tbuckley/cabot-search huggingface dataset:
Functional implications of spontaneous sarcoplasmic reticulum Ca2+ release in the heart
Authors: E. G Lakatta
Journal: Cardiovascular Research (1992)

The Cai oscillation generated by the sarcoplasmic reticulum in response to an action potential occurs relatively synchronously within and among cells. The sarcoplasmic reticulum can also generate spontaneous Cai oscillations (S-CaOs), ie, not triggered by sarcolemmal depolarisation. The local increase in Cai due to S-CaOs is equivalent to that induced by an action potential. Heterogeneity of diastolic Cai among cells within myocardial tissue caused by asynchronous S-CaOs leads to heterogeneous myofilament activation, the summation of which produces a Ca2+ dependent component to diastolic tone. The local increases in Cai due to S-CaOs also cause oscillatory sarcolemmal depolarisations due to Ca2+ modulation of the Na-Ca exchanger and of non-specific cation channels. When local S-CaOs within a myocardial cell is sufficiently synchronised the resultant depolarisation summates and can be sufficient to trigger a spontaneous action potential. Inhomogeneous levels of diastolic Cai among cells may lead to heterogeneity in cell coupling and thus may also affect the impulse conduction in myocardial tissue. The magnitude of the S-CaOs induced diastolic tonus and depolarisation varies with the extent to which S-CaOs are synchronised; partially synchronised S-CaOs following an action potential induced Ca2+ release produce an aftercontraction and afterdepolarisation. Inhomogeneity of diastolic sarcoplasmic reticulum Ca2+ loading and sarcomere lengths within individual cardiac cells due to S-CaOs leads to inhomogeneous systolic Cai levels and sarcomere inhomogeneities in response to a subsequent action potential, which compromise the systolic contraction amplitude. Heterogeneity of systolic Cai among cells due to diastolic S-CaOs also leads to heterogeneity of action potential repolarisation times, due to heterogeneous Cai modulation of the Na-Ca exchanger, the non-specific cation channel, the L type Ca2+ channel and, depending upon species, Ca2+ activated K+ channels. S-CaOs occurrence during a long action potential plateau may also modulate the removal of voltage inactivation of L type Ca2+ channels, and affects the likelihood of the occurrence of "early afterdepolarisations." Thus, as a single entity, S-CaOs may be implicated in diverse manifestation of heart failure--impaired systolic performance, increased diastolic tonus, and an increased probability for the occurrence of arrhythmias.
Altered miRNA processing disrupts brown/white adipocyte determination and associates with lipodystrophy
Authors: Marcelo A. Mori, Thomas Thomou, Jeremie Boucher, Kevin Y. Lee, Susanna Lallukka, Jason K. Kim, Martin Torriani, Hannele Yki-Järvinen, Steven K. Grinspoon, Aaron M. Cypess, C. Ronald Kahn
Journal: Journal of Clinical Investigation (2014)

miRNAs are important regulators of biological processes in many tissues, including the differentiation and function of brown and white adipocytes. The endoribonuclease dicer is a major component of the miRNA-processing pathway, and in adipose tissue, levels of dicer have been shown to decrease with age, increase with caloric restriction, and influence stress resistance. Here, we demonstrated that mice with a fat-specific KO of dicer develop a form of lipodystrophy that is characterized by loss of intra-abdominal and subcutaneous white fat, severe insulin resistance, and enlargement and “whitening” of interscapular brown fat. Additionally, KO of dicer in cultured brown preadipocytes promoted a white adipocyte–like phenotype and reduced expression of several miRNAs. Brown preadipocyte whitening was partially reversed by expression of miR-365, a miRNA known to promote brown fat differentiation; however, introduction of other miRNAs, including miR-346 and miR-362, also contributed to reversal of the loss of the dicer phenotype. Interestingly, fat samples from patients with HIV-related lipodystrophy exhibited a substantial downregulation of dicer mRNA expression. Together, these findings indicate the importance of miRNA processing in white and brown adipose tissue determination and provide a potential link between this process and HIV-related lipodystrophy.
Arms and the man
Authors: Theodore Dalrymple
Journal: BMJ (2007)

Many writers were also doctors, of course, and some were medical students who never qualified. Yet others were the children of doctors, as if the literary advantages of a medical career were heritable. Among them was John O'Hara, an American writer often dismissed because of his irascibility, self promotion, and reactionary political ideas as just a pulp writer.

