tbuckley/cabot-search huggingface dataset:
The Sea, Sewage and Salubrity
Authors: James W. Mosley
Journal: New England Journal of Medicine (1969)

A recent editorial1 in the British Medical Journal discusses the possible consequences for health of sewage discharged into the sea. Focusing attention exclusively upon contamination of beaches and bathing areas, our colleagues point to the doubtfulness of any assumed association between swimming and ensuing enteric illness. They conclude that we can object to pollution of coastal waters only on esthetic grounds, because there is "... no epidemiological evidence that sewage-contaminated sea water is a real risk to health."Evaluation of the health hazard posed by swimming in polluted sea water began at the close of the nineteenth century. A few . . .
The Sounds of the Normal Heart
Authors: Raymond Harris
Journal: JAMA (1973)

From Laennec (1781-1826) to Luisada, great strides have been made in our knowledge of cardiovascular physiology and the origin of intravascular sounds and murmurs. Dr. Luisada and his associates have played a major role over the last 30 years in expanding the scope and instrumentation of clinical phonocardiography and in compelling cardiologists and cardiovascular physiologists to reevaluate concepts of older clinicians. Some concepts summarized in this book based on Dr. Luisada's work remain controversial, but time may indeed prove their value. For example, Luisada's school suggests that the locations and designations of the areas of cardiac auscultation should be reevaluated and restated in terms of physiologic principles. As he points out, the location of the four auscultatory areas, empirically selected because of correlation between the murmur and the finding of a diseased valve at necropsy, had already been accepted in 1884 and had been challenged only recently. Furthermore, the demonstration
Differential upregulation of the three transforming growth factor beta isoforms in human osteoarthritic cartilage
Authors: M Pombo-Suarez, M T Castaño-Oreja, M Calaza, J Gomez-Reino, A Gonzalez
Journal: Annals of the Rheumatic Diseases (2008)

Objectives: Decreased levels of transforming growth factor beta (TGFβ) have been related to the failure of cartilage repair in experimental models of osteoarthritis. This study aimed to examine this aspect of osteoarthritis in human cartilage. Methods: Cartilage samples were obtained from 11 patients with hip osteoarthritis and 11 patients with femoral neck fracture who were undergoing total hip replacement. Gene expression of the three TGFβ isoforms, collagen type II (COL2A1) and aggrecan (AGC1) was analysed by reverse transcription quantitative PCR and immunohistochemistry. Results: Expression of the three TGFβ isoforms was increased in osteoarthritis cartilage. The upregulation was more marked for the TGFβ3 isoform (2.3-fold) than for TGFβ1 (1.6-fold) or TGFβ2 (1.7-fold). The messenger RNA levels of TGFβ1 and TGFβ2 were strongly correlated in osteoarthritis cartilage (r s = 0.83, p = 0.002), but levels of TGFβ3 were uncorrelated with any of the two other TGFβ isoforms. Immunohistochemistry showed an extension of immunoreactivity for the three TGFβ isoforms to more chondrocytes and to deeper cartilage layers in the more severe osteoarthritis lesions. No correlation of TGFβ isoforms with COL2A1 or AGC1 expression levels was found. Conclusions: The three isoforms of TGFβ were differentially upregulated in late osteoarthritis in relation to an increased percentage of TGFβ-positive chondrocytes. These results indicate that cartilage damage progresses in spite of the TGFβ stimulus for cartilage anabolism and that other causes of the failure to cope with the increased cartilage catabolism of osteoarthritis should be investigated.
Abstract 544: Recurrent DICER1 hotspot mutations in endometrial cancer and their impact on microRNA biogenesis
Authors: Jiamin Chen, Yemin Wang, Melissa McConechy, Michael Anglesio, Janine Senz, Winnie Yang, Jamie Rosner, Andy Chu, Grace Cheng, Gregg Morin, David Huntsman
Journal: Cancer Research (2014)

