tbuckley/cabot-search huggingface dataset:
Cellular distribution of insulin-degrading enzyme gene expression. Comparison with insulin and insulin-like growth factor receptors.
Authors: C A Bondy, J Zhou, E Chin, R R Reinhardt, L Ding, R A Roth
Journal: Journal of Clinical Investigation (1994)

Insulin-degrading enzyme (IDE) hydrolyzes both insulin and IGFs and has been proposed to play a role in signal termination after binding of these peptides to their receptors. In situ hybridization was used to investigate the cellular distribution of IDE mRNA and to compare it with insulin receptor (IR) and IGF-I receptor (IGFR) gene expression in serial thin sections from a variety of tissues in embryonic and adult rats. IDE mRNA is highly abundant in kidney and liver, tissues known to play a role in insulin degradation. IDE and IR mRNAs are highly coexpressed in brown fat and liver. The highest level IDE gene expression, on a per cell basis, is found in germinal epithelium. IDE and IGFR mRNAs are colocalized in oocytes, while IDE is colocalized with the IGF-II receptor in spermatocytes, suggesting that IDE may be involved with degradation of IGF-II in the testis. In summary, IDE expression demonstrates significant anatomical correlation with insulin/IGF receptors. These data are compatible with a role for IDE in degrading insulin and IGFs after they bind to and are internalized with their respective receptors and may also suggest a novel role for IDE in germ cells.
ELIMINATION OF PERITONEAL INFECTION AND PREVENTION OF SURGICAL PERITONITIS.
Authors: JOHN G. CLARK
Journal: JAMA (1901)

The physiologic, anatomic and pathologic laboratories are scientific workshops from which both the physician and surgeon may constantly derive points of the greatest value in the advancement of his science. In fact, the remarkable evolution in medicine and surgery of the past decade is largely based on principles established and accurately tested in the laboratory. Instead, therefore, of the laboratory archives being mere repositories of dry scientific facts, they may be of absorbing interest and incalculable value when carefully scanned by the practical eye seeking suggestions which may be applied in everyday medical and surgical work. For the last six years all investigations upon the functions and anatomy of the peritoneum have been of constant interest to me, for upon the facts established in these researches we are justified in reversing some of the apparently well-grounded principles in surgery. In 1896, as a result of the combined study of seventeen
Oscillatory Patterns in Sympathetic Neural Discharge and Cardiovascular Variables During Orthostatic Stimulus
Authors: Raffaello Furlan, Alberto Porta, Fernando Costa, Jens Tank, Lemont Baker, Richard Schiavi, David Robertson, Alberto Malliani, Rogelio Mosqueda-Garcia
Journal: Circulation (2000)

We tested the hypothesis that a common oscillatory pattern might characterize the rhythmic discharge of muscle sympathetic nerve activity (MSNA) and the spontaneous variability of heart rate and systolic arterial pressure (SAP) during a physiological increase of sympathetic activity induced by the head-up tilt maneuver.Ten healthy subjects underwent continuous recordings of ECG, intra-arterial pressure, respiratory activity, central venous pressure, and MSNA, both in the recumbent position and during 75 degrees head-up tilt. Venous samplings for catecholamine assessment were obtained at rest and during the fifth minute of tilt. Spectrum and cross-spectrum analyses of R-R interval, SAP, and MSNA variabilities and of respiratory activity provided the low (LF, 0.1 Hz) and high frequency (HF, 0.27 Hz) rhythmic components of each signal and assessed their linear relationships. Compared with the recumbent position, tilt reduced central venous pressure, but blood pressure was unchanged. Heart rate, MSNA, and plasma epinephrine and norepinephrine levels increased, suggesting a marked enhancement of overall sympathetic activity. During tilt, LF(MSNA) increased compared with the level in the supine position; this mirrored similar changes observed in the LF components of R-R interval and SAP variabilities. The increase of LF(MSNA) was proportional to the amount of the sympathetic discharge. The coupling between LF components of MSNA and R-R interval and SAP variabilities was enhanced during tilt compared with rest.During the sympathetic activation induced by tilt, a similar oscillatory pattern based on an increased LF rhythmicity characterized the spontaneous variability of neural sympathetic discharge, R-R interval, and arterial pressure.
NICE may be biased too
Authors: M. J. Toal
Journal: BMJ (2011)

John-Baptiste and Bell characterise the purported differences in health economic analyses as an industry driven bias.1 No consideration is given to the possibility that National Institute for Health and Clinical Excellence (NICE) appraisals are biased in the other direction.