His long story “The Doctor's Son” was written for a short story competition in 1931 whose prize money disappeared in the great depression. It is set in the middle of the Spanish influenza epidemic of 1918-9, in which many more people died than in the first world war. The story is narrated by the 15 …
Design and validation of a diagnostic score for biliary atresia
Authors: Mohamed Abdel-Salam El-Guindi, Mostafa Mohamed Sira, Ahmad Mohamed Sira, Tahany Abdel-Hameed Salem, Osama Lotfy El-Abd, Hatem Abdel-Sattar Konsowa, Dina Shehata El-Azab, Alif Abdel-Hakim Allam
Journal: Journal of Hepatology (2014)
Determinants of Procedural Pain Intensity in the Intensive Care Unit. The Europain® Study
Authors: Kathleen A. Puntillo, Adeline Max, Jean-Francois Timsit, Lucile Vignoud, Gerald Chanques, Gemma Robleda, Ferran Roche-Campo, Jordi Mancebo, Jigeeshu V. Divatia, Marcio Soares, Daniela C. Ionescu, Ioana M. Grintescu, Irena L. Vasiliu, Salvatore Maurizio Maggiore, Katerina Rusinova, Radoslaw Owczuk, Ingrid Egerod, Elizabeth D. E. Papathanassoglou, Maria Kyranou, Gavin M. Joynt, Gastón Burghi, Ross C. Freebairn, Kwok M. Ho, Anne Kaarlola, Rik T. Gerritsen, Jozef Kesecioglu, Miroslav M. S. Sulaj, Michelle Norrenberg, Dominique D. Benoit, Myriam S. G. Seha, Akram Hennein, Fernando J. Periera, Julie S. Benbenishty, Fekri Abroug, Andrew Aquilina, Júlia R. C. Monte, Youzhong An, Elie Azoulay
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

Intensive care unit (ICU) patients undergo several diagnostic and therapeutic procedures every day. The prevalence, intensity, and risk factors of pain related to these procedures are not well known.To assess self-reported procedural pain intensity versus baseline pain, examine pain intensity differences across procedures, and identify risk factors for procedural pain intensity.Prospective, cross-sectional, multicenter, multinational study of pain intensity associated with 12 procedures. Data were obtained from 3,851 patients who underwent 4,812 procedures in 192 ICUs in 28 countries.Pain intensity on a 0-10 numeric rating scale increased significantly from baseline pain during all procedures (P < 0.001). Chest tube removal, wound drain removal, and arterial line insertion were the three most painful procedures, with median pain scores of 5 (3-7), 4.5 (2-7), and 4 (2-6), respectively. By multivariate analysis, risk factors independently associated with greater procedural pain intensity were the specific procedure; opioid administration specifically for the procedure; preprocedural pain intensity; preprocedural pain distress; intensity of the worst pain on the same day, before the procedure; and procedure not performed by a nurse. A significant ICU effect was observed, with no visible effect of country because of its absorption by the ICU effect. Some of the risk factors became nonsignificant when each procedure was examined separately.Knowledge of risk factors for greater procedural pain intensity identified in this study may help clinicians select interventions that are needed to minimize procedural pain. Clinical trial registered with www.clinicaltrials.gov (NCT 01070082).
Abstract 3027: SIRT1 promotes N-Myc oncogenesis stabilizing N-Myc protein
Authors: Glenn M. Marshall, Pei Y. Liu, Samuele Gherardi, Christopher J. Scarlett, Antonio Bedalov, Ning Xu, Nunzio Iraci, Karen L. MacKenzie, Michelle Haber, Murray D. Norris, Andrew V. Biankin, Giovanni Perini, Tao Liu
Journal: Cancer Research (2011)

