tbuckley/cabot-search huggingface dataset:
Forced Myofiber Regeneration Promotes Dystrophin Gene Transfer and Improved Muscle Function Despite Advanced Disease in Old Dystrophic Mice
Authors: Ghiabe H. Guibinga, Satoru Ebihara, Josephine Nalbantoglu, Paul Holland, George Karpati, Basil J. Petrof
Journal: Molecular Therapy (2001)

Duchenne muscular dystrophy (DMD) is caused by defects in the dystrophin gene. In young dystrophic mdx mice, immature regenerating myofibers represent the principal substrate for adenovirus vector (AdV)-mediated dystrophin gene transfer. However, in DMD patients immature regenerating myofibers are generally sparse. Such a situation also exists in old mdx mice, which may represent a more realistic model. Therefore, here we have used old mdx mice (of 14- to 17 months of age) to test the hypothesis that one-time administration of a myonecrotic agent can transiently re-establish a population of immature myofibers susceptible to AdV-mediated dystrophin gene transfer. This strategy led to upregulation of the coxsackie/adenovirus attachment receptor by means of induction of regenerating myofibers, significantly augmented AdV-mediated dystrophin gene expression, and enhanced force-generating capacity. In addition, it led to an increased resistance to contraction-induced injury compared with untreated controls. The latter protective effect was positively correlated with the number of dystrophin-expressing myofibers (r=0.83, P<0.05). Accordingly, the risk:benefit ratio associated with the sequential use of forced myofiber regeneration and AdV-mediated dystrophin gene transfer was favorable in old mdx mice despite advanced disease. These findings have implications for the potential applicability of AdV-mediated gene therapy to DMD and other muscle diseases in which immature regenerating myofibers are lacking.
P502Supplementing exposure to hypoxia with a copper depleted diet does not exacerbate right ventricular remodeling in mice
Authors: EM Poels, N Bitsch, JM Slenter, C De Theije, ME Kooi, LJ De Windt, VPM Van Empel, PA Da Costa Martins
Journal: Cardiovascular Research (2014)

Background: Pulmonary hypertension (PH) is associated with high morbidity and mortality. Prognosis is determined by occurrence of right ventricular (RV) failure, a key characteristic of PH. Currently, there is no treatment for RV failure, in part due to lack of mechanistic understanding of the development of RV failure. Further research into the development of RV failure is therefore imperative. Exposure to hypoxic conditions is used as a model for PH and RV failure in rats, however, recent studies demonstrated that mice exhibit less severe pulmonary vascular remodeling when exposed to chronic hypoxia compared to rats. Additionally it has previously been shown that adding a low copper diet to pulmonary artery banding (PAB) leads to increased RV fibrosis and dilation due to capillary rarefaction. Here we hypothesize that adding a low-copper diet to chronic hypoxia in mice reinforces their individual effect and that the combination of mild pulmonary vascular remodeling and capillary rarefaction, induces RV failure. Methods: Six week old mice were subjected to normoxia (N; 21% O2) or hypoxia (H; 10% O2) during a period of 8 weeks. Additionally, both experimental groups received either normal chow diet (Cu+) or a copper depleted (Cu-) diet. Cardiac function in these mice was assessed by echocardiography/MRI. Cardiac ventricular tissue was analyzed by histology and immunohistochemistry, and cardiac stress marker expression levels were determined by qPCR. Results: Exposure to chronic hypoxia led to right ventricular hypertrophic growth when compared to normoxia, indicated by a significant increase in Fulton index (N/Cu+ 0.23 ± 0.01 vs. H/Cu+ 0.39 ± 0.02; H/Cu- 0.40±0.06 ; p< 0.05), as well as a significant decrease in RV ejection fraction at 8 weeks (N/Cu+ 71.7 ± 2.6% vs. H/Cu+ 58.8±3.3; H/Cu- 60.0 ± 4.2%, p<0.05). There was however, no further increase in Fulton index after adding a copper deficient diet to hypoxia treatment (H/Cu- 0.40± 0.06), nor was there a further decrease in ejection fraction. In addition, there was a trend towards an increase in cell size in the hypoxia groups, when compared to the N/Cu+ group, correlating with the observed changes in Fulton index and RV ejection fraction. Conclusion: Eight weeks of 10% hypoxia is sufficient to initiate RV hypertrophy and subsequent RV failure. Adding a low copper diet to chronic hypoxia, however, does not further exacerbate right ventricular remodeling, showing that the combination of hypoxia with a copper depleted diet is not an adequate model for RV failure in mice.
Points from Letters: Minors and Contraception
Authors: K. J. Barker, T. V. Barrow, P. L. Davis
Journal: BMJ (1974)

