tbuckley/cabot-search huggingface dataset:
ON THE ETIOLOGY OF TRENCH FEVER: (A Preliminary Communication.)
Authors: A. M. Pappenheimer, H. N. Vermilye, J. H. Mueller
Journal: BMJ (1917)

body, and the skin is marked at that point.In the case of non-magnetic foreign bodies, such as lead, brass, and nickel, or in the case where a magnetic foreign body is embedded in bone, and therefore cannot vibrate, we have recourse to the use of the telephone probe or, rather, forceps.This is of great assistance in locating the foreign body, either in the soft tissues or in the bone, and enables us to extract it with a minimum of damage to the tissues.In other cases, again, when the foreign body will not vibrate, or has possibly changed its position in the soft parts since the x-ray picture was taken (and this is notably so with foreign bodies in joints), we operate under the fluoroscopic screen.It should be borne in mind that practically all the stationary and general hospitals sent by Canada have come from the medical faculties of the universities.A list of these it would not at the present juncture be wise perhaps to publish, but the fact that each one inc?udes in its personnel the selected specialists and teachers in all branches of medicine and surgery from every medical faculty in the country, ensured from the outset a very high standard of professional efficiency.In addition, effective military administration has in miost cases been Secured, as in most of the universities there were medical men of military experience, both in the militia' and in the South African war, and in the Canadian permanent service.It is no improper divulging of official secrets to say that, both in the Mediterranean area and in France, the highest army medical authorities state that they have found these Canadian units second to none in the whole service.Their facilities for good service, too, are enhanced by the posses- sion in several instances of large funds subscribed by the friends of their universities at home for additions to their equipment and supplies.LABORATORY AND RESEARCH WORK.The third main topic suggested at the outset of this article was laboratory and research work.Again, figures and statistics may not be given, and in any case could be as yet only partial.But valuable work has been done by Canadian workers, both in Canadian mobile laboratories and in collaboration in British units, in Britain, in France, and in the Mediterranean.An enormous volume of work has been done also as part of the daily routine of the general and stationary hospitals, which requires time for the making of generalizations.Special researches of which one has heard have been made upon continued fevers, pyrexias of unknown origin, nephritis, trench fever, stomatitis, meningitis, and epidemic jaundice. DENTAL SERVICES.No account of the work of the C.A.M.C. would be adequate which failed to recognize the good work of the dental officers.
Treatment-Related Osteoporosis in Men with Prostate Cancer
Authors: Matthew R. Smith
Journal: Clinical Cancer Research (2006)

Abstract The intended therapeutic effect of gonadotropin-releasing hormone (GnRH) agonists is hypogonadism, a major cause of acquired osteoporosis in men. Consistent with this observation, GnRH agonists increase bone turnover and decrease bone mineral density, a surrogate for fracture risk. Large claims-based analyses and other retrospective studies provide compelling evidence that GnRH agonists increase risk of clinical fractures. Estrogens play a central role in homeostasis of the normal male skeleton, and estrogen deficiency rather than testosterone deficiency seems to be primarily responsible for the adverse skeletal effects of GnRH agonists. In randomized controlled trials, bisphosphonates (pamidronate and zoledronic acid) and selective estrogen receptor modulators (raloxifene and toremifene) increased bone mineral density in GnRH agonist–treated men. Two ongoing large randomized placebo-controlled studies will prospectively define fracture outcomes in men with prostate cancer and assess the efficacy of novel pharmacologic interventions (AMG162, toremifene) during GnRH agonist treatment.
Pseudopodial Actin Dynamics Control Epithelial-Mesenchymal Transition in Metastatic Cancer Cells
Authors: Jay Shankar, Anat Messenberg, Jackie Chan, T. Michael Underhill, Leonard J. Foster, Ivan R. Nabi
Journal: Cancer Research (2010)