Abstract Alternation in genes associated with microRNA (miRNA) biogenesis pathway may lead to miRNA dysregulation, and is implicated in a variety of human malignancies. Previously our group identified recurrent somatic “hotspot” mutations (E1705, D1709, D1810, E1813) in a critical miRNA-processing gene, DICER1, in rare sex cord-stromal tumors. During miRNA biogenesis, the two RNase III domains of DICER1 form an intramolecular dimer, which leads to the cleavage of the precursor miRNA (pre-miRNA) hairpin and generate mature 5p and 3p miRNAs from 5’ and 3’ arms of the precursor hairpin respectively. Studies have shown that the hotspot mutations in the RNase IIIb metal binding domain could impair DICER1's ability to generate mature 5p miRNAs, leading to global loss of 5p miRNAs. Recently, in collaboration with The Cancer Genome Atlas (TCGA), we identified DICER1 hotspot mutations in a small subset of endometrial cancer from TCGA cohort (6/248) as well as our own tumor bank (6/307), suggesting disruption of DICER1 is implicated in a common malignancy. We also found an additional recurrent mutation G1809R and demonstrated that it has similar detrimental effects on miRNA biogenesis as hotspot mutations through deep sequencing and realtime PCR. Using Illumina Miseq targeted resequencing and Sanger sequencing, we observed biallelic DICER1 mutations in RNase IIIb domain in some but not all cases. miRNA deep sequencing confirmed that 5p miRNAs are decreased in both cell line models and endometrial tumors with hotspot mutations. Bioinformatic analysis of RNA sequencing profiles from TCGA dataset predicted hotspot DICER1 mutations to have greater functional impact than non-hotspot DICER1 mutations on gene expression. The oncogenic properties of DICER1 hotspot mutations are currently under investigation. Citation Format: Jiamin Chen, Yemin Wang, Melissa McConechy, Michael Anglesio, Janine Senz, Winnie Yang, Jamie Rosner, Andy Chu, Grace Cheng, Gregg Morin, David Huntsman. Recurrent DICER1 hotspot mutations in endometrial cancer and their impact on microRNA biogenesis. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 544. doi:10.1158/1538-7445.AM2014-544
Child psychiatric disorder and relative age in school year: Holding back may cause more harm than good
Authors: T. Radecki
Journal: BMJ (2003)

EDITOR–If the increased psychiatric stress in the comparatively younger students in the study by Goodman et al is the result of inappropriate teacher expectations, holding back students may have no net benefit.1 The held back student becomes one of the older students, raising expectations and increasing stress for those younger. Some held back …
Immune complexes inhibit antimicrobial responses through interleukin-10 production. Effects in severe combined immunodeficient mice during Listeria infection.
Authors: C S Tripp, K P Beckerman, E R Unanue
Journal: Journal of Clinical Investigation (1995)

The presence of soluble antigen-antibody complexes renders mice highly susceptible to infection with the intracellular pathogen Listeria monocytogenes. In this report we show that this inhibition is manifest at the level of the innate immune response and is mediated by IL-10. Like immuno-competent mice, mice with the severe combined immunodeficient mutation (SCID) injected with immune complexes died from a sublethal dose of L. monocytogenes. These mice were protected if pretreated with neutralizing antibodies to IL-10. In vitro, immune complexes stimulated IL-10 production by SCID splenocytes and splenic macrophages. Likewise, immune complexes inhibited TNF and IFN-gamma production by SCID splenocytes cultured with heat-killed-L. monocytogenes. This inhibition was reversed by neutralization of IL-10 but not IL-4 or TGF-beta. Immune complexes and rIL-10 inhibited cytokine production by SCID splenocytes if added before or simultaneously with heat-killed-L. monocytogenes. These data support a model in which immune complexes modulate host defense and the immune response by stimulating the production of IL-10 from macrophages.
Diabetes Treated with Carbonate of Ammonia, Administered Largely
Authors: F. W. Pavy
Journal: BMJ (1869)

eTHE R)TUIxf'ML41z 70C7 4- rUm z, i predicate the same of the hyoidean and mandibular arches; but are we to stop there ?May not the maxillo-palatine processes and the trabe- cule cranii be the most anterior members of the same lateral series?
Ultrasound Evaluation of Systolic Anterior Septal Motion in Patients With and Without Right Ventricular Volume Overload
Authors: ARTHUR D. HAGAN, GARY S. FRANCIS, DAVID J. SAHN, JOEL S. KARLINER, WILLIAM F. FRIEDMAN, ROBERT A. O'ROURKE
Journal: Circulation (1974)

