tbuckley/cabot-search huggingface dataset:
Relative Contributions of the Atrial Systole-Ventricular Systole Interval and of Patterns of Ventricular Activation to Ventricular Function during Electrical Pacing of the Dog Heart
Authors: WILLARD M. DAGGETT, JESUS A. BIANCO, W. JOHN POWELL, W. GERALD AUSTEN
Journal: Circulation Research (1970)

In areflexic canine right heart bypass preparations, little difference in ventricular function was observed as a result of atrial pacing, sequential atrioventricular pacing, or atrial-His bundle pacing at an appropriate atrial systole-ventricular systole (As-Vs) interval. Ventricular function was depressed during ventricular pacing and during atrioventricular pacing with an inappropriate As-Vs interval. In areflexic isovolumic left ventricle preparations, ventricular function was depressed during ventricular pacing compared to atrial pacing, and changes in the As-Vs interval during atrioventricular pacing were accompanied by changes in ventricular function only in association with changing patterns of ventricular activation. In animals with heart block under conditions of right heart bypass, wherein changes in the pattern of ventricular activation were precluded during atrioventricular pacing, ventricular function deteriorated pari passu with shortening of the As-Vs interval. These data indicate that both the temporal relation between atrial and ventricular contraction and the pattern of ventricular activation importantly influence ventricular function during cardiac pacing. The marked changes in ventricular function observed as a function of the As-Vs interval, for any given pattern of electrical activation, suggest that the As-Vs interval is the more important determinant of ventricular function during cardiac pacing.
Epidemiology and Etiology
Authors: Denis P. Burkitt
Journal: JAMA (1975)

ALL AVAILABLE epidemiologic evidence must be considered in any attempt to formulate an adequate hypothesis for the possible cause of large-bowel tumors. <h3>Geographic and Racial Distribution.—</h3> The incidence of cancer of the colon and rectum is related to economic development more closely than any other form of cancer is; the highest incidence occurs in the most sophisticated areas of North America and in the more industrialized countries of Northern Europe, where it is the second commonest cause of death from cancer, bronchial carcinoma being the most common. The lowest incidence is in rural communities in Africa; intermediate levels occur in India and South America.<sup>1,2</sup> Genetic factors are not likely to play a major role since the present prevalence of the disease is closely comparable in white and black Americans; in many countries, urban communities are significantly more affected than are people in rural areas. <h3>Relationship to Other Noninfective Diseases</h3>
Statin guidelines should give best statin
Authors: Hisashi Moriguchi, Takamoto Uemura, Chifumi Sato
Journal: BMJ (2006)

Editor—Manuel et al show that guidelines on statin treatment should focus on people with the highest risk of coronary heart disease.1 However, concerns about the optimal choice of statins remain.

A recent meta-analysis (n = 71 108) of randomised controlled trials has shown that the occurrence of myalgia is less common with fluvastatin, pravastatin, and simvastatin than atorvastatin (odds ratio 0.28, 95% confidence interval 0.18 to 0.44; 0.43, 0.36 to 0.51; 0.23, 0.19 to 0.28; respectively).2 This observation could also be supported by Japanese postmarketing surveys for both atorvastatin and pitavastatin.3,4 For example, atorvastatin had an increased risk of musculoskeletal adverse events including the elevations of serum creatine phosphokinase as an important indicator of rhabdomyolysis compared with pitavastatin in Japanese common clinical practice (atorvastatin 144/4805, pitavastatin 154/7930; risk ratio 1.54, confidence interval 1.23 to 1.93; P = 0.0001 by using the Mann-Whitney U test).3,4 This difference was shown between atorvastatin and pitavastatin, although pitavastatin at 1 mg, 2 mg, 4 mg seems to be as efficacious as atorvastatin at 10 mg, 20 mg, 40 mg in the rate of reduction of low density lipoprotein cholesterol.3 Thus, the rate of muscle related adverse events differs among statins.2 The common shared belief is that the cause of myotoxity with statins is dose dependent.5 We therefore think that lower doses of statin can be tolerated without the risk of muscle related adverse events.

