema, understand other co-existing injuries that ultimately may have an impact on management.
What can quality improvement learn from evidence-based medicine?
Authors: Amitava Banerjee, Emma Stanton, Claire Lemer, Martin Marshall
Journal: Journal of the Royal Society of Medicine (2012)

Evidence-based medicine and quality improvement are among the most commonly-used terms in healthcare and health systems. Evidence-based medicine is credited as one of the greatest medical advances of the 20th century and has influenced spheres far beyond health, from ‘evidence-based policy’ to ‘evidence-based conservation’. Quality improvement has been variably defined,1 but was recently championed in Darzi's future vision of the NHS.2 With increasing interest in the incorporation of quality improvement into daily clinical practice, comparison of quality improvement with evidence-based medicine may provide insights to inform the future progress of the quality improvement movement. By process of literature review and discussion with opinion leaders, the history, definitions, successes and failures of the two movements are analysed.
European Intergroup Studies (MMT4-89 and MMT4-91) on Childhood Metastatic Rhabdomyosarcoma: Final Results and Analysis of Prognostic Factors
Authors: M. Carli, R. Colombatti, O. Oberlin, G. Bisogno, J. Treuner, E. Koscielniak, G. Tridello, A. Garaventa, R. Pinkerton, M. Stevens
Journal: Journal of Clinical Oncology (2004)

Final results are presented from two consecutive European studies for patients with metastatic rhabdomyosarcoma (RMS) to identify prognostic variables and determine the value of high-dose chemotherapy (HDCT) in complete remission.A total of 174 patients aged 3 months to 18 years participated. From 1989 to 1991, patients received four cycles of intensive multiagent chemotherapy. From 1991 to 1995, patients achieving complete remission received consolidation with HDCT. All received local therapy (surgery, radiation therapy) according to response.At a median follow-up of 8 years, 5-year overall survival (OS) and event-free survival (EFS) for the whole group were 24% and 20%, respectively. No statistical difference was found between HDCT and standard chemotherapy (5-year OS, 36% v 27%; EFS 29% v 23%). Univariate analysis identified primary tumor in parameningeal, extremity, or other sites; age younger than 1 year and older than 10 years; bone or bone marrow metastases; multiple metastases; and multiple sites of metastases as unfavorable prognostic factors for OS and EFS. Multivariate analysis identified unfavorable site, bone or bone marrow involvement, and unfavorable age as independently unfavorable factors. Two subgroups were identified. Those with fewer than two unfavorable factors had 5-year EFS and OS of 40% and 47%, respectively. Patients with > or = two unfavorable factors had 5-year EFS and OS of 7.5% and 9%, respectively.A minority of patients with metastatic RMS have better survival than overall results for this population suggest. Those in the highest risk group have such poor survival that they are candidates for first-line novel therapies. There is no evidence that consolidation with HDCT improves outcome.
A Novel Role of MicroRNA in Late Preconditioning
Authors: Chang Yin, Fadi N. Salloum, Rakesh C. Kukreja
Journal: Circulation Research (2009)

MicroRNAs (miRNAs) are noncoding RNAs of 18 to 24 nucleotides that are involved in posttranscriptional regulation of protein expression. Their role in ischemic preconditioning (IPC) is currently unknown. We hypothesized that miRNAs induced after IPC in the heart may create a preconditioned phenotype through upregulating proteins including endothelial nitric oxide synthase (eNOS)/inducible nitric oxide synthase (iNOS) and heat shock protein (HSP)70, which are implicated in the late-phase protection of IPC. miRNAs were extracted from hearts of ICR mice following IPC. The purified miRNAs were injected in vivo into the left ventricular wall of mice, and, 48 hours later, the hearts were subjected to regional ischemia/reperfusion injury by left anterior descending artery ligation for 30 minutes followed by reperfusion for 24 hour. IPC caused no changes in miRNA-23b and miRNA-483 whereas miRNA-1, miRNA-21and miRNA-24 were significantly increased. The IPC-miRNA treatment caused an increase in eNOS mRNA and protein, whereas iNOS was not changed. HSF-1 (heat shock transcription factor 1) and HSP70 were also increased with IPC-miRNA treatment versus control. Moreover, injection of IPC-miRNA protected the hearts against ischemia/reperfusion injury, as shown by a reduction of infarct size as compared with saline or non-IPC miRNA-treated control. We conclude that IPC-induced miRNAs trigger cardioprotection similar to the delayed phase of IPC, possibly through upregulating eNOS, HSP70, and the HSP70 transcription factor HSF-1.
The TRIFRA trial: efforts employed to minimise expectation bias
Authors: Qian-wen Lv, Wen Zhang, Qun Shi, Wen-jie Zheng, Peter E Lipsky, Xuan Zhang
Journal: Annals of the Rheumatic Diseases (2014)

