tbuckley/cabot-search huggingface dataset:
Species differences in myocardial beta-adrenergic receptor regulation in response to hyperthyroidism.
Authors: B Crozatier, J B Su, A Corsin, None Bouanani N el-H
Journal: Circulation Research (1991)

The coupling between myocardial beta-adrenergic receptors, adenylate cyclase activity, and the in vivo cardiac response to catecholamines is controversial in hyperthyroidism. The possibility of species differences in beta-adrenoceptor regulation after thyroxine treatment was studied in dogs and in rats. In dogs instrumented with a left ventricular (LV) pressure micromanometer, hyperthyroidism was induced by L-thyroxine (0.5 mg/kg/day i.v. for 10 days). After hyperthyroidism, heart rate was increased to 167 +/- 10 beats/min (control, 107 +/- 8 beats/min; p less than 0.005) with an increase of peak LV dP/dt from 4,243 +/- 471 to 6,105 +/- 862 mm Hg/sec (p less than 0.01). LV response to injection of increasing doses of isoproterenol and dobutamine was not significantly different before and after induction of the hyperthyroid state, as shown by the unchanged slopes of the LV peak dP/dt versus the log of the dose of isoproterenol and dobutamine. Bmax of beta-receptors measured in crude membranes using 3H-CGP 12177 and in homogenates using 125I-cyanopindolol was not increased in hyperthyroid animals as compared with a control group. Basal adenylate cyclase activity was not different in control and hyperthyroid dogs (32 +/- 3 versus 29 +/- 3 pmol/mg/min), and maximal adenylate cyclase activity response to isoproterenol was similar in control and hyperthyroid dogs. In contrast, in rats subjected to hyperthyroidism (0.5 mg/kg/day i.p. L-thyroxine for 10 days), Bmax of adrenoceptors measured using the same methods was significantly increased as compared with control (+72.5% using 3H-CGP 12177 and +41% using 125I-cyanopindolol, but adenylate cyclase activity was not increased in hyperthyroid rats. We conclude that both adenylate cyclase activity and LV response to catecholamines are not increased by thyroxine-induced hyperthyroidism in dogs and that, in contrast with rats, beta-adrenergic density is not increased in hyperthyroid dogs. This indicates a species difference in myocardial beta-adrenoceptor regulation in response to hyperthyroidism.
Clinical Pharmacology of Resveratrol and Its Metabolites in Colorectal Cancer Patients
Authors: Ketan R. Patel, Victoria A. Brown, Donald J.L. Jones, Robert G. Britton, David Hemingway, Andrew S. Miller, Kevin P. West, Tristan D. Booth, Marjorie Perloff, James A. Crowell, Dean E. Brenner, William P. Steward, Andreas J. Gescher, Karen Brown
Journal: Cancer Research (2010)

Resveratrol is a phytochemical with chemopreventive activity in preclinical rodent models of colorectal carcinogenesis. Antiproliferation is one of the many chemopreventive modes of action it has been shown to engage in. Concentrations of resveratrol, which can be achieved in human tissues after p.o. administration, have not yet been defined. The purpose of this study was to measure concentrations of resveratrol and its metabolites in the colorectal tissue of humans who ingested resveratrol. Twenty patients with histologically confirmed colorectal cancer consumed eight daily doses of resveratrol at 0.5 or 1.0 g before surgical resection. Resveratrol was found to be well tolerated. Normal and malignant biopsy tissue samples were obtained before dosing. Parent compound plus its metabolites resveratrol-3-O-glucuronide, resveratrol-4'-O-glucuronide, resveratrol-3-O-sulfate, resveratrol-4'-O-sulfate, resveratrol sulfate glucuronide, and resveratrol disulfate were identified by high-performance liquid chromatography (HPLC) with UV or mass spectrometric detection in colorectal resection tissue. Quantitation was achieved by HPLC/UV. Cell proliferation, as reflected by Ki-67 staining, was compared in preintervention and postintervention tissue samples. Resveratrol and resveratrol-3-O-glucuronide were recovered from tissues at maximal mean concentrations of 674 and 86.0 nmol/g, respectively. Levels of resveratrol and its metabolites were consistently higher in tissues originating in the right side of the colon compared with the left. Consumption of resveratrol reduced tumor cell proliferation by 5% (P = 0.05). The results suggest that daily p.o. doses of resveratrol at 0.5 or 1.0 g produce levels in the human gastrointestinal tract of an order of magnitude sufficient to elicit anticarcinogenic effects. Resveratrol merits further clinical evaluation as a potential colorectal cancer chemopreventive agent.
Risks of Nontraumatic Lower-Extremity Amputations in Patients with Type 1 Diabetes
Authors: Junmei Miao Jonasson, Weimin Ye, Pär Sparén, Jan Apelqvist, Olof Nyrén, Kerstin Brismar
Journal: Diabetes Care (2008)