A key cellular process associated with the invasive or metastatic program in many cancers is the transformation of epithelial cells toward a mesenchymal state, a process called epithelial to mesenchymal transition or EMT. Actin-dependent protrusion of cell pseudopodia is a critical element of mesenchymal cell migration and therefore of cancer metastasis. However, whether EMT occurs in human cancers and, in particular, whether it is a prerequisite for tumor cell invasion and metastasis, remains a subject of debate. Microarray and proteomic analysis of actin-rich pseudopodia from six metastatic human tumor cell lines identified 384 mRNAs and 64 proteins common to the pseudopodia of six metastatic human tumor cell lines of various cancer origins leading to the characterization of 19 common pseudopod-specific proteins. Four of these (AHNAK, septin-9, eIF4E, and S100A11) are shown to be essential for pseudopod protrusion and tumor cell migration and invasion. Knockdown of each of these proteins in metastatic cells resulted in reduced actin cytoskeleton dynamics and induction of mesenchymal-epithelial transition (MET) that could be prevented by the stabilization of the actin cytoskeleton. Actin-dependent pseudopodial protrusion and tumor cell migration are therefore determinants of EMT. Protein regulators of pseudopodial actin dynamics may represent unique molecular targets to induce MET and thereby inhibit the metastatic potential of tumor cells.
(33) Pyoderma gangrenosum with cellular immunity deficit treated with plasmaphoresis and leukocyte transfusion
Authors: R. Clayton, M. Feiwel, H. Valdimarsson
Journal: British Journal of Dermatology (2006)

Eccrine sweat collected from the human skin surface contains at least five different esterases. One of them is a cholinesterase. A non-specific carboxylesterase with the electrophoretic mobility of an alpha-globulin appears to be a serum protein. Besides this, there are two isoenzymes of human origin migrating with the same electrophoretic mobility as gamma-globulins. These two isoenzymes are immunologically identical with a non-specific carboxylesterase occurring in numerous organs and body fluids. Lipase activity could not be demonstrated.
Proteinuria Increases Plasma Phosphate by Altering Its Tubular Handling
Authors: Sophie de Seigneux, Marie Courbebaisse, Joseph M. Rutkowski, Alexandra Wilhelm-Bals, Marie Metzger, Stellor Nlandu Khodo, Udo Hasler, Hassib Chehade, Eva Dizin, Arezoo Daryadel, Bénedicte Stengel, E. Girardin, Dominique Prié, Carsten A. Wagner, Philipp E. Scherer, Pierre-Yves Martin, Pascal Houillier, Eric Feraille
Journal: Journal of the American Society of Nephrology (2014)

Proteinuria and hyperphosphatemia are cardiovascular risk factors independent of GFR. We hypothesized that proteinuria induces relative phosphate retention via increased proximal tubule phosphate reabsorption. To test the clinical relevance of this hypothesis, we studied phosphate handling in nephrotic children and patients with CKD. Plasma fibroblast growth factor 23 (FGF-23) concentration, plasma phosphate concentration, and tubular reabsorption of phosphate increased during the proteinuric phase compared with the remission phase in nephrotic children. Cross-sectional analysis of a cohort of 1738 patients with CKD showed that albuminuria≥300 mg/24 hours is predictive of higher phosphate levels, independent of GFR and other confounding factors. Albuminuric patients also displayed higher plasma FGF-23 and parathyroid hormone levels. To understand the molecular mechanisms underlying these observations, we induced glomerular proteinuria in two animal models. Rats with puromycin-aminonucleoside-induced nephrotic proteinuria displayed higher renal protein expression of the sodium-phosphate co-transporter NaPi-IIa, lower renal Klotho protein expression, and decreased phosphorylation of FGF receptor substrate 2α, a major FGF-23 receptor substrate. These findings were confirmed in transgenic mice that develop nephrotic-range proteinuria resulting from podocyte depletion. In vitro, albumin did not directly alter phosphate uptake in cultured proximal tubule OK cells. In conclusion, we show that proteinuria increases plasma phosphate concentration independent of GFR. This effect relies on increased proximal tubule NaPi-IIa expression secondary to decreased FGF-23 biologic activity. Proteinuria induces elevation of both plasma phosphate and FGF-23 concentrations, potentially contributing to cardiovascular disease.
Efficacy and safety of leflunomide compared with placebo and sulphasalazine in active rheumatoid arthritis: a double-blind, randomised, multicentre trial
Authors: Josef S Smolen, Joachim R Kalden, David L Scott, Blaz Rozman, Tore K Kvien, Arvi Larsen, Iris Loew-Friedrich, Christine Oed, Ronald Rosenburg
Journal: The Lancet (1999)
Pelvic girdle pain in pregnancy
Authors: R William Stones, Kathleen Vits
Journal: BMJ (2005)

