tbuckley/cabot-search huggingface dataset:
Surgery of the Biliary Passages and the Pancreas.
Authors: Walter Hess
Journal: Annals of Internal Medicine (1965)

The chapter on "Radiation therapy in childhood" by Darte of Canada is up-to-date and informative.This author recommends conventional therapy (orthovoltage) for most patients with Wilms' Tumors, combined as a rule with appropriate abdominal surgery.He also uses radiation of the same energy range for retinoblastoma.The full flowering of Parkinson's Law is illustrated in the staff requirements recommended by Kaplan for clin- ical investigative programs in radiotherapy.This author also fails to mention the notable examples completed and the standards set by the Manchester group.Finally, there are useful chapters on statistical evaluation of the results of treatment of cancer by Phillips and on education of medical students by Kramer.One senses the unexpressed conclusion that radiation therapy should be taught to medical students much as surgical therapy is taught ... along with and as a part of the general training program and not as a separate exercise in oncology alone.Indeed, the observations endorse the report of the Council on Medical Education (J.A.M.A., 192:142, May 10, 1965) that "The great need in this country is still for the physician trained in all aspects of the specialty of radiology."Most parts of the country neither need nor can support a separate radiation therapist.The results in most forms of treatable human cancer are as good if not better in the hands of the general radiologist as compared to the results obtained by the physician limiting his practice ex- clusively to radiation therapy of cancer.
Unorthodox angiogenesis in skeletal muscle
Authors: Stuart Egginton, Ai-Ling Zhou, Margaret Brown, Olga Hudlicka
Journal: Cardiovascular Research (2001)

Objective: The morphological pattern of angiogenesis occurring in mature, differentiated skeletal muscle in response to chronically increased muscle blood flow, muscle stretch or repetitious muscle contractions was examined to determine (a) whether capillary neoformation follows the generally accepted temporal paradigm, and (b) how the growth pattern is influenced by mechanical stimuli. Methods: Adult rats were treated for a maximum of 14 days either with the vasodilator prazosin, to elevate skeletal muscle blood flow, or underwent surgical removal of one ankle flexor, to induce compensatory overload in the remaining muscles, or had muscles chronically stimulated by implanted electrodes. Extensor digitorum longus and/or extensor hallucis proprius muscles were removed at intervals and processed for electron microscopy. A systematic examination of capillaries and their ultrastructure characterised the sequence of morphological changes indicative of angiogenesis, i.e., basement membrane disruption, endothelial cell (EC) sprouting and proliferation [immunogold labelling after bromodeoxyuridine (BrdU) incorporation]. Results: Capillary growth in response to increased blood flow occurred by luminal division without sprouting or basement membrane (BM) breakage. In stretched muscles, EC proliferation and abluminal sprouting gave rise to new capillaries, with BM loss only at sprout tips. These distinct mechanisms appear to be additive as in chronically stimulated muscles (increased blood flow with repetitive stretch and shortening during muscle contractions) both forms of capillary growth occurred. Endothelial cell numbers per capillary profile, mitotic EC nuclei, and BrdU labelling confirmed cell proliferation prior to overt angiogenesis. Conclusions: Physiological angiogenesis within adult skeletal muscle progresses by mechanisms that do not readily conform to the consensus view of capillary growth, derived mainly from observations made during development, pathological vessel growth, or from in vitro systems. The temporal and spatial pattern of growth is determined by the polarity of the mechanical stimulus, i.e., by intra-luminal (increased shear stress) or abluminal (external stretch) stimuli.
Book Review Pediatric Trauma: Initial care of the injured child Edited by Robert M. Arensman, with Mindy B. Statter, Daniel J. Ledbetter, and Thomas Vargish. 272 pp. Philadelphia, Lippincott–Raven, 1995. $59. 0-7817-0260-7
Authors: I. David Todres
Journal: New England Journal of Medicine (1996)
Acute and Short-term Effects of Secondhand Smoke on Lung Function and Cytokine Production
Authors: Andreas D. Flouris, Giorgos S. Metsios, Andres E. Carrillo, Athanasios Z. Jamurtas, Konstantinos Gourgoulianis, Theodoros Kiropoulos, Manolis N. Tzatzarakis, Aristidis M. Tsatsakis, Yiannis Koutedakis
Journal: American Journal of Respiratory and Critical Care Medicine (2009)

