tbuckley/cabot-search huggingface dataset:
Respiratory effects of non-tobacco cigarettes.
Authors: J W Bloom, W T Kaltenborn, P Paoletti, A Camilli, M D Lebowitz
Journal: BMJ (1987)

Data from the Tucson epidemiological study of airways obstructive disease on smoking of non-tobacco cigarettes such as marijuana were analysed to determine the effect of such smoking on respiratory symptoms and pulmonary function. Among adults aged under 40, 14% had smoked non-tobacco cigarettes at some time and 9% were current users. The prevalence of respiratory symptoms was increased in smokers of non-tobacco cigarettes. After tobacco smoking had been controlled for men who smoked non-tobacco cigarettes showed significant decreases in expiratory flow rates at low lung volumes and in the ratio of the forced expiratory volume in one second to the vital capacity. This effect on pulmonary function in male non-tobacco cigarette smokers was greater than the effect of tobacco cigarette smoking. These data suggest that non-tobacco cigarette smoking may be an important risk factor in young adults with respiratory symptoms or evidence of airways obstruction.
Traumatic Arteriovenous Fistulas Involving Middle Meningeal Vessels
Authors: Charles B. Wilson, Frank Cronic
Journal: JAMA (1964)

Two fistulas involving the middle meningeal artery and veins were situated over the convexity of the skull. Neurosurgery was required in one case; spontaneous closure took place in the second. The anatomic basis of meningeal fistulas was related to the origin of extradural hemorrhage. An extradural hematoma was a concomitant finding in one case.
N-Type Calcium Channels Control Sympathetic Neurotransmission in Human Heart Atrium
Authors: G. J. Molderings, J. Likungu, M. Göthert
Journal: Circulation (2000)

Background —Because knowledge about the type of calcium channels involved in action potential–induced norepinephrine release from the human peripheral sympathetic nervous system is sparse, we investigated which types of calcium channels are functionally important in the sympathetic nerves of human cardiac tissue. Methods and Results —In superfused segments of human right atrial appendages, the type of calcium channels that control [ 3 H]norepinephrine release evoked by transmural electrical stimulation was determined. [ 3 H]norepinephrine release was almost abolished by 0.2 μmol/L ω-conotoxin GVIA (a selective blocker of N-type channels) but was not modified by 0.1 μmol/L ω-agatoxin IVA (a selective blocker of P- and Q-type channels). Mibefradil (a T-type and N-type calcium channel blocker) at concentrations of 0.3 to 3 μmol/L reduced the evoked tritium overflow in a frequency- and calcium-dependent manner, whereas 0.1 to 10 μmol/L amlodipine, diltiazem, and verapamil (selective blockers of L-type channels) were ineffective. Conclusions —Norepinephrine release from cardiac sympathetic nerves is triggered by Ca 2+ influx via N-type but not L- and P/Q-type calcium channels. The inhibitory effect of mibefradil on norepinephrine release at clinically relevant concentrations is probably due to its blocking action on N-type Ca 2+ channels. This property of mibefradil is unique among the calcium channel blockers that have been or still are therapeutically applied and may considerably contribute to its slight negative chronotropic effect in vivo.
The Unheard Diastolic Murmur in Acute Rheumatic Fever
Authors: Alvan R. Feinstein, Rodolfo Di Massa
Journal: New England Journal of Medicine (1959)

A CRUCIAL feature in the clinical diagnosis of rheumatic heart disease is the demonstration of certain characteristic cardiac murmurs that presumably indicate valvular deformity.1 These murmurs can exist with or without a positive history or associated abnormalities in the patient's physical examination, laboratory and other data.2 For this reason, the major diagnostic procedure in rheumatic heart disease is auscultation. Despite advances in acoustic and electronic technics, the auscultatory instrument in most general use is a combination of the ears, stethoscope and mind of the physician. The frequency and consequences of occasional imperfect function of this instrument are considered below.Methods . . .
Clinical Trial of Synthetic Oxytocin
Authors: H. H. Francis, W. J. A. Francis
Journal: BMJ (1956)

