tbuckley/cabot-search huggingface dataset:
"Author pays" publishing model: Answering to some objections
Authors: P. Suber
Journal: BMJ (2003)

Outcomes of screening to prevent cancer Think of screening as insuranceEditor-Raffle et al provide interesting new data on the outcome of cervical screening. 1It is particularly useful to be able to tell women that over 20 years of five yearly screening, around 16% will have an abnormal smear test result, 8% will have a biopsy, and 4% will be treated for high grade disease.The authors also estimate the number of cancers and deaths that might be prevented over 30 years in such a cohort.How they obtained their estimates is unclear, but numbers are surprisingly low.When estimating the number of premature deaths avoided in screened women, they apply the factor 60%, obtained from a population in which approximately one in five eligible women are not screened regularly.In screened women the figure should be closer to 75%, which is more in keeping with the results from case-control studies. 2 3 Fitting an age cohort model to mortality data from England and Wales for 1950-87 and extrapolating to 2011, we estimate the cumulative number of deaths in an unscreened cohort to be some 50% greater than do Raffle et al.Assuming that 75% of the deaths after 1996 would be prevented in a screened cohort, the number of premature deaths avoided is 2.4 times greater than in the paper.Over the next 30 years, the effect of screening in women born in the early 1960s will be much greater-some 2% of those screened will be prevented from developing cervical cancer.Describing the benefits of screening in terms of the number needed to be screened to prevent one death equates screening with treatment.Screening is not treatment.It is perhaps better to think of it as insurance.The issue is not how many need to be insured for one person to avoid bankruptcy.It is not even simply a question of whether the cost of an insurance premium is more or less than the expected pay out (it will always be more).Insurance is put in place to avoid catastrophic consequences of an unlikely event.Women need to be aware of the common negative consequences of regular screening, but they should perhaps think of it as a costly and imperfect insurance policy that may save them from the horrors of invasive cervical cancer.
”Cat scratch” colon: an impressive but innocent endoscopic finding
Authors: P. Katsinelos, J. Kountouras, G. Chatzimavroudis, C. Zavos, G. Paroutoglou
Journal: Endoscopy (2007)

We have read with great interest the article by McDonnell et al. [1] on a new endoscopic finding in the cecum and ascending colon, characterized by bright erythematous linear marks resembling scratches, thereby creating the neologism ”cat scratch” colon. Here we describe a similar case to expand the experience with this endoscopic entity.
Evolution of Amino Acid Frequencies in Proteins Over Deep Time: Inferred Order of Introduction of Amino Acids into the Genetic Code
Authors: Dawn J. Brooks, Jacques R. Fresco, Arthur M. Lesk, Mona Singh
Journal: Molecular Biology and Evolution (2002)

To understand more fully how amino acid composition of proteins has changed over the course of evolution, a method has been developed for estimating the composition of proteins in an ancestral genome. Estimates are based upon the composition of conserved residues in descendant sequences and empirical knowledge of the relative probability of conservation of various amino acids. Simulations are used to model and correct for errors in the estimates. The method was used to infer the amino acid composition of a large protein set in the Last Universal Ancestor (LUA) of all extant species. Relative to the modern protein set, LUA proteins were found to be generally richer in those amino acids that are believed to have been most abundant in the prebiotic environment and poorer in those amino acids that are believed to have been unavailable or scarce. It is proposed that the inferred amino acid composition of proteins in the LUA probably reflects historical events in the establishment of the genetic code.
Pemphigus antibody interaction with human epidermal cells in culture.
Authors: J R Schiltz, B Michel, R Papay
Journal: Journal of Clinical Investigation (1978)