Exercises may help, and evidence is increasing that acupuncture reduces pain 

M usculoskeletal pain in the pelvic area is common during pregnancy and can cause substantial distress and disruption of function. The lack of any standard definitions of such pain, however, makes it difficult to compare reports of prevalence, treatments, and outcomes. Useful terms for different clinical subgroups include pregnancy related pelvic girdle pain and pregnancy related low back pain.1 Authors of British review articles and case reports often use the term symphysis pubis dysfunction to describe the pain, but others consider that such dysfunction is more often a secondary problem coexisting with lumbar or sacroiliac pain.

A systematic review of 28 studies that used the two terms pregnancy related pelvic girdle pain and pregnancy related low back pain found that prevalence ranged from 3.9% to 89.9% (mean 45.3%).1 This wide range illustrates the problems of definition, identification, and classification. The authors found that estimates of prevalence depended on the inclusion or exclusion of patients with coexisting pain higher in the back and the definition(s) of musculoskeletal …
Factors associated with severity of symptoms in patients with chronic unexplained muscular aching.
Authors: E Kolar, A Hartz, A Roumm, L Ryan, R Jones, E Kirchdoerfer
Journal: Annals of the Rheumatic Diseases (1989)

Subjects with chronic, diffuse, unexplained muscular aching were recruited--21 from a primary care practice, nine from a rheumatology practice, and two from a pain clinic. No additional criteria were used to select subjects. Subjects with mild or moderate symptoms differed from those with severe symptoms with respect to the following characteristics: the presence of fatigue on awakening, the number of tender points, difficulty in sleeping, and the degree of tenderness in typical fibromyalgia areas as measured by a dolorimeter. These findings suggest that muscular aching is likely to be of greater severity if other symptoms or signs of fibromyalgia are also present.
Using a global proteomic approach to identify proteins affected by estrogen therapy
Authors: Timothy D Veenstra
Journal: Genome Medicine (2009)

With the increase in technological capabilities for measuring biological molecules, there is a greater trend to conduct non-biased, discovery-driven studies that collect information on hundreds of molecules in a single study. The hope is that novel findings can be detected within these large datasets. For protein analysis, these non-biased studies are particularly challenging as no technology is presently capable of providing a view of the entire proteome. The ability of non-biased studies to accurately detect specific differences within the proteomes of samples obtained from differentially treated individuals must be conclusively demonstrated before investigators will routinely adopt these methods as part of their experimental protocols. This need is especially true for clinical and epidemiological studies in which limited amounts of samples are available.
Intrinsic Properties of Uncorrected and Highly Corrected Leads
Authors: DANIEL A. BRODY, ROBERT C. ARZBAECHER, Harry A. Phillips
Journal: Circulation (1966)

An improved experimental method was employed to determine the dipolar and nondipolar sensing characteristics of various lead connections in an electrically homogeneous human torso model. The intrinsic properties of the cube and tetrahedron leads were compared with those of an ideal vectorcardiographic system. The conventional precordial leads, V 1 through V 6 , were analyzed anatomically and electrically with respect to corresponding ideal unipolar leads, with similar treatment of the augmented unipolar extremity leads. Finally, methods of constructing highly corrected anteroposterior and transverse vectorcardiographic leads were developed. The study of the cube and tetrahedron systems confirms in strict quantitative terms that they are not suited for accurate vectorcardiographic registration. The defects of existing Z leads are greatly minimized by the use of a grid system in which the electrodes of the anteriorly applied array are individually weighted. An X lead of similar quality was achieved by a transverse grid in which the left-sided electrodes, including the arm connection, were also weighted individually. These two corrected leads, together with a previously described vertical connection, form a vectorcardiographic system whose inherent properties approach those of an ideal system. Analysis of the precordial unipolar leads demonstrates that they are in fact proximity electrodes and some of them are approximately unipolar in their behavior. Leads aV R and aV L are classed as semi-remote, and lead aV F as remote. Thoracic structures are not electrically homogeneous or isotropic. Nevertheless, lacking definitive information on the manner in which these factors influence the electrocardiographic transfer properties of the body, the study of electrolyte-filled models remains a valid experimental basis for lead analysis and synthesis.
Proteomic Profiling Identifies Afamin as a Potential Biomarker for Ovarian Cancer
Authors: David Jackson, Rachel A. Craven, Richard C. Hutson, Ina Graze, Paul Lueth, Robert P. Tonge, Joanne L. Hartley, Janice A. Nickson, Steve J. Rayner, Colin Johnston, Benjamin Dieplinger, Michael Hubalek, Nafisa Wilkinson, Timothy J. Perren, Sean Kehoe, Geoffrey D. Hall, Guenter Daxenbichler, Hans Dieplinger, Peter J. Selby, Rosamonde E. Banks
Journal: Clinical Cancer Research (2007)