Given that the efficacy in reducing low density lipoprotein cholesterol and cholesterol is the same respectively for atorvastatin 20 mg and 40 mg, pitavastatin 2 mg and 4 mg, rosuvastatin 2.5 mg and 10 mg, and simvastatin 40 mg and 80 mg,2,5 lower doses of statins should be chosen in terms of optimal disease management.
Elevated FDG Uptake in Right Middle Segmental Bronchus Impacted With Foreign Body
Authors: Yan Xing, Jinhua Zhao, Xiang Chen, Jianhua Song
Journal: Clinical Nuclear Medicine (2009)

A 62-year-old man with recurrent episodes of coughing underwent a whole-body FDG PET/CT scan to evaluate possible lung malignancy. The PET images showed increased FDG uptake in the right side of the bronchus corresponding to a foreign body on the concurrent CT images. The foreign body was subsequently removed through bronchofiberscopy and was proven to be a fishbone.
Written informed consent and selection bias in observational studies using medical records: systematic review
Authors: M. E Kho, M. Duffett, D. J Willison, D. J Cook, M. C Brouwers
Journal: BMJ (2009)

<b>Objectives</b> To determine whether informed consent introduces selection bias in prospective observational studies using data from medical records, and consent rates for such studies. <b>Design</b> Systematic review. <b>Data sources</b> Embase, Medline, and the Cochrane Library up to March 2008, reference lists from pertinent articles, and searches of electronic citations. <b>Study selection</b> Prospective observational studies reporting characteristics of participants and non-participants approached for informed consent to use their medical records. Studies were selected independently in duplicate; a third reviewer resolved disagreements. <b>Data extraction</b> Age, sex, race, education, income, or health status of participants and non-participants, the participation rate in each study, and susceptibility of these calculations to threats of selection and reporting bias. <b>Results</b> Of 1650 citations 17 unique studies met inclusion criteria and had analysable data. Across all outcomes there were differences between participants and non-participants; however, there was a lack of consistency in the direction and the magnitude of effect. Of 161 604 eligible patients, 66.9% consented to use of data from their medical records. <b>Conclusions</b> Significant differences between participants and non-participants may threaten the validity of results from observational studies that require consent for use of data from medical records. To ensure that legislation on privacy does not unduly bias observational studies using medical records, thoughtful decision making by research ethics boards on the need for mandatory consent is necessary.
Pemetrexed Indirectly Activates the Metabolic Kinase AMPK in Human Carcinomas
Authors: Scott B. Rothbart, Alexandra C. Racanelli, Richard G. Moran
Journal: Cancer Research (2010)

Abstract The chemotherapeutic drug pemetrexed, an inhibitor of thymidylate synthase, has an important secondary target in human leukemic cells, aminoimidazolecarboxamide ribonucleotide formyltransferase (AICART), the second folate-dependent enzyme of purine biosynthesis. The purine intermediate aminoimidazolecarboxamide ribonucleotide (ZMP), which accumulates behind this block, transmits an inhibitory signal to the mTORC1 complex via activation of the cellular energy sensor AMP-activated kinase (AMPK). Given that the PI3K-AKT-mTOR pathway is frequently deregulated during carcinogenesis, we asked whether the indirect activation of AMPK by pemetrexed offers an effective therapeutic strategy for carcinomas with defects in this pathway. Activation of AMPK by ZMP in pemetrexed-treated colon and lung carcinoma cells and the downstream consequences of this activation were strikingly more robust than previously seen in leukemic cells. Genetic experiments demonstrated the intermediacy of AICART inhibition and the centrality of AMPK activation in these effects. Whereas AMPK activation resulted in marked inhibition of mTORC1, other targets of AMPK were phosphorylated that were not mTORC1-dependent. Whereas AMPK activation is thought to require AMPKα T172 phosphorylation, pemetrexed also activated AMPK in carcinoma cells null for LKB1, the predominant AMPKα T172 kinase whose deficiency is common in lung adenocarcinomas. Like rapamycin analogs, pemetrexed relieved feedback suppression of PI3K and AKT, but the prolonged accumulation of unphosphorylated 4E-BP1, a tight-binding inhibitor of cap-dependent translation, was seen following AMPK activation. Our findings indicate that AMPK activation by pemetrexed inhibits mTORC1-dependent and -independent processes that control translation and lipid metabolism, identifying pemetrexed as a targeted therapeutic agent for this pathway that differs significantly from rapamycin analogs. Cancer Res; 70(24); 10299–309. ©2010 AACR.
Validity of the Xenon 133 Method for Measurement of Muscle Blood Flow Evaluated by Simultaneous Venous Occlusion Plethysmography
Authors: NIELS A. LASSEN, IB F. LINDBJERG, INGE DAHN
Journal: Circulation Research (1965)