Most people involved in health economics know that analyses ultimately boil down to two main considerations—the data selected for input to the …
Putting the Risk of Breast Cancer in Perspective
Authors: Kelly-Anne Phillips, Gordon Glendon, Julia A. Knight
Journal: New England Journal of Medicine (1999)

Educating the public about the risk of breast cancer promises to contribute to the prevention or early detection of the disease. Data on the risk of breast cancer are widely available to physicians and the public. However, for this information to be interpretable, it should be presented in a form that enables the risk to be understood in context. This is rarely the case, because of the difficulties involved in conveying such inherently complex information to a population and to individual women.Several studies have shown that women tend to overestimate their risk of breast cancer and that many fail . . .
Treatment of HIV Infection — Progress in Perspective
Authors: Lawrence Corey, Thomas R. Fleming
Journal: New England Journal of Medicine (1992)

ALTHOUGH the past five years have brought advances in treatment, the article by Hamilton and associates in this issue of the Journal demonstrates that the human immunodeficiency virus (HIV) as a viral infection and the acquired immunodeficiency syndrome (AIDS) as an illness are still inexorably progressive.1 The Veterans Affairs Cooperative Study Group on AIDS Treatment randomly assigned patients with symptomatic HIV infection and CD4+ counts between 0.2×109 and 0.5×109 per liter (200 and 500 per cubic millimeter) (mean, 0.355 per liter [355 per cubic millimeter]) to receive either placebo or zidovudine (1500 mg daily) until an AIDS-defining illness developed or . . .
Percutaneous Mitral Annular Reduction Provides Continued Benefit in an Ovine Model of Dilated Cardiomyopathy
Authors: Melissa J. Byrne, David M. Kaye, Mark Mathis, David G. Reuter, Clif A. Alferness, John M. Power
Journal: Circulation (2004)

Functional mitral valve regurgitation plays a key role in the symptomatic severity and progression of heart failure. In an ovine model of dilated cardiomyopathy, we examined the chronic functional consequences of mitral regurgitation reduction using a recently developed novel percutaneous mitral annular reduction (PMAR) device.Fourteen adult sheep were paced right ventricularly at 180 to 190 bpm for 5 weeks, leading to the development of moderate mitral valve regurgitation. After echocardiographic, hemodynamic, and neurohormonal analysis, 9 animals underwent PMAR. All animals were subsequently paced for another 28 days, and a final echocardiographic and hemodynamic study was conducted. Animals that had undergone PMAR showed significantly increased negative and positive dP/dt, whereas pulmonary capillary wedge pressure and mitral valve regurgitation were significantly reduced compared with those at device implant despite continued pacing. In conjunction, significant improvements in plasma norepinephrine and brain natriuretic peptide were apparent.The application of PMAR in animals with pacing-induced dilated cardiomyopathy and functional mitral valve regurgitation resulted in continued improvements in hemodynamic and neurohormonal parameters.
Meta-analysis: Age and Effectiveness of Prophylactic Implantable Cardioverter-Defibrillators
Authors: Pasquale Santangeli, Luigi Di Biase, Antonio Dello Russo, Michela Casella, Stefano Bartoletti, Pietro Santarelli, Gemma Pelargonio, Andrea Natale
Journal: Annals of Internal Medicine (2010)

