tbuckley/cabot-search huggingface dataset:
Immunofluorescence mapping in inherited epidermolysis bullosa: a study of 86 cases from India
Authors: R. Hiremagalore, A. Kubba, S. Bansel, H. Jerajani
Journal: British Journal of Dermatology (2014)

Epidermolysis bullosa (EB) poses diagnostic challenges in infancy. In India, the diagnosis is largely clinical. There were no facilities to perform immunofluorescence mapping (IFM) until recently, and electron microscopy, which requires expertise to interpret, is limited to a few research laboratories.To describe the patterns of IFM staining in the various forms of EB in Indian patients and to correlate these findings with clinical diagnosis.We conducted a cross-sectional study of IFM findings in EB. Antibodies against type IV collagen, cytokeratin 14, laminin 332 and type VII collagen were used. Clinical correlation was performed in all cases, and concordance-discordance rates were calculated.Eighty-six patients with a diagnosis of EB were included in the study. There were 29 with EB simplex (EBS), 18 with junctional EB (JEB) and 15 with dystrophic EB (DEB). The remaining 24 cases included rare variants, cases with overlapping clinical features and cases where the type of EB was not known. On IFM diagnosis, there were 32 cases of EBS, 15 JEB, 17 DEB and two Kindler syndrome. Two cases were not EB and 18 were inconclusive. IFM could establish the type in 12 of 15 cases (80%) that had overlapping clinical features. Most of these cases were under 1 year of age. Overall the concordance was 57% and was seen best in cases of EBS.This is the first large study of IFM of the subtypes of EB in Indian patients. The study provides a framework for better understanding of EB in Indian patients and for better diagnosis and management, particularly in infancy.
D-Dimer Levels and Risk of Recurrent Venous Thromboembolism
Authors: Sabine Eichinger
Journal: JAMA (2003)

Widespread screening of patients with venous thromboembolism (VTE) for thrombophilic risk factors has become common clinical practice. Because of the increasing number of risk factors, assessing the risk of recurrence in an individual patient is intricate; therefore, a laboratory method that measures multifactorial thrombophilia is required.To prospectively study the relationship between the risk of recurrent VTE and D-dimer, a global marker of coagulation activation and fibrinolysis.Prospective cohort study of 610 patients older than 18 years who were treated with oral anticoagulants for at least 3 months with a first spontaneous VTE, in whom D-dimer levels were measured shortly after discontinuation of oral anticoagulation. The study was conducted at the Department of Internal Medicine I, University Hospital, Vienna, Austria. Patients entered the study at time of discontinuation of oral anticoagulants and were observed at 3-month intervals during the first year and every 6 months thereafter from July 1992 to October 2002.Objectively documented symptomatic recurrent VTE.A total of 79 (13%) of 610 patients had recurrent VTE with a mean observation time of 38 months. Patients with recurrence had significantly higher D-dimer levels compared with those without recurrence (553 ng/mL vs 427 ng/mL, P =.01). Compared with patients with D-dimer levels of 750 ng/mL or higher, the relative risk (RR) of recurrence was 0.6 (95% confidence interval [CI], 0.3-1.4), 0.6 (95% CI, 0.3-1.2), and 0.3 (95% CI, 0.1-0.6) in patients with D-dimer levels of 500 to 749 ng/mL, 250 to 499 ng/mL, and less than 250 ng/mL, respectively. The cumulative probability of recurrent VTE at 2 years was 3.7% (95% CI, 0.9%-6.5%) among patients with D-dimer levels of less than 250 ng/mL compared with 11.5% (95% CI, 8.0%-15.0%) among patients with higher levels (P =.001). Patients with D-dimer levels of less than 250 ng/mL had a 60% lower RR of recurrence compared with patients with higher levels (RR, 0.4; 95% CI, 0.2-0.8).Patients with a first spontaneous VTE and a D-dimer level of less than 250 ng/mL after withdrawal of oral anticoagulation have a low risk of VTE recurrence.
Intrauterine Fetal Transfusion
Authors: John L. Duhring
Journal: JAMA (1966)