Calf blood flow has been measured simultaneosuly by the Xe 133 clearance method in m. tibialis anterior and m. gastrocnemius and by venous occlusion plethysmography in normal man and in patients with intermittent claudication. At rest Xe 133 muscle blood flow ( MBF xe ) averaged 1.6 ml/100 g/min while plethysmographic total calf blood flow (calf BF) was higher in each instance and averaged 3.0 ml/100 g/min. There was no difference between normal legs and legs with occlusive vascular disease in this respect. Following one to five minutes of arterial occlusion, reactive hyperemia was seen with both methods, the rapid changes being most readily observed with the plethysmographic method. After exhaustive muscular exercise during ischemia in normal man maximal MBF xe averaged 40 ml/100 g/min (48 ml/100 g/min over m. tibialis anterior and 32 ml/100 g/min over m. gastrocnemius). The maximal calf BF averaged 42 ml/100 g/min. The rate of return of blood flow to the resting level was also quite similar with both methods. In the patients with claudication both methods showed a subnormal and delayed hyperemic reaction following ischemic work, but the MBF xe was consistently lower. The results obtained indicate that the Xe 133 modification of Kety's local clearance method for measurement of muscular blood flow in man is essentially valid.
Bacterial Interference Treatment of Recurrent Furunculosis
Authors: Walter G. Strauss
Journal: JAMA (1969)

Three patients with furunculosis due to a pathogenic strain of Staphylococcus aureus became free of furuncles after S aureus strain 502A was purposely substituted. Relapse of furunculosis occurred when 502A was lost and the original strain reacquired. Nine other patients lost their furuncles after replacement of a pathogenic strain by 502A. Abscess formation is a strain-related phenomenon in these patients, and disappearance of furuncles was not a chance event but was related to the implantation of strain 502A.
Elevated serum and BAL cytokeratin 19 fragment in pulmonary fibrosis and acute interstitial pneumonia
Authors: N Dobashi, J Fujita, Y Ohtsuki, I Yamadori, T Yoshinouchi, T Kamei, J Takahara
Journal: European Respiratory Journal (1999)

Cytokeratin 19 fragment (CK19) levels in serum have already been documented as a useful tumour marker for lung cancer. In the present study, it was hypothesized that CK19 may be increased in the serum and epithelial lining fluid of the respiratory tract from patients with pulmonary fibrosis. CK19 was measured in the serum and bronchoalveolar lavage fluid (BALF) of patients with pulmonary fibrosis and the correlation between CK19 levels and clinical parameters evaluated. Nineteen patients diagnosed with idiopathic pulmonary fibrosis (IPF), eight with pulmonary fibrosis associated with a collagen vascular disorder (PF-CVD), seven patients with acute interstitial pneumonia (AIP), and 10 normal smokers as a control group were studied. CK19 levels in sera of patients with IPF and patients with PF-CVD were significantly increased compared to those of normal smokers. CK19 levels in sera of patients with AIP were significantly increased compared to those of other groups. CK19 values in the BALF of patients with pulmonary fibrosis were significantly elevated compared to those of normal smokers. CK19 values in sera charged according to the progression or improvement of the acute lung injury. Immunohistochemical study using pulmonary tissues obtained from patients with AIP demonstrated that the hyaline membrane and proliferating type II pneumocytes were stained by anti-human cytokeratin 19 antibody. These data demonstrated that the measurement of cytokeratin 19 fragment is a useful parameter to evaluate the activity of lung epithelial cell damage and repair.
Neutral endopeptidase inhibits prostate cancer cell migration by blocking focal adhesion kinase signaling
Authors: Makoto Sumitomo, Ruoqian Shen, Marc Walburg, Jie Dai, Yiping Geng, Daniel Navarro, Guy Boileau, Christos N. Papandreou, Filippo G. Giancotti, Beatrice Knudsen, David M. Nanus
Journal: Journal of Clinical Investigation (2000)

