tbuckley/cabot-search huggingface dataset:
Risk Factors for Deep Venous Thrombosis of the Upper Extremities
Authors: Ida Martinelli, Marco Cattaneo, Daniela Panzeri, Emanuela Taioli, Pier Mannuccio Mannucci
Journal: Annals of Internal Medicine (1997)

Background: Hypercoagulable states and triggering factors (surgery, trauma, immobilization, pregnancy, and use of oral contraceptives) are associated with an increased risk for deep venous thrombosis of the lower extremities. In contrast, risk factors for deep venous thrombosis of the upper extremities have not been identified. Objective: To evaluate the prevalence of hypercoagulable states and triggering factors in patients with primary deep venous thrombosis of the upper extremities. Design: Frequency-matched case–control study. Setting: Hemophilia and thrombosis center at a university hospital. Patients: 36 patients who had primary deep venous thrombosis of the upper extremities, 121 patients who had primary deep venous thrombosis of the lower extremities, and 108 healthy controls. Patients who had deep venous thrombosis of the lower extremities and study controls were frequency-matched by age, sex, geographic origin, and social status with patients who had deep venous thrombosis of the upper extremities. Measurements: Resistance to activated protein C was evaluated by a clotting method based on the activated partial thromboplastin time. If test results were abnormal or borderline, DNA analysis for substitution in coagulation factor V gene was done. Antithrombin, protein C, protein S, antiphospholipid antibodies, and total plasma homocysteine levels were also measured. Results: Prevalences of abnormalities of the natural anticoagulant system (9%) and hyperhomocysteinemia (6%) in patients who had deep venous thrombosis of the upper extremities were similar to prevalences of both factors in controls (6% and 7%, respectively) but lower than in patients who had deep venous thrombosis of the lower extremities (31% and 14%, respectively). Antiphospholipid antibodies were found only in patients who had venous thrombosis of the lower extremities (7%). The overall prevalence of hypercoagulable states in patients who had thrombosis of the upper extremities (15%) was similar to that in controls (12%) but was significantly lower than that in patients who had thrombosis of the lower extremities (56%). A recent history of strenuous exercise of muscles in the affected extremity was the most frequent triggering factor for patients who had deep venous thrombosis in the upper extremities (33%). Conclusions: This preliminary study indicates that the prevalence of hypercoagulable states is low in patients who have primary deep venous thrombosis of the upper extremities.
Stunned peri-infarct canine myocardium is characterized by degradation of troponin T, not troponin I
Authors: D COLANTONIO
Journal: Cardiovascular Research (2004)

Degradation of cardiac troponin I (cTnI) has been proposed to represent the underlying molecular mechanism responsible for post-ischemic contractile dysfunction of viable but 'stunned' myocardium. However, this concept is largely derived from models of brief, sublethal ischemia essentially devoid of necrosis, and there is speculation that defects in cTnI may be model-dependent. Accordingly, our primary aim was to evaluate the integrity of cardiac troponins-i.e., cTnI, as well as cTnT and cTnC-in viable but stunned peri-infarct tissue. In addition, we addressed the as-yet unexplored issue of whether the profound reduction of infarct size evoked by brief preconditioning ischemia (PC) was accompanied by a favorable attenuation in ischemia/reperfusion-induced degradation of cTnI, cTnT or cTnC in the remaining viable subepicardium.Anesthetized open-chest dogs received 10 min of PC ischemia or a comparable control period, followed by 1 h of sustained coronary occlusion and 3 h of reperfusion. Subepicardial biopsies from the center of the soon-to-be ischemic territory were obtained at baseline and at 30 min and 3 h post-reflow, and myofilament protein integrity (intact cTnI, cTnT and cTnC, as well as degradation bands and covalent complexes) were assessed by Western immunoblotting. In addition, in all dogs, wall thickening was measured by echocardiography, collateral blood flow was assessed during sustained occlusion by injection of radiolabeled microspheres, and infarct size was delineated by tetrazolium staining.Although PC was, as expected, cardioprotective (infarct size of 2 +/- 1% of the risk region vs. 17 +/- 6% in controls; p < 0.05), both control and PC groups exhibited profound and comparable contractile dysfunction following reflow (mean wall thickening reduced to 20-22% of baseline values). There was, however, no significant degradation of cTnI in the viable but stunned, peri-infarct tissue. We did observe degradation of cTnT in the stunned subepicardium, an effect that was attenuated in dogs that received antecedent PC ischemia. However, there was no correlation between post-ischemic wall thickening and the immunoreactivity of the intact cTnT band, or wall thickening and the intensity of the cTnT degradation products.Our results suggest cTnI degradation is not a universal determinant of post-ischemic myocardial stunning. Moreover, the dissociation between cTnT degradation and wall thickening argue against a direct 'cause-and-effect' relationship between proteolysis of cTnT and acute, post-ischemic contractile dysfunction of stunned peri-infarct myocardium.
<i>ODC1</i> Is a Critical Determinant of <i>MYCN</i> Oncogenesis and a Therapeutic Target in Neuroblastoma
Authors: Michael D. Hogarty, Murray D. Norris, Kimberly Davis, Xueyuan Liu, Nicholas F. Evageliou, Candace S. Hayes, Bruce Pawel, Rong Guo, Huaqing Zhao, Eric Sekyere, Joanna Keating, Wayne Thomas, Ngan Ching Cheng, Jayne Murray, Janice Smith, Rosemary Sutton, Nicola Venn, Wendy B. London, Allen Buxton, Susan K. Gilmour, Glenn M. Marshall, Michelle Haber
Journal: Cancer Research (2008)