Abstract Purpose: To discover and validate serum glycoprotein biomarkers in ovarian cancer using proteomic-based approaches. Experimental Design: Serum samples from a “discovery set” of 20 patients with ovarian cancer or benign ovarian cysts or healthy volunteers were compared by fluorescence two-dimensional differential in-gel electrophoresis and parallel lectin-based two-dimensional profiling. Validation of a candidate biomarker was carried out with Western blotting and immunoassay (n = 424). Results: Twenty-six proteins that changed significantly were identified by mass spectrometric sequencing. One of these, confirmed by Western blotting, was afamin, a vitamin E binding protein, with two isoforms decreasing in patients with ovarian cancer. Validation using cross-sectional samples from 303 individuals (healthy controls and patients with benign, borderline, or malignant ovarian conditions and other cancers) assayed by ELISA showed significantly decreased total afamin concentrations in patients with ovarian cancer compared with healthy controls (P = 0.002) and patients with benign disease (P = 0.046). However, the receiver operating characteristic areas for total afamin for the comparison of ovarian cancer with healthy controls or benign controls were only 0.67 and 0.60, respectively, with comparable figures for CA-125 being 0.92 and 0.88 although corresponding figures for a subgroup of samples analyzed by isoelectric focusing for afamin isoform 2 were 0.85 and 0.79. Analysis of a further 121 samples collected prospectively from 9 patients pretreatment through to relapse indicated complementarity of afamin with CA-125, including two cases in whom CA-125 was noninformative. Conclusions: Afamin shows potential complementarity with CA-125 in longitudinal monitoring of patients with ovarian cancer, justifying prospective larger-scale investigation. Changes in specific isoforms may provide further information.
Mitochondrial oxidative stress and dysfunction in myocardial remodelling
Authors: H. Tsutsui, S. Kinugawa, S. Matsushima
Journal: Cardiovascular Research (2008)

Recent experimental and clinical studies have suggested that oxidative stress is enhanced in myocardial remodelling and failure. The production of oxygen radicals is increased in the failing heart, whereas normal antioxidant enzyme activities are preserved. Mitochondrial electron transport is an enzymatic source of oxygen radical generation and can be a therapeutic target against oxidant-induced damage in the failing myocardium. Chronic increases in oxygen radical production in the mitochondria can lead to a catastrophic cycle of mitochondrial DNA (mtDNA) damage as well as functional decline, further oxygen radical generation, and cellular injury. Reactive oxygen species induce myocyte hypertrophy, apoptosis, and interstitial fibrosis by activating matrix metalloproteinases. These cellular events play an important role in the development and progression of maladaptive myocardial remodelling and failure. Therefore, oxidative stress and mtDNA damage are good therapeutic targets. Overexpression of the genes for peroxiredoxin-3 (Prx-3), a mitochondrial antioxidant, or mitochondrial transcription factor A (TFAM), could ameliorate the decline in mtDNA copy number in failing hearts. Consistent with alterations in mtDNA, the decrease in mitochondrial function was also prevented. Therefore, the activation of Prx-3 or TFAM gene expression could ameliorate the pathophysiological processes seen in mitochondrial dysfunction and myocardial remodelling. Inhibition of oxidative stress and mtDNA damage could be novel and effective treatment strategies for heart failure.
Biologic therapies for psoriasis: practical experience in a U.K. tertiary referral centre
Authors: R.B. Warren, B.C. Brown, D. Lavery, D.M. Ashcroft, C.E.M. Griffiths
Journal: British Journal of Dermatology (2008)