Neutral endopeptidase 24.11 (NEP, CD10) is a cell-surface enzyme expressed by prostatic epithelial cells that cleaves and inactivates neuropeptides implicated in the growth of androgen-independent prostate cancer (PC). NEP substrates such as bombesin and endothelin-1 induce cell migration. We investigated the mechanisms of NEP regulation of cell migration in PC cells, including regulation of phosphorylation on tyrosine of focal adhesion kinase (FAK). Western analyses and cell migration assays revealed an inverse correlation between NEP expression and the levels of FAK phosphorylation and cell migration in PC cell lines. Constitutively expressed NEP, recombinant NEP, and induced NEP expression using a tetracycline-repressive expression system inhibited bombesin- and endothelin-1–stimulated FAK phosphorylation and cell migration. This results from NEP-induced inhibition of neuropeptide-stimulated association of FAK with cSrc protein. Expression of a mutated catalytically inactive NEP protein also resulted in partial inhibition of FAK phosphorylation and cell migration. Coimmunoprecipitation experiments show that NEP associates with tyrosine-phosphorylated Lyn kinase, which then binds the p85 subunit of phosphatidylinositol 3-kinase (PI3-K) resulting in an NEP-Lyn-PI3-K protein complex. This complex competitively blocks FAK-PI3-K interaction, suggesting that NEP protein inhibits cell migration via a protein-protein interaction independent of its catalytic function. These experiments demonstrate that NEP can inhibit FAK phosphorylation on tyrosine and PC cell migration through multiple pathways and suggest that cell migration which contributes to invasion and metastases in PC cells can be regulated by NEP.
The experimental generation of antibodies to alpha-melanocyte stimulating hormone and adrenocorticotropic hormone.
Authors: J McGuire, R McGill, S Leeman, T Goodfriend
Journal: Journal of Clinical Investigation (1965)

MSH, melanocyte stimulating hor- mone; ACTH, adrenocorticotropic hormone; RSA, rab- bit serum albumin; anti-ACTH, serum from rabbits that have received injections of rabbit serum albumin conjugated with ACTH; anti-MSH, serum from rabbits that have received inj ections of rabbit serum albumin conjugated with a-MSH; eicosapeptide "ACTH," the synthetic N-terminal eicosapeptide of ACTH.
Future of Australia's supervised injecting centre is now more certain
Authors: M. Sweet
Journal: BMJ (2010)

After operating on a trial basis for more than nine years, Australia’s only medically supervised injecting centre is to become a regular health service, ensuring it a more certain future.

The centre opened in May 2001 in Sydney’s Kings Cross area as an 18 month trial and has since needed endorsement by the New South Wales parliament every four years to continue ( BMJ 2008,337:a732, doi:10.1136/bmj.a732). However, the state government has announced plans to make the centre an ongoing health service that will be subject to regular evaluation and monitoring, “as would any other government programme or treatment …
Balloon dilatation of porcine bioprosthetic valves in the pulmonary position.
Authors: J D Waldman, F J Schoen, S E Kirkpatrick, J W Mathewson, L George, J J Lamberti
Journal: Circulation (1987)

Balloon dilatation (BD) of bioprosthetic valves was investigated in vivo and in vitro. Four children with stenotic bioprosthetic porcine valves in the pulmonary position underwent BD of the valve 10 to 24 months after its insertion. Average valve gradient was reduced from 47.5 to 27 mm Hg. Obstruction at the conduit-branch pulmonary artery connection became apparent after dilatation of the valve. These distal stenoses were also dilated. BD technique was tested in vitro with the use of nonstenotic valves in fresh conduits. No damage to the valve or to the conduit was found when oversized balloons were used in a standard fashion or intentionally inflated until rupture. It is concluded that conduit replacement may be deferred by balloon dilatation of obstructed biological valves and/or a stenotic conduit-pulmonary artery anastomosis.
Recessive Symptomatic Focal Epilepsy and Mutant Contactin-Associated Protein-like 2
Authors: Kevin A. Strauss, Erik G. Puffenberger, Matthew J. Huentelman, Steven Gottlieb, Seth E. Dobrin, Jennifer M. Parod, Dietrich A. Stephan, D. Holmes Morton
Journal: New England Journal of Medicine (2006)