SIR,-A revealing point about the work load and remuneration of general practitioners was made by a delegate at the 1974 Annual Conference of Representatives of Local Medical Committees but was not mentioned in your summary.It is worthy of consider- ation by B.M.A. members generally.
The Future of Quality Measurement and Management in a Transforming Health Care System
Authors: David Blumenthal
Journal: JAMA (1997)

A MIDDLE-AGED MAN came to see me recently complaining of stomach pain and low-grade fever. He was tender in his left lower quadrant. I thought he had diverticulitis. As he was dressing, he said, almost to himself, "I forgot to do the test where you push on a part of the stomach where it doesn't hurt and see if that makes it hurt where you are having pain." He was referring to the physical examination for rebound tenderness, which he had. "How did you know about rebound tenderness?" I asked. "I found out about it on the Web," he said. "I looked up 'abdominal pain' and then 'left lower quadrant pain.' I decided I might have diverticulitis. Then I went to some medical school's Web site and they had a section for the physical exam." I told him I wanted him to see a surgeon, and the choice would be
Correction: Data in Review on Magnetic Resonance Imaging
Authors: Daniel Kent
Journal: Annals of Internal Medicine (1988)

Letters and Corrections1 September 1988Correction: Data in Review on Magnetic Resonance ImagingDaniel Kent, MDDaniel Kent, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-109-5-438_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the Editor: In the article on magnetic resonance (MR) imaging (1), there is an error in Table 2.In this table, the true-positive ratio for the "Alternate" column and the first reference were transposed with the true-positive ratio for "MR Imaging" and the second reference. The 0.67 and its confidence interval in the "MR Imaging" column should replace the 0.98 and its confidence interval in the "Alternate" column. The 0.98 and its confidence interval should replace the 0.67 under "MR Imaging."The text corresponding to this part of the table appears on page 405. The fifth sentence in the...Reference1. KentLarson DE. Magnetic resonance imaging of the brain and spine: is clinical efficacy established after the first decade? Ann Intern Med. 1988;108:402-24. LinkGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: University of Washington Seattle, WA 98195 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 September 1988Volume 109, Issue 5Page: 438-438KeywordsConfidence intervalsMagnetic resonance imaging Issue Published: 1 September 1988 PDF DownloadLoading ...
Triptan Therapy in Migraine
Authors: Elizabeth Loder
Journal: New England Journal of Medicine (2010)

A 23-year-old woman presents with migraine headaches that are unresponsive to analgesics. Triptan therapy is recommended. Triptans are serotonin agonists that were originally thought to provide migraine relief by causing cranial vasoconstriction; other mechanisms are now also proposed. Chest pain is a common side effect, but cardiac ischemia is rare and usually associated with known cardiovascular disease or risk factors.
868 STROMAL-DERIVED FACTOR-1 (SDF-1) – CXCR4 AXIS HAS AN IMPORTANT ROLE ON THE INTERACTION OF HUMAN HEPATIC STELLATE CELLS (HHSC) AND CC CELL LINES
Authors: A. Gentilini, K. Rombouts, S. Galastri, T. Mello, M. Brogi, A. Caligiuri, F. Marra, M. Pinzani
Journal: Journal of Hepatology (2010)
Who Should We Treat? Law, Patients and Resources in the NHS
Authors: L. J Donaldson
Journal: BMJ (1996)