The acute effect of secondhand smoke (SHS) on lung function and the duration of system disruption remain unknown.To assess the SHS effects and their duration on lung function and inflammatory markers.In a randomized single-blind crossover experiment data were obtained from 16 (8 women) nonsmoking adults at baseline and at 0, 1, and 3 hours after a 1-hour SHS exposure set at bar/restaurant SHS levels.Serum and urine cotinine, lung function, and cytokines IL-4, IL-5, IL-6, tumor necrosis factor (TNF)-alpha, and IFN-gamma. At 0 hours most lung function parameters were significantly reduced (indicative: FEV(1), 4.3 +/- 0.4 vs. 3.8 +/- 0.3 L; FEV(1)/FVC, 0.9 +/- 0.1 vs. 0.8 +/- 0.1; P < 0.05) but at 3 hours they were at baseline levels. In contrast, cotinine (serum, 8.9 +/- 3.2 vs. 35.5 +/- 10.2 ng x ml(-1)), IL-4 (41.3 +/- 5.8 vs. 44.2 +/- 4.5 pg x ml(-1)), IL-5 (36.1 +/- 3.2 vs. 60.1 +/- 7.0 pg x ml(-1)), IL-6 (2.5 +/- 0.3 vs. 7.6 +/- 1.4 pg x ml(-1)) and IFN-gamma (0.3 +/- 0.2 vs. 0.6 +/- 0.2 IU x ml(-1)) at 3 hours were higher than at baseline (P < 0.05). IL-4 and TNF-alpha increased only in men, whereas IL-5, IL-6, and IFN-gamma were different between sexes after exposure (P < 0.05). Regression analyses revealed inverse associations of FEV(1) and FEV(1)/FVC ratio with IL-5 (P < 0.05) in men and with IL-5 (P = 0.01), IL-6 (P < 0.001), IFN-gamma (P = 0.034) and serum cotinine (P < 0.001) in women.We conclude that 1 hour of SHS exposure at bar/restaurant levels is accompanied by significant decrements on lung function and marked increases in inflammatory cytokines, particularly in men. More importantly, whereas most smoke-induced effects on lung function appear to recede within 60 minutes, inflammatory cytokines remain elevated for at least 3 hours after exposure to SHS.
Current Concepts on the Management of Shock
Authors: MAX H. WEIL
Journal: Circulation (1957)

In the handling of a patient with shock it is essential to identify the underlying cause in order to plan rational treatment. On the basis of information presently available, the specific causes of shock have been classified into 6 groups: hypovolemia, cardiac failure, bacteremia, hypersensitivity, neurogenic factors, and obstruction to blood flow. Treatment was discussed with reference to these groups. Vasopressor agents are helpful in most instances of shock related to cardiac failure, bacteremia, and hypersensitivity. They usually are contraindicated in shock due to vascular obstruction and in hypovolemic shock until optimal replacement of fluid has been achieved. Recent studies have indicated that metaraminol may be the pressor amine of choice because it is therapeutically effective, simple to administer, without risk of injury to skin and subcutaneous tissues, and available for injection without additional fluid (thus especially suitable for patients with renal failure). Rigorous attention to the fluid and electrolyte state is of special importance. In the presence of acidosis, the response to vasopressor agents is greatly diminished. The use of molar solution of sodium lactate to re-establish this responsiveness has met with limited success and seems worthy of trial in selected cases. Adrenocortical hormones may be of striking benefit in shock due to bacteremia or hypersensitivity when an overwhelming response to inflammation threatens life. These drugs may be used also to augment the effectiveness of vasopressor drugs. Relatively little risk is involved, provided that the periods of employment are short and that antibiotics are used concurrently. The indications for the use of digitalis glycosides in shock are the same as at other times, and their routine use is of no proved benefit and may be injurious. Atropine is of value when excessive vagal activity with bradycardia produces or complicates the hypotensive state. Chlorpromazine is of no proved worth in the treatment of shock, and possible benefits achieved with anticoagulants are not established as yet. Preliminary observations suggest that hypothermia may be of some value. The head-down position provides only transient benefit in patients with shock, and its prolonged or routine use may delay recovery.
Somatic Mutations in the Connexin 40 Gene (<i>GJA5</i>) in Atrial Fibrillation
Authors: Michael H. Gollob, Douglas L. Jones, Andrew D. Krahn, Lynne Danis, Xiang-Qun Gong, Qing Shao, Xiaoqin Liu, John P. Veinot, Anthony S.L. Tang, Alexandre F.R. Stewart, Frederique Tesson, George J. Klein, Raymond Yee, Allan C. Skanes, Gerard M. Guiraudon, Lisa Ebihara, Donglin Bai
Journal: New England Journal of Medicine (2006)