Cancer is a genetic disease fueled by somatic evolution. Hierarchical tissue organization can slow somatic evolution by two qualitatively different mechanisms: by cell differentiation along the hierarchy “washing out” harmful mutations (Nowak et al. 2003, Werner et al. 2013) and by limiting the number of cell divisions required to maintain a tissue (Derényi and Szöllősi 2017). Here we explore the effects of compartment size on somatic evolution in hierarchical tissues by considering cell number regulation that acts on cell division rates such that the number of cells in the tissue has the tendency to return to its desired homeostatic value. Introducing mutants with a proliferative advantage we demonstrate the existence of a third fundamental mechanism by which hierarchically organized tissues are able to slow down somatic evolution. We show that tissue size regulation leads to the emergence of a threshold proliferative advantage, below which mutants cannot persist. We find that the most significant determinant of the threshold selective advantage is compartment size, with the threshold being higher the smaller the compartment. Our results demonstrate that in sufficiently small compartments even mutations that confer substantial proliferative advantage cannot persist, but are expelled from the tissue by differentiation along the hierarchy. The resulting selective barrier can significantly slow down somatic evolution and reduce the risk of cancer by limiting the accumulation of mutations that increase the proliferation of cells. <h3>Significance Statement</h3> Renewed tissues of multicellular organism accumulate mutations that lead to ageing and cancer. To mitigate these effects self-renewing tissues produce cells along differentiation hierarchies, which have been shown to suppress somatic evolution both by limiting the number of cell divisions, and thus reducing mutational load, and by differentiation “washing out” mutations. Our analytical results reveal the existence of a third mechanism: a compartment size dependent threshold in proliferative advantage, below which mutations cannot persist, but are rapidly expelled from the tissue by differentiation. In sufficiently small compartments the resulting selective barrier can greatly slow down somatic evolution and reduce the risk of cancer by preventing the accumulation of mutations even if even they confer substantial proliferative advantage.
P311 and DAP3: Glioblastoma invasion genes identified by laser capture microdissection, differential display and QRT-PCR
Authors: Luigi Mariani, Wendy McDonough, Christian Beaudry, Dominique Hoelzinger, Elzbieta Kaczmarek, Alf Giese, Stephen Coons, Rolf Seiler, Kristen Ross, Michael Berens
Journal: Nature Genetics (2001)
Abstract 4432: Discovery of novel Pin1 inhibitors by structure-guided fragment evolution that downregulate cyclin D1 expression in PC-3 prostate cancer cells
Authors: Jonathan D. Moore, Andrew Potter, Stuart Ray, Victoria Oldfield, Claire L. Nunns, Christophe Fromont, Christopher J. Northfield, Louisa Gueritz, Christopher J. Bryant, Simon F. Scrace, David Robinson, Natalia Matassova, Lisa Baker, Allan E. Surgenor, Pawel Dukurno, Ben Davis, Christine M. Richardson, James B. Murray
Journal: Cancer Research (2010)

Abstract Pin1 is a peptidyl-prolyl isomerase (PPIase) that is specialized for catalysing isomerization around pSer/Thr-Pro bonds. As isomerisation around such bonds can promote major conformational changes within proteins, Pin1 is able to influence signaling dynamics and outcomes within pathways regulated by proline-directed kinases such as: MAP kinases, cyclin-dependent kinases and GSK-3β. Pin1 overexpression is only weakly oncogenic in itself, but enhances transformation by ErbB2 or activated Ras alleles. Remarkably however, cells from Pin1 deficient mice are resistant to transformation by Ras and ErbB2. As Pin1-deficient mice have a mild phenotype, there are considerable grounds for hope that Pin1 inhibitors will have value for the therapy of cancer and also inflammatory disorders. Here we report the discovery of our second series of cell active Pin1 inhibitors. Screening of a 700 member fragment library at high concentrations in a PPIase assay revealed 37 potential novel hits. Only two of these hits could be verified to bind Pin1 by 2D NMR, and we were able to obtain a crystal structure of just one of the novel hits bound to Pin1, a pyridyl pyrazole acid. After examining a number of 6-5 unfused ring system acids, we selected a phenyl-imidazole acid as a start point. A program of structure-guided medicinal chemistry led to the discovery of a series of ligands that occupied a novel combination of surfaces within the Pin1 active site, distinct from that occupied by our previously published amino acid-derived inhibitors. This effort culminated in VER-158197, a sub-micromolar (∼750 nM) inhibitor of Pin1 that exhibits high permeability in a CaCo-2 permeability assays and inhibits the growth of Pin1-dependent PC-3 prostate cancer cells (GI50 ∼ 13 uM). Mode of action studies indicated that VER-158197 downregulated cyclin D1 expression and prevented the phosphorylation of p70 S6 Kinase on Thr389 that is normally observed in repsonse to insulin stimulation. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4432.
A double-blind study of the effects of 13-cis-retinoic acid on acne, sebum excretion rate and microbial population
Authors: KATHRINE KING, D.H. JONES, DIANA C. DALTREY, W.J. CUNLIFFE
Journal: British Journal of Dermatology (1982)