Christopher Newdick Oxford University Press, £15.99, pp 323 ISBN 0 19 825925 55

In Britain, the task of assessing populations' health needs and deciding what should be the priorities for spending money to meet them became formalised through the reforms to the National Health Service of 1990. When hospitals no longer had automatic entitlement to funds but received them only after the deliberations of local health authorities and fundholding general practices, a debate about rationing became inevitable. Over the past few years, certain treatments (for example, removal of …
Postural Augmentation of Plasma Renin Activity and Aldosterone Excretion in Normal People*
Authors: E. L. Cohen, J. W. Conn, D. R. Rovner
Journal: Journal of Clinical Investigation (1967)

Peripheral plasma renin activity and aldosterone excretion rates have been measured in normal people during recumbency, recumbent exercise, tilting, and continuous ambulation. Upright posture induces a prompt elevation in peripheral plasma renin activity beginning in 15 minutes and peaking between 60 and 120 minutes. Aldosterone excretion is increased during 120 minutes of upright posture and correlates directly with the elevation in renin activity. Upright posture induces increased plasma renin activity regardless of the level of sodium intake in the preparatory diet. Concomitant measurements of endogenous creatinine clearance and the rates of excretion of sodium and potassium suggest that a fall in renal arterial perfusion resulting from upright posture induces increased release of renin and the subsequent secondary stimulation of aldosterone secretion. Our data indicate that the changes in plasma renin activity are due to changes in the amount of the enzyme rather than to changes in other elements of the reninangiotensin systm. This report discusses the physiologic importance of postural augmentation of renin production, emphasizing that for proper interpretation of values of plasma renin activity, posture as well as dietary factors must be considered and controlled.
Asian mothers' risk factors for perinatal death--the same or different? A 10 year review of Leicestershire perinatal deaths.
Authors: M. Clarke, D. G. Clayton, E. S. Mason, J. MacVicar
Journal: BMJ (1988)

A case-control study of all perinatal deaths in Leicestershire was established in 1976. By 1985 some 1342 singleton perinatal deaths had occurred. Perinatal mortality among patients of Asian origin was consistently higher than that among European women. Many of the sociomedical risk factors for perinatal death known at booking were common to both population groups. In this population of Asian women, however, low social class was not associated with perinatal risk and illegitimacy hardly ever occurred. In contrast, previous infertility among the Asian women was associated with risk of perinatal death, while no such association was found with European women. In 19% of perinatal deaths care was either inadequately provided or taken up. The case-control design in these circumstances provides a practicable way to evaluate causal factors and at the same time to provide information of value to educators and health service planners.
ER stress–mediated autophagy promotes Myc-dependent transformation and tumor growth
Authors: Lori S. Hart, John T. Cunningham, Tatini Datta, Souvik Dey, Feven Tameire, Stacey L. Lehman, Bo Qiu, Haiyan Zhang, George Cerniglia, Meixia Bi, Yan Li, Yan Gao, Huayi Liu, Changhong Li, Amit Maity, Andrei Thomas-Tikhonenko, Alexander E. Perl, Albert Koong, Serge Y. Fuchs, J. Alan Diehl, Ian G. Mills, Davide Ruggero, Constantinos Koumenis
Journal: Journal of Clinical Investigation (2012)

The proto-oncogene c-Myc paradoxically activates both proliferation and apoptosis. In the pathogenic state, c-Myc–induced apoptosis is bypassed via a critical, yet poorly understood escape mechanism that promotes cellular transformation and tumorigenesis. The accumulation of unfolded proteins in the ER initiates a cellular stress program termed the unfolded protein response (UPR) to support cell survival. Analysis of spontaneous mouse and human lymphomas demonstrated significantly higher levels of UPR activation compared with normal tissues. Using multiple genetic models, we demonstrated that c-Myc and N-Myc activated the PERK/eIF2α/ATF4 arm of the UPR, leading to increased cell survival via the induction of cytoprotective autophagy. Inhibition of PERK significantly reduced Myc-induced autophagy, colony formation, and tumor formation. Moreover, pharmacologic or genetic inhibition of autophagy resulted in increased Myc-dependent apoptosis. Mechanistically, we demonstrated an important link between Myc-dependent increases in protein synthesis and UPR activation. Specifically, by employing a mouse minute (L24+/–) mutant, which resulted in wild-type levels of protein synthesis and attenuation of Myc-induced lymphomagenesis, we showed that Myc-induced UPR activation was reversed. Our findings establish a role for UPR as an enhancer of c-Myc–induced transformation and suggest that UPR inhibition may be particularly effective against malignancies characterized by c-Myc overexpression.
Sensitization to the fungus <i>Hemileia vastatrix</i> (coffee leaf rust)
Authors: M. A. Croce Portocarrero, E. Rosa Da Costa Manso, W. Gambale, L. Takayama, C. E. Oliveira Andrade, J. H. Pereira Pinto, F. F. Morato Castro, J. Croce
Journal: Allergy (2001)

