tbuckley/cabot-search huggingface dataset:
Cyclical Variation in HbA1c Values During the Year: Clinical and Research Implications
Authors: Nathan R. Hill, Catherine J. Peters, Rebecca J. Thompson, David R. Matthews, Peter C. Hindmarsh
Journal: Diabetes Care (2013)

The association between glycated hemoglobin (HbA1c) and long-term diabetes complications is well established (1). Although HbA1c is a key process and outcome measure in clinical and research settings, reporting varies from single annual measurements to an average of interval measurements per year. Seasonal HbA1c variability within an individual may impact on audit and intervention studies in clinical trials (2). Previous seasonal variability studies have used small datasets and short time intervals. Six equidistant samples are required to describe a cycle of seasonal variation, which means that a minimum dataset of 3 years is required.

We examined seasonal variation using HbA1c measurements collected quarterly from children aged 2–21 years (mean 12.9 years) attending a single clinic between 1999 and 2012. HbA1c was measured using the Diabetes Control and Complications Trial–aligned DCA1000 (Siemens Healthcare Diagnostics Inc., Deerfield, IL). Bias …
Herpes gestationis: ultrastructural identification of the extracellular antigenic sites in diseased skin using immunogold techniques
Authors: S. KARPATI, W. STOLZ, M. MEURER, O. BRAUN-FALCO, T. KRIEG
Journal: British Journal of Dermatology (1991)

Using a direct immunogold technique, we studied the level of immunological events in the skin basement membrane in a patient with herpes gestationis during blister formation. Within the lamina lucida, IgG and C3 were localized beneath the basement membrane of basal keratinocytes, 30-40 nm above the lamina densa. In many areas of blister formation sub-basal dense plates, but probably also the upper parts of the hemidesmosomes were separated from the roof of the blister. In the perilesional lamina lucida and in the blister, IgG and C3 containing amorphous grains, most probably immunocomplex aggregates, were detected. They covered the basement membrane of keratinocytes and left free a 30-40 nm band above the lamina densa. Our study indicates that in herpes gestationis the cleavage, accompanied by IgG, C3 and immunocomplex deposition, occurs at the level of the sub-basal dense plate. However, cleavage through upper hemidesmosomal structures can occur in parallel. These data further support the involvement of hemidesmosomes in the pathogenesis of the disease and therefore in its relationship to bullous pemphigoid.
Transfer of a cathelicidin peptide antibiotic gene restores bacterial killing in a cystic fibrosis xenograft model
Authors: Robert Bals, Daniel J. Weiner, Rupalie L. Meegalla, James M. Wilson
Journal: Journal of Clinical Investigation (1999)

Recent studies suggest that the gene defect in cystic fibrosis (CF) leads to a breach in innate immunity. We describe a novel genetic strategy for reversing the CF-specific defect of antimicrobial activity by transferring a gene encoding a secreted cathelicidin peptide antibiotic into the airway epithelium grown in a human bronchial xenograft model. The airway surface fluid (ASF) from CF xenografts failed to kill Pseudomonas aeruginosa or Staphylococcus aureus. Partial reconstitution of CF transmembrane conductance regulator expression after adenovirus-mediated gene transfer restored the antimicrobial activity of ASF from CF xenografts to normal levels. Exposure of CF xenografts to an adenovirus expressing the human cathelicidin LL-37/hCAP-18 increased levels of this peptide in the ASF three- to fourfold above the normal concentrations, which were equivalent in ASF from CF and normal xenografts before gene transfer. The increase of LL-37 was sufficient to restore bacterial killing to normal levels. The data presented describe an alternative genetic approach to the treatment of CF based on enhanced expression of an endogenous antimicrobial peptide and provide strong evidence that expression of antimicrobial peptides indeed protects against bacterial infection.
Effects of Industrial Noise
Authors: J. D. K. Dawes
Journal: BMJ (1970)

can neurosurgeon, has written a series of essays pleading for more humanity and less prodigal laboratory "science" in the handl- ing of patients.He invokes without, I think, strict applicability, William of Occam's principle Entia non sunt multi- plicanda praeter necessitatem to support his passionate belief that the more thoughtful and able the physician, the fewer laboratory and special tests are required.He de- nounces the demand for "a complete workup" before a careful history is taken and a thorough physical examination per- formed, but curiously, in view of his address on profitable malpractice suits, main- tains that routine skull x-rays are to be avoided in head injuries if palpation reveals no depression and clinical examination no abnormality.His views on the provision of super- specialist surgical centres should be read and re-read by our N.H.S. planners.It
Halothane Hepatitis
Authors: Geoffrey Farrell, Debra Prendergast, Michael Murray
Journal: New England Journal of Medicine (1985)