Forty‐eight acne patients were treated orally with 13‐cis‐retinoic acid in a double‐blind dose response study. There was a marked clinical improvement with a concomitant reduction in sebum excretion rate (SER) and production rate of free fatty acids (FFA). Microbial numbers decreased significantly; the decrease in propionibacteria was greater than that of aerobic bacteria. The decline in micro‐organisms occurred after the reduction in sebum and FFA production. This suggests that the effect of the drug upon micro‐organisms is secondary to the change in sebum excretion but it is nevertheless an important factor in the resolution of the acne.
A longitudinal study of a harlequin infant presenting clinicallyas non-bullous congenital ichthyosiform erythroderma
Authors: M. HAFTEK, F. CAMBAZARD, D. DHOUAILLY, A. RÉANO, M. SIMON, A. LACHAUX, G. SERRE, A. CLAUDY, D. SCHMITT
Journal: British Journal of Dermatology (1996)

Over the past 8 years, we have followed a child born as a harlequin baby, who survived due to treatment with retinoids. His condition evolved clinically towards the erythrodermic form of lamellar ichthyosis (non-bullous congenital ichthyosiform erythroderma, NBCIE). According to ultrastructural and biochemical criteria, our patient originally presented with type II harlequin ichthyosis. Investigations showed an abnormal keratinosome structure and extrusion, a keratin pattern characteristic for epidermal hyperproliferation, and an absence of conversion of profilaggrin to filaggrin. Persisting keratinocyte hyperproliferation, associated with the presence of a dermal infiltrate, is in agreement with the present clinical picture of severe NBCIE. However, abnormal lamellar body production and defective filaggrin processing, which is not one of the diagnostic criteria of NBCIE, persist in the patient's skin. Further studies of the epidermal lipid composition, and of possible mutations of the keratinocyte transglutaminase gene performed on epidermal cell cultures of harlequin ichthyosis, will be necessary before type II harlequin ichthyosis can be accepted as an extremely severe form of NBCIE.
Abstract 2472: Peritoneal mechanobiology and metastatic success in epithelial ovarian cancer
Authors: Rebecca J. Burkhalter, Yueying Liu, Michael Marszow, Zhe Sun, Gerald Meininger, Diane Wagner, M. Sharon Stack
Journal: Cancer Research (2012)

Abstract Less than 30% of women diagnosed with epithelial ovarian cancer (EOC) survive for 5 years due to metastatic disease. EOC progression is accompanied by accumulation of ascites (up to 4 liters), changing intraperitoneal (i.p.) fluid pressure from subatmospheric (-5 mmHg) to &amp;gt;20 mmHg with tense ascites. The overall consequence of altered peritoneal mechanobiology on EOC metastatic success is currently unknown. Due to altered i.p. fluid dynamics the peritoneal mesothelium, an elastic soft tissue, may be modified by exposure to tensional force (strain). Mechanical strain (stretching) on intact murine mesothelial explants causes increased tissue stiffness, as determined by atomic force microscopy, and enhances ovarian tumor cell adhesion. To approximate the compressive force environment on EOC cells in tense ascites, cells were seeded in suspension in polystyrene bags and cultured under a compressive load (Instron, 25mmHg, 8h). Increased fluid pressure enhances proliferation in multiple cell lines and increases expression of N-cadherin, a mesenchymal marker, in Dov13 cells. These data suggest that ascites-induced changes in peritoneal mechanobiology may potentiate EOC metastatic success. Support: NIH-R01CA109545, NIH R01CA086984, NIH F31 R01CA086984-12S1. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2472. doi:1538-7445.AM2012-2472
Abstract 4506: Photocaged molecules in targeted drug delivery.
Authors: Deboleena Mitra, Martin Michael Dcona, Matthew C.T. Hartman
Journal: Cancer Research (2013)