The mechanism of pemphigus acantholysis has been studied with an in vitro system. Freshly prepared human skin epidermal cells were incubated in F-10 medium which contained the immunoglobulin G fraction from either pemphigus serum or normal human serum. During 18-h incubation periods, the pemphigus antibody became bound to the surface of the epidermal cells, caused the destruction of 75% of the viable cells as compared to only 14% in the normal immunoglobulin G controls (trypan blue exclusion), prevented the accumulation of newly synthesized proteins by nearly 60% as determined by radioactive tracer studies, and caused a dramatic shift in distribution of the newly synthesized proteins from an insoluble cell-associated fraction to an extracellular soluble fraction. These effects on the accumulation and partitioning of newly synthesized proteins were antibody concentration-dependent. Kinetic studies showed that at a fixed pemphigus antibody concentration the inhibition of protein accumulation preceded solubilization by about 1 h, at which time rapid solubilization of up to 70% of the insoluble cellular material occurred. Several lines of evidence suggested that this phenomenon was caused by enzymatic activity. Epidermal extracts solubilized a prepared substrate of radioactivity labeled insoluble epidermal cell material. This activity was heat labile and pH dependent, with pH optima ranging from 4.5 to 6.5. Enzymes with pH optima between 6 and 6.5 were recovered in the culture medium after a 2-day incubation of pure, intact epidermis with the pemphigus antibody. We proposed the following hypothesis to account for pemphigus acantholysis. The pemphigus antibody reacts with the epidermal cell surface and produces such a severe disturbance that the integrity of the cell surface is lost. As a result of these primary perturbations, the cell is killed and during the process, responds by release or activiation of soluble hydrolytic enzymes. This autolytic process results in the characteristic acantholysis of pemphigus.
Prospective randomized trial comparing the direct method using a 24 Fr bumper-button-type device with the pull method for percutaneous endoscopic gastrostomy
Authors: A. Horiuchi, Y. Nakayama, N. Tanaka, H. Fujii, M. Kajiyama
Journal: Endoscopy (2008)

See also: Commentaire de travail de A. Horiuchi et al., pp. 722Endoscopy 2008; 40(09): 967-967DOI: 10.1055/s-0032-1306866
Increased granulocyte colony-stimulating factor responsiveness but normal resting granulopoiesis in mice carrying a targeted granulocyte colony-stimulating factor receptor mutation derived from a patient with severe congenital neutropenia.
Authors: M L McLemore, J Poursine-Laurent, D C Link
Journal: Journal of Clinical Investigation (1998)

The role of mutations of the granulocyte colony-stimulating factor receptor (G-CSFR) in the pathogenesis of severe congenital neutropenia (SCN) and the subsequent development of acute myeloid leukemia (AML) is controversial. Mice carrying a targeted mutation of their G-CSFR that reproduces the mutation found in a patient with SCN and AML have been generated. The mutant G-CSFR allele is expressed in a myeloid-specific fashion at levels comparable to the wild-type allele. Mice heterozygous or homozygous for this mutation have normal levels of circulating neutrophils and no evidence for a block in myeloid maturation, indicating that resting granulopoiesis is normal. However, in response to G-CSF treatment, these mice demonstrate a significantly greater fold increase in the level of circulating neutrophils. This effect appears to be due to increased neutrophil production as the absolute number of G-CSF-responsive progenitors in the bone marrow and their proliferation in response to G-CSF is increased. Furthermore, the in vitro survival and G-CSF-dependent suppression of apoptosis of mutant neutrophils are normal. Despite this evidence for a hyperproliferative response to G-CSF, no cases of AML have been detected to date. These data demonstrate that the G-CSFR mutation found in patients with SCN is not sufficient to induce an SCN phenotype or AML in mice.
Colonoscopy: An Increased Detection Yield?
Authors: R. Lambert, J. F. Rey
Journal: Endoscopy (2001)

The frequent occurrence of flat or nonpolypoid neoplastic colorectal lesions has been reported recently in the Japanese literature, and also now in Western countries. In the large series collected by S. Kudo [1] [2] [3] at the Akita Red Cross Hospital in Japan, 45 % of early neoplastic lesions detected at colonoscopy were found to have a nonpolypoid morphology. The figure was only slightly lower (32 %) in the revisited results of the National Polyp Study in the USA [4]. In Japan, nonpolypoid lesions (adenoma or cancer) are classified as variants of superficial lesions of types 0-II, i. e. superficially elevated (0-II a), completely flat and flush with the surrounding mucosa (0-II b) or superficially depressed without frank ulcer (0-II c). In mixed types, both depression and elevation are present (II a + II c or II c + II a). Depressed lesions represent less than 5 % of all early neoplastic colorectal lesions.
Characterization of Platelet-activating Factor Acetylhydrolase in Human Bronchoalveolar Lavage
Authors: MASSIMO TRIGGIANI, VALERIA De MARINO, MATTEO SOFIA, STANISLAO FARAONE, GIUSEPPE AMBROSIO, LUIGI CARRATÙ, GIANNI MARONE
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

