tbuckley/cabot-search huggingface dataset:
Network integration of the adrenergic system in cardiac hypertrophy
Authors: L BARKIHARRINGTON
Journal: Cardiovascular Research (2004)

Adrenergic receptors play a pivotal role in regulating cardiac function in response to a constantly changing environment. Altered α and β adrenergic receptor signaling in vivo is associated with cardiac hypertrophy and failure. This review focuses on the different roles of adrenergic receptors in regulating cardiac function under normal and pathological conditions. Understanding the signaling mechanisms of these receptors in the context of the heart is likely to provide a better therapeutic approach towards treatment of heart failure.
Fall in total cholesterol concentration over five years in association with changes in fatty acid composition of cooking oil in Mauritius: cross sectional survey
Authors: U. Uusitalo, E. J M Feskens, J. Tuomilehto, G. Dowse, U. Haw, D. Fareed, F. Hemraj, H. Gareeboo, K G. M M Alberti, P. Zimmet
Journal: BMJ (1996)

<h3>Abstract</h3> <b>Objective</b>: To determine the extent to which reducing the saturated fatty acid composition of a ubiquitously used cooking oil influenced changes in cholesterol concentration in the population during a five year intervention programme in Mauritius. <b>Design</b>: Cross sectional surveys in 1987 and 1992 determined mean total cholesterol concentrations in the population. A random sample of respondents in the 1992 survey completed a nutrition questionnaire that included questions on diet in the previous 24 hours. <b>Setting</b>: Mauritius. <b>Intervention</b>: In 1987 the government of Mauritius changed the composition of the commonly used cooking oil from being mostly palm oil (high in saturated fatty acids) to being wholly soya bean oil (high in unsaturated fatty acids). <b>Subjects</b>: 5080 and 5162 subjects in 1987 and 1992 cross sectional surveys. 2059 subjects aged 30–64 years were randomly selected from the respondents of the 1992 survey to take part in the nutrition survey <b>Main outcome measures</b>: Fatty acid composition of phospholipids in pooled serum samples from men and women from the two surveys; measured and predicted change in serum cholesterol concentration. <b>Results</b>: From 1987 to 1992 total cholesterol concentrations fell significantly by 0.79 mmol/l (P&lt;0.001) in men and 0.82 mmol/l (P&lt;0.001) in women. The estimated intake of saturated fatty acids decreased by 3.5% of energy intake in men and by 3.6% in women, and the intake of polyunsaturated fatty acids increased by 5.5% and 5.6% of energy intake, respectively. These changes were reflected in changes in the fatty acid composition of serum phospholipids, and according to Keys9 formula these changes explained much of the decrease in serum cholesterol concentrations (predicted decrease of 0.38 mmol/l in men and by 0.40 mmol/l in women). <b>Conclusion</b>: Dietary changes that entailed a reduction in the saturated fat content of a ubiquitous cooking oil explained most of the observed decrease in serum cholesterol concentration over five years in the population of Mauritius. <h3>Key messages</h3> The saturated fatty acid intake of Mauritians was reduced by modifying the composition of the widely used cooking oil Mean serum cholesterol concentration decreased by 15% after the cooking oil intervention was introduced nationwide Effective, low cost prevention programmes for chronic disease are needed in less industrialised countries. Simple action in dietary policy could be one such strategy
Lung Reperfusion Injury after Chronic or Acute Unilateral Pulmonary Artery Occlusion
Authors: ELIE FADEL, GUY-MICHEL MAZMANIAN, ALAIN CHAPELIER, BRUNO BAUDET, HÉLÈNE DETRUIT, VINCENT de MONTPREVILLE, JEAN-MARIE LIBERT, MYRIAM WARTSKI, PHILIPPE HERVE, PHILIPPE DARTEVELLE
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