Little information is available concerning the normal systolic pattern of movement of the interventricular septum in man. Accordingly, we studied 242 patients without clinical or catheterization evidence of right ventricular volume overload (RVVO) employing the ultrasound continuous recording technique. In the plane of the mitral valve, systolic anterior septal motion (SASM) was present in 111 patients; in 38 patients the septum did not move during systole while in 74 patients, septal motion was variably anterior and posterior during the same recording. Normal posterior septal motion occurred in only 19 patients. However, at or below the level of the chordae tendineae, 226 of the 242 patients (93%) had normal posterior septal motion. The other 16 patients had severely impaired left ventricular function. In 56 patients with RVVO, 34 had abnormal septal motion at the level of the chordae tendineae (24 with SASM, 7 with variable motion and 3 with no movement). To evaluate septal motion further, 100 normal subjects were studied using a phased multicrystal ultrasound system designed by Bom which provided a sagittal plane image of the cardiac structures. In all 100 subjects the superior septum moved anteriorly in systole with the aortic root, and the upper one-third of the septum acted as a "hinge" for the lower two-thirds which moved posteriorly. In 8 of 21 patients with RVVO studied by the multicrystal method, the entire septum moved anteriorly during systole; variable patterns occurred in 7 patients, while normal septal motion was present in 6 patients. We conclude that 1) normal septal motion consists of anterior movement of the superior segment of the septum during systole; 2) below a pivot point, the inferior two-thirds of the septum moves posteriorly during systole; 3) the normal pivot point of the septum frequently results in SASM when recordings are made in the plane of the mitral valve in patients with and without RVVO; and 4) paradoxical septal motion is not always present in patients with RVVO even when echocardiographic recordings are obtained at or below the level of the chordae tendineae.
Immune Mechanisms of Cardiac Disease
Authors: Franklin H. Epstein, Louis G. Lange, George F. Schreiner
Journal: New England Journal of Medicine (1994)

The heart shares with other organs a susceptibility to immune-mediated injury. However, the unique clinical expressions of myocardial inflammation have only recently received investigative scrutiny. It is now clear that numerous cardiac diseases characterized by the presence of inflammatory cells within the myocardium result from immune sensitization to endogenous or exogenous cardiac antigens. The consequent reaction of cardiac myocytes to immune injury can range from reversible modulation of their electrical and mechanical capabilities to cell death.Immune Pathways of InjuryEffector mechanisms of immune-mediated injury are traditionally divided into humoral and cellular types. Humoral immunity requires recognition of an epitope . . .
Surrogate markers of B cell non-Hodgkin's lymphoma in patients with hepatitis C virus-related cryoglobulinaemia vasculitis
Authors: Guillaume Geri, Benjamin Terrier, Oren Semoun, David Saadoun, Damien Sène, Frédéric Charlotte, Hélène Merle-Béral, Lucile Musset, Matthieu Resche-Rigon, Patrice Cacoub
Journal: Annals of the Rheumatic Diseases (2010)

To evaluate clinical and biological surrogate markers associated with the presence of B cell non-Hodgkin's lymphoma (B-NHL) in patients with hepatitis C virus (HCV) with mixed cryoglobulinaemia (MC) vasculitis.A total of 104 patients with HCV-MC vasculitis (including 20 with B-NHL) were included. The main clinical and biological markers associated with the presence of B-NHL were evaluated.Patients with B-NHL compared to those without showed higher rates of poor general status (40% vs 16.7%; p = 0.032), purpura (90% vs 66.7%; p = 0.05), renal (50% vs 28.6%; p = 0.11) and cardiac involvement (15% vs 0%; p = 0.0006), higher cryoglobulin levels (1.44 g/litre vs 0.67 g/litre; p = 0.0004), and lower C4 (0.025 g/litre vs 0.06 g/litre; p=0.001) and γ-globulin levels (5.3 g/litre vs 13.3 g/litre; p < 0.0001). The free light chain κ/λ ratio was more frequently abnormal in patients with than without B-NHL (64.3% vs 33.3%, p = 0.10). On multivariate analysis, only γ-globulin level was associated with the presence of B-NHL (OR 0.77 (95% CI -0.44 to -0.13), p = 0.0006). The optimal cut-off value for γ-globulin level was 9 g/litre, with sensitivity, specificity, positive and negative predictive values for the presence of B-NHL of 75%, 82%, 50% and 93%, respectively.In patients with HCV-MC, a low γ-globulin level (< 9 g/litre) is strongly associated with the presence of B-NHL.
Postgraduate medical education in South Asia
Authors: Lalitha Mendis, B V Adkoli, R K Adhikari, M Muzaherul Huq, Asma Fozia Qureshi
Journal: BMJ (2004)

Time to move on from the postcolonial era 

Undergraduate and postgraduate education increased rapidly in the post-independence era in South Asia—except for Bhutan and the Maldives, which do not have medical schools. Now in India alone, 136 medical schools admit more than 6000 trainees into postgraduate programmes.1