THE WORK of Bevis,<sup>1</sup>Walker,<sup>2</sup>and Liley<sup>3</sup>demonstrated that spectrophotometric analysis of an amniotic-fluid biopsy could provide a precise index of the status of Rh iso-immunized pregnancies. This work has made possible a major revision in the management of these complicated cases. Their work has been confirmed by others.<sup>4,5</sup>With the availability of this improved diagnostic technique, attention has been directed toward therapy for the condition of the jeopardized fetus. One of the contributing factors to intrauterine fetal loss in erythroblastosis is high-output congestive heart failure due to anemia. Liley made the first definitive attempt to correct this anemia. In his study of amniotic-fluid biopsy he had occasionally, inadvertently entered a fetal abdomen distended with ascitic fluid. He subsequently made deliberate attempts to enter the peritoneal cavity of such a jeopardized fetus to infuse blood. Encouraged by his initial results he reported these experiments in 1963.
Genetic Compensation in a Human Genomic Disorder
Authors: Nadège Carelle-Calmels, Pascale Saugier-Veber, Françoise Girard-Lemaire, Gabrielle Rudolf, Bérénice Doray, Eric Guérin, Pierre Kuhn, Mathilde Arrivé, Catherine Gilch, Evelyne Schmitt, Séverine Fehrenbach, Albert Schnebelen, Thierry Frébourg, Elisabeth Flori
Journal: New England Journal of Medicine (2009)

A R YCytogenetic studies of the parents of a girl with the DiGeorge (or velocardiofacial) syndrome, who carried a deletion at 22q11.2, revealed an unexpected rearrangement of both 22q11.2regions in the unaffected father.He carried a 22q11.2deletion on one copy of chromosome 22 and a reciprocal 22q11.2duplication on the other copy of chromosome 22.Genetic compensation, which is consistent with the normal phenotype of the father, was shown through quantitative-expression analyses of genes located within the genetic region associated with the DiGeorge syndrome.This finding has implications for genetic counseling and represents a case of genetic compensation in a human genomic disorder.
Cancer doctors pledge to widen access to pain relief in developing countries
Authors: T. Anderson
Journal: BMJ (2010)

Cancer advocates plan to broker deals with drug companies to get cheaper, more plentiful supplies of pain relief drugs to patients in developing countries using models pioneered in the field of HIV/AIDS.

The plans form part of the Global Access to Pain Relief Initiative (GAPRI), a strategy launched at the World Cancer Congress, in China on 19 August. Led by the International Union Against Cancer (UICC), which represents 350 cancer charities including Cancer Research UK, GAPRI has the backing of organisations including the World Health Organization, the American Cancer Society, and the World Economic Forum.

GAPRI will tackle the lack of access to strong opioid based pain relief. Today, a few rich nations, including the UK and US, consume …
Diagnosis of Gastric Cancer up to Three Years after Negative Upper Gastrointestinal Endoscopy
Authors: O. Hosokawa, S. Tsuda, E. Kidani, K. Watanabe, Y. Tanigawa, S. Shirasaki, H. Hayashi, T. Hinoshita
Journal: Endoscopy (1998)

Background and Study Aims: The degree of accuracy of gastroscopy for the detection of gastric cancer is poorly understood. The aim of this retrospective study was to determine the accuracy of gastroscopy by using cancer registry records.
Are Appropriateness Criteria Ready for Use in Clinical Practice?
Authors: Paul G. Shekelle
Journal: New England Journal of Medicine (2001)

Every day, physicians must decide whether to recommend medical procedures that may benefit their patients, such as coronary revascularization for a patient with angina, hysterectomy for a patient with dysfunctional uterine bleeding, or carotid endarterectomy for a patient with transient neurologic symptoms. How should physicians make these judgments? Ideally, one would like conclusive evidence, such as the results of randomized clinical trials, regarding the balance between the benefits of the procedure and the harm it may cause. Unfortunately, even in the case of procedures that have been the subject of numerous randomized clinical trials, such as coronary revascularization and carotid . . .
Glucocorticoids induce the production of the chemoattractant CCL20 in airway epithelium
Authors: G. Jan Zijlstra, Fatemeh Fattahi, Dennie Rozeveld, Marnix R. Jonker, Nathalie M. Kliphuis, Maarten van den Berge, Machteld N. Hylkema, Nick H.T. ten Hacken, Antoon J.M. van Oosterhout, Irene H. Heijink
Journal: European Respiratory Journal (2014)