Atrial fibrillation is the most common type of cardiac arrhythmia and a leading cause of cardiovascular morbidity, particularly stroke. The cardiac gap-junction protein connexin 40 is expressed selectively in atrial myocytes and mediates the coordinated electrical activation of the atria. We hypothesized that idiopathic atrial fibrillation has a genetic basis and that tissue-specific mutations in GJA5, the gene encoding connexin 40, may predispose the atria to fibrillation.We sequenced GJA5 from genomic DNA isolated from resected cardiac tissue and peripheral lymphocytes from 15 patients with idiopathic atrial fibrillation. Identified GJA5 mutations were transfected into a gap-junction-deficient cell line to assess their functional effects on protein transport and intercellular electrical coupling.Four novel heterozygous missense mutations were identified in 4 of the 15 patients. In three patients, the mutations were found in the cardiac-tissue specimens but not in the lymphocytes, indicating a somatic source of the genetic defects. In the fourth patient, the sequence variant was detected in both cardiac tissue and lymphocytes, suggesting a germ-line origin. Analysis of the expression of mutant proteins revealed impaired intracellular transport or reduced intercellular electrical coupling.Mutations in GJA5 may predispose patients to idiopathic atrial fibrillation by impairing gap-junction assembly or electrical coupling. Our data suggest that common diseases traditionally considered to be idiopathic may have a genetic basis, with mutations confined to the diseased tissue.
Retinal Vascular Lesions in Patients of Caucasian and Asian Origin With Type 2 Diabetes
Authors: Ronald P. Stolk, Mary J. van Schooneveld, J. Kennedy Cruickshank, Alun D. Hughes, Alice Stanton, Juming Lu, Anushka Patel, Simon A. McG. Thom, Diederick E. Grobbee, Johannes R. Vingerling
Journal: Diabetes Care (2008)

The objective of this study was to describe prevalent vascular retinal lesions among patients with type 2 diabetes enrolled in the ADVANCE Retinal Measurements (AdRem) study, a substudy of the Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE) trial.Seven-field stereoscopic photographs of both eyes were obtained at the baseline assessment of the ADVANCE trial. All photographs were graded in a central reading center. Gradable retinal images were received from 1,605 patients.The number of patients with any retinopathy (Early Treatment of Diabetic Retinopathy Study [ETDRS] score > or = 20) was 645 (40.2% [95% CI 37.8-42.6]); of these, 35 (2.2% [1.6-3.0]) had severe diabetic retinopathy (ETDRS score > or = 50). Focal arterial narrowing, venous beading, and arteriovenous nicking were present in 3.8, 5.1, and 9.8% of participants, respectively. Among participants included in this study, Chinese and South-Asian patients had more retinopathy than Caucasians, as defined both by ETDRS score (49.4, 46.0, and 31.3%, respectively; P < 0.001, adjusted for age, sex, A1C, systolic blood pressure, and duration of diabetes) and specific vascular lesions (e.g., arteriovenous nicking 12.3, 8.5, and 7.5%, respectively; adjusted P < 0.005). A1C, duration of diabetes, and systolic blood pressure were similarly associated with increased retinal lesions in Chinese, South-Asian, and Caucasian patients.Using a sensitive diagnostic procedure, more than one-third of patients with type 2 diabetes enrolled in the AdRem study had retinal lesions at baseline. Despite differences in prevalence and severity of retinopathy among Chinese, South-Asian, and Caucasian patients included in this study, the cross-sectional associations among established risk factors for retinopathy and retinal lesions were similar across ethnic groups.
TCT-181 Safety and Efficacy of a Novel Abluminal Groove-Filled Biodegradable Polymer Sirolimus-Eluting Stent for the Treatment of De Novo Coronary Lesions: 12-Month Results from the Prospectively Patient-Level Pooled Analysis of the TARGET I and TARGET II Trials
Authors: Run-Lin Gao, Bo Xu, Alexandra Lansky, Yuejin Yang, Ruiyan Zhang, Ma Changsheng, Hui Li, Shao Liang Chen, Yaling Han, Zuyi Yuan, Yong Huo, Wei Li, Yelin Zhao, Martin Leon
Journal: Journal of the American College of Cardiology (2013)
The Use and Misuse of Upper Gastrointestinal Endoscopy
Authors: Katherine L. Kahn
Journal: Annals of Internal Medicine (1988)