We studied susceptibility to halothane hepatitis with an in vitro test that detects cell damage from electrophilic drug intermediates. Metabolites of phenytoin were generated by incubation of phenytoin with rat hepatic microsomes in the presence of the epoxide hydrolase inhibitor 1,1,1-trichloropropene oxide (TCPO), which prevents the further metabolism of phenytoin to an inert metabolite. In lymphocytes exposed to this system, cytotoxicity was measured by trypan blue dye exclusion and was expressed as the percentage increase in trypan blue—positive cells after the addition of TCPO. In the presence of TCPO, lymphocytes from 11 patients with halothane hepatitis exhibited an increase in cytotoxicity at 0.06 mM phenytoin that was eight times greater than the increase in healthy controls (54±10 per cent [mean ±S.E.M.] vs. 7.1±2.2 per cent, P<0.0001). Patients with other liver diseases and persons recently exposed to halothane without adverse effects did not differ from healthy controls. In three patients with halothane hepatitis who were studied serially, the lymphocyte abnormality was still present after 13 months. Family studies revealed abnormal results on 10 cytotoxicity tests among 19 members of four families. We propose that there is a familial, constitutional susceptibility factor that predisposes persons to halothane hepatitis. (N Engl J Med 1985; 313:1310–4.)
Incidence of Pentosuria
Authors: William T. Wright
Journal: New England Journal of Medicine (1961)

IN ten years the John Hancock Mutual Life Insurance Company's Home Office medical laboratory discovered 22 pentosuric reactions among 895,000 insurance applicants, or 1:41,000. This agrees sufficiently with the 1:20,000 to 1:30,000 reported by Barach,1 and the 1:50,000 by Blatherwick.2 Its limitation to the Hebrew race could not be checked. Several applicants gave their race, quite properly, as: white, American. However, all the names sounded Hebrew.The sugar in the urine of a person with pentosuria is L-xylulose, as distinguished from other five-carbon-atom sugars. The condition is considered benign.3 If otherwise acceptable persons with pentosuria may obtain insurance from the . . .
Improvement in Atrophic Gastritis and Intestinal Metaplasia in Patients in Whom <i>Helicobacter pylori</i> Was Eradicated
Authors: Toshifumi Ohkusa, Kazuhiko Fujiki, Ichizen Takashimizu, Jiro Kumagai, Toru Tanizawa, Yoshinobu Eishi, Tetsuji Yokoyama, Mamoru Watanabe
Journal: Annals of Internal Medicine (2001)

Background: Glandular atrophy and intestinal metaplasia are precancerous lesions; whether Helicobacter pylori eradication affects these lesions is controversial. Objective: To determine whether H. pylori eradication is associated with improvement in glandular atrophy and intestinal metaplasia after at least 1 year. Design: Single-blind, uncontrolled prospective trial. Setting: Academic gastroenterology clinic in Japan. Patients: 163 consecutive patients with dyspepsia and H. pylori infection. Intervention: One-week course of a proton-pump inhibitor and antibiotic therapy. Measurements: Endoscopic examination with antral and corporal biopsy was done before treatment and at 1 to 3 and 12 to 15 months after treatment. Gastritis, atrophy, and metaplasia were graded according to the updated Sydney System. Results: In the 115 patients in whom H. pylori was eradicated, inflammation and mean neutrophil activity had decreased by 1 to 3 months, and both glandular atrophy in the corpus and intestinal metaplasia in the antrum had decreased by 12 to 15 months. Glandular atrophy in the corpus improved in 34 (89%) of 38 patients with atrophy before treatment, and intestinal metaplasia in the antrum improved in 28 (61%) of 46 patients who had metaplasia at baseline. In the 48 patients in whom eradication was unsuccessful, no significant histologic changes were observed. Conclusion: In the year after successful H. pylori eradication, precancerous lesions improved in most patients.
How are children different from adults?
Authors: C F Bearer
Journal: Environmental Health Perspectives (1995)