Abstract The N-Myc oncoprotein is a critical factor in neuroblastoma tumorigenesis which requires additional mechanisms converting low-level to high-level N-Myc expression. N-Myc protein is stabilized when phosphorylated at Serine 62 by phosphorylated ERK protein. Here we describe a novel positive feedback loop whereby N-Myc directly induced the transcription of the histone deacetylase SIRT1, which in turn increased N-Myc protein stability. SIRT1 binds to Myc Box I domain of N-Myc protein to form a novel transcriptional repressor complex at gene promoter of mitogen-activated protein kinase phosphatase 3 (MKP3), leading to transcriptional repression of MKP3, ERK protein phosphorylation, N-Myc protein phosphorylation at Serine 62 and N-Myc protein stabilization. Importantly, SIRT1 was up-regulated, MKP3 down-regulated, in pre-cancerous cells, and preventative treatment with the SIRT1 inhibitor, Cambinol, reduced tumorigenesis in TH-MYCN transgenic mice. Our data demonstrate the important roles of SIRT1 in N-Myc oncogenesis and SIRT1 inhibitors in the prevention and therapy of N-Myc-induced neuroblastoma. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3027. doi:10.1158/1538-7445.AM2011-3027
TCT-80 Incidence of Periprocedual Myocardial Infarction in Chronic Total Occlusion PCI and Impact on Clinical Outcome
Authors: Tasuku Hasegawa, Cosmo Godino, Stefano Galaverna, Sandeep Basavarajaiah, Toru Naganuma, Masanori Kawaguchi, Massimo Slavich, Francesco Giannini, Alessandro Durante, Santo Ferrarello, Chiara Bernelli, Giacomo Viani, Gill Buchanan, Filippo Figini, Azeem Latib, Alaide Chieffo, Matteo Montorfano, Mauro Carlino, Antonio Colombo
Journal: Journal of the American College of Cardiology (2012)
Metabolic effects of liver transplantation in cirrhotic patients.
Authors: L Luzi, G Perseghin, E Regalia, L P Sereni, A Battezzati, D Baratti, E Bianchi, I Terruzzi, H Hilden, L C Groop, A Pulvirenti, M R Taskinen, L Gennari, V Mazzaferro
Journal: Journal of Clinical Investigation (1997)

To assess whether liver transplantation (LTx) can correct the metabolic alterations of chronic liver disease, 14 patients (LTx-5) were studied 5+/-1 mo after LTx, 9 patients (LTx-13) 13+/-1 mo after LTx, and 10 patients (LTx-26) 26+/-2 months after LTx. Subjects with chronic uveitis (CU) and healthy volunteers (CON) were also studied. Basal plasma leucine and branched-chain amino acids were reduced in LTx-5, LTx-13, and LTx-26 when compared with CU and CON (P < 0.01). The basal free fatty acids (FFA) were reduced in LTx-26 with respect to CON (P < 0.01). To assess protein metabolism, LTx-5, LTx-13, and LTx-26 were studied with the [1-14C]leucine turnover combined with a 40-mU/m2 per min insulin clamp. To relate changes in FFA metabolism to glucose metabolism, eight LTx-26 were studied with the [1-14C]palmitate and [3-3H]glucose turnovers combined with a two-step (8 and 40 mU/m2 per min) euglycemic insulin clamp. In the postabsorptive state, LTx-5 had lower endogenous leucine flux (ELF) (P < 0.005), lower leucine oxidation (LO) (P < 0.004), and lower non-oxidative leucine disposal (NOLD) (P < 0.03) with respect to CON (primary pool model). At 2 yr (LTx-26) both ELF (P < 0.001 vs. LTx-5) and NOLD (P < 0.01 vs. LTx-5) were normalized, but not LO (P < 0.001 vs. CON) (primary and reciprocal pool models). Suppression of ELF by insulin (delta-reduction) was impaired in LTx-5 and LTx-13 when compared with CU and CON (P < 0.01), but normalized in LTx-26 (P < 0.004 vs. LTx-5 and P = 0.3 vs. CON). The basal FFA turnover rate was decreased in LTx-26 (P < 0.01) and CU (P < 0.02) vs. CON. LTx-26 showed a lower FFA oxidation rate than CON (P < 0.02). Tissue glucose disposal was impaired in LTx-5 (P < 0.005) and LTx-13 (P < 0.03), but not in LTx-26 when compared to CON. LTx-26 had normal basal and insulin-modulated endogenous glucose production. In conclusion, LTx have impaired insulin-stimulated glucose, FFA, and protein metabolism 5 mo after surgery. Follow-up at 26 mo results in (a) normalization of insulin-dependent glucose metabolism, most likely related to the reduction of prednisone dose, and, (b) maintenance of some alterations in leucine and FFA metabolism, probably related to the functional denervation of the graft and to the immunosuppressive treatment.
Timing of initiation of induction of labour can affect out of hours work
Authors: R Matijevic, T A Johnston, R Maxwell
Journal: BMJ (1998)