This article has been corrected. The original version (PDF) is appended to this article as a supplement. Background: Implantable cardioverter-defibrillators (ICDs) for the primary prevention of sudden cardiac death have been proven effective in several clinical trials. Purpose: To summarize evidence about the effectiveness of ICDs versus standard medical therapy for the primary prevention of sudden cardiac death in different age groups of patients with severe left ventricular dysfunction. Data Sources: MEDLINE, Embase, CENTRAL, BioMed Central, Cardiosource, ClinicalTrials.gov, and ISI Web of Science (January 1970 to April 2010) were searched with no language restrictions. Study Selection: Two independent reviewers screened titles and abstracts to identify randomized, controlled trials of prophylactic ICD versus medical therapy in patients with severe left ventricular dysfunction that provided data about mortality outcomes for different age groups. Data Extraction: Two independent reviewers assessed risk for bias of trials and extracted patient and study characteristics and hazard ratios (HRs) relevant to all-cause mortality. Data Synthesis: Five trials (MADIT-II, DEFINITE, DINAMIT, SCD-HeFT, and IRIS) that enrolled 5783 patients (44% were elderly) were included. The primary analysis, which excluded the 2 trials enrolling patients early after acute myocardial infarction (DINAMIT and IRIS), found that prophylactic ICD therapy reduced mortality in younger patients (HR, 0.65 [95% CI, 0.50 to 0.83]; P < 0.001). A smaller survival benefit was found in elderly patients (HR, 0.75 [95% CI, 0.61 to 0.91]) that was not confirmed when MADIT-II patients older than 70 years were excluded or when data from DINAMIT and IRIS were included. Limitations: Four potentially eligible trials were not included in the meta-analysis because mortality data by age group were not available. Adjustment for differences in comorbid conditions and medical therapies among patients enrolled in the trials was not possible. Conclusion: Available data suggest that prophylactic ICD therapy may be less beneficial for elderly patients with severe left ventricular dysfunction than for younger patients. Primary Funding Source: None.
Occupational asthma and contact urticaria from dried flowers of <i>Limonium tataricum</i>
Authors: S. Quirce, B. García‐Figueroa, J. M. Olaguíbel, M. D. Muro, A. I. Tabar
Journal: Allergy (1993)

Dried flowers of Limonium tataricum (LT) are widely used for semipermanent floral arrangements. We report a case of a floral industry worker in whom exposure to LT precipitated rhinoconjunctivitis, asthma, and contact urticaria. Studies revealed the presence of immediate skin test reactivity and positive leukocyte histamine release in response to LT extract. Specific anti‐LT antibodies were detected in the patient's serum by direct RAST. Bronchial challenge with LT extract also resulted in an isolated immediate asthmatic response. Both the positive methacholine inhalation test and the significant changes observed in PEFR measurements when the patient handled LT supported the diagnosis of occupational asthma. These findings strongly suggest that an IgE‐mediated immunologic mechanism is responsible for the patient's respiratory and cutaneous symptoms.
FACTORS INFLUENCING THE CORRELATION BETWEEN DIFFERENCES OF ELECTRIC POTENTIAL IN THE SKIN OF HUMAN SUBJECTS AND BASAL METABOLISM
Authors: Charlotte Purdy, Charles Sheard
Journal: The Journal of Experimental Medicine (1931)

High metabolic rates are associated normally with small differences of electric potential, whereas low metabolic rates are associated with large differences of electric potential as measured on the extremities of the body. Within the normal range of metabolism there appears to be a definite correlation between the metabolic rates and the difference of electric potential over a specified area of the skin, provided the person under test has no abnormalities of the circulatory system or of the functions of the skin. If there are no dysfunctions of the circulation or of the skin, the metabolic rate may be calculated, within +/-4 points, from the expression See PDF for Equation where x is the metabolic rate and y is the difference of electric potential across the specified areas of skin (electrodes 12 cm. apart). In general, there are abnormalities of the circulation of the blood or of the functions of the skin of persons for whom the metabolic rates determined by the two methods (difference of electric potentials and gasometric procedures) do not agree with +/-4 points. Manifest retardation or return to normality in the rate of circulation of the blood, such as may be produced by the sphygmomanometric cuff under varying pressures, produces marked changes in the difference of electric potentials obtained across a specified intervening area of skin. Retardation of flow of blood produces increased differences of electric potential. Preliminary investigations indicate that there is an inverse correlation between cutaneous temperatures and differences of electric potential. Day by day variations, emotive effects and the partaking of food have less effect, in general, on the electric potentials across a specified area of skin than they have on the metabolic rates. These experimental results indicate that there may be a more direct correlation between electric potentials and the circulation of the blood per se than between electric potentials and the metabolism of the body per se. When normality of circulation of the blood and of the functions of the skin exists in the areas under test for differences of electric potential, there is apparently a correlation between metabolic rates and electric potentials.
Abstract B6: Folylpoly-glutamate synthetase and thymidylate synthase are associated with clinical outcome from pemetrexed-based therapy in non-small cell lung cancer (NSCLC)
Authors: Daniel C. Christoph, Heike Loewendick, Anja Peglow, Martin Schuler, Wilfried E. Eberhardt, Fred R. Hirsch, Bernadette Reyna Asuncion, Murry W. Wynes, Thomas C. Gauler, Jeremias Wohlschlaeger, Dirk Theegarten, Stefan Welter, Cindy Tran, Biftu Hassan
Journal: Clinical Cancer Research (2012)