Abstract Neuroblastoma is a frequently lethal childhood tumor in which MYC gene deregulation, commonly as MYCN amplification, portends poor outcome. Identifying the requisite biopathways downstream of MYC may provide therapeutic opportunities. We used transcriptome analyses to show that MYCN-amplified neuroblastomas have coordinately deregulated myriad polyamine enzymes (including ODC1, SRM, SMS, AMD1, OAZ2, and SMOX) to enhance polyamine biosynthesis. High-risk tumors without MYCN amplification also overexpress ODC1, the rate-limiting enzyme in polyamine biosynthesis, when compared with lower-risk tumors, suggesting that this pathway may be pivotal. Indeed, elevated ODC1 (independent of MYCN amplification) was associated with reduced survival in a large independent neuroblastoma cohort. As polyamines are essential for cell survival and linked to cancer progression, we studied polyamine antagonism to test for metabolic dependence on this pathway in neuroblastoma. The Odc inhibitor α-difluoromethylornithine (DFMO) inhibited neuroblast proliferation in vitro and suppressed oncogenesis in vivo. DFMO treatment of neuroblastoma-prone genetically engineered mice (TH-MYCN) extended tumor latency and survival in homozygous mice and prevented oncogenesis in hemizygous mice. In the latter, transient Odc ablation permanently prevented tumor onset consistent with a time-limited window for embryonal tumor initiation. Importantly, we show that DFMO augments antitumor efficacy of conventional cytotoxics in vivo. This work implicates polyamine biosynthesis as an arbiter of MYCN oncogenesis and shows initial efficacy for polyamine depletion strategies in neuroblastoma, a strategy that may have utility for this and other MYC-driven embryonal tumors. [Cancer Res 2008;68(23):9735–45]
Gastric adenocarcinoma with a submucosal cyst treated by endoscopic submucosal dissection (ESD)
Authors: N. Ishii, M. Matsuda, T. Setoyama, S. Suzuki, S. Uchida, M. Uemura, Y. Iizuka, K. Fukuda, N. Horiki, Y. Fujita
Journal: Endoscopy (2009)

Isolated gastric submucosal cysts that consist of heterotopic glands are often encountered in the resected stomach. However, the presence of neoplastic tissue in such cysts is relatively rare [1] [2]. A close relation between diffuse gastric submucosal cysts and gastric cancer has been reported, but the mechanism has not been clarified. Chronic gastritis and intestinal metaplasia have been observed in the mucosa surrounding diffuse gastric submucosal cysts [1]. A major causative factor for gastric inflammation is Helicobacter pylori infection. Repeated erosion is induced by the chronic gastric inflammation, and following regeneration this may cause cancer as well as an aberration of the gastric glands. Diffuse submucosal cysts may give rise to a paracancerous lesion rather than a predisposing condition to gastric cancer. We report a rare case of early gastric cancer associated with a submucosal cystic lesion treated by endoscopic submucosal dissection (ESD).
Ginevra: Turned Left or Right? Leonardo: Straight or Gay?
Authors: Frank S. Tolone
Journal: JAMA (1987)