Editor—The new deal for junior doctors' hours1 and the recommendations from the report of a confidential enquiry into perioperative deaths2 put pressure on all specialties to reduce the out of hours workload, particularly out of hours operating. One specialty in which it remains difficult to achieve this is obstetrics, as the timing of labour is generally beyond the control of doctors. As a result, junior obstetricians and midwives remain busy throughout the 24 hours.

The one area in which a degree of control …
Abstract IA2: Genomic comparisons of coincident prostate cancer foci
Authors: Elaine R. Mardis, Peter Humphrey, Sean McGrath, Ryan Demeter, Vincent Magrini, Nathan Dees, Krishna Kanthi, Christopher Maher, Li Ding, Adam Kibel
Journal: Cancer Research (2012)

Abstract We have an interest in distinguishing patients with aggressive from those with indolent prostate cancer. The present best indicator of disease aggressiveness is Gleason grade, assigned by histopathological examination of carcinoma in prostate tissue. Clinically speaking, Gleason pattern 4 tumors are more aggressive while Gleason pattern 3 tumors are more indolent. As such, we sought to characterize both patterns at the genomic level by sequencing and analyzing foci of Gleason 3 and 4 patterns from the same patient. By combining laser capture microdissection of coincident Gleason 3 and 4 foci in the same patients, with next-generation sequencing of the derived DNA by our ultr-alow input sequencing library construction techniques, we were able to generate whole genome sequencing data for these samples. Advanced analysis of the aligned whole genome data has permitted an examination of the genomic relatedness of Gleason 3 and 4 foci for two patients. I will present our results to-date from these analyses, shedding light on the fundamental genomic progression evident as Gleason scores increase. More recently, we have complimented these studies with additional whole genome sequencing and analysis of aggressive prostate cancers. Our preliminary findings for these samples also will be reported. Citation Format: Elaine R. Mardis, Peter Humphrey, Sean McGrath, Ryan Demeter, Vincent Magrini, Nathan Dees, Krishna Kanthi, Christopher Maher, Li Ding, Adam Kibel. Genomic comparisons of coincident prostate cancer foci [abstract]. In: Proceedings of the AACR Special Conference on Advances in Prostate Cancer Research; 2012 Feb 6-9; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(4 Suppl):Abstract nr IA2.
Heritability of Platelet Responsiveness to Aspirin in Activation Pathways Directly and Indirectly Related to Cyclooxygenase-1
Authors: Nauder Faraday, Lisa R. Yanek, Rasika Mathias, J. Enrique Herrera-Galeano, Dhananjay Vaidya, Taryn F. Moy, M. Daniele Fallin, Alexander F. Wilson, Paul F. Bray, Lewis C. Becker, Diane M. Becker
Journal: Circulation (2007)