Abstract Background: The antifolate pemetrexed targets multiple enzymes involved in pyrimidine and purine synthesis including thymidylate synthase (TS). After entry into cells, pemetrexed is converted to polyglutamated forms by folylpoly-γ-glutamate synthetase (FPGS), a critical step to achieve full target inhibition. We hypothesized that FPGS and TS protein expression may predict outcome following pemetrexed-treatment of patients with advanced NSCLC, like in malignant pleural mesotheliomas (Christoph et al., J Clin Oncol. 2011: 29 suppl.). This is the largest report on pemetrexed-treatment outcome based on TS and FPGS in Caucasian patients with advanced NSCLC. Methods: Pretreatment tumor samples from 161 patients (pts) with metastatic NSCLC, treated with pemetrexed combined with platinum (74 pts (46%)) or as single agent (82 pts (51%)) or within other combinations (5 pts (3%)), were retrospectively analyzed. FPGS and TS protein expression levels were evaluated by IHC using the H-Scoring system (0–300), which relies on the product of intensity (range 0 to 3) and the percentage of positive tumor cells (0–100%). Radiographic evaluation of response was performed according to RECIST criteria (version 1.1). Results: Median pretreatment H-scores were 180 for FPGS (range: 0–280) and 205 (range: 120–290) for TS. Using the log-rank test and the median H-score as cut-off, we found a significant association between low TS protein expression and improved progression-free survival (PFS) (median PFS of 5.5 months vs. 3.4 months; hazard ratio [HR] 0.66, 95% CI, 0.45 to 0.96; P=0.03) or prolonged overall survival (median OS of 33.9 months vs. 15.0 months; hazard ratio [HR] 0.52, 95% CI, 0.31 to 0.86; P=0.01). Moreover, high FPGS protein expression was only associated with better PFS (median PFS of 5.5 months vs. 3.4 months; hazard ratio [HR] 0.58, 95% CI, 0.37 to 0.89; P=0.03). Considering exclusively patients suffering from adenocarcinomas (110 pts (68%)), TS was associated with objective response to pemetrexed-based treatment (mean H-score 192 for responders vs. 210 for non-responders, P=0.03). Conclusions: We have investigated FPGS and TS protein expressions in tumor specimens from the largest series of pemetrexed-treated Caucasian NSCLC patients. Baseline determination of TS and FPGS expression by IHC using the H-score system is associated with clinical outcome from pemetrexed-based therapy in advanced NSCLC. Further prospective validation studies are warranted.
Regulation of the myo-inositol and betaine cotransporters by tonicity
Authors: Joseph S. Handler, H. Moo Kwon
Journal: Kidney International (1996)

Cells of the hypertonic renal medulla accumulate high concentrations of the non-perturbing osmolytes myo-inositol, betaine, and taurine, and are thereby protected from the perturbing effects of hypertonicity. Kidney-derived MDCK cells accumulate high levels of these three non-perturbing osmolytes when cultured in hypertonic medium and have been used to study their accumulation. The increase in the intracellular concentration of these non-perturbing osmolytes is the result of an increase in the abundance of the mRNA for the specific cotransporter for each osmolyte and the ensuing increase in the activity of the three specific sodium coupled transporters. The increased abundance of mRNA for the myo-inositol and the betaine cotransporters is driven by an increase in the rate of transcription of their genes. We have identified a 13 basepair cis-acting element in the 5' flanking region of the gene for the betaine cotransporter. The element is an enhancer that mediates the transcriptional response to hypertonicity. The protein(s) that binds to the tonicity responsive element is much more active in hypertonic than in isotonic cells, and is in all likelihood the mediator of the transcriptional response to changes in tonicity.
Effect of Topically Applied Atropine, Methysergide and Chlorpheniramine on Nasal Challenge with Serotonin
Authors: P. Tønnesen
Journal: Allergy (1985)