<h3>To the Editor.—</h3> Dr Crosby,<sup>1</sup>writing about Leonardo da Vinci, states that "Leonardo painted<i>only</i>women, an interesting track record for a homosexual." Historically, all that is known is that Leonardo was accused two times of being a homosexual and two times brought to trial. In an age and in a city in which (unfortunately) homosexuals were despised more than murderers and avoided more than lepers, and in which a conviction would have meant the death penalty, Leonardo was found innocent both times. I wonder on what basis Dr Crosby finds him posthumously guilty.
Acellular Pertussis Vaccines for Infants
Authors: Kathryn M. Edwards, Michael D. Decker
Journal: New England Journal of Medicine (1996)

Whole-cell vaccines, which are suspensions of killed Bordetella pertussis organisms, are among our most effective and least satisfactory vaccines. Before immunization was routine, pertussis was endemic in the United States, with up to 260,000 cases and 9000 deaths per year.1 By 1976 there were only 1010 cases and 7 deaths.1 Although the whole-cell vaccines have been effective, adverse effects are common. Worse still, pertussis vaccine has been temporally associated with devastating events such as sudden infant death. Although most careful studies suggest no causal relation, the existing pertussis vaccines have remained a source of disquiet to physicians and parents alike. . . .
Endogenous expression of type II cGMP-dependent protein kinase mRNA and protein in rat intestine. Implications for cystic fibrosis transmembrane conductance regulator.
Authors: T Markert, A B Vaandrager, S Gambaryan, D Pöhler, C Häusler, U Walter, H R De Jonge, T Jarchau, S M Lohmann
Journal: Journal of Clinical Investigation (1995)

Certain pathogenic bacteria produce a family of heat stable enterotoxins (STa) which activate intestinal guanylyl cyclases, increase cGMP, and elicit life-threatening secretory diarrhea. The intracellular effector of cGMP actions has not been clarified. Recently we cloned the cDNA for a rat intestinal type II cGMP dependent protein kinase (cGK II) which is highly enriched in intestinal mucosa. Here we show that cGK II mRNA and protein are restricted to the intestinal segments from the duodenum to the proximal colon, with the highest amounts of cGK II protein in duodenum and jejunum. cGK II mRNA and protein decreased along the villus to crypt axis in the small intestine, whereas substantial amounts of both were found in the crypts of cecum. In intestinal epithelia, cGK II was specifically localized in the apical membrane, a major site of ion transport regulation. In contrast to cGK II, cGK I was localized in smooth muscle cells of the villus lamina propria. Short circuit current (ISC), a measure of Cl- secretion, was increased to a similar extent by STa and by 8-Br-cGMP, a selective activator of cGK, except in distal colon and in monolayers of T84 human colon carcinoma cells in which cGK II was not detected. In human and mouse intestine, the cyclic nucleotide-regulated Cl- conductance can be exclusively accounted for by the cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channel. Viewed collectively, the data suggest that cGK II is the mediator of STa and cGMP effects on Cl- transport in intestinal-epithelia.
Musculoskeletal Disorders: Regional Examination and Differential Diagnosis
Authors: Reginald R. Cooper
Journal: JAMA (1978)

This rather inclusive text presents a step-wise approach to the differential diagnosis of musculoskeletal disease. According to the author of chapter 1, the two parts of examination consist of observation of the whole patient and inspection of the musculoskeletal system. In a sense, the book follows this format. The initial five chapters address certain components essential to examining any patient. The remaining sections portray a method of diagnosing regional musculoskeletal diseases and disorders. The various authors adhere to a common format, which takes up in turn anatomy, regional examination, and differential diagnosis. Profuse illustrations and photographic and roentgenographic reproductions provide a valuable counterpart to a well-written, concise text. Chapter 1, on general diagnosis, contains a useful entry on common laboratory values and their alterations in various disorders. Likewise, the chart and discussion on synovial fluid alterations are useful in treating patients with joint diseases. The section on x-ray film interpretation
AN AUTOMATIC DISTRIBUTOR FOR NEUTRAL SOLUTION OF CHLORINATED SODA (DAKIN'S SOLUTION)
Authors: Lyman J. Strong
Journal: JAMA (1918)

The successful use of Dakin's solution (neutral solution of chlorinated soda) depends on its delivery in sufficient quantity to all parts of the infected wound at regular and frequent intervals. These conditions can be obtained by a simple apparatus. Wounds vary in size; therefore, this apparatus has two controls, one for time and one for quantity. An irrigator can,<i>A</i>, is elevated on the head of the bed. A short piece of rubber tubing connects with a drop tube,<i>B</i>. A screw clamp on this piece of tubing controls the rate of flow through the dripping apparatus. For example, to deliver 80 c.c. every two hours, the screw clamp is set so that 10 drops each minute fall from the drop tube. A large size test tube,<i>D</i>, of about 100 c.c. capacity, is fitted with a three hole rubber stopper. This test tube serves as a reservoir to collect
Acute Respiratory Diseases and Carboxyhemoglobin Status in School Children of Quito, Ecuador
Authors: Bertha Estrella, Ramiro Estrella, Jorge Oviedo, Ximena Narváez, María T. Reyes, Miguel Gutiérrez, Elena N. Naumova
Journal: Environmental Health Perspectives (2005)

