tbuckley/cabot-search huggingface dataset:
Prognostic Value of Tc-99m-MIBI Performed During Middle Course of Preoperative Chemotherapy in Patients With Malignant Bone and Soft-Tissue Tumors
Authors: Hiroshi Wakabayashi, Junichi Taki, Anri Inaki, Hisashi Sumiya, Yoh Zen, Hiroyuki Tsuchiya, Seigo Kinuya
Journal: Clinical Nuclear Medicine (2011)

This study was aimed to determine whether Tc-99m-hexakis-2-methoxyisobutylisonitrile (MIBI) scintigraphy performed in the middle of preoperative chemotherapy has a prognostic value in patients with malignant bone and soft tissue tumors (MBST).In 90 patients with MBST, Tc-99m-MIBI scintigraphy was performed 15 minutes after tracer injection before the first and after the third chemotherapy cycles. After 5 cycles of chemotherapy and tumor resection, therapeutic effect was assessed by histopathology. The percent reduction of uptake ratio (ΔUR) was calculated according to the following equation: 100 × ([prechemotherapy UR - post-middle course of chemotherapy UR]/prechemotherapy UR).The average follow-up for the entire population was 52 months. Twenty-one patients had clinically detectable metastases at initial presentation (primary metastasis). Kaplan-Meier analysis demonstrated that absence of metastasis was associated with good survival in all patients, in patients with bone tumor, and those with soft tissue tumor (P < 0.0001, P < 0.0001, and P = 0.0003, respectively), and ΔUR ≧30% was also associated with survival in all patients and patients with bone tumor (P = 0.011 and P = 0.047, respectively), but was marginal in those with soft tissue tumor (P = 0.091). Multivariate analysis showed that primary metastasis was the most powerful independent predictor of a lethal clinical outcome in all patients, in both patients with bone and soft tissue tumors (hazard ratio [HR]: 4.9, 95% confidence interval [CI]: 2.61-9.08, P < 0.0001; HR: 15.1, CI: 4.86-52.7, P < 0.0001; HR: 3.7, CI: 1.45-8.94, P = 0.0069, respectively) and showed that Tc-99m-MIBI scintigraphy had a good independent long-term prognostic value in all patients and patients with bone tumor (HR: 2.2, CI: 1.14-4.43, P = 0.017; HR: 6.0, CI: 2.01-21.6, P = 0.0009, respectively) but not in those with soft tissue tumor (HR: 1.5, CI: 0.61-4.09, P = 0.38). Good disease-free survival was associated with ΔUR ≧30% in all patients and patients with soft tissue tumor (P = 0.0093 and P = 0.017, respectively) but not in those with bone tumor (P = 0.19).Tc-99m-MIBI scintigraphy at the middle course of preoperative chemotherapy could be used as a prognostic indicator in patients with MBST.
MicroRNAs in control of cardiac hypertrophy
Authors: Paula A. Da Costa Martins, Leon J. De Windt
Journal: Cardiovascular Research (2012)

MicroRNAs refer to a subfamily of small non-coding RNA species that are designed to influence gene expression in nearly all cell types studied to date. Studies from the past decade have demonstrated that microRNAs are atypically expressed in the cardiovascular system under specific pathological conditions. Gain- and loss-of-function studies using in vitro and in vivo models have revealed distinct roles for specific microRNAs in cardiovascular development, physiological functions, and cardiac pathological conditions. In this review, the current relevant findings on the role of microRNAs in cardiac hypertrophic growth are updated, the target genes of these microRNAs are summarized, and the future of microRNAs as potential therapeutic targets is discussed.
Neuroscience, Molecular Biology, and the Childhood Roots of Health Disparities
Authors: Jack P. Shonkoff, W. Thomas Boyce, Bruce S. McEwen
Journal: JAMA (2009)

A scientific consensus is emerging that the origins of adult disease are often found among developmental and biological disruptions occurring during the early years of life. These early experiences can affect adult health in 2 ways—either by cumulative damage over time or by the biological embedding of adversities during sensitive developmental periods. In both cases, there can be a lag of many years, even decades, before early adverse experiences are expressed in the form of disease. From both basic research and policy perspectives, confronting the origins of disparities in physical and mental health early in life may produce greater effects than attempting to modify health-related behaviors or improve access to health care in adulthood.
Nitric Oxide–Induced Downregulation of Cdk2 Activity and Cyclin A Gene Transcription in Vascular Smooth Muscle Cells
Authors: Kun Guo, Vicente Andrés, Kenneth Walsh
Journal: Circulation (1998)