Background: The aim of the present study was to determine the existence of sensitization to the fungus Hemileia vastatrix (coffee leaf rust) in a sample of the Brazilian population. This fungus attacks coffee plantations, and in some regions of Brazil the concentration of its spores in the air can be very high. Methods: A total of 378 individuals underwent skin tests (prick and intradermal tests) with H. vastatrix extract. The subjects were divided into four groups according to the occurrence of atopy and the region where they lived (coffee‐growing or non‐coffee‐growing regions), and another group (V) consisted of 50 rural workers employed on coffee plantations. The presence of specific IgE against the fungus H. vastatrix in sensitized individuals was demonstrated in vitro by immunoblotting. Results: There was no statistical difference in comparing the results with intradermal or prick tests. The incidence of positive tests was significantly higher among atopic individuals residing in coffee‐growing regions (14.7%). Among rural workers, 10% showed positive tests. Immunoblotting revealed specific IgE against 20 protein bands of H. vastatrix . Conclusions: The fungus H. vastatrix may be an important allergen in coffee‐producing countries. The sensitization is more frequent among atopic individuals residing in coffee‐growing regions.
Monstrosities Induced by Hypoxia
Authors: Theodore H. Ingalls, F. Randolf Philbrook
Journal: New England Journal of Medicine (1958)

DESPITE an increased understanding of the causes of fetal defects that has come since 1940, when the role of rubella in their etiology was detected, not much new has been learned of the genesis of "monstrous" deformities in the human embryo. For example, gross deformities like those shown in Figure 1 have not been reported to occur after first-trimester rubella, and yet their origin is surely as early, if not earlier, in pregnancy as that of postrubella defects. However, some clinical clues are implicit in selected case histories such as the following, which suggest that embryonic development may be permanently altered by . . .
Pilonidal Sinus of the Suprapublic Region
Authors: B. H. Page
Journal: BMJ (1953)

<h3>Introduction</h3> The Emergency Cardiology Service is a front line ANP led, consultant directed, protocol driven, clinical service focused on treating often high acuity patients with a wide range of general cardiac complaints early in their emergency department journey. Our service provides expert consult, diagnosis, and treatment, facilitating early discharge to outpatient ambulatory diagnostics/ANP led Rapid-access Virtual Clinic, or admission for inpatient diagnostics. In the 17 years prior to February 2021, patients determined to have a high pre-test probability of coronary disease based upon their typicality of symptoms, risk profile, ECG and biomarkers, would be discussed with the consultant cardiologist prior to an angiogram being ordered to ensure the test was justified. In 2020, the NMBI expanded the referring scope of practice for nurses referring for ionising radiation to include all medical radiological and other imaging procedures for nurses who had completed a comprehensive post graduate level 8 award, containing both academic and clinical components as set down by NMBI (NMBI, 2020) and contained within SI 256 of 2018. In order to enhance our service, we developed additional standard operating procedures (SOPs) [figure 1], [figure 2] which led to a memorandum of understanding on 6th February 2021 between the consultant cardiology group and radiology department, to allow our cardiology ANP group to refer for coronary angiogram, making our ANP service the first in Ireland to refer for coronary angiogram. <h3>Methodology</h3> A retrospective audit of referrals for coronary angiogram made by the ANP service to the consultant group from February 6th 2021 were audited to ensure adherence to our SOP and SI256 with regards to the principle of justification including: •Have a corresponding signature •Have evidence of prior thorough examination •Have a clear justification •Adhere to local and national protocols •Adhere to radiation safety policies. <h3>Results</h3> 67 in-patient and out-patient coronary angiogram requests were made on McKesson radiology or referred by letter to private rooms by the ANP service between 6th February to date. All coronary angiograms with deemed justified by the practitioner (consultant cardiologist) and subsequently completed. All ANP requests adhered to our SOP and met the standards in relation to the principle of justification set out in SI256. <h3>Conclusion</h3> Our initial experience of cardiology ANP as referrer for coronary angiogram is positive. We have demonstrated that working within our scope of practice framework and standard operating procedures has ensured that all referrals were considered justified by the consultants who ultimately performed the tests. <h3>Implications</h3> Cardiology ANP referral for coronary angiogram has the potential to safely streamline the management of patients across the country provided there is consultant support, adequate training/education and standard operating procedures are in place prior to commencement.
Epicardial Pacing to Control Arrhythmias Following Cardiac Surgery
Authors: PAUL D. HARRIS, JAMES R. MALM, FREDERICK O. BOWMAN, BRIAN F. HOFFMAN, GERARD A. KAISER, DONALD H. SINGER
Journal: Circulation (1968)