Study Objective: To determine how appropriately physicians in 1981 did upper gastrointestinal endoscopy in a randomly selected, community-based sample of Medicare patients. Design: We developed a comprehensive and clinically detailed list of 1069 indications for upper gastrointestinal endoscopy. A national panel of nine clinicians rated the appropriateness of the indications. We categorized the indications as appropriate, inappropriate, or equivocal. We did a clinically detailed medical record review of a random sample of 1585 patients having upper gastrointestinal endoscopy to assess the appropriateness of using upper gastrointestinal endoscopy. Setting: Patients were sampled from large geographic areas in three states. Two areas represented high use, and one area, low use. Patients: Random sample of patients 65 years of age or older receiving diagnostic upper gastrointestinal endoscopy. Interventions: None; the study was retrospective. Measurement and Results: Patient characteristics, histories, and clinical indications for upper gastrointestinal endoscopy were similar across low- and high-use areas. Overall, 72% of the endoscopies were done for appropriate indications, 11% for equivocal indications, and 17% for inappropriate indications. Upper gastrointestinal bleeding (26%), follow-up to an abnormal upper gastrointestinal series (21%), dysphagia (18%), and dyspepsia (15%) were the most frequent clinical reasons for doing endoscopy. Inpatient endoscopies were more often appropriate and less often inappropriate than outpatient endoscopies. Conclusions: This analysis of practice patterns among study sites provides the clinical basis for understanding the use of upper gastrointestinal endoscopy. The finding of 17% inappropriate use may be cause for concern.
Rescue of a Dystrophin-like Protein by Exon Skipping In Vivo Restores GABAA-receptor Clustering in the Hippocampus of the mdx Mouse
Authors: Cyrille Vaillend, Caroline Perronnet, Carine Ros, Carole Gruszczynski, Aurélie Goyenvalle, Serge Laroche, Olivier Danos, Luis Garcia, Elise Peltekian
Journal: Molecular Therapy (2010)

Dystrophin, the cytoskeletal protein whose defect is responsible for Duchenne muscular dystrophy (DMD), is normally expressed in both muscles and brain. Genetic loss of brain dystrophin in the mdx mouse model of DMD reduces the capacity for type A γ-aminobutyric acid (GABAA)-receptor clustering in central inhibitory synapses, which is thought to be a main molecular defect leading to brain and cognitive alterations in this syndrome. U7 small nuclear RNAs modified to encode antisense sequences and expressed from recombinant adeno-associated viral (rAAV) vectors have proven efficient after intramuscular injection to induce skipping of the mutated exon 23 and rescue expression of a functional dystrophin-like product in muscle tissues of mdx mice in vivo. Here, we report that intrahippocampal injection of a single dose of rAAV2/1-U7 can rescue substantial levels of brain dystrophin expression (15–25%) in mdx mice for months. This is sufficient to completely restore GABAA-receptor clustering in pyramidal and dendritic layers of CA1 hippocampus, suggesting exon-skipping strategies offer the prospect to investigate and correct both brain and muscle alterations in DMD. This provides new evidence that in the adult brain dystrophin is critical for the control of GABAA-receptor clustering, which may have an important role in activity-dependent synaptic plasticity in hippocampal circuits. Dystrophin, the cytoskeletal protein whose defect is responsible for Duchenne muscular dystrophy (DMD), is normally expressed in both muscles and brain. Genetic loss of brain dystrophin in the mdx mouse model of DMD reduces the capacity for type A γ-aminobutyric acid (GABAA)-receptor clustering in central inhibitory synapses, which is thought to be a main molecular defect leading to brain and cognitive alterations in this syndrome. U7 small nuclear RNAs modified to encode antisense sequences and expressed from recombinant adeno-associated viral (rAAV) vectors have proven efficient after intramuscular injection to induce skipping of the mutated exon 23 and rescue expression of a functional dystrophin-like product in muscle tissues of mdx mice in vivo. Here, we report that intrahippocampal injection of a single dose of rAAV2/1-U7 can rescue substantial levels of brain dystrophin expression (15–25%) in mdx mice for months. This is sufficient to completely restore GABAA-receptor clustering in pyramidal and dendritic layers of CA1 hippocampus, suggesting exon-skipping strategies offer the prospect to investigate and correct both brain and muscle alterations in DMD. This provides new evidence that in the adult brain dystrophin is critical for the control of GABAA-receptor clustering, which may have an important role in activity-dependent synaptic plasticity in hippocampal circuits.
THE REGENERATION OF PHARMACY A VITAL NECESSITY OF SCIENTIFIC MEDICINE.
Authors: OSCAR OLDBERG
Journal: JAMA (1898)