The purpose of this study was to estimate the risks of nontraumatic lower-extremity amputations (LEAs) in patients with type 1 diabetes.We identified 31,354 patients with type 1 diabetes (15,001 women and 16,353 men) in the Swedish Inpatient Register between 1975 and 2004. The incidence of nontraumatic LEAs was followed up until 31 December 2004 by cross-linkage in the Inpatient Register and linkage to the Death and Migration registers. Poisson regression modeling was used to compare the risks of nontraumatic LEAs during different calendar periods of follow-up, with adjustment for both sex and attained age at follow-up. Standardized incidence ratios (SIRs) were used to estimate the relative risks (RRs) with the age-, sex-, and calendar period-matched general Swedish population as reference. The cumulative probability of nontraumatic LEAs was calculated by the Kaplan-Meier method.In total, 465 patients with type 1 diabetes underwent nontraumatic LEAs. The risk was lower during the most recent calendar period (2000-2004) than during the period before 2000 (RR 0.6 [95% CI 0.5-0.8]). However, even in this most recent period, the risk for nontraumatic LEAs among these relatively young patients was 86-fold higher than that in the matched general population (SIR 85.8 [72.9-100.3]). By age 65 years, the cumulative probability of having a nontraumatic LEA was 11.0% for women with type 1 diabetes and 20.7% for men with type 1 diabetes.Although the risks appeared to have declined in recent years, patients with type 1 diabetes still have a very high risk for nontraumatic LEAs.
Noncontraceptive Estrogen Use and the Risk of Breast Cancer
Authors: David W. Kaufman
Journal: JAMA (1984)

The relation between the risk of breast cancer and the use of noncontraceptive estrogens was investigated in a hospital-based study of 1,610 women with breast cancer and 1,606 with other conditions. The overall relative risk estimate for conjugated estrogens first taken at least 18 months before admission, compared with never-use of any noncontraceptive estrogens, was 0.9 (95% confidence interval, 0.7 to 1.1). For other estrogens first taken at least 18 months before admission, the estimate was 0.8 (0.6 to 1.1). The results were similar when known risk factors for breast cancer were taken into account. Among postmenopausal women, conjugated estrogens did not appear to increase the risk of breast cancer, even when taken for many years or in the distant past. There was no evidence of an increased risk due to conjugated estrogen use among subgroups of women defined according to various risk factors for breast cancer. The results of this study suggest that noncontraceptive estrogens do not increase the risk of breast cancer.
Toward Smoke-Free VA Hospitals
Authors: TedfordC. Luck
Journal: JAMA (1989)

<h3>To the Editor. —</h3> The letter by Drs Joseph and Korn<sup>1</sup>in the Sept 16 issue of<i>JAMA</i>discusses the attitudes of veterans toward smoking restrictions in a Veterans Administration (VA) hospital and the feasibility of smoke-free VA hospitals. We were encouraged and delighted to hear that the Minneapolis VA Medical Center has become a totally smoke-free hospital. All other VA hospitals, on the other hand, still allow smoking by patients and staff in a number of areas. The number of places where smoking is allowed in the Denver VA Medical Center has been reduced significantly in the last few years, but further efforts to restrict smoking have met with considerable resistance. To determine the extent of this resistance among patients, we gave a questionnaire (June through August 1987) to outpatients awaiting primary care clinic appointments. Completed questionnaires were received from 84% (468/553); 40% were current smokers, 45% were
"Verities Yet in Their Chaos"
Authors: C. McNeil
Journal: BMJ (1950)