Background —Nitric oxide (NO) inhibits vascular smooth muscle cell (VSMC) proliferation and neointima formation after balloon injury. However, the molecular mechanisms underlying NO-mediated growth arrest are poorly understood. In the present study, we examined the effects of the NO donors sodium nitroprusside (SNP) and S -nitroso- N -acetylpenicillamine (SNAP) on cell cycle activity in VSMCs. Methods and Results —Stimulation of quiescent rat VSMCs with serum leads to an increase in cyclin-dependent kinase (cdk)2 kinase activity that correlates with a marked induction of cyclin A protein expression. The addition of SNP or SNAP to VSMC cultures at the time of serum stimulation abrogates the induction of cdk2 activity without suppressing protein levels of cdk2 or cyclin E. These NO donors block serum-stimulated upregulation of cyclin A mRNA and protein and repress the serum induction of cyclin A promoter activity in VSMCs. Conclusions —The addition of the nitric oxide donors SNP or SNAP to mitogen-stimulated VSMCs prevents activation of cdk2, a key regulator of the G 1 and S phases of the cell cycle. These NO donors do not affect the expression of cdk2 protein but block the mitogen-induced expression of cyclin A, an activating subunit of cdk2. SNP and SNAP also repress the mitogen-stimulated activation of the cyclin A promoter. These data suggest that the antiproliferative effect of NO on VSMCs results, at least in part, from the repression of cyclin A gene transcription.
Congenital Syphilis Diagnosed by Bone Changes
Authors: K. L. Marks
Journal: BMJ (1954)

With 'the improvement in medical care of the syphilitic woman at the time of marriage-and during pregnancy, congenital syphilis is becoming a comparative rarity.Many working outside special centres have never had the opportunity of examining an infant who is suffering from the disease.The following is a case history of a patient presenting in the classical manner.Case Report A full-term male child born on December 13, 1952, was brought to the casualty department on February 25, 1953, with the history that after an outing in his perambulator the preceding afternoon he had refused to move the left upper limb.When his mother attempted to move the arm the child screamed with pain.He was referred to the fracture clinic as a possible case of pulled elbow or as a doubtful case of greenstick fracture of the left upper humerus.Clinical examination showed a normal healthy-looking baby of 10 weeks.Movements of all the limbs except the left upper limb were normal.That limb was held by the side, and any attempt at movement was resented.There was tenderness on palpation over the metaphysis at both the proximal and the distal end of the left humerus.A doubtful greenstick fracture of the upper humeral shaft without displacement was demonstrated radiologically.The arm was placed in a collar-and-cuff sling and an appoint- ment was made for the child to be seen in a week's time.The next day the mother returned to the clinic stating that not only did the child resent movement of the arm but he now refused to move the left lower limb.Further clinical examination confirmed the loss of fLnc- tion of both the left upper and lower limbs.(There were no visible physical signs other than the " paralysis," but the metaphysial regions of all four limbs were found to be tender on palpation.Radiographic examination demon- strated well-marked osteochondritis and chondro-epipihysitis in the long bones of all four limbs.Figs. 1 and 2 (Special Plate) show the right upper limb and the left lower limb.
Pain sensitivity and vasopressin analgesia are mediated by a gene-sex-environment interaction
Authors: Jeffrey S Mogil, Robert E Sorge, Michael L LaCroix-Fralish, Shad B Smith, Anny Fortin, Susana G Sotocinal, Jennifer Ritchie, Jean-Sebastien Austin, Ara Schorscher-Petcu, Kara Melmed, Jan Czerminski, Rosalie A Bittong, J Brad Mokris, John K Neubert, Claudia M Campbell, Robert R Edwards, James N Campbell, Jacqueline N Crawley, William R Lariviere, Margaret R Wallace, Wendy F Sternberg, Carey D Balaban, Inna Belfer, Roger B Fillingim
Journal: Nature Neuroscience (2011)
Endothelin produces vasoconstrictions more potently in the resistance portion than in the conduit portion of human mesenteric arteries
Authors: Takashi Miyauchi, Tomohisa Ishikawa, Yoko Tomobe, Reiko Shiba, Masashi Yanagisawa, Sadao Kimura, Yasuro Sugishita, Iwao Ito, Katsutoshi Goto, Tomoh Masaki
Journal: Journal of the American College of Cardiology (1990)
EFFECTS IN MAN OF ACUTE EXPERIMENTAL RESPIRATORY ALKALOSIS AND ACIDOSIS ON IONIC TRANSFERS IN THE TOTAL BODY FLUIDS 1
Authors: J. R. Elkinton, R. B. Singer, E. S. Barker, J. K. Clark
Journal: Journal of Clinical Investigation (1955)