Medication is indispensable to the healing art. The physician without drugs is powerless. Indeed, the greater the need of the physician's services, the more urgent is, in most cases, the need of the medicine. The purpose of this paper is a plea for the more faithful and effective performance of duty in the preparation and dispensing of medicines. If medicine is not of importance in the treatment of disease, then let materia medica and pharmacy be abandoned. But if drugs or medicines are really so indispensable that the physician can do little or nothing without them, then it must be one of the highest duties of the physician to give heed to the character of the medicine he employs. This truth is apparently to a great extent ignored. But it is as important to the welfare of humanity as the science of medicine itself. To deny the necessity of faithfulness
Facilitating genome navigation: survey sequencing and dense radiation-hybrid gene mapping
Authors: Christophe Hitte, Jennifer Madeoy, Ewen F. Kirkness, Catherine Priat, Travis D. Lorentzen, Fabrice Senger, Dan Thomas, Thomas Derrien, Christina Ramirez, Carol Scott, Gwenaelle Evanno, Barbara Pullar, Edouard Cadieu, Vinay Oza, Kristelle Lourgant, David B. Jaffe, Sandrine Tacher, Stéphane Dréano, Nadia Berkova, Catherine André, Panagiotis Deloukas, Claire Fraser, Kerstin Lindblad-Toh, Elaine A. Ostrander, Francis Galibert
Journal: Nature Reviews Genetics (2005)
THE NEWSPAPER PRESS AND QUACKERY
Authors: H. Sewill
Journal: BMJ (1911)

Adherent human blood monocytes were stimulated with heat-killed Staphylococcus albus or Escherichia coli lipopolysaccharide in the presence of 35S-methionine-, [3H]leucine-, or 14C-labeled amino acids. After incubation, interleukin 1 (IL 1) activity in the supernatant medium was purified over an anti-human IL 1 immunoadsorbent followed by gel filtration and chromatofocusing. The purity of the IL 1 was assessed by fluorography of one- and two-dimensional SDS-polyacrylamide gel electrophoresis. Isoelectric and chromatofocusing of low m.w. proteins (less than 20,000 m.w.) revealed three charged 18,000 m.w. species of IL 1 with approximate pI9s of 7, 6, and 5, with the most abundant form at pI 7. During the purification procedures, lymphocyte co-mitogenic activity, fever in rabbits, and prostaglandin E2 release from dermal fibroblasts co-eluted in the same fractions. In addition, these fractions were active when injected into endotoxin-resistant C3H/HeJ mice for the production of fever, the induction of serum amyloid A protein, a decrease in serum iron concentration, and an increase in the number of circulating neutrophils. Fluorography revealed homogeneous bands with an m.w. of about 18,000 which correlated with these biological activities. The specific activity of the pI 6 or 5 IL 1, as judged by the ratio of T cell co-mitogenic activity to incorporated radiolabeled amino acid, was at least 10-fold greater than that observed for the pI 7 form. This result suggests that the amino acid compositions of the two 18,000 m.w. acidic forms are unrelated to the pI 7 species. These results also demonstrate that the pI 7 human monocyte IL 1 is the predominant 18,000 m.w. form synthesized and, furthermore, that homogeneous pI 7 IL 1 exhibits multiple biological properties on various tissues by modulating immunologic, inflammatory, metabolic, and neurologic functions. Data are also presented for the existence of a high m.w. (32,000) human pro-IL 1 molecule as the predominant monocytic intracellular form. This pro-IL 1 is degraded artifactually during isolation to lower m.w. forms in the presence of an extracellular serine protease activity. These data are consistent with a model for IL 1 secretion in which pro-IL 1 is first synthesized within the cell and is processed during or after extracellular transport.
Suburban Shaman: Tales from Medicine's Frontline
Authors: Des Spence
Journal: BMJ (2006)

T he order has come down the line and the next big health push is on. The barrage of health promotion literature has paused after weeks of bombardment. Comrades in arms, we stand on the duckboards taking deep draws on our fags, the acrid smoke of cynicism and sarcasm filling our lungs. The fresh faced recruits are naive and excited, but few will ever return. New officers have replaced the wounded who now lie in distant hospitals but will never leave.

The whistle blows and we are going over the top. …
Somatic and germline CACNA1D calcium channel mutations in aldosterone-producing adenomas and primary aldosteronism
Authors: Ute I Scholl, Gerald Goh, Gabriel Stölting, Regina Campos de Oliveira, Murim Choi, John D Overton, Annabelle L Fonseca, Reju Korah, Lee F Starker, John W Kunstman, Manju L Prasad, Erum A Hartung, Nelly Mauras, Matthew R Benson, Tammy Brady, Jay R Shapiro, Erin Loring, Carol Nelson-Williams, Steven K Libutti, Shrikant Mane, Per Hellman, Gunnar Westin, Göran Åkerström, Peyman Björklund, Tobias Carling, Christoph Fahlke, Patricia Hidalgo, Richard P Lifton
Journal: Nature Genetics (2013)