a contemporary and familiar friend of William Harvey.Hobbes has described the life of man as " nasty, brutish, and short."He knew something both of life and of medicine.He had studied anatomy and read Vesalius in Paris; and he lived to the age of 90 by a health system of his own, and by keeping clear of doctors.A strong point in his system was exercise, and a favourite exercise was singing.This is described by Aubrey (Lives of Eminent Men): " At night when he was abed and the doors made fast, and was sure nobody heard him, he sang aloud (not that he had a good voice) but for his health's sake: he did believe it did his lungs good, and conduced much to prolong his life."Aubrey adds: " He seldom used any physique.He was wont to say that he had rather have the advice or take physique from an experienced old woman who had been at many sick people's bedsides, than from the most learned but unexperienced physician."This story suggests the low state and repute of medical practice in 1602, when Harvey came back to London from Padua, like Portia, " a young and learned doctor."Yet he brought back with him from Padua the best medical science of that time.It was the system of Galen brought up to date: Galen's anatomy revised and added to by Vesalius and Fabricius; his physiology, hardly modified but brilliantly expounded by Fernel in his Physiologia.It was the physiology that specially interested the young Harvey, and that was to be his life-long study.There were the four elements and temperaments; the four humours; the three coctions; the three spirits derived from the three great organs-liver, heart, and brain.The blood, carrying nutriment to every part, flowed out and came back by the same vessels-veins and arteries: and the blood was also charged with innate heat.But almost nothing was known of the true function of the heart, lungs, brain and nerves, muscles, and digestion.Although the human body with its great organs had been dissected for sixty years by the accurate standards of Vesalius, there was confusion and almost complete ignorance of how these organs worked.These humours and spirits and innate heat and the rest had truth in.them; but they were dim shapes, " without form and void "; they were "medical verities yet in their chaos."And so pestilence raged, disease prevailed, and humanity suffered.
Influence of temporary transvenous endocardial pacing on signs and symptoms of heart failure in acute myocardial infarction complicated by serious bradycardia
Authors: Nebojsa Radovanovic, Zorana Vasiljevic, Mina Radosavljevic, A. Karadzic, Branislav Stefanovic, Vladan Vukcevic, Branka Terzic, Predrag Mitrovic
Journal: European Journal of Heart Failure (2000)
Prolonged Activity and Movement After a Penetrating Stab Wound of the Heart
Authors: J. Davidson, F. S. Fiddes
Journal: BMJ (1956)

ELEPHANTIASIS IN TANGANYIKA BRgDIAJsHfor these cases.The endemic focus of A. perstans infec- tion noted above extends round the north of Lake Victoria and includes the Kampala area (Hawking, 1940).The cases described by Loewenthal had a verrucose condition of the feet, and Clark (1948) reported a series of elephantiasis cases with this verrucose condition from the area round the Aberdare Mountains in Kenya.There are no reports of A. perstans or W. bancrofti occurring in this area.The velvety appearance of the skin was seen in many cases of elephantiasis of filarial and non-filarial origin.It is not regarded as a clinical entity (Strong, 1944), but appears to complicate elephantiasis of varied aetiologies.Jelliffe (1951) reported the condition in elephantiasis of tertiary yaws.No detailed pathological investigations were possible in any of the cases, and no post-mortem material has become available for study.Until such studies can be made the true nature of the causative agent must remain a matter for conjecture. SummyA series of elephantiasis cases seen in an area free of bancroftian filariasis to the south-west of Lake Victoria is compared with a series of cases of elephantiasis of bancroftian origin.The possibility of these cases being due to A. perstans infection is discussed, and other reports of non-bancroftian elephantiasis in East Africa are noted.
Proteomic analyses of normal and malignant breast tissue—Identification of a tumor-specific protein expression profile
Authors: G. Hudelist, C. Singer, K. Pischinger, K. Kaserer, M. Manavi, E. Kubista, K. Czerwenka
Journal: Journal of Clinical Oncology (2006)

10524 Background: Gene expression analysis has become a promising tool in predicting the clinical course of malignant disease and the response to antineoplastic therapy. Suprisingly, only little is known about the protein expression pattern of human tumors. Recent advances in proteomic analysis allow to identify proteins of interest by their expression and/or modification pattern in 2D-PAGE rather than using the traditional approach of translating gene expression data. Methods: In order to identify a proteomic pattern that is characteristic for malignant breast epithelium, we performed differential 2D-PAGE analysis in sets of microdissected malignant breast epithelia and corresponding adjacent normal breast epithelia from 5 patients with invasive breast carcinoma. Results: Thirty-two protein spots were found to be selectively regulated in malignant epithelium, and were subjected to MALDI-TOF and/or immunoblotting for protein identification. Thirteen of the identified proteins had previously not been associated with breast cancer. The validity of these findings was confirmed by literature review and immunohistochemistry for identified proteins in an independent cohort of 50 breast cancer specimens. Conclusions: We here describe a proteomic analysis of matched normal and malignant epithelia from invasive breast carcinomas. This strategy leads to a better understanding of oncogenesis at an operational level and helps to characterize the malignant phenotype of individual tumors and thereby to identify novel targets for antineoplastic therapy. No significant financial relationships to disclose.
A Complication of Heart-Valve Replacement
Authors: Wayne R. Rogers
Journal: JAMA (1966)