We thank the readers for their interest in our manuscript reporting the comparative impact of an extract of TwHF and methotrexate, or the combination in subjects with rheumatoid arthritis.1 We completely agree with the readers that the study must be interpreted with caution because it was carried out in an open-label manner owing to cost considerations. We discussed this in detail in the section on Limitations in the Discussion of the paper. However, it is difficult to predict how patient expectation might bias the study. On the one hand, extracts of TwHF have been used for hundreds of years in China to treat various symptoms and, over the past 30 years, extracts of TwHF have become a standard therapy …
Crowd and environmental management during mass gatherings
Authors: Anders Johansson, Michael Batty, Konrad Hayashi, Osama Al Bar, David Marcozzi, Ziad A Memish
Journal: The Lancet Infectious Diseases (2012)

Crowds are a feature of large cities, occurring not only at mass gatherings but also at routine events such as the journey to work. To address extreme crowding, various computer models for crowd movement have been developed in the past decade, and we review these and show how they can be used to identify health and safety issues. State-of-the-art models that simulate the spread of epidemics operate on a population level, but the collection of fine-scale data might enable the development of models for epidemics that operate on a microscopic scale, similar to models for crowd movement. We provide an example of such simulations, showing how an individual-based crowd model can mirror aggregate susceptible-infected-recovered models that have been the main models for epidemics so far.
The guinea-pig: an animal model for human skin absorption of hydrocortisone, testosterone and benzoic acid?
Authors: KLAUS E. ANDERSEN, HOWARD I. MAIBACH, MARK D. ANJO
Journal: British Journal of Dermatology (1980)

SUMMARY 14C ring-labelled hydrocortisone, testosterone and benzoic acid dissolved in acetone were applied to the backs of guinea-pigs (4 μg/cm2). Percutaneous absorption was quantified by following the excretion of tracer in urine and faeces for 5 days. Absorption of hydrocortisone and benzoic acid was 2.4% (s. d. = 0.5; n = 3) and 31.4% (s. d. = 9.1; n = 3) of the applied dose respectively, similar to published human absorption data. Testosterone was absorbed to a greater extent in guinea-pigs (34.9%± 5.4; n = 5) than man. A thioglycollate based depilatory cream significantly increased the skin absorption of testosterone, while the absorption velocity was unaltered. Two analytical methods were compared, direct counting versus wet ashing; results were in the, same range for the three compounds. Two methods of quantifying skin absorption were compared; urine recovery corrected for incomplete urinary excretion after parenteral administration versus the addition of urine and faecal recovery. For benzoic acid, excreted mainly in the urine (88.1 %), the two methods gave similar results; for testosterone, excreted in the urine to a lesser extent (46.8%), the method of addition of urine and faecal recovery appeared to be more correct.
Interactions between malaria and human immunodeficiency virus anno 2014
Authors: J.-P. Van geertruyden
Journal: Clinical Microbiology and Infection (2014)