Contactin-associated protein-like 2 (CASPR2) is encoded by CNTNAP2 and clusters voltage-gated potassium channels (K(v)1.1) at the nodes of Ranvier. We report a homozygous mutation of CNTNAP2 in Old Order Amish children with cortical dysplasia, focal epilepsy, relative macrocephaly, and diminished deep-tendon reflexes. Intractable focal seizures began in early childhood, after which language regression, hyperactivity, impulsive and aggressive behavior, and mental retardation developed in all children. Resective surgery did not prevent the recurrence of seizures. Temporal-lobe specimens showed evidence of abnormalities of neuronal migration and structure, widespread astrogliosis, and reduced expression of CASPR2.
Delayed Infection After Total Hip Replacement
Authors: John H. Arnett
Journal: JAMA (1973)

<h3>To the Editor.—</h3> An increasing number of sufferers from arthritis of the hip are receiving total hip replacements. A few of those operated on will develop infection around the implant that will manifest itself shortly after the operation, or even after an interval of a year or more, as in the following case. <h3>Report of a Case.—</h3> A 77-year-old otherwise healthy housewife suffered from increasing pain and disability in both hips, especially the left. X-ray films revealed slowly progressing osteoarthritis (Fig 1). Over a period of 19 years, 62 steroid injections into the joint gave temporary relief. On Jan 7, 1971, she underwent a Sbarbaro replacement of the left hip comprising two vitalium components and no cement (Fig 2). The wound healed perfectly, and in about a month she walked on crutches, and later with a cane. Pain was often present, however, and often a "clunk" accompanied walking. Exercises, aspirin,
MYTHOLOGY AND MEDICINE
Authors: M Malaguarnera, G Pistone, M Motta
Journal: BMJ (1995)

The elderly and quality of life

The goddess Eos (Aurora) fell in love with the mortal Tithonus and begged Zeus to grant him immortality. Alas, she forgot to ask for eternal youth and vigour and after many years of happiness Tithonus aged and life became unsupportable. Initially Eos looked after him but when his appearance became unsightly she confined him in a room and changed him into a grasshopper. Elderly Tithonus could no longer move and only the sound of his voice could …
Pneumocholecystitis
Authors: William G. Abel, Louis M. Rousselot
Journal: New England Journal of Medicine (1952)

PNEUMOCHOLECYSTITIS (a term coined by Heifetz and Senturia1) describes gas in the gall bladder with associated infection. It may be present within the lumen, in the wall or both. Gas within the gall bladder or biliary tree is a not too uncommon finding at present, as a result of the increasingly routine use of the roentgen ray. Gas may gain access to the biliary tree in one of three ways: fistulous communication between the gall bladder or biliary tree with some portion of the gastrointestinal tract — this fistula may result from an inflammatory process or be secondary to . . .
Annular lichen planus showing a change in metallothionein expression on immunohistochemistry
Authors: None Matsuura, None Tsukifuji, None Shinkai
Journal: British Journal of Dermatology (1998)

The immunohistochemical localization of metallothioneins (MTs), low-molecular-weight metal-binding proteins, was investigated in a case of annular lichen planus (LP) that enlarged centrifugally with healing in the centre after a month. The annular lesion was found to exhibit the early, developed and late stages of LP, as judged by the clinical and histopathological findings. Immunostaining for MTs was increased around the lesion, discontinuous around the rim of the erythema and undetectable in the centre of the lesion. MT expression was examined in eight specimens of idiopathic LP. Discontinuous immunostaining for MTs was observed in six specimens and increased staining around the lesion was observed in two specimens. These results suggest that MT expression changes depending on the inflammatory stage of LP. Although the role of MTs in dermatological disease is still unknown, their expression might be related to the pathological process of LP.