Because the lungs receive their blood supply from both the pulmonary and bronchial systems, chronic pulmonary artery obstruction does not necessarily result in severe ischemia. Ischemia-reperfusion (IR) lung injury may therefore be attenuated after long-term pulmonary artery obstruction. To test this hypothesis, isolated left lungs of pigs were reperfused two days (acute IR group) or 5 wk (chronic IR group) after left pulmonary artery ligation and compared to those of sham-operated animals. The severity of IR-lung injury after 60 min ex vivo reperfusion of the left lung was assessed based on lung histology and measurements of filtration coefficient (Kfc), pulmonary arterial resistance (Rpa), and lung myeloperoxidase (MPO) activity. Marked bronchial circulation hypertrophy was seen in the chronic IR group. Hemorrhagic alveolar edema was found in all acute IR lungs but not in sham or chronic IR lungs. Compared with the sham-operated controls, Kfc and Rpa increased two-fold and threefold, and MPO 1.5-fold and twofold in the chronic and acute IR groups, respectively. In conclusion, IR-induced lung injury was markedly reduced when it occurred 5 wk after pulmonary artery ligation, probably because the systemic blood supply to the lung had time to develop, limiting ischemia.
Fusion Lymphoscintigraphy with a 24-Hour Tc-99m MDP Bone Scan for Sentinel Lymph Node Detection and Imaging
Authors: VISWESWARA R. TATINI, HOWARD J. DWORKIN
Journal: Clinical Nuclear Medicine (2001)

A 62-year-old woman with right breast carcinoma who had a breast biopsy 3 weeks earlier was referred for a whole-body Tc-99m MDP bone scan to identify possible osseous metastases. Twenty-four hours later, she underwent lymphoscintigraphy using four peritumoral injections of 250 microCi filtered Tc-99m sulfur colloid of 0.22 microm each. The lymphoscintigraphic images showed good delineation of three right axillary lymph nodes in relation to the rib cage. Performing a bone scan just before lymphoscintigraphy for sentinel node detection may help the surgeon to identify sentinel lymph nodes. This is more anatomically precise than using a flood source to delineate body contour. A Tc-99m MDP bone scan followed by lymphoscintigraphy should be considered in patients with breast carcinoma who will have both bone imaging and lymphoscintigraphy.
Changes in cyclic AMP dependent protein kinase and active stiffness in the rat volume overload model of heart hypertrophy
Authors: S. Lavandero, G. Cartagena, E. Guarda, R. Corbalan, I. Godoy, M. Sapag-Hagar, J. E Jalil
Journal: Cardiovascular Research (1993)

The aim was to clarify the role of cyclic AMP dependent protein kinase (PKA) and changes in mechanical heart function during development of cardiac hypertrophy induced by volume overload.Protein and DNA contents, PKA activity, and peak systolic stress-strain relationships in hearts from animals submitted to aortocaval shunt were assessed as a function of time. Sham operated (control) rats were used as controls.Heart weight to body weight ratio and cardiac protein content per heart increased from d 7 (p < 0.005 and p < 0.01, respectively) reaching their highest values by d 56; the same occurred with cardiac DNA content. PKA activity.g-1 tissue in soluble extracts of hearts from rats with aortocaval shunt increased by 2.7-fold on d 2 (p < 0.005), reached a ninefold peak increase by d 7 (p < 0.0001) and declined to fourfold by d 56 with respect to control values. The end peak systolic stress-strain relation slopes were: control, 368(SEM 14) g.cm-2 (n = 16); aortocaval shunt values: 2 d, 514(28) g.cm-2 (n = 6); 7 d, 579(10) g.cm-2 (n = 7); and 56 d, 554(28) g.cm-2 (n = 7). The force generating capacity at 0% strain was also significantly higher in the shunt groups as compared to sham operated controls (p < 0.01). Early activation of PKA was also confirmed through endogenous cardiac protein phosphorylation. SDS-PAGE gel electrophoretogram and autoradiography showed more heavily phosphorylated bands in aortocaval shunt hearts than in the control group.PKA activity and the slope of systolic stress-strain regression line followed a similar trend throughout the study, with an early increase in both variables by d 2 in the shunt group, reaching a peak at d 7, and decreasing thereafter but remaining higher than in controls. PKA activity appears to be related to increased force generating capacity rather than to hypertrophy or increased cardiac protein content. Thus PKA activation is an early biochemical event after aortocaval shunt, followed later by cardiac hypertrophy. Changes in PKA activity showed a similar trend to mechanical heart function over time. These findings help to explain the changes in the mechanical properties of the heart preceding the development of cardiac hypertrophy in the rat model of volume overload.
Protein Binding by Specific Receptors on Human Placenta, Murine Placenta, and Suckling Murine Intestine in Relation to Protein Transport across These Tissues
Authors: Jonathan D. Gitlin, David Gitlin
Journal: Journal of Clinical Investigation (1974)