Platelet-activating factor (PAF) is a mediator produced in human airways during acute and chronic inflammatory lung diseases. The levels of PAF are regulated by acetylhydrolase (AH), the enzyme that converts PAF to lyso-PAF. To determine whether AH was present in human bronchoalveolar lavage (BAL) fluid, BAL was obtained from normal donors (n = 18) and from adult patients with mild bronchial asthma (n = 15) or with lung fibrosis (n = 15). AH activity was consistently found in the cell-free BAL fluid. BAL-AH is an enzyme different from secretory phospholipase A2 and from plasma AH and erythrocyte AH. Furthermore, BAL-AH is inhibited as much as 95% by exposure to an oxygen radical-generating system (xanthine/xanthine oxidase). BAL-AH is significantly correlated with the number of BAL macrophages (rs = 0.63; p < 0.02). In addition, BAL macrophages release AH both spontaneously and after stimulation with tumor necrosis factor-alpha (TNF- α ) (100 ng/ml). BAL-AH activity in patients with bronchial asthma (1.32 ± 0.18 pmol of PAF converted to lyso-PAF/min) is significantly lower than that in normal donors (2.25 ± 0.26 pmol/min; p < 0.001). In contrast, BAL-AH activity in patients with lung fibrosis (6.13 ± 0.81 pmol/min) is higher than that found in normal donors (p < 0.01). The variations in BAL-AH activity in patients with bronchial asthma or lung fibrosis are due to a reduction and to an increase, respectively, in the number of active molecules rather than to changes in enzyme affinity. These data demonstrate that human BAL fluid contains an extracellular AH activity that inactivates PAF released in the airways. BAL-AH is secreted by alveolar macrophages and is highly sensitive to oxygen radical-induced damage. The secretion and inactivation of BAL-AH may influence the levels of this enzyme in BAL fluid during acute and chronic inflammatory lung diseases and, ultimately, regulate the proinflammatory activities of PAF in these disorders.
Changing pattern of poisoning in children in Newcastle, 1974-81.
Authors: G R Lawson, A W Craft, R H Jackson
Journal: BMJ (1983)

All children aged under 15 years admitted to hospital in Newcastle upon Tyne between 1974 and 1981 with a diagnosis of poisoning were studied. After the introduction in 1976 of child resistant containers for salicylates and paracetamol, salicylate poisonings fell dramatically. The other most important medicines to cause poisoning in young children were tricyclic antidepressants, benzodiazapines, Lomotil (diphenoxylate and atropine), and iron preparations; these should also be packaged in child resistant containers by regulation. Few children had symptoms after poisoning with household products, but bleach, turpentine, and paraffin might also be packaged in child resistant containers. The numbers of adolescent girls admitted after deliberate self poisoning and of teenage boys admitted after ingestion of alcohol increased over the study period.
Awareness and Experience of General Practitioners of Selected Drug Interactions
Authors: J. C. Petrie, J. G. R. Howie, D. Durno
Journal: BMJ (1974)

The awareness of general practitioners of selected adverse drug interactions has been assessed. The drugs studied included adrenergic neurone blockers, warfarin, antidiabetic agents, and monoamine oxidase inhibitors. The findings must be interpreted with caution but they suggest that there is a clear need to improve the effectiveness of communication of information about adverse drug interactions if unnecessary iatrogenic disease is to be avoided.
Résistance et Survivance du Bacille Tuberculeux aux Médications Antibacillaires
Authors: Sol Roy Rosenthal
Journal: JAMA (1967)

If the tubercle bacillus did not develop resistance to medicaments, no progressive tuberculosis would exist today. Since no unanimity of opinion exists regarding the cause of resistance, this volume is timely. It is unique in its goal of gathering the world literature and adding the author's own laboratory and clinical experience in the field of resistance as it relates to the tubercle bacillus.  author is a member of the famous Laennec Hospital in Paris in the service of Prof Etienne Bernard.   book has three sections.  first, The Resistance of the Tubercle Bacillus, with 12 chapters and 524 pages, considers such topics as origin, specificity, measure of resistance and its resultant metabolic and morphological changes, and factors influencing the appearance of resistance clinically and its prevention.  second section, Survival of the Tubercle Bacillus to Antibacterial Medication, with six chapters and 152 pages, covers the entire gamut of
A granddaughter's distress leads to lymphedema aid
Authors: Marsha F. Goldsmith
Journal: JAMA (1984)