Although the concept of tissue buffering was formulated early in the study of acid-base dis- turbances, attention in the past has been directed primarily towards the effects of these disturbances on blood and extracellular fluid.More recently the demonstration by Darrow and his co-workers (1-3) of exchanges of intracellular cations during clinical and experimental potassium deficiency stimulated renewed interest in the quantitative aspects of the buffering action of intracellular fluid.Accordingly, some years ago the authors under- took quantitative estimation of the effects in man of acute experimental respiratory alkalosis and acidosis on the components of the multiphase system of red cells, plasma, interstitial fluid, and "in- tracellular" fluid (calculated as the non-chloride space), as well as on exchanges in the kidney.The latter renal effects will be reported in another paper (4).Our results indicate that in man the effects of acute hyperventilation or carbon dioxide inhala- tion are buffered to a large extent by a series of linked ionic exchanges with a phase or phases out- side the chloride space, as well as with buffer sys- tems within the blood and extracellular fluid.Since these findings were reported in abstract (5-8) similar conclusions have been reached by Giebisch, Berger, and Pitts (9), on the basis of experimental respiratory disturbances in the dog.Estimates of the importance of tissue buffering
Government warns of tough competition for trainee posts next year after Appeal Court ruling
Authors: Lynn Eaton
Journal: BMJ (2007)

The Appeal Court's ruling against the Department of Health's plan to restrict the number of medical graduates from outside the European Union who can apply for UK training posts will mean an average of three doctors applying for each post in 2008, government officials say.

The health department plans to appeal against the judges' ruling on the case, which was brought by the British Association for Physicians of Indian Origin (BAPIO) ( BMJ 2007;335:1009, 17 Nov doi: 10.1136/bmj.39398.720012.DB). But this could take several months. Meanwhile the status quo will prevail—and department officials say that this will be the case until the 2009 intake at the earliest.

The Appeal Court's ruling means that medical graduates who gained their degree overseas—including many doctors from the Indian subcontinent and Africa who are already working in Britain—will still be able to apply in the next recruitment round, which starts in January.

Additionally, an unknown number of …
Limb Blood Flow and Vascular Conductance Are Reduced With Age in Healthy Humans
Authors: Frank A. Dinenno, Pamela P. Jones, Douglas R. Seals, Hirofumi Tanaka
Journal: Circulation (1999)

Background —We tested the hypothesis that basal (resting) limb blood flow and vascular conductance are reduced with age in adult humans and that these changes are related to elevations in sympathetic vasoconstrictor nerve activity and reductions in limb oxygen demand. Methods and Results —Sixteen young (28±1 years; mean±SEM) and 15 older (63±1 years) healthy normotensive adult men were studied. Diastolic blood pressure and body fat were higher ( P &lt;0.005) in the older men, but there were no other age-related differences in subject characteristics. Femoral artery blood flow (Doppler ultrasound) was 26% lower in the older men ( P &lt;0.005), despite similar levels of cardiac output (systemic arterial blood flow) in the 2 groups. Femoral artery vascular conductance was 32% lower and femoral vascular resistance was 45% higher in the older men ( P &lt;0.005). Muscle sympathetic nerve activity (peroneal microneurography) was 74% higher in the older men ( P &lt;0.001) and correlated with femoral artery blood flow ( r =−0.55, P &lt;0.005), vascular conductance ( r =−0.65, P &lt;0.001), and vascular resistance ( r =0.61, P &lt;0.001). The age-related differences in femoral hemodynamics were no longer significant after correction for the influence of muscle sympathetic nerve activity. There were no significant age-group differences in leg tissue mass (by dual-energy x-ray absorptiometry), but estimated leg oxygen consumption was 15% lower in the older men ( P &lt;0.001). Femoral artery blood flow was directly related to estimated leg oxygen consumption ( r =0.78, P &lt;0.001). The age-group differences in femoral artery blood flow were no longer significant after correction for estimated leg oxygen consumption by ANCOVA. Conclusions —(1) Basal whole-leg arterial blood flow and vascular conductance are reduced with age in healthy adult men; (2) these changes are associated with elevations in sympathetic vasoconstrictor nerve activity; and (3) the lower whole-limb blood flow is related to a lower oxygen demand that is independent of tissue mass.
Five priorities of care for dying people replace Liverpool care pathway
Authors: J. Wise
Journal: BMJ (2014)

Five priorities for care of a dying person, which are based on individual needs and wishes, will replace the Liverpool care pathway in England, the government has announced.