Background Large‐scale clinical trials provide clear evidence of the efficacy and short‐term toxicity of biologic therapies for psoriasis. However, to date, there are few reports of the practical use of these therapies outside of the trial setting and, to our knowledge, none from a U.K. cohort of patients with psoriasis. Objectives (i) To assess efficacy and safety of efalizumab, etanercept and infliximab in a U.K. cohort of patients with psoriasis, with mean Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index 21·8 and 21·7, respectively, outside of the clinical trial setting. (ii) To examine our approach to the processes involved in the initiation of biologic therapies in the era of National Institute for Health and Clinical Excellence guidance. Methods A retrospective case‐note review to identify all patients initiated on biologic therapies for psoriasis in a U.K. tertiary referral centre. Results At 3 months of treatment the efficacy of efalizumab (n =28), etanercept (n =70) and infliximab (n =20), as assessed by PASI 75 (75% decrease from baseline score), was 24%, 35% and 85%, respectively. All three biologics used were well tolerated. Combination therapy with traditional systemic agents was required either at transition to, or to counter relapse while established on, a biologic therapy in 30% of cases. Streamlined approaches to screening and funding significantly (P ≤ 0·05) hastened the initiation of biologic therapies. Conclusions In a cohort of U.K. patients with severe psoriasis, biologic therapies have proved to be a significant step forward in expanding the therapeutic armamentarium for psoriasis. Pharmacovigilance, in the form of registries, is essential to assess the long‐term safety of such drugs.
Targeted therapy in lymphoma
Authors: Patrick B Johnston, RuiRong Yuan, Franco Cavalli, Thomas E Witzig
Journal: Journal of Hematology & Oncology (2010)

Abstract Discovery of new treatments for lymphoma that prolong survival and are less toxic than currently available agents represents an urgent unmet need. We now have a better understanding of the molecular pathogenesis of lymphoma, such as aberrant signal transduction pathways, which have led to the discovery and development of targeted therapeutics. The ubiquitin-proteasome and the Akt/mammalian target of rapamycin (mTOR) pathways are examples of pathological mechanisms that are being targeted in drug development efforts. Bortezomib (a small molecule protease inhibitor) and the mTOR inhibitors temsirolimus, everolimus, and ridaforolimus are some of the targeted therapies currently being studied in the treatment of aggressive, relapsed/refractory lymphoma. This review will discuss the rationale for and summarize the reported findings of initial and ongoing investigations of mTOR inhibitors and other small molecule targeted therapies in the treatment of lymphoma.
Effects of Progesterone on Human Endometrial Carcinoma Cells In Vivo and In Vitro 2
Authors: Isamu Ishiwata, Yasuhiro Udagawa, Hideo Okumura, Shiro Nozawa
Journal: JNCI Journal of the National Cancer Institute (1978)

The effects of progesterone on the growth and differentiation of human endometrial adenocarcinoma cells (cell lines SNG-P and SNG-M derived from primary and metastatic tumors, respectively) were assessed in vitro and in vivo. Progesterone suppressed their growth and induced cell differentiation in vitro. The suppressive effect of progesterone was stronger in the primary tumor cells than in the metastatic ones. Progesterone produced morphologic changes such as multinucleation, multinucleolation, vacuolation, extensive Golgi apparatus, and papillary arrangement of cells. The cells were transplanted sc into nude BALB/c mice where they produced undifferentiated adenocarcinomas in untreated mice and well-differentiated adenocarcinomas in progesterone-treated ones. Progesterone reduced tumor growth and decreased transplantability in nude mice. This hormone produced no change in the distribution of the chromosome numbers or in the karyology.
Prostate cancer drug may be useful for prevention
Authors: J. Hopkins Tanne
Journal: BMJ (2003)

The American Cancer Society and the National Cancer Institute have hailed the trial of a drug for prostate cancer as a milestone for cancer prevention, although the treatment can increase the aggressiveness of the cancer in some cases. And some commentators have questioned its use as a preventive, given the trial results.

Finasteride (Proscar), which is manufactured by Merck, reduced the incidence of prostate cancer by nearly 25% in a large, randomised, controlled trial and reduced symptoms of benign prostatic hypertrophy.

But prostate cancers that developed during the course …