Serotonin challenge in the nose produces sneezing and rhinorrhoea. To study the mode of action of serotonin in the nose, 14 normal persons, in a double‐blind, randomized study, were provoked with serotonin in three concentrations. Fifteen minutes before challenge, they were pretreated in the nose with either a cholinoceptor antagonist (atropine), a serotonin antagonist (methysergide), an H 1 ‐histamine antagonist (chlorpheniramine) or isotonic saline. The number of sneezes was noted, and the amount of secretions measured. Serotonin induced dose‐related increase in sneezing and hypersecretion ( P &lt; 0.02). Atropine pretreatment reduced the amount of secretion ( P &lt; 0.05 and P &lt; 0.1), but had no effect on sneering. Methysergide and chlorpheniramine had no effect on the serotonin‐induced nasal symptoms. Unilateral challenge with serotonin induced secretions from both sides, suggesting that serotonin‐induced nasal symptoms are partly reflex‐mediated.
THE TREATMENT OF BRONCHIAL FISTULAS
Authors: W. L. KELLER
Journal: JAMA (1923)

In the brief time allotted to each subject, it is impossible to summarize even superficially the important points in the treatment of bronchial fistulas, and I will therefore be compelled to omit the masterly discussions of others and confine myself to the observations based on thirty-five cases that have been transferred to my service for treatment and final disposition. These fistulas were encountered in a large series of chronic empyema cases varying in duration from two to seven years, and were all demonstrated by direct observation, as the many-stage open method of exposure was used in all cases. When I speak of chronic empyema, I refer especially to the surgical failures, many of which have had all forms of radical operations; and, regardless of these surgical measures, the empyema and bronchial fistulas persisted. In addition to the radical procedures previously mentioned, in some cases there was muscle implantation over the
MULE SPINNERS' CANCER IN THE UNITED STATES
Authors: Frederick L. Hoffman
Journal: JAMA (1928)

To the Editor:  —It is only about five years since the term  spinners'  first gained currency. Most of the observations concerning this peculiar disease have reference to conditions in the English cotton industry. It has frequently been asserted that no cases of mule spinners' cancer have ever occurred in the United States. To test this assertion, I prevailed on the chief statistician of the division of vital statistics of the census to abstract for me from the cancer death certificates of 1926 all cases of cancer of the scrotum. Accordingly, thirty-three certificates were furnished and these have just been carefully examined. Much to my surprise, I find three certificates of cancer of the scrotum, specifically designating the occupation as that of mule spinners, while in three additional cases the occupation is referred to as a textile worker.  The first case is that of a mule spinner, aged 78,
Effect of regular nedocromil sodium or albuterol on bronchial inflammation in chronic asthma☆☆☆★★★
Authors: Alan Altraja, Annika Laitinen, Sulev Meriste, Sirje Marran, Tiiu Märtson, Heinart Sillastu, Lauri A. Laitinen
Journal: Journal of Allergy and Clinical Immunology (1996)
General practitioners' practice expenses.
Authors: J Ford
Journal: BMJ (1986)

General practitioners are unlikely to receive the exact level of remuneration recommended in the 16th report of the doctors' and dentists' review body1 even if the level was accepted in full by the government and implemented from 1 April. This alarming sounding position is so because general practitioners' remuneration is a series of fees and allowances designed to produce an average income across all unrestricted principals and would be realised in gross terms only if changes in volume (including increases in the number of general practitioners) were as expected by the review body. It will be achieved in net terms only if the amounts set aside for   turn out to be an accurate forecast of actual expenditure. The term practice expenses is used here to refer only to those  which fall to be met from gross fees and allowances and excludes those reimbursed directly to general practitioners by family prac? titioner committees?for example, it excludes the 70% of staff salaries which qualifies for direct reimbursement but includes the 30% which does not. For both gross income and   to combine to yield the desired average level of net income would therefore be unlikely if not im? possible. The possibility of compensating errors occurring in the two variables such as  being higher than expected while gross income is overachieved may result in a misleading level of accuracy, and nobody should underestimate the difficulty of the review body's task in setting fees and allowances to achieve its stated intention. Practice  element
How often should patients be reviewed after treatment with iodine-131 for thyrotoxicosis?
Authors: A D Toft, W J Irvine, J Seth, E H Cameron
Journal: BMJ (1978)

Six to 18 years after treatment with iodine-131 for thyrotoxicosis 69 euthyroid patients with raised serum thyrotrophin (TSH) concentrations (mean 25.0 +/- SE 2.0 mU/l) and 61 with normal concentrations (mean 4.0 +/- 0.2 mU/l) were included in a prospective five-year follow-up study beginning in 1972. During this period 13 patients from the original group with raised serum TSH concentrations became hypothyroid. In contrast it was five years before hypothyroidism developed in a single patient from the group with normal serum TSH concentrations in 1972, although raised concentrations were recorded in 19 of these patients during the study.