In July 2013 the Liverpool care pathway was criticised in an independent review headed by the rabbi and peer Julia Neuberger.1 2 It found that where the pathway was used well it delivered good care but that, in many cases, it was regarded as a tick box exercise. In many cases relatives and carers did not feel involved in discussions about the care plan. The review by Neuberger recommended that the Liverpool care pathway should be phased out over 6-12 months.

A coalition of 21 organisations, known as the Leadership Alliance for the Care of Dying People, has now published its response to that review, called One chance to get it right.3 This response focused on giving compassionate care and emphasised that, in many cases, planning for death should start well before a person reaches the end of life. The priorities outlined in the …
ATP-Binding Cassette Transporter A1 Expression and Apolipoprotein A-I Binding Are Impaired in Intima-Type Arterial Smooth Muscle Cells
Authors: Hong Y. Choi, Maziar Rahmani, Brian W. Wong, Sima Allahverdian, Bruce M. McManus, J. Geoffrey Pickering, Teddy Chan, Gordon A. Francis
Journal: Circulation (2009)

Background— Accumulation of excess cholesterol by intimal arterial smooth muscle cells (SMCs) contributes to the formation of foam cells in atherosclerotic lesions. The purpose of this study was to examine the expression and activity of ATP-binding cassette transporter A1 (ABCA1) in model intimal and medial arterial SMCs, in human atherosclerotic coronary artery intimal and medial layers, and in human intimal and medial SMCs. Methods and Results— Model intimal arterial SMCs showed increased cholesteryl ester accumulation, absence of apolipoprotein A-I–mediated lipid efflux, markedly diminished ABCA1 expression, and poor apoA-I binding compared with medial-layer SMCs. Total ABCA1 mRNA and SMC-specific ABCA1 protein levels were diminished in the intimal layer compared with the medial layer of atherosclerotic human coronary arteries. Increased expression of ABCA1 by liver X receptor agonist treatment or gene transfection failed to correct apolipoprotein A-I binding, lipid efflux, or high-density lipoprotein particle formation by intima-type SMCs. In addition to impaired ABCA1 expression, intima-type SMCs appear to lack a critical binding factor or factors required for the apolipoprotein A-I–ABCA1 interaction, cholesterol efflux, and high-density lipoprotein particle formation. Conclusion— ABCA1 expression is reduced in cultured model intimal and human atherosclerotic lesion SMCs, suggesting that reduced ABCA1 activity contributes to smooth muscle foam cell formation in the intima.
A guinea pig’s history of biology
Authors: Anne E. Kwitek
Journal: Journal of Clinical Investigation (2008)

The triumphs of recent biology - understanding hereditary disease, the modern theory of evolution - are all thanks to the fruit fly, the guinea pig, the zebra fish and a handful of other organisms, which have helped us unravel one of life's greatest mysteries - inheritance.Jim Endersby traces his story from Darwin hand-pollinating passion flowers in his back garden in an effort to find out whether his decision to marry his cousin had harmed their children, to today's high-tech laboratories, full of shoals of shimmering zebra fish, whose bodies are transparent until they are mature, allowing scientists to watch every step as a single fertilised cell multiples to become millions of specialised cells that make up a new fish. Each story has - piece by piece - revealed how DNA determines the characteristics of the adult organism. Not every organism was as cooperative as the fruit fly or zebra fish, some provided scientists with misleading answers or encouraged them to ask the wrong questions.
Prevalent myocarditis at necropsy in the acquired immunodeficiency syndrome
Authors: David W Anderson, Renu Virmani, Joseph M Reilly, Timothy O'Leary, Robert E Cunnion, Max Robinowitz, Abe M Macher, Usha Punja, Siocgo T Villaflor, Joseph E Parrillo, William C Roberts
Journal: Journal of the American College of Cardiology (1988)
THE EFFECT OF LITHIUM PERIODATE ON CRYSTALLINE BOVINE SERUM ALBUMIN
Authors: Walther F. Goebel, Gertrude E. Perlmann
Journal: The Journal of Experimental Medicine (1949)