Human, rat, and mouse placentas and rat and mouse intestines were homogenized in buffered saline, and fraction consisting primarily of cell membranes was separated from each of the homogenates by differential centrifugation. Human, bovine, and guinea pig IgG, and human IgE, Bence-Jones protein, serum albumin, insulin, and growth hormone were labeled with 131I or 125I, and the binding of these proteins by the cell membrane fractions was investigated. Rat and mouse sucklings were given labeled proteins intragastrically, and the amount of each protein absorbed after a given interval of time was determined. It was found that the degree and specificity of protein binding by the cell membrane fractions from human and murine placentas strikingly paralleled the relative rate and specificity of protein transport from mother to fetus in the respective species at or near term. Similarly, the degree and specificity of protein binding by the cell membrane fractions from suckling rat and mouse intestines tended to parallel the rate and specificity of protein absorption from the gastrointestinal tract in these animals. However, some discordance between protein binding and protein transport was also observed. The data suggest that: (a) the binding of a protein by specific receptors on cell membranes may be a necessary first step in the transcellular transport of the protein; (b) specific protein binding by cell receptors does not ensure the transport of that protein across the tissue barrier; and (c) specific transport mechanisms other than or in addition to specific cell membrane receptors are involved in the active transport of proteins across the human or murine placenta or the suckling murine intestine.
Prolonged remission maintenance in acute myeloid leukaemia.
Authors: A S Spiers, J M Goldman, D Catovsky, C Costello, D A Galton, C S Pitcher
Journal: BMJ (1977)

Twenty-five patients with acute myeloid leukaemia were treated with three quadruple drug combinations in predetermined rotation: TRAP (thioguanine, daunorubicin, cytarabine, prednisolone); COAP (cyclophosphamide, vincristine, cytarabine, prednisolone); and POMP (prednisolone, vincristine, methotrexate, mercaptopurine). Fifteen patients (60%) achieved complete remission and five (20%) partial remission. For maintenance, five-day courses of drugs were administered every 14 to 21 days and doses were increased to tolerance. The median length of complete remission was 66 weeks. In eight patients remission maintenance treatment was discontinued and some remained in complete remission for over two years. In this series the remission induction rate was comparable with that reported for other regimens and complete remission lasted longer with this intensive maintenance regimen than with others. Nevertheless, the TRAP programme must still be regarded as only palliative treatment for acute myeloid leukaemia.
AMA Annual Convention 1978
Authors: William R. Barclay
Journal: JAMA (1978)

Sufficient time has now passed that we can view the annual meeting of the American Medical Association held in St Louis June 18 through 22 in a detached and objective manner. Two notable features will give this meeting historical importance and make it a point of reference for years to come; it was the last of a traditional format in which a scientific session was held conjointly with the meeting of the House of Delegates, and the House gave its major attention to the problem of controlling the rising costs of medical care. The matter of divorcing the scientific session from the meeting of the House is of no small importance and should be subject to periodic review. Science has always been very much the business of the AMA, and physicians like to think of themselves as scientists first and as all other descriptors, including politicians, second. Although most of
Neurological Differential Diagnosis
Authors: D. Shooman
Journal: BMJ (2009)

John Patten, a former consultant neurologist, first produced this timeless text in 1977 in an attempt to make neurology less intimidating to the beginner. It was one of the first medical books to convey complex concepts in a digestible and understandable form by combining skilful illustrations with case vignettes and thumbnail sketches of illnesses. He cites Biological Drawings by Maud Jepson (1938), Bedside Diagnosis by Charles Seward (1949), and Frank Walsh’s Clinical Neuroophthalmology (1947) as the eclectic mix of medical classics that influenced his unique approach.

It seems unlikely that any book could be recommended in equally effusive measures by neurologists and neurosurgeons alike, but this volume invariably appears on the bookshelves of both groups. Often revered as the …
Hypoglycemia Following Inadvertent and Factitious Sulfonylurea Overdosages
Authors: David C Klonoff, Barbie J Barrett, Martha S Nolte, Robert M Cohen, Richard Wyderski
Journal: Diabetes Care (1995)