Several factors alter an individual's risk for an environmentally related illness. A major determinant is the age of the individual. The toxicodynamic processes that determine exposure, absorption, metabolism, excretion, and tissue vulnerability are all age related. This paper discusses each of these processes and their variability with age, and illustrates these points with examples of environmentally related disease cases.
Abstract PD3-3: Next generation sequencing shows clonal selection after treatment with anastrozole or fulvestrant in a randomized trial of postmenopausal patients with large operable or locally-advanced hormone-receptor-positive breast cancer
Authors: RD Iggo, HM Wood, P Rabbitts, N Quenel-Tueux, L Mauriac, G MacGrogan, H Bonnefoi
Journal: Cancer Research (2013)

Abstract Background: Unlike chemotherapy, endocrine therapy is not clastogenic or mutagenic, so genetic changes arising during treatment are unlikely to be secondary events provoked by iatrogenic DNA damage. Endocrine therapy for breast cancer is thus a clean setting in which to explore the evolution of tumour genomes under treatment, and the changes seen are likely to be biologically meaningful. To identify such changes we have analysed pre and post treatment biopsies from a clinical trial that compared two endocrine therapies. Patients and methods: DNA was extracted from pre and post treatment samples from 20 patients enrolled in the HORGEN trial. Postmenopausal patients with large operable or locally-advanced hormone-receptor-positive breast cancer were randomly assigned to receive either neoadjuvant anastrozole or fulvestrant for 6 months in this multicenter randomized phase II study. Low depth next generation sequencing was used to generate DNA copy number profiles for each sample. Results: The copy number profiles were similar before and after treatment in 10 cases. In three cases new amplicons appeared. In one case the amplicon contained the ESR1 gene, in another the FOXA1 gene, and in the third the NCOA3 gene. In the remaining seven cases where the profiles changed after treatment, the differences affected whole chromosomal arms. In six of these cases the profiles became simpler, indicating that clones with gains and losses of chromosomal arms had been counterselected by the treatment. Conclusions: Differences between the pre and post treatment biopsies were surprisingly frequent and informative. Genes directly implicated in estrogen signalling were amplified in three cases. This suggests that specific amplicons confer resistance to endocrine therapy. From a clinical perspective, their appearance in a post treatment biopsy probably indicates that the treatment should be changed. A possible explanation for the chromosomal arm changes after treatment, a phenomenon we have dubbed the “wandering arms” phenotype, is that endocrine therapy deprives tumour cells of signals that are necessary for the survival of clones with copy number changes affecting whole chromosomal arms. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr PD3-3.
Diffusion capacity and BMPR2 mutations in pulmonary arterial hypertension
Authors: Pia Trip, Barbara Girerd, Harm-Jan Bogaard, Frances S. de Man, Anco Boonstra, Gilles Garcia, Marc Humbert, David Montani, Anton Vonk-Noordegraaf
Journal: European Respiratory Journal (2013)

To the Editor: 

Pulmonary arterial hypertension (PAH) is a disease in which remodelling of the small pulmonary arteries leads to an increase in pulmonary artery pressure (PAP). The most important genetic predisposing factor related to PAH is a mutation in the bone morphogenetic protein receptor type 2 gene ( BMPR2 ) [1, 2]. BMPR2 mutation carriers are known to present with disease at an earlier age and with worse haemodynamics [3]. We recently showed in a cohort of patients with idiopathic and hereditary PAH that a very low diffusion capacity for carbon monoxide ( D LCO) is exclusively found in some of the patients without identified BMPR2 mutations, whereas BMPR2 mutation carriers have a relatively preserved D LCO [4]. D LCO is a noninvasive marker of the quality of the alveolar capillary structure [5] and the observed difference in D LCO supports the hypothesis that distinct vascular disease processes are at play in BMPR2 mutation-related PAH and non BMPR2 mutation-related idiopathic PAH. Until recently, insufficient availability of lung samples has prohibited the performance of a detailed comparison of the pulmonary vascular pathologies in these two disease groups [6]. Therefore, we sought, in the present study, to confirm the previously found influence of BMPR2 mutations on diffusion capacity in a much larger multinational patient cohort.