Satisfaction over the numbers who have completed postgraduate education conceals the challenges facing the region. Specialist training is in the traditional apprenticeship style rather than an appraisal based approach. Selection of assessment tools is not governed by modern educational theory. Some postgraduate examinations rely on outmoded assessments, such as essays and long cases. Training in research, ethical issues, concepts of team work, and management is variable. Standards …
A Notch for Noncoding RNA in Melanoma
Authors: Levi A. Garraway
Journal: New England Journal of Medicine (2014)

A recent study implicates Notch, which mediates cell–cell communication and cell differentiation, in the initiation and progression of melanoma and uncovers a link between Notch and proteins encoded by oncogenes known to cause melanoma (BRAF and NRAS).
Role of circulating somatostatin in regulation of gastric acid secretion, gastrin release, and islet cell function. Studies in healthy subjects and duodenal ulcer patients.
Authors: T J Colturi, R H Unger, M Feldman
Journal: Journal of Clinical Investigation (1984)

Studies were designed (a) to determine whether somatostatin is released into the circulation after meals in sufficient amounts to regulate gastric or pancreatic islet function in humans and (b) to investigate the possible role of somatostatin in the pathogenesis of duodenal ulcer disease. Mean plasma somatostatin-like immunoreactivity (SLI) increased from 6.2 +/- 1.5 pg/ml to a peak level of 13.8 +/- 1.3 pg/ml in eight healthy subjects after a 1,440-cal steak meal (P less than 0.005). When somatostatin-14 was infused intravenously, basal and food-stimulated gastric acid secretion and also basal and food-simulated plasma insulin and glucagon concentrations were reduced significantly at mean plasma SLI concentrations within the range seen after a meal. Thus, the amount of somatostatin reaching the systemic circulation after a steak meal was sufficient to inhibit gastric acid secretion and islet cell function. On the other hand, basal and food-stimulated plasma gastrin concentrations were reduced by intravenous somatostatin only at plasma SLI concentrations that were several-fold greater than post-prandial SLI concentrations. Although duodenal ulcer patients had significantly higher basal, food-stimulated, and peak pentagastrin-stimulated gastric acid secretion rates than healthy controls, duodenal ulcer patients and controls had nearly identical basal and food-stimulated SLI concentrations. Moreover, food-stimulated gastric acid secretion and gastrin release were inhibited by intravenous somatostatin to the same extent in ulcer patients and controls. These studies suggest that duodenal ulcer patients release normal amounts of somatostatin into the circulation and that target cells controlling acid secretion and gastrin release are normally sensitive to somatostatin in these patients.
Conscience and nuclear war
Authors: J M Cundy
Journal: BMJ (1984)

corresponding increase in the use of glucose as well as sucrose in processed foods has resulted in the consumption of sugars in the United Kingdom remaining static for the past 30 years.4In 1982 figures from the Ministry of Agri- culture, Fisheries, and Food showed that the total amount of sugars moving into production in the United Kingdom was 46-2 kg (101 lb) per person.7This figure excludes sugars in imported goods and also naturally occurring sugars.While some sugars produced are not consumed, there is no reason to suppose that this small wastage figure has fluctuated greatly.The public health problem represented by the high consumption of refined sugars in the United Kingdom is therefore not solving itself.Food manufacturers would inform the choice of consumers by stating on the label the percentage of all sugars contained in foods.
Clinical Significance of Enhanced Detection of HBsAg by a Monoclonal Radioimmunoassay
Authors: Edna Ben-Porath, Jack Wands, Mignon Gruia, Kurt Isselbacher
Journal: Hepatology (1984)

We assessed the significance of the enhanced detection by monoclonal radioimmunoassay (M-RIA) of HBsAg in serum of patients with hepatitis B virus (HBV) infection. In acute HBV infection, the M-RIA detected HBsAg in the blood for a far longer period of time than previously recognized. In some patients, the “window phase” of HBV infection (defined as the presence of anti-HBc and the lack of detectable HBsAg and anti-HBs) was shortened or completely eliminated. Furthermore, 26% of individuals with anti-HBc as the only serologic marker of recent or past HBV infection were reactive only in the M-RIA. Analysis of patients tested for HBsAg because of suspected underlying liver disease revealed additional HBsAg-positive sera, unrecognized by polyvalent RIA, thus adding important information in the immunodiagnosis of HBV infection. The enhanced performance of the monoclonal RIA compared to conventional polyvalent RIA was due in part to the increased sensitivity of the assay and the observation that M-RIA may detect “hidden” HBV antigens in immune complexes.
Reflex Tachycardia Due to Temporary Coronary Occlusion in the Conscious Dog
Authors: D. FRED PETERSON, ROBERT L. KASPAR, VERNON S. BISHOP
Journal: Circulation Research (1973)