OBJECTIVE To recognize unreported sulfonylurea overdosages in hypoglycemic patients. CASES We describe three patients with hypoglycemia due to inadvertent (in two patients) and factitious (in one patient) sulfonylurea overdosages. We review the world literature and summarize 43 previously published cases of inadvertently administered and 23 previously published cases of factitiously self-administered sulfonylurea overdosages with hypoglycemia. RESULTS An inadvertently administered fulsonylurea overdosage usually occurred when a sulfonylurea was accidentally substituted for an intended medication with a similar generic or trade name. Features of the patients with a factitiously self-administered sulfonylurea overdosage included: 1) a history of the patient or patient's spouse having a medical job or sulfonylurea-treated diabetes mellitus; 2) an unusual affect or psychiatric history; 3) an abrupt onset of severe symptoms without previous milder symptoms; and 4) an absent hypoglycemic or hyperinsulinemic response to provocative testing. These features are not typical for an insulinoma. CONCLUSIONS When a hypoglycemic patient denies antidiabetic medication use, we recommend sequentially performing: 1) a thorough pill inspection; 2) an interview for recently altered pill appearances; 3) a measurement of serum insulin and C-peptide levels during hypoglycemia; and 4) a blood or urine sulfonylurea screen. Discovery of an unreported sulfonylurea overdosage can eliminate the need to search for an insulinoma and prevent further overdosages from occurring.
Risk Factors for Intrahepatic and Extrahepatic Cholangiocarcinoma in the United States: A Population-Based Case-Control Study
Authors: Tania M. Welzel, Barry I. Graubard, Hashem B. El–Serag, Yasser H. Shaib, Ann W. Hsing, Jessica A. Davila, Katherine A. McGlynn
Journal: Clinical Gastroenterology and Hepatology (2007)
EFFECT OF THE DUAL PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR ALPHA/GAMMA AGONIST, MURAGLITAZAR, ON CARDIAC STRUCTURE AND FUNCTION IN TYPE 2 DIABETIC PATIENTS
Authors: Vijay U. Rao, Dean Alokozai, Polina Voloshko, Nelson B. Schiller
Journal: Journal of the American College of Cardiology (2010)
Beri-Beri in Louisiana.
Authors: Frank Fenwick Young
Journal: JAMA (1903)

Abbeville, La., Dec. 22, 1902. <h3>To the Editor:</h3> —The history of this disease dates back many years, occurring principally in the Orient, along the coast of China and Africa. I have been unable to get much information on the subject. A short article appeared inThe Journal, if I remember correctly, concerning it some time ago. In no work on practice or in any medical literature am I able to find a record of a single case occurring in Louisiana. Still, that this disease exists here has been proven beyond a question of reasonable doubt in my mind as well as in the minds of several physicians of prominence in southwest Louisiana. We have had many cases in our practice during the last five years. As to its causes there seems to be little known. Some writers claim that beri-beri is due to a parasite, others to certain miasmatic germs
Video analysis of falls experienced by paediatric iceskaters and roller/inline skaters
Authors: C L Knox, R D Comstock
Journal: British Journal of Sports Medicine (2006)

Objectives: To evaluate differences in the way iceskaters and roller/inline skaters fall. Methods: Children’s falls related to skating were videotaped and categorised based on type of skating activity, child’s estimated age, direction of fall, whether the child attempted to break the fall, and whether the head struck the skating surface. Results: In total, 216 iceskating and 201 roller/inline skating falls were captured on videotape. In both iceskating and roller/inline skating, the majority of falls were forward in direction. The skaters attempted to break the falls with their arms or hands in over 90% of falls in both iceskating (93.1%) and roller/inline skating (94.5%). A greater proportion of falls in iceskating resulted in the head striking the skating surface (13.0%) than did those in roller/inline skating (3.0%) (odds ratio = 4.8; 95% confidence interval 1.9 to 13.3; p&lt;0.001). Conclusions: This study found that paediatric iceskaters and roller/inline skaters fall similarly and that both types of skaters try to break their falls with their arms or hands; however, because iceskating takes place on a low friction surface, attempts to break falls with the arms or hands are often unsuccessful, leading to head and face injuries. The development of a new type of protective gear, a wrist guard with a non-slip palm, should stop iceskaters from striking the head, protect against upper extremity fractures, and unlike a bulky helmet, should not discourage children from skating.
The role of poor oesophageal clearance in patients with suspected laryngopharyngeal reflux
Authors: K. Tan, A. Raeburn, A. Emmanuel
Journal: Gut (2011)