Possible pathophysiological, clinical and epidemiological interactions between human immunodeficiency virus (HIV) and tropical pathogens, especially malaria parasites, constitute a concern in tropical areas. Two decades of research have shown that HIV-related immunosuppression is correlated with increased malaria infection, burden, and treatment failure, and with complicated malaria, irrespective of immune status. The recent role out of antiretroviral therapies and new antimalarials, such as artemisinin combination therapies, raise additional concerns regarding possible synergistic and antagonistic effects on efficacy and toxicity. Co-trimoxazole, which is used to prevent opportunistic infections, has been shown to have strong antimalarial prophylactic properties, despite its long-term use and increasing antifolate resistance. The administration of efavirenz, a non-nucleoside reverse transcriptase inhibitor, with amodiaquine-artesunate has been associated with increased toxicity. Recent in vivo observations have confirmed that protease inhibitors have strong antimalarial properties. Ritonavir-boosted lopinavir and artemether-lumefantrine have a synergistic effect in terms of improved malaria treatment outcomes, with no apparent increase in the risk of toxicity. Overall, for the prevention and treatment of malaria in HIV-infected populations, the current standard of care is similar to that in non-HIV-infected populations. The available data show that the wider use of insecticide-treated bed-nets, co-trimoxazole prophylaxis and antiretroviral therapy might substantially reduce the morbidity of malaria in HIV-infected patients. These observations show that those accessing care for HIV infection are now, paradoxically, well protected from malaria. These findings therefore highlight the need for confirmatory diagnosis of malaria in HIV-infected individuals receiving these interventions, and the provision of different artemisinin-based combination therapies to treat malaria only when the diagnosis is confirmed.
Modern Approaches to Conceptualizing and Measuring Human Life Stress
Authors: Scott M. Monroe
Journal: Annual Review of Clinical Psychology (2008)

The idea that adverse life circumstances and negative life events contribute to disorder and disease has long been held. Advances in conceptualizing and defining these conditions under the common label of life stress have led to progress in measuring both the environmental and individual response characteristics that may promote disorder and disease. In general, a substantial and growing research literature supports the basic premise that life stress plays an important role in the development of many psychological and physical problems. Recent research, too, strongly suggests that interest in life stress in relation to health and disease will accelerate over the coming years. Yet debates and controversies remain concerning how to best conceptualize and measure life stress, which presents distinctive challenges for advancing the field. The present review examines the major issues pertaining to these debates, controversies, and challenges, for they will be crucial to resolve if progress is to be made in understanding ways in which life stress may or may not contribute to psychological and physical disorders.
International standardized approach for flow cytometric residual disease monitoring in chronic lymphocytic leukaemia
Authors: A C Rawstron, N Villamor, M Ritgen, S Böttcher, P Ghia, J L Zehnder, G Lozanski, D Colomer, C Moreno, M Geuna, P A S Evans, Y Natkunam, S E Coutre, E D Avery, L Z Rassenti, T J Kipps, F Caligaris-Cappio, M Kneba, J C Byrd, M J Hallek, E Montserrat, P Hillmen
Journal: Leukemia (2007)
Effects of Dietary Sodium and Hydrochlorothiazide on the Antiproteinuric Efficacy of Losartan
Authors: Liffert Vogt, Femke Waanders, Frans Boomsma, Dick de Zeeuw, Gerjan Navis
Journal: Journal of the American Society of Nephrology (2008)

There is large interindividual variability in the antiproteinuric response to blockade of the renin-angiotensin-aldosterone system (RAAS). A low-sodium diet or addition of diuretics enhances the effects of RAAS blockade on proteinuria and BP, but the efficacy of the combination of these interventions is unknown. Therefore, this randomized, double-blind, placebo-controlled trial to determine the separate and combined effects of a low-sodium diet and hydrochlorothiazide (HCT) on proteinuria and BP was performed. In 34 proteinuric patients without diabetes, mean baseline proteinuria was 3.8 g/d, and this was reduced by 22% by a low-sodium diet alone. Losartan monotherapy reduced proteinuria by 30%, and the addition of a low-sodium diet led to a total reduction by 55% and the addition of HCT to 56%. The combined addition of HCT and a low-sodium diet reduced proteinuria by 70% from baseline (all <i>P</i> &lt; 0.05). Reductions in mean arterial pressure showed a similar pattern (all <i>P</i> &lt; 0.05). In addition, individuals who did not demonstrate an antiproteinuric response to losartan monotherapy did respond when a low-sodium diet or a diuretic was added. In conclusion, a low-sodium diet and HCT are equally efficacious in reducing proteinuria and BP when added to a regimen containing losartan and especially seem to benefit individuals who are resistant to RAAS blockade. Combining these interventions in sodium status is an effective method to maximize the antiproteinuric efficacy of RAAS blockade.
The incidence of major clinical complications in a Dutch transport IVF programme
Authors: J Roest, H V Mous, G H Zeilmaker, A Verhoeff
Journal: Human Reproduction Update (1996)