Th17-mediated neutrophilic airway inflammation has been implicated in decreased response to glucocorticoids in asthma. We aimed to investigate the effect of glucocorticoids on the airway epithelial release of the neutrophilic and Th17-cell chemoattractant CCL20. We studied CCL20 and CXCL8 sputum levels in asthmatic subjects using inhaled glucocorticoids or not, and the effect of budesonide on CCL20 and CXCL8 production in primary bronchial epithelial cells. The mechanism behind the effect of budesonide-induced CCL20 production was studied in 16HBE14o- cells using inhibitors for the glucocorticoid receptor, intracellular pathways and metalloproteases. We observed higher levels of CCL20, but not CXCL8, in the sputum of asthmatics who used inhaled glucocorticoids. CCL20 levels correlated with inhaled glucocorticoid dose and sputum neutrophils. Budesonide increased tumour necrosis factor (TNF)-α-induced CCL20 by primary bronchial epithelium, while CXCL8 was suppressed. In 16HBE14o- cells, similar effects were observed at the CCL20 protein and mRNA levels, indicating transcriptional regulation. Although TNF-α-induced CCL20 release was dependent on the ERK, p38 and STAT3 pathways, the increase by budesonide was not. Inhibition of glucocorticoid receptor or ADAM17 abrogated the budesonide-induced increase in CCL20 levels. We show that glucocorticoids enhance CCL20 production by bronchial epithelium, which may constitute a novel mechanism in Th17-mediated glucocorticoid-insensitive inflammation in asthma.
AN AURAL MASSEUR.
Authors: EDWARD J. BROWN
Journal: JAMA (1896)

At the present time an aural masseur which is practical, safe and not too expensive, would seem to be a much felt want. As a very simple and reasonably effective instrument I can commend the Ziegle otoscope with stiff rubber bag attachment, which I purchased in Heidelberg six years ago. With a soft rubber tube for fitting the otoscope tightly in the external canal, any safe and desirable amount of exhaustion or pressure may be secured. No competent aurist would ever think of applying such a force to the drum membrane without being able to note the effect. Having the instrument in position I have been in the habit of drumming upon the bag with the four fingers of the right hand, having found that by this means I could make from 500 to 600 distinct impressions upon the membrana tympani in a minute. The stiff bag is not a
ABC of palliative care: Emergencies
Authors: S. Falk, M. Fallon
Journal: BMJ (1997)

Influenza A virus (IAV) infection-associated morbidity and mortality are a key global healthcare concern, necessitating the identification of novel therapies capable of reducing the severity of IAV infections. In this study, we show that the consumption of a low-carbohydrate, high-fat ketogenic diet (KD) protects mice from lethal IAV infection and disease. KD feeding resulted in an expansion of γδ T cells in the lung that improved barrier functions, thereby enhancing anti-viral resistance. Expansion of these protective γδ T cells required metabolic adaptation to a ketogenic diet, as neither feeding mice a high-fat high-carbohydrate diet nor providing chemical ketone body substrate that bypasses hepatic ketogenesis protected against infection. Therefore, KD mediated immune-metabolic integration represents a viable avenue towards preventing or alleviating influenza disease.
CANDO Médical et Pharmaceutique: Classification Alpha-Numérique de la Documentation
Authors: Roger A. Côté
Journal: JAMA (1985)

Since MeSH (Medical Subject Headings), the system used for classifying documents for the<i>Index Medicus</i>, is unavailable in French, Professor Chevallier, of the René Descartes University in Paris, created CANDO, an alpha-numeric classification for biomedical documents. This classification has two axes or facets: one is represented by two numbers (01, 02, etc), the other by two letters (AB to ZZ). In this fourth edition there are 79 two-digit rubrics or descriptions representing subject headings in medicine and basic sciences, methods of investigation, prevention and therapeutics, and general pathology. These headings are considered to be common denominators. The second axis contains two-letter descriptors, which are actually locators related to humans and their environment. This facet is based on the assumptions that a human being is a physical structure, an agglomerate of chemical substances, a juxtaposition of cells and living tissues, the sum total of body parts, regions, and organs; and that humans
Dataset on deaths related to taking ecstasy looks incomplete
Authors: A R W Forrest
Journal: BMJ (2003)

EDITOR—I wonder whether the data of Schifano et al, on deaths related to taking ecstasy in England and Wales, are complete.1 During their study (1 August 1997 to 31 July 2000), 45 coroners' cases in which the toxicological findings indicated that one of the “ecstasy” group of drugs was implicated in the cause of death were investigated in my …
Use of Placebo Surgery in Controlled Trials of a Cellular-Based Therapy for Parkinson's Disease
Authors: T B Freeman, D E Vawter, P E Leaverton, J H Godbold, R A Hauser, C G Goetz, C W Olanow
Journal: New England Journal of Medicine (1999)