<h3>Introduction</h3> Laryngopharyngeal reflux (LPR) disease is thought to occur in one-third of gastro-oesophageal reflux disease (GORD) patients. Currently, there is no gold standard investigation for patients with suspected LPR. The ResTech Dx-pH measurement system is reported to be capable of detecting liquid or aerosolized acid reflux in the upper airway, and may be a valid objectifiable measure of LPR. The authors postulated that elevated ResTech Dx-pH results may be related to poor oesophageal clearance of acid. <h3>Methods</h3> 38 consecutive patients referred for investigations of LPR underwent standard stationary oesophageal manometry and ambulatory dual channel pH-metry with sensors 5 and 20 cm above the lower oesophageal sphincter. The ResTech Dx-pH sensor was placed in the oropharynx transnasally. The RYAN composite score was generated by the ResTech Dx-pH analysis software. A positive RYAN score would suggest high levels of pharyngeal acid exposure. Patients were stratified into two groups based on the total percentage of time pH&lt;4 detected in the distal channel of pH-metry. Group A had a total percentage of time more than 4.5% and Group B less than 4.5%. <h3>Results</h3> Five patients were excluded in the analysis due to technical or equipment errors. In Group A (n=16), 50% of the patients had positive RYAN score. The average age of these patients with positive RYAN score was significant higher (58±12.5 vs 43±12.7 years, p=0.0389) compare to patients with negative RYAN score. In Group B (n=17), 47% had positive RYAN score. Their average age was higher (55±9.4 vs 43±13.8 years, p=0.0581). The observed proximal and distal amplitude of oesophageal contractions within the RYAN score subgroups of Group A and B did not differ significantly. However, mid oesophageal contraction amplitude was significantly higher in Group A (47±25.9 vs 22±8.1 mm Hg, p=0.04894). There was no difference in lower oesophageal sphincter (LOS) pressure in between RYAN subgroups in Group A. However, the LOS pressure was significantly lower in patients with positive than negative RYAN score in Group B (9±2.6 vs 14±3.9 mm Hg, p=0.01347). <h3>Conclusion</h3> In this tertiary-referred population with LPR symptoms, almost 50% had significant acidification in the upper airway possibly explaining their symptoms. Poor oesophageal clearance of refluxed acid, reflected in reduced contraction amplitude in the oesophageal body may also play a role. Interestingly, patients with normal distal acidification who have high levels of pharyngeal acid exposure tend to have lower LOS pressure and poor body motility.
Abstract 2964: The codon 47 Pro47Ser polymorphism influences p53 phosphorylation and apoptotic function
Authors: Matthew Jennis, Monica Hollstein, Maureen E. Murphy
Journal: Cancer Research (2014)

Abstract The p53 tumor suppressor protein is a central signaling protein in response to oncogenic, genotoxic and metabolic stress. Single nucleotide polymorphisms (SNPs) in p53 can have a marked impact on p53 tumor suppressor function, and have been associated with increased cancer risk. Amino acid 47 of p53 is a conserved residue, located within the second transactivation domain of this protein. In wild type p53, this residue is proline (P47, or WT). Importantly, this proline is critical for the ability of proline-directed kinases to phosphorylate p53 on the adjacent residue, serine 46. Phosphorylation of serine 46 of p53 greatly enhances the ability of p53 to transactivate certain target genes, and to induce apoptosis. In some Africans and African Americans, amino acid 47 of p53 encodes serine (S47) instead of proline. We have shown that the S47 polymorphism eliminates phosphorylation on serine 46, and reduces p53's ability to induce apoptosis by at least 3-fold. We have created mice that contain the humanized p53 gene (Hupki) for either the S47 or WT alleles of p53. In new data, we show that tissues from these mice have significantly decreased apoptosis after gamma radiation. We also show that apoptosis induced by cisplatin is markedly defective in S47 mice and cell lines. Further, MEFs from S47 mice have a 15-fold increase in IC50 for cisplatin, indicating that this polymorphism will impact the efficacy of cisplatin therapy in Africans and African Americans. Finally, we have identified two critical p53 target genes, GLS2 (metabolism) and NOXA (apoptosis), which show significantly impaired transactivation by S47. The long-term objective of this research is to further characterize the function of the S47 variant, and to identify the contribution of this variant to cancer risk and progression in Africans and African Americans. Citation Format: Matthew Jennis, Monica Hollstein, Maureen E. Murphy. The codon 47 Pro47Ser polymorphism influences p53 phosphorylation and apoptotic function. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2964. doi:10.1158/1538-7445.AM2014-2964