Outdoor carbon monoxide comes mainly from vehicular emissions, and high concentrations occur in areas with heavy traffic congestion. CO binds to hemoglobin, forming carboxyhemoglobin (COHb), and reduces oxygen delivery. We investigated the link between the adverse effects of CO on the respiratory system using COHb as a marker for chronic CO exposure. We examined the relationship between acute respiratory infections (ARIs) and COHb concentrations in school-age children living in urban and suburban areas of Quito, Ecuador. We selected three schools located in areas with different traffic intensities and enrolled 960 children. To adjust for potential confounders we conducted a detailed survey. In a random subsample of 295 children, we determined that average COHb concentrations were significantly higher in children attending schools in areas with high and moderate traffic, compared with the low-traffic area. The percentage of children with COHb concentrations above the safe level of 2.5% were 1, 43, and 92% in low-, moderate-, and high-traffic areas, respectively. Children with COHb above the safe level are 3.25 [95% confidence interval (CI), 1.65-6.38] times more likely to have ARI than children with COHb < 2.5%. Furthermore, with each percent increase in COHb above the safety level, children are 1.15 (95% CI, 1.03-1.28) times more likely to have an additional case of ARI. Our findings provide strong evidence of the relation between CO exposure and susceptibility to respiratory infections.
Evidence for Statin Pleiotropy in Humans
Authors: Ping-Yen Liu, Yen-Wen Liu, Li-Jen Lin, Jyh-Hong Chen, James K. Liao
Journal: Circulation (2008)

By inhibiting 3-hydroxy-3-methylglutaryl coenzyme A reductase, statins not only reduce cholesterol biosynthesis but also decrease the formation of isoprenoids, which are important for mediating signaling through the Rho-associated coiled-coil containing protein kinase (ROCK) pathway. Increased ROCK activity has been implicated in endothelial dysfunction and vascular inflammation. We hypothesize that ezetimibe, which inhibits intestinal cholesterol absorption, may not exert similar cholesterol-independent or pleiotropic effects of statins and, when used with a lower dose of statin, have less effect on ROCK activity than a higher dose of statin.In a prospective, randomized, observer-blinded study, we treated 60 dyslipidemic subjects without cardiovascular disease with simvastatin 40 mg/d, simvastatin/ezetimibe 10/10 mg/d, or placebo tablets for 28 days (n=20 in each arm). We evaluated baseline demographics and lipid levels, ROCK activity, C-reactive protein, and flow-mediated dilation before and after treatment. Compared with the placebo group, both treatment regimens decreased low-density lipoprotein cholesterol by 38% and C-reactive protein by 38% to 40% after 28 days (P<0.01 for both compared with placebo). Although the low-density lipoprotein cholesterol and C-reactive protein reductions were comparable with either lipid-lowering regimen, only simvastatin 40 mg reduced ROCK activity and improved flow-mediated dilation (P<0.01 for both compared with baseline). Reduction in ROCK activity with simvastatin 40 mg remained significant even after controlling for changes in low-density lipoprotein cholesterol (P=0.01) and correlated with improvement in flow-mediated dilation (R(2)=-0.78, P<0.01). No correlation was found between changes in flow-mediated dilation and changes in low-density lipoprotein cholesterol or C-reactive protein.These results indicate that high-dose statin monotherapy exerts greater effects on ROCK activity and endothelial function, but not on C-reactive protein, than low-dose statin plus ezetimibe. These findings provide additional evidence of statin benefits beyond cholesterol lowering.
Replacement of an Avulsed Phalanx with Tissue-Engineered Bone
Authors: Charles A. Vacanti, Lawrence J. Bonassar, Martin P. Vacanti, John Shufflebarger
Journal: New England Journal of Medicine (2001)