Surgical procedures are frequently introduced into general practice on the basis of uncontrolled studies that are less rigorous than those required for the approval of medical interventions.1 The standard for the evaluation of surgical therapy is lower because of the complexity of designing and conducting scientifically valid and ethically acceptable clinical trials of surgical procedures.2 As a result, many surgical trials fail to control for investigator bias or placebo effects.3,4 The list of inadequately studied invasive or surgical procedures that became part of standard medical practice only to be abandoned after closer scrutiny includes bloodletting, routine tonsillectomy, routine circumcision, . . .
Genome-Wide Scan in a Novel IgA Nephropathy Model Identifies a Susceptibility Locus on Murine Chromosome 10, in a Region Syntenic to Human IGAN1 on Chromosome 6q22–23
Authors: Hitoshi Suzuki, Yusuke Suzuki, Takahiro Yamanaka, Sachiko Hirose, Hiroyuki Nishimura, Junichi Toei, Satoshi Horikoshi, Yasuhiko Tomino
Journal: Journal of the American Society of Nephrology (2005)

Genetic factors are considered to be involved in the initiation and progression of IgA nephropathy (IgAN) on the basis of racial differences in the prevalence and familial aggregation. The ddY mouse is a spontaneous animal model of human IgAN, with a highly variable incidence and extent of glomerular injury as a result of the heterogeneous background, resembling the human situation. It was hypothesized that susceptibility genes for IgAN can be detected by a genome-wide scan using this model. First, serial renal biopsies were performed at 20, 40, and 60 wk of age in 361 ddY mice. The ddY mice were classified into three groups on the basis of the onset of glomerular injury: Early onset at 20 wk (31.9%), late onset at 40 wk (37.9%), and quiescent even at 60 wk (30.2%). The severity of glomerular lesions in both onset groups correlated with the intensity of glomerular IgA deposition but not with serum IgA level. The genome-wide scan with 270 microsatellite markers identified three chromosomal regions on chromosomes 1, 9, and 10, which were significantly associated with the glomerular injuries. Surprisingly, the peak marker D10MIT86 on chromosome 10 is located on the region syntenic to human 6q22–23 with IGAN1, which is the responsible candidate of familial IgAN. In addition, D1MIT16 on chromosome 1 was very closely located at the locus of selectin gene, which is a known candidate of human IgAN. In conclusion, the three-group ddY mouse model can be a useful tool for identifying the susceptibility genes and also to examine their roles in the pathogenesis of IgAN.
Defining smooth muscle cells and smooth muscle injury
Authors: William M. Mahoney, Stephen M. Schwartz
Journal: Journal of Clinical Investigation (2005)

For 3 decades, terms such as synthetic phenotype and contractile phenotype have been used to imply the existence of a specific mechanism for smooth muscle cell (SMC) responses to injury. In this issue of the JCI, Hendrix et al. offer a far more precise approach to examining the mechanisms of SMC responses to injury, focused not on general changes in phenotype but on effects of injury on a single promoter element, the CArG [CC(A/T)6GG] box, in a single gene encoding smooth muscle (SM) α-actin. Since CArG box structures are present in some, but not all, SMC genes, these data suggest that we may be progressing toward establishing a systematic, molecular classification of both SMC subsets and the response of SMCs to different injuries.
Essentials of pediatric psychiatry.
Authors: Eugene I. Falstein
Journal: JAMA (1963)

At first glance one might well wonder why the efforts of four capable and distinguished gentlemen were required to produce and develop this comparatively small book, the avowed purpose of which is to provide the pediatrician with some answers to questions concerning the psychological development and problems of the infant child and adolescent. After reading the meaty material, carefully and comprehensively classified and condensed in a simple but flawless style, the reviewer is convinced that the authors have more than fulfilled their purpose. While of unquestionable value to any open-minded pediatrician, this book might well serve as a text in the medical-school teaching of child and adolescent psychiatry, where its initial impact on all future doctors could be experienced long before specialization in pediatrics would call for a profitable review of its contents. The seven chapters consist of an introduction, a discussion of psychic development, a presentation of normal development
An inexpensive and edible aid for the diagnosis of puberty in the male: multispecies evaluation of an alternative orchidometer
Authors: P. Bhalla, None Sally, None Pippa, G. Williams
Journal: BMJ (2001)

Increasing testicular volume—a useful index of puberty in the male—is measured with an orchidometer, a graded series of ovoid beads on a string.1 This instrument is reliable, but at £28.50 ($43.00) it is prohibitively expensive, and it is usually unobtainable when needed.2

Deeply concerned by the national shortage of orchidometers, two of us (PB and GW) made a serendipitous discovery that led to this study. Briefly, Teasers and Truffle, two chocolates in the Celebrations assortment (Mars UK, Slough), are uncannily similar in size and shape to the 8 ml orchidometer bead (figure). This observation presented a timely opportunity to cut clinic waiting times and costs, two problems that continue to dog the NHS. We therefore compared the conventional orchidometer with its chocolate surrogates, focusing on the key properties of reliability, durability, and palatability.