ABSTRACT To the Editor:— Lamkin et al (194: 1019, 1965) have done a service in calling attention to the commonest late complication of heart-valve replacement, namely, thromboembolism. In discussing the genesis of the thromboemboli in their patient, the authors did not consider the loud apical holosystolic murmur. Such a finding in the presence of a Starr-Edwards mitral prosthesis usually means regurgitation through a break in the suture line about the valve. After angiographic confirmation, closure of the defect is indicated, because this will probably reduce the likelihood of thromboembolism.
Use of Imipramine in Diabetics
Authors: Stanley M. Kaplan
Journal: JAMA (1960)

SEVERAL new drugs for the treatment of depression have been introduced over the past several years. Among them is imipramine hydrochloride (Tofrānil), chemically 5-(3-dimethylaminopropyl)-10, 11-dihydro-5 H-dibenz [b, f] azepine hydrochloride. The effectiveness of this drug in the treatment of depression was initially described by Kuhn,<sup>1</sup>and later confirmed by others.<sup>2-3</sup>The mechanism of action of the drug has not been established, but structurally it is similar to drugs with a phenothiazine base. During the treatment of several mildly diabetic patients who were also depressed, we observed a diminution of glycosuria concomitant with the administration of imipramine, with a return to premedication levels of glycosuria when use of the imipramine was discontinued. We have now noted this effect in 5 subjects, 4 of whom were depressed, while the 5th was not. These clinical observations seemed sufficiently important to warrant further study, especially since it is only in the past
Health and Obesity
Authors: David P. Barr
Journal: New England Journal of Medicine (1953)

IN his delightful monograph on obesity, Leonard Williams1 has occasion to discuss its classification, as follows:The unlovely condition called corpulence or obesity has been divided into three stages known respectively as the enviable, the comical, and the pitiful. Such classification is based upon a false estimate of values, for no case of obesity is enviable. Most of them are in a sense comical, and all are pitiable.It is not difficult to demonstrate that obesity is both disadvantageous and dangerous. A mere list of its hazards, disabilities and discomforts is formidable. Obesity predisposes to diabetes, increases che tendency to . . .
Concreted Cornhusker Sent Back to Loam, Sweet Loam. Aw Shucks!
Authors: William H. B. Howard
Journal: JAMA (1987)

To the Editor.—  I enjoyed the discussion by Elizabeth Knoll 1 of the artwork on the cover of the Sept 11 issue of JAMA . However, I suspect that Ms Knoll's roots are planted in concrete rather than in loam, and I offer a mild reproach on her terminology before my less tolerant brethren in Iowa or Nebraska take a shot at her.  The objects scattered on the floor with which the young boy is playing are cobs, not husks, while the basket at the old man's right holds ears of corn, not cobs. Any husks, the parchmentlike covering of the ears, that may have resulted from this process are probably still lying in the field where the corn had been shucked a couple of months before.  Moreover, it is interesting to note that every part of this crop was used. The grain went for feed, the stalks for fodder, and
The Mechanism of Nitrazepam-Induced Drooling and Aspiration
Authors: Elaine Wyllie, Robert Wyllie, Robert P. Cruse, A. David Rothner, Gerald Erenberg
Journal: New England Journal of Medicine (1986)