A study of the chemical, physicochemical, and immunological changes in bovine serum albumin, brought about by oxidation with lithium periodate, has been made. It has been shown that destruction of certain amino acids occurs, that a change in the absorption spectrum takes place, and that the electrophoretic behavior of the protein is altered. Prolonged contact of bovine albumin with lithium periodate destroys its ability to incite antibodies in experimental animals.
Lengthening of Hamstrings by Operation for Contracture after Burn
Authors: W. F. Brook
Journal: BMJ (1900)

in February, I899, for con- traction of the left knee-joint, due to a burn at the age of 3 years.An extensive cicatricial web stretched from the middle of the leg to a point two-thirds of the way up the thigh, preventing extension beyond a right angle.The head
Evaluation of Volatile Organic Emissions from Hazardous Waste Incinerators
Authors: Richard M. Sedman, John R. Esparza
Journal: Environmental Health Perspectives (1991)

Conventional methods of risk assessment typically employed to evaluate the impact of hazardous waste incinerators on public health must rely on somewhat speculative emissions estimates or on complicated and expensive sampling and analytical methods. The limited amount of toxicological information concerning many of the compounds detected in stack emissions also complicates the evaluation of the public health impacts of these facilities. An alternative approach aimed at evaluating the public health impacts associated with volatile organic stack emissions is presented that relies on a screening criterion to evaluate total stack hydrocarbon emissions. If the concentration of hydrocarbons in ambient air is below the screening criterion, volatile emissions from the incinerator are judged not to pose a significant threat to public health. Both the screening criterion and a conventional method of risk assessment were employed to evaluate the emissions from 20 incinerators. Use of the screening criterion always yielded a substantially greater estimate of risk than that derived by the conventional method. Since the use of the screening criterion always yielded estimates of risk that were greater than that determined by conventional methods and measuring total hydrocarbon emissions is a relatively simple analytical procedure, the use of the screening criterion would appear to facilitate the evaluation of operating hazardous waste incinerators.
The Safety of Aspartame
Authors: Lewis D. Stegink
Journal: JAMA (1987)

To the Editor.—  Dr Pardridge 1 has criticized the review of aspartame safety issues published in JAMA  2 and suggested that adverse effects may arise from the phenylalanine content of aspartame. We disagree with Dr Pardridge's contention that available data show a potential for adverse effects at normal levels of aspartame use.  To support his thesis, Dr Pardridge claims that data of Levy and Waisbren 3 (correlating infant IQ with maternal plasma phenylalanine concentrations in hyperphenylalaninemia) show a 10.5-point drop in IQ of children per 250-μmol/L increment in maternal plasma phenylalanine concentration. Dr Pardridge claims that this effect is linear and applicable down to maternal plasma phenylalanine concentrations of 200 μmol/L or lower. Dr Pardridge ignores the fact that when data correlating IQ with normal blood phenylalanine concentrations (40 to 120 μmol/L) are added to the graph, the plot is clearly biphasic and shows a threshold effect. Indeed, Levy and
Hot Topics in Tetralogy of Fallot
Authors: Juan Villafañe, Jeffrey A. Feinstein, Kathy J. Jenkins, Robert N. Vincent, Edward P. Walsh, Anne M. Dubin, Tal Geva, Jeffrey A. Towbin, Meryl S. Cohen, Charles Fraser, Joseph Dearani, David Rosenthal, Beth Kaufman, Thomas P. Graham
Journal: Journal of the American College of Cardiology (2013)
Systemic activation of dendritic cells by Toll-like receptor ligands or malaria infection impairs cross-presentation and antiviral immunity
Authors: Nicholas S Wilson, Georg M N Behrens, Rachel J Lundie, Christopher M Smith, Jason Waithman, Louise Young, Simon P Forehan, Adele Mount, Raymond J Steptoe, Ken D Shortman, Tania F de Koning-Ward, Gabrielle T Belz, Francis R Carbone, Brendan S Crabb, William R Heath, Jose A Villadangos
Journal: Nature Immunology (2006)
The Incidentally Discovered Adrenal Mass
Authors: William F. Young
Journal: New England Journal of Medicine (2007)

A 68-year-old woman is incidentally found to have a left adrenal mass, 2.8 cm in diameter, on abdominal computed tomography that was ordered to evaluate right lower abdominal discomfort (which has since resolved). Her medical history is notable only for hypertension that has been well controlled with hydrochlorothiazide, at a dose of 25 mg daily. She reports no sweating, palpitations, headache, weight gain, or proximal muscle weakness. Her physical examination is unremarkable. How should she be evaluated?