Conventional 8 ml orchidometer bead …
Kaposi's Sarcoma
Authors: Karen Antman, Yuan Chang
Journal: New England Journal of Medicine (2000)

In 1872, Moritz Kaposi, a Hungarian dermatologist, described five men with aggressive "idiopathic multiple pigmented sarcomas of the skin."1 One patient died of gastrointestinal bleeding 15 months after the initial appearance of the skin lesions, and an autopsy showed visceral lesions in the lungs and the gastrointestinal tract. Subsequently, other investigators described four clinical variants of Kaposi's sarcoma that had identical histologic features but developed in specific populations and had different sites of involvement and rates of progression (Table 1). In the light of recent discoveries regarding the viral pathogenesis of Kaposi's sarcoma, these variants most likely represent different manifestations . . .
Complex multipathways alterations and oxidative stress are associated with Hailey-Hailey disease
Authors: S. Cialfi, C. Oliviero, S. Ceccarelli, C. Marchese, L. Barbieri, G. Biolcati, D. Uccelletti, C. Palleschi, L. Barboni, C. De Bernardo, P. Grammatico, A. Magrelli, M. Salvatore, D. Taruscio, L. Frati, A. Gulino, I. Screpanti, C. Talora
Journal: British Journal of Dermatology (2009)

Hailey-Hailey disease (HHD) is an autosomal dominant disorder characterized by suprabasal cutaneous cell separation (acantholysis) leading to the development of erosive and oozing skin lesions. While a strong relationship exists between mutations in the gene that encodes the Ca(2+)/Mn(2+)-adenosine triphosphatase ATP2C1 and HHD, we still have little understanding of how these mutations affect manifestations of the disease.This study was designed to determine early signalling events that affect epithelial cell growth and differentiation during HHD development.Expression of key regulatory signals important for maintaining skin homeostasis were evaluated by Western blot analysis and by reverse transcriptase-polymerase chain reaction in primary keratinocytes obtained from skin biopsies of patients with HHD. Reactive oxygen species accumulation in primary keratinocytes derived from lesional skin of patients with HHD was assessed by dihydrorhodamine 123 (DHR) assay.HHD-derived keratinocytes showed downregulation of both Notch1 and differential regulation of different p63 isoforms. Itch and p63 are co-expressed in the epidermis and in primary keratinocytes where Itch controls the p63 protein steady-state level. We found that the Itch protein was significantly decreased in HHD-derived keratinocytes whereas the expression of its target, c-Jun, remained unaffected. We also found that HHD-derived keratinocytes undergo oxidative stress, which may explain both Notch1 and Itch downregulation.Our attempt to explore the molecular mechanism underlying HHD indicates a complex puzzle in which multi-hit combinations of altered signal pathways may explain the wide spectrum of defects in HHD.
Mechanism of Elevated Innominate Artery Pressures in Supravalvular Aortic Stenosis
Authors: ROBERT E. GOLDSTEIN, STEPHEN E. EPSTEIN
Journal: Circulation (1970)

Patients with supravalvular aortic stenosis frequently have higher phasic and mean blood pressures in the innominate artery than in the aorta distal to the stenosis, a finding never fully explained. Theoretically, this phenomenon could result from the impact of a jet upon blood within the innominate artery. Slowing of the jet would convert kinetic into potential energy, thus increasing pressure within the innominate artery. The aorta distal to the innominate artery would receive blood whose kinetic energy had been dissipated and would consequently remain at the same pressure as the aorta proximal to the origin of the innominate artery. This hypothesis was tested in a model simulating supravalvular aortic stenosis. Cinematography showed a jet directed into the innominate artery. Only after this jet was dispersed, did fluid turn backward to flow into the distal portion of the aorta. Observed pressure rises in the innominate artery corresponded closely with values predicted from the estimated kinetic energy of the jet. Dispersion of the jet by replacement of the stenotic orifice with an equally obstructive screen or proximal displacement of the stenosis (simulating valvular aortic stenosis) abolished the pressure difference. The results obtained were thus entirely consistent with the mechanism proposed to explain the elevated innominate artery pressures seen in supravalvular aortic stenosis.