Four different major clinical complications were identified in a retrospective analysis of 2495 in-vitro fertilization (IVF) cycles resulting in oocyte retrieval. The severe form of ovarian hyperstimulation syndrome (OHSS) occurred in 18 patients, giving a prevalence for this complication of 0.7%. Seven (39%) of these 18 patients had previously been diagnosed as having polycystic ovaries. Eleven patients were admitted with moderate OHSS. Adnexal torsion was diagnosed in two patients. Ovariectomy was considered necessary in both cases. Complications of the transvaginal procedure occurred in seven cases (0.3%): one patient had an acute appendicitis with puncture holes in the appendix, six patients were admitted shortly after oocyte retrieval with a pelvic inflammatory disease. Of the 624 pregnancies obtained, 13 were ectopic, giving an ectopic pregnancy rate of 2.1%. It is concluded that serious clinical complications of IVF treatment are rare. However, patients should be counselled for the occurrence of serious procedure-related complications before entering an IVF programme.
Pathogenic serum IgG anticardiolipin antibodies and the idiotypic network.
Authors: J Cohen, R Bakimer, M Blank, G Valesini, Y Shoenfeld
Journal: Annals of the Rheumatic Diseases (1993)

OBJECTIVES--To determine whether active immunisation of mice with pathogenic anticardiolipin antibodies (IgG and IgM), derived from the serum of a patient with the antiphospholipid syndrome, could dysregulate the idiotypic cascade and induce the production of anti-anti-anti-cardiolipin (Ab3) with anticardiolipin activity by the mice with the association of overt antiphospholipid syndrome. METHODS--Anticardiolipin antibodies were purified from the serum of a patient with the antiphospholipid syndrome. The purified anticardiolipin antibodies were used to immunise mice at the footpads and the mice were then followed up for serological and clinical manifestations of the antiphospholipid syndrome. RESULTS--The IgG anticardiolipin antibody was found to be monospecific and to bind cardiolipin with high affinity. Immunisation of naive BALB/c mice with the purified IgG anticardiolipin antibody was followed by production in the mice of sustained high titres of IgG anticardiolipin antibody, associated with a prolonged activated partial thromboplastin time (64.5 (9.7) v 30.1 (1.7) seconds in control mice) and thrombocytopenia (0.4 (0.06) x 10(9) v 1.0 (0.09) x 10(9)/l platelets in controls). The titres of other autoantibodies (for example, antibodies to DNA, histone), though high after the immunisation, decreased rapidly and were almost undetected one month after the boost injection. The mice immunised with the IgG anticardiolipin antibody showed low fecundity (36% of mice became pregnant v 62% in the group immunised with control IgG). The pregnant mice had an increased resorption rate (the equivalent of fetal loss in the human) of 61 (9)% v 5 (4)% in the control group. The mean (SD) embryo and placental weights in mice with the antiphospholipid syndrome were significantly lower than in the mice injected with control IgG (641 (210) and 103 (14) mg v 1303 (105) and 145 (8) mg respectively. The IgM anticardiolipin antibodies purified from the same patient were found to be polyspecific, binding with low affinity to anticardiolipin antibodies and double stranded DNA, and carried the anti-DNA idiotype 16/6. Mice immunised with the purified IgM anticardiolipin antibodies, though showing reduced fecundity (30%), had only a slightly increased resorption rate (12 (9) v 3 (5)% in controls) and only a slight and statistically non-significant decrease in mean (SD) embryo and placental weights (1134 (188) and 136 (11) mg respectively). CONCLUSIONS--The results confirm the induction of pathogenic anticardiolipin antibodies by immunisation with serum anticardiolipin, dysregulating the idiotypic network, and point to the higher pathogenic potential of serum IgG v IgM anticardiolipin antibodies.