Love may not always be enough. But combined with an understanding of fluid dynamics, a grandfather's love has led to the development of a device that gives young victims of a rare form of chronic lymphedema their first opportunity to live a normal life. At the recent American Academy of Dermatology meeting in Chicago, dermatologist Guinter Kahn, MD, of North Miami Beach, Fla, presented the case of an 11-year-old girl with Klippel-Trenaunay-Weber syndrome—now controlled with use of the Wright linear pump. Klippel-Trenaunay-Weber syndrome, a congenital condition of unknown cause, is characterized by hemihypertrophy of soft tissue (usually of an extremity) and, in some cases, of the skeleton as well. Patients have vascular and lymphatic overgrowth. Open lesions that can lead to osteomyelitis and eventual limb loss are common. There is no cure, and victims have been doomed to lonely and immobile lives because of both social ostracism and the difficulty
Hydrolysis of milk fat globules by pancreatic lipase. Role of colipase, phospholipase A2, and bile salts.
Authors: B Borgström, C Erlanson-Albertsson
Journal: Journal of Clinical Investigation (1982)

Human milk fat globules require colipase to be hydrolyzed by pancreatic lipase in the presence of bile salts. This is contrary to a recent report in this Journal (J. Clin. Invest. 67: 1748-1752.) according to which inhibition of lipase by bile salt could be overcome by the addition of colipase or phospholipase A2. This latter finding is shown to be due to contamination of commercially available pancreatic phospholipase A2 by colipase.
Hepatojugular Reflux: Useful in the Bedside Diagnosis of Tricuspid Regurgitation
Authors: ALAN S. MAISEL
Journal: Annals of Internal Medicine (1984)

Using phonocardiography and auscultation, we ascertained the presence or absence of hepatojugular reflux and Carvallo's maneuver in three groups of 15 patients. The first group had isolated tricuspid regurgitation; the second, isolated mitral regurgitation; and the third was a control group with no murmurs. The specificity and sensitivity of hepatojugular reflux were 100% and 66%, and those of Carvallo's maneuver were 100% and 80%. All but 1 patient in our series had a positive response to one or the other maneuver (combined sensitivity, 93%). Thus, hepatojugular reflux is a useful adjunct to Carvallo's maneuver in the diagnosis of tricuspid regurgitation.
A Mouse Model for the Molecular Characterization of Brca1-Associated Ovarian Carcinoma
Authors: Deyin Xing, Sandra Orsulic
Journal: Cancer Research (2006)

Abstract Little is known about the mechanisms that underlie Brca1-associated ovarian tumorigenesis, mainly due to the lack of an appropriate experimental model. We developed genetically defined primary mouse ovarian surface epithelial (OSE) cell lines in which the loss of functional Brca1 and p53 recapitulates the events that are thought to occur in early ovarian cancer development in patients with Brca1 mutations. This system allows for the introduction of additional oncogenes that are thought to cooperate with the loss of Brca1 and p53 to induce tumorigenesis. We showed that Myc is sufficient to induce transformation of ovarian cells that are deficient for both Brca1 and p53 but not sufficient for the transformation of cells that are deficient for either Brca1 or p53. The transformed Brca1-deficient OSE cells display an increased number of centrosomes, acquire complex chromosome aberrations, and lack Rad51 nuclear foci in the presence of DNA-damaging agents, such as mitomycin C and cisplatin. Immunocompetent mice injected with transformed OSE cells develop tumors that resemble human metastatic serous ovarian carcinoma, the most common type of ovarian cancer in women. Consistent with the reported platinum chemosensitivity in patients with Brca1-associated ovarian cancer, the Brca1-deficient OSE cells have increased sensitivity to the DNA-damaging agent cisplatin, whereas sensitivity to the microtubule poison paclitaxel is similar between Brca1 wild-type and Brca1-deficient cells. The Brca1 wild-type and Brca1-deficient mouse ovarian tumors and cell lines provide a new experimental system for the evaluation of therapies that target the Brca1 pathway. (Cancer Res 2006; 66(18): 8949-53)
Nonadrenergic noncholinergic innervation. Anatomic distribution of calcitonin gene-related peptide-immunoreactive tissue in the dog heart.
Authors: P C Ursell, C L Ren, A Albala, P Danilo
Journal: Circulation Research (1991)