We performed a retrospective collaborative study at the VU University Medical Center in Amsterdam, the Netherlands and the Universite Paris-Sud, Assistance Publique Hopitaux de Paris, Le Kremlin-Bicetre, France. Patients were eligible for this study when classified in the database with idiopathic or familial PAH, and when the results from BMPR2 mutation analysis and D LCO measurements were available. Patients were diagnosed with idiopathic …
Anaphylactic Cardiac Arrest in a Parturient
Authors: Roberto Levi
Journal: JAMA (1981)

To the Editor.—  I have read the report by Baraka and Sfeir entitled Anaphylactic Cardiac Arrest in a Parturient: Response of the Newborn (1980;243:1745). Aside from the fact that apparently the fetus was not involved in the anaphylactic reaction, the case is particularly interesting because, in my opinion, it represents additional evidence that the heart is a target organ in systemic immediate hypersensitivity reactions. The patient experienced tachycardia and  arrest, presumably caused by ventricular fibrillation. Both of these are pathognomonic signs of direct cardiac involvement in the anaphylactic reaction, as demonstrated in the laboratory by us 1,2 and others. 3   Antigen reacts with antibodies bound to cardiac mast cells, and this elicits the intracardiac release of mediators such as histamine, prostaglandins, and slow-reacting substance of anaphylaxis, all of which—either alone or in combination with reflexly released catecholamines—cause severe cardiac dysfunction. Several clinical reports, some published in JAMA (1959;170:1628; 1970;211:627)
Clinical Features of Infection with Hemadsorption Viruses
Authors: Robert H. Parrott, Andrew Vargosko, Alia Luckey, Hyun Wha Kim, Christine Cumming, Robert Chanock
Journal: New England Journal of Medicine (1959)

IN October, 1957, two new myxoviruses, hemadsorption viruses Types 1 and 2, were isolated from the oropharynx of children.1 Subsequent controlled studies have indicated that these viruses have an etiologic role in pediatric respiratory-tract disease.2 3 4 This paper describes the clinical findings in affected children, who, in general, show a wide spectrum of respiratory-tract illness varying from rhinitis and bronchitis with or without fever through relatively severe croup syndrome or bronchopneumonia.MethodIn this study swabs of the posterior oropharynx of infants and children with respiratory-tract disease and of age-matched controls were tested in several types of tissue culture, including monkey . . .
Chronic Congestive Heart Failure Elicits Adaptations of Endurance Exercise in Diaphragmatic Muscle
Authors: Boris Tikunov, Sanford Levine, Donna Mancini
Journal: Circulation (1997)

Background During rest and exercise, patients with heart failure hyperventilate; therefore, the diaphragm can be viewed as undergoing constant moderate-intensity exercise. Accordingly, we hypothesized that heart failure elicits adaptations in the diaphragm similar to those elicited by endurance exercise in the limb muscles of normal subjects. Methods and Results Costal diaphragmatic biopsy samples were obtained from 7 normal subjects (age, 36±20 years) and 10 patients (age, 50±6 years; left ventricular ejection fraction, 18±8%) at the time of transplant or left ventricular assist-device placement. We measured the distribution of myosin heavy chain isoforms I, IIa, and IIb by SDS gel electrophoresis. We also measured the activities of the following enzymes: citrate synthase, a marker of oxidative metabolism; β-hydroxyacyl-CoA dehydrogenase, a marker of lipolytic metabolism; and lactate dehydrogenase, a marker of glycolytic metabolism. In normal subjects, the distribution of myosin heavy chain isoforms I, IIa, and IIb was 43±2%, 40±2%, and 17±1%, respectively. In contrast, in heart failure subjects, the fiber distribution was 55±2%, 38±2%, and 7±2% for types I, IIa, and IIb, respectively. Therefore, in heart failure, myosin heavy chain I is increased ( P &lt;.0001) and myosin heavy chain IIb decreased from normal levels ( P &lt;.001). Additionally, citrate synthase activity (normal, 0.33±0.14; heart failure, 0.54±0.21 μmol·min −1 ·mg protein −1 ; P &lt;.05) and β-hydroxyacyl-CoA dehydrogenase activity (normal, 0.27±0.04; heart failure, 0.38±0.02 μmol·min −1 ·mg protein −1 ; P &lt;.05) were greater in heart failure patients than in normal subjects, whereas lactate dehydrogenase activity was significantly less in heart failure patients than in normal subjects (normal, 11.6±4.6; heart failure,: 4.3±2.2 μmol·min −1 ·mg protein −1 ; P &lt;.01). Conclusions In the diaphragm in heart failure, there is a shift from fast to slow myosin heavy chain isoforms with an increase in oxidative capacity and a decrease in glycolytic capacity. These diaphragmatic muscle changes are consistent with those elicited by endurance training of the limb muscles in normal subjects.
Inadequacy of Papanicolaou Smears in the Detection of Endometrial Cancer
Authors: John R. Burk, Herman F. Lehman, Frederick S. Wolf
Journal: New England Journal of Medicine (1974)