Abstract We have developed a new targeted therapy that uses light to deliver cytotoxic agents into cancer cells. This strategy is based on the concept of photocaging in which a biologically active molecule is made inactive by the attachment of a light-cleavable blocking group. Upon exposure to UV radiation the photocleavable entity is removed and the biologically active molecule is released. Using this concept we have designed a prodrug that consists of a cell impermeable hydrophilic photocage attached to doxorubicin. The hydrophilic moiety makes the entire prodrug cell impermeable in the dark. Upon irradiation with non-toxic doses of UV light, the photosensitive group is removed and cytotoxic doxorubicin is released into the cells. In the presence of light the IC50 has been found to be 1.6 ±1.0 μM in JH-Eso-Ad1 cells. The FACS studies further confirmed that the cytotoxicity was due to light triggered release of free doxorubicin from the cell impermeable prodrug. This concept has been further developed by attaching a receptor binding molecule to the photocaged drug to enhance specificity. Specifically, we have attached folic acid and the PSMA binding ligand, DUPA to the photocaged doxorubicin. These targeting groups enable cancer cell selective drug delivery with light. Citation Format: Deboleena Mitra, Martin Michael Dcona, Matthew C.T. Hartman. Photocaged molecules in targeted drug delivery. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4506. doi:10.1158/1538-7445.AM2013-4506
Multiple Candida Abscesses Resulting from Insulin Injections
Authors: Wil B. Nelp
Journal: New England Journal of Medicine (1963)

ALTHOUGH numerous types of cutaneous and localized infections due to candida have been observed1 2 3 the following case represents a unique type of infection resulting as a complication of insulin therapy in a young patient with diabetes.Case ReportA 17-year-old girl had received daily insulin injections in the upper thighs since the age of 12. Regulation of the diabetes was generally poor owing to her inability to adhere to an appropriate diet. During the 1st week of February she complained of mild pruritus of the vulva and mentioned that several areas in the upper thighs at sites of insulin injections . . .
CHROMOSOME 9P21 CDKN2A/CDKN2B GENE VARIATION EXPLAINS 12&amp;percnt; OF INCIDENT CARDIOVASCULAR EVENTS IN THE POPULATION BUT DOES NOT ADD INCREMENTAL VALUE ON RISK PREDICTION BEYOND TRADITIONAL RISK FACTORS- THE MALM&amp;ouml; DIET AND CANCER STUDY
Authors: Klas Gr&auml;nsbo, Peter Almgren, Marketa Sj&ouml;gren, Gustav Smith, Gunnar Engstr&ouml;m, Bo Hedblad, Olle Melander
Journal: Journal of the American College of Cardiology (2012)
ABDOMINAL SURGERY WITHOUT DETACHED PADS AND SPONGES
Authors: H. S. CROSSEN
Journal: JAMA (1923)

The subject I have chosen is one of much importance in abdominal work. While we, as pelvic and abdominal surgeons, are busy devising better operative procedures for the lesions of the various organs, we must not lose sight of the fact that a dangerous feature still persists in the general technic of abdominal section. I refer to the numerous sponges, large and small, used in and about the cavity. Infection and hemorrhage have been largely eliminated, but the dangerous detached sponges are still seen in every operating room. A sponge left in the peritoneal cavity following an operation constitutes one of the most deplorable accidents of abdominal surgery. This is not a new subject. Much has been written concerning it, and many cases have been reported and many suggestions have been made as to preventive measures. In my original paper<sup>1</sup>on the subject in 1909, a summary of reported
Canadian hospitals fight a rise in infections with Clostridium difficile
Authors: David Spurgeon
Journal: BMJ (2004)

Hospitals in Montreal and Calgary are fighting a rise in infections with Clostridium difficile , which has killed more people in the past 18 months than were killed by last year's outbreak of SARS (severe acute respiratory syndrome), a report in CMAJ, the Canadian Medical Association Journal, says.

The report appeared as an early release on the journal's website on 4 June (www.cmaj.ca/pdfs/171\_1\_news.pdf). “ CMAJ 's investigation has elicited reports of the deaths of at least 79 patients in several institutions, all of whom contracted the infection in 2003 or the first few months of 2004,” says the journal. “By comparison, in all of Canada 44 people died from SARS during last year's outbreak in Ontario.”