Nitrazepam, a benzodiazepine anticonvulsant, is used in the treatment of myoclonic, akinetic, absence, generalized tonic–clonic, and complex partial epilepsies.1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 Adverse reactions to the drug include sedation, hypotonia, ataxia, nausea, and vomiting.1 2 3 4 5 6 7 8 9 , 12 , 13 , 16 17 18 19 Nitrazepam-induced drooling,4 , 7 8 9 , 12 eating difficulty,9 and aspiration pneumonia5 , 7 8 9 , 13 have been attributed to (unproved) salivary and bronchial hypersecretion.5 , 8 , 9 , 12 , 13 We conducted manometric examinations of two children with nitrazepam-induced drooling and aspiration and found that the onset of the cricopharyngeal relaxation during swallowing was delayed until after the onset of the hypopharyngeal contraction. This abnormality was not seen in any age-matched controls. These cases of drug-induced cricopharyngeal incoordination indicate that the drooling and . . .
TCT-238 The Instantaneous Wave-Free Ratio (iFR) and Fractional Flow Reserve (FFR) Have Equivalent Diagnostic Categorisation When Compared To Flow Based Indices
Authors: Sayan Sen, Sukhjinder Nijjer, Ricardo Petraco, Kaleab Asrress, Christopher Broyd, Nicolas Foin, Rodney Foale, Iqbal Malik, Ghada Mikhail, Christopher Baker, Masood Khan, Muhammed Khawaja, Amarjit Sethi, Darrel Francis, Alun Hughes, Jamil Mayet, Carlo Di Mario, Javier Escaned, Simon Redwood, Justin Davies
Journal: Journal of the American College of Cardiology (2012)
Bidirectional case-crossover studies of air pollution: bias from skewed and incomplete waves.
Authors: J T Lee, H Kim, J Schwartz
Journal: Environmental Health Perspectives (2000)

The case-crossover design compares exposures during the period of time of failure with one or more periods when failure did not occur and evaluates the potential excess risk using conditional logistic regression. In this simulation study, we applied several control sampling approaches to control for confounding by various temporal patterns of an exposure variable and evaluated the usefulness of symmetric bidirectional control strategies. We simulated true relative risks (RRs; true ss = 0.001) of deaths of 1.051 per 50-ppb increase of sulfur dioxide and included confounding by right- or left-skewed seasonal waves, linear long-term time trends, or a combination of both. The range of the estimated RRs from symmetric bidirectional control sampling approaches was 1.044 approximately 1. 056 at either a long-term trend or any skewed seasonal wave of SO(2) levels, which indicated the bidirectional control sampling methods would successfully control confounding by design. The simulations with bidirectional sampling, however, show that biases may occur if waves are incomplete (20-43% underestimated RRs). In conclusion, our simulations show that the symmetric bidirectional case-crossover design can substantially control for confounding by linear long-term trends and/or seasonality of an exposure variable by design as well. However, unidirectional control sampling would fail to control confounding by those variations of air pollution. Simulation results also show that even the bidirectional case-crossover design can be biased in a situation where the exposure variable shows incomplete cyclic waves, and therefore it cannot completely control for temporal confounding.
Daubert v Merrell Dow. The Supreme Court tackles scientific evidence in the courtroom
Authors: J. A. Gold
Journal: JAMA (1993)

ON JUNE 28, 1993, the US Supreme Court handed down a decision that, in the words of one commentator, "could affect almost every piece of litigation in the Federal courts from this point forward."<sup>1</sup>The decision in<i>Daubert v Merrell Dow Pharmaceuticals</i><sup>2</sup>sets forth criteria that federal courts must follow in admitting scientific evidence or excluding it from consideration by juries. While the decision will not apply directly to state courts, states are likely to look to the High Court for guidance. This article will analyze the decision and discuss its implications for medicine, medical publishing, and expert testimony. <h3>THE CASE</h3> The drug for morning sickness, Bendectin (doxylamine), was driven off the market in 1983 by the pressure of lawsuits asserting that it caused birth defects. Before Bendectin was taken off the market, millions of women had used it.<sup>3</sup>Of 30 published epidemiologic studies involving over 130
Indian Sandal Strap Dermatitis
Authors: Peter J. Lynch, Andrew J. Rudolph
Journal: JAMA (1969)

To the Editor:—  During the past 18 months we have seen six young adults with identical eczematous lesions on the dorsal surface of the feet. In each instance the location of the eruption corresponded exactly with the straps of sandals they had recently worn ( Figure). The sandals were strikingly similar, and all had been made in India. The eruption quickly subsided when the patients applied topical corticosteroids and stopped wearing the sandals. Two of the patients were patch tested to the leather from their sandal straps, formalin 5%, potassium dichromate 0.25%, paraphenylenediamine 1%, and rubber mix. The latter is Hollister-Steir's preparation of diphenylguanidine 0.1%, mercaptobenzothiazole 1%, and tetramethylthiuram disulfide 1%. Both patients had reactions only to the leather from their sandals. Four unaffected persons patch-tested to the same leather had no reactions.  Contact dermatitis to foot wear is generally related to rubber compounds, linings, adhesives, dyes, or leather. The positive