Reflex increases in heart rate which occurred during 1-minute occlusions of the left circumflex coronary artery were studied in conscious dogs. The results indicated that occlusion produced tachycardia (latency to onset 8.5 seconds) preceded by a rise in left atrial pressure (7.2 seconds) and followed by a small fall in arterial pressure (19.5 seconds). Bilateral baroreceptor denervation indicated that the onset of the changes in heart rate could not be accounted for by subtle baroreceptor sensitivity, although the peak response was much reduced (from 34.0 beats/min to 17.5 beats/min), indicating that the magnitude of the response did depend on intact baroreceptors. Beta-receptor blockade with propranolol or cardiac sympathectomy reduced the peak response from 34.0 beats/min to 16.1 beats/min or 12.2 beats/min, respectively. Vagal blockade with atropine reduced the response to 5.3 beats/min, indicating that the remainder of the response was carried in the vagus. Responses were much reduced after baroreceptor denervation plus β-receptor blockade (5.2 beats/min), indicating that the efferent vagal branch of the reflex originated primarily in the arterial baroreceptors. Tachycardia during coronary occlusion, then, is initiated by receptors in or near the heart, and the magnitude of the response is a combination response from these receptors and the arterial baroreceptors.
Background to Migraine
Authors: Charles D. Aring
Journal: JAMA (1971)

This little volume, for general practitioners, contains ten short chapters by as many physicians, discussing some problems of diagnosis and therapy of migraine. A general review of migraine is followed by discussions of the disorder as seen in a city clinic, a migraine clinic, and in general practice. A chastening chapter on epidemiology, by the Cardiff epidemiologist Waters, suggests that we be wary about what we read on this subject in textbooks. Then come discussions of psychiatric aspects, the association of migraine and the pill, and migraine and flying. The final chapters concern the circulatory effects of ergot compounds, and the Sandoz Lecture by the editor entitled, "Migraine, a Biochemical Disorder?" There is a two-page index. The syndrome of migraine is ubiquitous and varied, and it is useful to become familiar with its vagaries and with methods for helping its victims. This little book can be read in a single
The Development of the Infant and Young Child: Normal and Abnormal
Authors: Frances K. Widmann
Journal: JAMA (1964)

Every physician who sees children must frequently answer the question, "Is my child normal? Advanced? Retarded?" In this book, R. S. Illingworth provides an excellent yardstick for the examining physician, and a series of cautionary notes on the use of any yardstick. New chapters on general and neurological examination of fullterm and premature newborns bring together details not readily available to the physician who does not specialize in infant evaluation. The schedule of normal development is less detailed than the classic descriptive accounts, but the emphasis is on prognostically important findings. The author discusses the dangers of too-early and too-definite predictions, and emphasizes the need for repeated examination, and evaluation of all aspects of a child's development. Illingworth is necessarily brief when taking up such classic problems as the relative importance of heredity and environment. He catalogs rather than discusses the everincreasing number of genetic and metabolic disorders which affect
Fetal lung compliance in premature and term lambs after two methods of in utero repair of diaphragmatic hernia.
Authors: D W Parsons, W D Ford, J C Cool, A J Martin, R E Staugas, J D Kennedy
Journal: Thorax (1994)

BACKGROUND--In utero surgery was used to correct a surgically induced model of congenital diaphragmatic hernia (CDH) in premature and term lambs, resulting in an improvement in lung mechanics at birth. METHODS--The differences between the in utero "patch" repair method and the "silo" repair method were assessed in 55 lambs by measuring the static respiratory system compliance (CST,RS) at birth in term (approximately 145 day) and in premature (128 day) animals. RESULTS--Both methods resulted in similar improvements in CST,RS in term lambs, but in premature lambs only the silo method produced an increase in compliance. Comparisons of specific compliance related to length or birth weight did not alter these findings; however, corrections related to lung weight or a measure of lung volume showed there was no difference between any experimental groups in either term or premature lambs. CONCLUSIONS--These findings suggest that there was no difference in the intrinsic compliance of the lung tissue between normal, unrepaired and repaired animals, and that the differences in respiratory system compliance measured at birth may be due primarily to differences in lung size. The silo repair method appears to provide an earlier improvement in CST,RS than the patch repair method.