Epicardial electrodes were chronically implanted on the surface of atria and ventricles in 60 patients at the time of open-heart surgery. Eighteen patients developed bigeminy or multiple premature ventricular contractions associated with slow heart rates in the immediate postoperative period. The ectopic ventricular activity was abolished by pacing the atria or ventricles faster than the spontaneous cardiac rate. In seven patients, low cardiac output associated with low heart rates was improved by pacing at more optimal rates. When feasible, atrial pacing is preferred to ventricular pacing to utilize atrial systole to improve ventricular filling and increase cardiac output. The safety and ease of implantation of these electrodes enable them to be used routinely for diagnostic and therapeutic application in all patients undergoing open-heart surgery.
High Court quashes suspension of surgeon whose clinical competence was not in question
Authors: C. Dyer
Journal: BMJ (2012)

The High Court in London has quashed an order by the UK’s medical regulator suspending a consultant surgeon from practice pending a full hearing into allegations against him.

The court set aside an order made by an interim orders panel of the Medical Practitioners Tribunal Service—the operationally independent arm of the General Medical Council that took over fitness to practise hearings last June—suspending the orthopaedic surgeon Shirzad Houshian.

The four High Court judgments since last September overturning interim suspensions or conditions restricting doctors’ ability to practise pending a final hearing raise questions as to whether panels are too ready to use these powers, which are meant to be reserved for the most serious cases.1 2 3

Houshian was suspended last August by the interim orders panel and faces a 20 day fitness to practise hearing before the …
GlcNAcylation Plays an Essential Role in Breast Cancer Metastasis
Authors: Yuchao Gu, Wenyi Mi, Yuqing Ge, Haiyan Liu, Qiong Fan, Cuifang Han, Jing Yang, Feng Han, Xinzhi Lu, Wengong Yu
Journal: Cancer Research (2010)

GlcNAcylation, a dynamic posttranslational modification, is involved in a wide range of biological processes and some human diseases. Although there is emerging evidence that some tumor-associated proteins are modified by GlcNAcylation, the role of GlcNAcylation in tumor progression remains unclear. Here, we show that GlcNAcylation enhances the migration/invasion of breast cancer cells in vitro and lung metastasis in vivo. The decrease of cell surface E-cadherin is the molecular mechanism underlying GlcNAcylation-induced breast cancer metastasis. p120 and beta-catenin, but not E-cadherin, are GlcNAcylated; the GlcNAcylation of p120 and beta-catenin might play roles in the decrease of cell surface E-cadherin. Moreover, immunohistochemistry analysis indicated that the global GlcNAcylation level in breast tumor tissues is elevated significantly as compared with that in the corresponding adjacent tissues; further, GlcNAcylation was significantly enhanced in metastatic lymph nodes compared with their corresponding primary tumor tissues. This is the first report to clearly elucidate the roles and mechanisms whereby GlcNAcylation influences the malignant properties of breast cancer cells. These results also suggest that GlcNAcylation might be a potential target for the diagnosis and therapy of breast cancer.