Calcitonin gene-related peptide (CGRP) has inotropic and chronotropic effects in rat and guinea pig hearts. It also may mediate nonadrenergic noncholinergic regulation of canine cardiac electrophysiology. In this study, immunohistochemistry was used to determine the anatomic distribution of CGRP in mature dog heart and autonomic ganglia controlling cardiac function. The stellate ganglia had scattered CGRP-immunoreactive cells and nerve processes; intracardiac ganglia contained stained nerve processes but no CGRP-immunoreactive cells. Although the extramural coronary arteries were modestly innervated by varicose individual nerve processes, the great majority of CGRP-immunoreactive neural tissue in the heart existed adjacent to the sinoatrial node where varicose nerve processes coursed in numerous large nerve bundles. Each bundle contained only a few stained processes, however, indicating that CGRP-immunoreactive nerve processes were accompanying another type of autonomic tissue. Double staining and immunoultrastructure confirmed that the nerve bundles were heterogeneous. Similar nerve bundles were fewer in the left atrium, the region of the atrioventricular node, atrioventricular bundle, and the ventricles. In contrast to the distribution of sympathetic neural tissue, CGRP-immunoreactive nerve processes virtually were nonexistent among muscle fibers. We conclude that 1) CGRP-immunoreactive neural tissue likely affects sympathetic and parasympathetic ganglia that control cardiac function, 2) the preponderance of this nonadrenergic noncholinergic tissue near regions of specialized muscle (especially the sinoatrial node) suggests an efferent function in the canine heart, and 3) the presence of varicosities along CGRP-immunoreactive nerve processes within heterogeneous nerve bundles may indicate that direct axo-axonal contact is the mechanism by which these nonadrenergic noncholinergic nerve processes modulated other autonomic neural tissue.
Effect of epinephrine on fibrinogen receptor exposure by aspirin‐treated platelets and platelets from concentrates in response to ADP and thrombin
Authors: Ellinor I. B. Peerschke
Journal: American Journal of Hematology (1984)

Abstract Synergistic effects between agonists on platelet aggregation have long been appreciated. Recently epinephrine was reported to induce maximal aggregation of aspirin‐treated platelets when combined with ADP or thrombin, and to increase fibrinogen binding of nonaspirin‐treated platelets stimulated with low doses of ADP. The present study extends these observations to correlate fibrinogen binding in response to various combinations of ADP, epinephrine, and thrombin with platelet aggregation and 14 C‐serotonin release using aspirin‐treated platelets as well as platelets from stored concentrates. When fresh platelets were stimulated with epinephrine (5 μM) together with either ADP (10 μM) or thrombin (150 mU/ml), fibrinogen binding increased by 180% compared to binding observed in response to ADP or thrombin alone. This was accompanied by enhanced platelet aggregation, but no increase in 14 C‐serotonin release. While both ADP and epinephrine potentiated the aggregation and fibrinogen binding of stored platelets in response to high doses of thrombin (150 mU/ml), maximal aggregation was achieved only with thrombin (150 mU/ml) and epinephrine (5μM) in combination. The data thus suggest that 1) epinephrine induces maximal aggregation of aspirin‐treated platelets stimulated with thrombin or ADP by significantly enhancing fibrinogen receptor exposure independently of the cyclooxygenase‐mediated release reaction; 2) epinephrine stimulates platelets by a mechanism different from that of thrombin or ADP; and 3) as demonstrated by others, the ability of platelets from stored concentrates to aggregate and to bind fibrinogen in response to ADP can be enhanced by epinephrine, and, in addition, these platelets can aggregate and bind fibrinogen maximally when stimulated with combinations of epinephrine and thrombin.
Choice of Anesthetic Technique in Patients With Acute Pulmonary Disease
Authors: William K. Hamilton
Journal: JAMA (1966)

A 75-year-old woman was admitted to the hospital two days following an intertrochanteric fracture of her left hip. She had been hospitalized in another hospital for the two-day period. Past history revealed an episode of pneumonia of the middle lobe of the right lung four years prior to admission and pneumonia of the lower lobe of the right lung six months prior to admission. She had had asthma for several years. She had daily a productive cough producing thick tenacious sputum, quantity unknown; she denied having dyspnea. Physical examination revealed a reasonably healthy old woman. There were rales throughout her left lung field, and chest x-ray films revealed a marked tracheal deviation and apparent near-total collapse of the left lung (Figure). On the basis of traditional concepts that inhalation anesthesia may be injurious to the lungs and not tolerated well by patients with lung disease, regional anesthesia was strongly recommended