For several decades, various approaches have been used to replace bone lost to trauma and disease. In 1908, Lexer1 described attempts to reconstruct joints with newly amputated or cadaveric allografts. In more recent years, autografts2 and allografts3,4 have been used extensively to replace bone. Several natural or synthetic bone substitutes have also been used alone5–9 or in conjunction with demineralized bone10 or autologous bone as vascularized or free (nonvascularized) grafts.11,12 There have been numerous reports on the use of polypeptides13,14 or demineralized bone powder14,15 to stimulate the differentiation of mesenchymal tissue into bone. More recently, . . .
Glucose-free fatty acid cycle operates in human heart and skeletal muscle in vivo.
Authors: P Nuutila, V A Koivisto, J Knuuti, U Ruotsalainen, M Teräs, M Haaparanta, J Bergman, O Solin, L M Voipio-Pulkki, U Wegelius
Journal: Journal of Clinical Investigation (1992)

Positron emission tomography permits noninvasive measurement of regional glucose uptake in vivo in humans. We employed this technique to determine the effect of FFA on glucose uptake in leg, arm, and heart muscles. Six normal men were studied twice under euglycemic hyperinsulinemic (serum insulin approximately 500 pmol/liter) conditions, once during elevation of serum FFA by infusions of heparin and Intralipid (serum FFA 2.0 +/- 0.4 mmol/liter), and once during infusion of saline (serum FFA 0.1 +/- 0.01 mmol/liter). Regional glucose uptake rates were measured using positron emission tomography-derived 18F-fluoro-2-deoxy-D-glucose kinetics and the three-compartment model described by Sokoloff (Sokoloff, L., M. Reivich, C. Kennedy, M. C. Des Rosiers, C. S. Patlak, K. D. Pettigrew, O. Sakurada, and M. Shinohara. 1977. J. Neurochem. 28: 897-916). Elevation of plasma FFA decreased whole body glucose uptake by 31 +/- 2% (1,960 +/- 130 vs. 2,860 +/- 250 mumol/min, P less than 0.01, FFA vs. saline study). This decrease was due to inhibition of glucose uptake in the heart by 30 +/- 8% (150 +/- 33 vs. 200 +/- 28 mumol/min, P less than 0.02), and in skeletal muscles; both when measured in femoral (1,594 +/- 261 vs. 2,272 +/- 328 mumol/min, 25 +/- 13%) and arm muscles (1,617 +/- 411 to 2,305 +/- 517 mumol/min, P less than 0.02, 31 +/- 6%). Whole body glucose uptake correlated with glucose uptake in femoral (r = 0.75, P less than 0.005), and arm muscles (r = 0.69, P less than 0.05) but not with glucose uptake in the heart (r = 0.04, NS). These data demonstrate that the glucose-FFA cycle operates in vivo in both heart and skeletal muscles in humans.
Mortality from asthma: a new epidemic in New Zealand
Authors: R. T Jackson, R. Beaglehole, H. H Rea, D. C Sutherland
Journal: BMJ (1982)

Trends in mortality attributed to asthma in the 5-34-year age group were examined in New Zealand, Australia, England and Wales, the United States, Canada, and West Germany for the years 1959-79. An epidemic of deaths from asthma occurred in the mid-1960s in New Zealand, Australia, and England and Wales but not in the other countries. In Australia and England and Wales the death rate quickly returned to pre-epidemic levels, but in New Zealand the decline in mortality was slow, and by 1974 the death rate was still almost double the pre-epidemic level. Of great concern was an abrupt increase in reported deaths from asthma in New Zealand after 1976 with the mortality rate during 1977-9 being greater than during the previous epidemic. In contrast, asthma mortality had remained relatively stable in the other populations.The new epidemic in New Zealand was investigated and appeared to be real. It could not be explained by changes in the classification of deaths from asthma, inaccuracies in death certification, or changes in diagnostic fashions. The most likely explanation appeared to be related to the management of asthma in New Zealand, and this is being investigated.
Topics in Radiology
Authors: Z. Danilevicius
Journal: JAMA (1974)

A busy physician is often confronted with clinical problems that are outside of his field of expertise. One specialty that every practicing physician is in contact with is radiology. Because there are many areas in radiology that non-radiologists must be familiar with,The Journalis introducing a new section, TOPICS IN RADIOLOGY.  Under the direction of Benjamin Felson, MD, professor and chairman of the Department of Radiology, University of Cincinnati, College of Medicine, a number of noted radiologists will present weekly articles on topics in radiological diagnosis and therapy. Of the four or five monthly issues of JAMA , one will contain information on radiological diagnosis, another on radiotherapy, a third will present a gamut (presenting the differential diagnostic possibilities offered by a variety of roentgen signs), a fourth will feature an intriguing radiological picture of the month and, if there is a fifth issue that month, it will be set