At least 12 Montreal hospitals have been trying to contain the outbreaks …
Elevated Intraocular Pressure Following Corticosteroid Eye Drops
Authors: Bernard Becker
Journal: JAMA (1963)

IN THE COURSE of studies on immunogenic mechanisms in primary glaucoma, 1,2 a series of over 100 patients receiving topical corticosteroid drops to one eye was carefully followed. This brief report is presented to alert physicians to the large and significant increases in intraocular pressure observed in so many of the patients studied. A more detailed publication of the investigation is planned for the ophthalmologic literature. 3   Method  In the series were 43 patients with proved primary open-angle glaucoma (unoperated on) selected because of their excellent pressure control (all values 20 mm Hg or less; mean value 17.1 mm Hg). All patients were over 40 years old; 15 of the patients had untreated early glaucoma. The remainder were continued on whatever ocular or systemic medication they had been using for their glaucoma.  In addition, the series contained 25 volunteers selected so as to exclude individuals with any suspicion of glaucoma,
GPs should be allowed to provide good quality patient centred care to encourage a person centred NHS
Authors: S. J. Finnikin
Journal: BMJ (2014)

I agree with Greenfield that patient centred care is a crucial facet of general practice and that the confines of 10 minute consultations are incongruous with the demands of modern primary care, but the proposed solution is erroneous.1

Although evidence shows that payment by results improves specific clinical outcomes, the evidence supporting the adoption of …
Flow-Induced Vascular Remodeling in the Rat Carotid Artery Diminishes With Age
Authors: Jody K. Miyashiro, Veronica Poppa, Bradford C. Berk
Journal: Circulation Research (1997)

Vascular remodeling is regulated by a combination of hemodynamic, environmental, and genetic factors and may be influenced by age. To evaluate age-dependent remodeling in rats, we developed and used a quantitative highly reproducible model of carotid flow alteration. Fourteen juvenile (99+/-3 g) and 9 adult (199+/-5 g) male inbred Fischer rats underwent ligation of the left internal and external carotid arteries under anesthesia. Left common carotid blood flow immediately decreased by approximately 93%, whereas flow in the contralateral carotid increased by approximately 46%. After 4 weeks, the left carotid outer diameter (OD) significantly decreased in both juvenile and adult rats (as measured in vivo and by histological morphometry) compared with sham-operated rats. Changes in shear stress acutely mirrored the changes in blood flow. OD increased and shear stress returned to initial values after chronic exposure to increased flow in juvenile but not adult rats. To develop a simple quantitative index of remodeling that would not require killing the animals, we measured the OD in vivo and compared the ratio of right to left OD (OD ratio [ODR]) between groups. The initial ODR for all groups was approximately 1.0. After 4 weeks of altered flow, the ODR was significantly greater in juvenile than in adult rats (1.48+/-0.05 versus 1.29+/-0.04, respectively; P=.030), indicating that juvenile rats experienced more extensive remodeling than did the adult rats. We also found that unilateral carotid ligation caused a left versus right difference in endothelial NO synthase protein levels after 4 weeks that was not present in the sham-operated animals. Thus, the model described here shows that flow-induced vascular remodeling is dependent on age and supports the hypothesis that the driving force for remodeling involves shear stress and possibly NO. Because the model is quantitative, it allows dissection of the genetic factors that regulate remodeling in inbred rat strains.
Biliary Endoprosthesis as an Alternative to Endoscopic Nasobiliary Drainage in Patients with Acute Cholangitis
Authors: S. P. Misra, M. Dwivedi
Journal: Endoscopy (1996)

Conventionally, acute cholangitis is managed by placing a nasobiliary drainage catheter. We have attempted to place a biliary endoprosthesis in such patients as an alternative to using nasobiliary catheter drainage.Twenty-seven patients with acute cholangitis were managed by placement of 7-Fr straight biliary endoprostheses instead of using nasobiliary drainage catheters to decompress the biliary system. The procedure was carried out without sphincterotomy and without image intensification.Biliary endoprosthesis placement was successfully carried out in all the patients. Definitive treatment was then provided to all but four patients, who either had inoperable cancer or were at high risk for surgery. Early stent occlusion occurred in one patient, and in another patient the Dormia basket became entrapped while stones were being removed from the common bile duct. There were no mortalities.Biliary endoprosthesis placement is safe, easy to perform, and is a cheaper alternative to endoscopic nasobiliary drainage.
Blood DNA methylation biomarkers predict clinical reactivity in food-sensitized infants
Authors: David Martino, Thanh Dang, Alexandra Sexton-Oates, Susan Prescott, Mimi L.K. Tang, Shyamali Dharmage, Lyle Gurrin, Jennifer Koplin, Anne-Louise Ponsonby, Katrina J. Allen, Richard Saffery
Journal: Journal of Allergy and Clinical Immunology (2015)