BY State law and appropriate regulation the State Health Department initiated an Alabama Cancer Registry (A.C.R.) in 1961. This data bank provides the basis for this report.Kistner et al. have suggested a rising incidence of endometrial cancer.1 Jones et al. found a lowering of the ratio of cervical to endometrial cancer.2 The A.C.R. shows a ratio of 4.9:1 in 1962 to 3.3:1 in 1972. Sharon et al. reported a reversal of the cervical to endometrial cancer ratio in Israel.3 MethodsThe usefulness of the Papanicolaou technic for detection of endometrial cancer was studied by arbitrary selection of both all . . .
Cancer and the Kidney
Authors: Max Haid
Journal: JAMA (1983)

<i>Why Cancer and the Kidney?</i>Drs Rieselbach and Garnick have had the insight to realize that cancers, their treatment, and the kidney are inextricably entwined. As oncological subspecialties continue to mature, the permutations of these three entities are encountered with increasing frequency. This book will probably be the progenitor of a variety of books reviewing "Cancer and Your Organ of Greatest Interest." <i>Cancer and the Kidney</i>is divided into five sections covering basic nephrology germane to oncology, humoral effects of malignant neoplasm on the kidney, mechanical tumor effects on the kidney, renal complications of antineoplastic therapy, and renal disease or its treatment as a carcinogenic force. Each section is preceded by a medical illustration, which adds little and takes up space. Those of us who are accustomed to the Frank Netter type of drawing will find these sketches primitive. However, they do not detract from the overall value of the
Microcapsules engineered to support mesenchymal stem cell (MSC) survival and proliferation enable long-term retention of MSCs in infarcted myocardium
Authors: Anna Blocki, Sebastian Beyer, Jean-Yves Dewavrin, Anna Goralczyk, Yingting Wang, Priscilla Peh, Michael Ng, Shehzahdi S. Moonshi, Susmitha Vuddagiri, Michael Raghunath, Eliana C. Martinez, Kishore K. Bhakoo
Journal: Biomaterials (2015)
SAFETY AND EFFICACY OF DABIGATRAN VERSUS WARFARIN IN PATIENTS WITH PERSISTENT AND LONG-ACTING ATRIAL FIBRILLATION UNDERGOING ELECTRICAL CARDIOVERSION
Authors: Oskars Kalejs, Sandis Sakne, Olga Litunenko, Aldis Strelnieks, Maija Vikmane, Marina Kovalova, Ginta Kamzola, Milana Zabunova, Kaspars Kupics, Aivars Lejnieks, Andrejs Erglis
Journal: Journal of the American College of Cardiology (2014)
A Re-Evaluation of the Graham-Steell Murmur
Authors: Albert N. Brest, Vasant Udhoji, William Likoff
Journal: New England Journal of Medicine (1960)

THE Graham-Steell murmur was originally described in 1888.¶ Since that time little factual information has been accumulated concerning this bruit. A search of the American literature during the past ten years has, in fact, failed to reveal any significant contribution in this regard. It therefore seems appropriate to review our own experience with 10 patients with early diastolic murmurs along the left sternal border that categorically fit the description of the Graham-Steell murmur.Material and MethodsTen patients with mitral stenosis and an accompanying early diastolic murmur along the left sternal border were selected for this study. In each the . . .
Fatal Varicella in a Child With Congenital Heart Disease
Authors: Thomas P. Foley
Journal: JAMA (1967)

Clinically and pathologically confirmed primary varicella pneumonia and generalized varicella associated with asymptomatic congenital heart disease (coarctation of the aorta, patent ductus arteriosus, and mitral stenosis) occurred in a 4-year-old girl. The patient had not been treated with adrenal cortical hormones or immunosuppressive drugs.
Liver Transplantation for the Abernathy Malformation
Authors: Nahel Elias, Christina V. Scirica, Martin Hertl
Journal: New England Journal of Medicine (2008)

To the Editor: Previously in the Journal, we reported on a 4-year-old boy with the hepatopulmonary syndrome, a condition characterized by intrapulmonary shunting due to dilatation of pulmonary vess...
Comparison of the effects of nitroprusside and nifedipine on diastolic properties in patients with hypertrophic cardiomyopathy: Altered left ventricular loading or improved muscle inactivation?
Authors: Walter J. Paulus, Beverly H. Lorell, William E. Craig, Joshua Wynne, Joseph P. Murgo, William Grossman
Journal: Journal of the American College of Cardiology (1983)