The inability of aspirin (acetylsalicylic acid [ASA]) to adequately suppress platelet function is associated with future risk of myocardial infarction, stroke, and cardiovascular death. Genetic variation is a proposed but unproved mechanism for insufficient ASA responsiveness.We examined platelet ASA responsiveness in 1880 asymptomatic subjects (mean age, 44+/-13 years; 58% women) recruited from 309 white and 208 black families with premature coronary heart disease. Ex vivo platelet function was determined before and after ingestion of ASA (81 mg/d for 2 weeks) with the use of a panel of measures that assessed platelet activation in pathways directly and indirectly related to cyclooxygenase-1, the enzyme inhibited by ASA. The proportion of phenotypic variance related to CHD risk factor covariates was determined by multivariable regression. Heritability of phenotypes was determined with the use of variance components models unadjusted and adjusted for covariates. ASA inhibited arachidonic acid-induced aggregation and thromboxane B2 production by > or = 99% (P<0.0001). Inhibition of urinary thromboxane excretion and platelet activation in pathways indirectly related to cyclooxygenase-1 was less pronounced and more variable (inhibition of 0% to 100%). Measured covariates contributed modestly to variability in ASA response phenotypes (r2=0.001 to 0.133). Phenotypes indirectly related to cyclooxygenase-1 were strongly and consistently heritable across races (h2=0.266 to 0.762; P<0.01), but direct cyclooxygenase-1 phenotypes were not.Heritable factors contribute prominently to variability in residual platelet function after ASA exposure. These data suggest a genetic basis for the adequacy of platelet suppression by ASA and potentially for differences in the clinical efficacy of ASA.
The Canonical NF-κB Pathway Governs Mammary Tumorigenesis in Transgenic Mice and Tumor Stem Cell Expansion
Authors: Manran Liu, Toshiyuki Sakamaki, Mathew C. Casimiro, Nicole E. Willmarth, Andrew A. Quong, Xiaoming Ju, John Ojeifo, Xuanmao Jiao, Wen-Shuz Yeow, Sanjay Katiyar, L. Andrew Shirley, David Joyce, Michael P. Lisanti, Christopher Albanese, Richard G. Pestell
Journal: Cancer Research (2010)

Abstract The role of mammary epithelial cell (MEC) NF-κB in tumor progression in vivo is unknown, as murine NF-κB components and kinases either are required for murine survival or interfere with normal mammary gland development. As NF-κB inhibitors block both tumor-associated macrophages (TAM) and MEC NF-κB, the importance of MEC NF-κB to tumor progression in vivo remained to be determined. Herein, an MEC-targeted inducible transgenic inhibitor of NF-κB (IκBαSR) was developed in ErbB2 mammary oncomice. Inducible suppression of NF-κB in the adult mammary epithelium delayed the onset and number of new tumors. Within similar sized breast tumors, TAM and tumor neoangiogenesis was reduced. Coculture experiments demonstrated MEC NF-κB enhanced TAM recruitment. Genome-wide expression and proteomic analysis showed that IκBαSR inhibited tumor stem cell pathways. IκBαSR inhibited breast tumor stem cell markers in transgenic tumors, reduced stem cell expansion in vitro, and repressed expression of Nanog and Sox2 in vivo and in vitro. MEC NF-κB contributes to mammary tumorigenesis. As we show that NF-κB contributes to expansion of breast tumor stem cells and heterotypic signals that enhance TAM and vasculogenesis, these processes may contribute to NF-κB–dependent mammary tumorigenesis. Cancer Res; 70(24); 10464–73. ©2010 AACR.
Brachial Neuralgia and the Carpal Tunnel Syndrome
Authors: B. Crymble
Journal: BMJ (1968)

The carpal tunnel syndrome can cause severe pain and disability, both of which are avoidable if the condition is diagnosed and treated early in its course. Two sets of circumstances-delay in the correct diagnosis and recurrence of symptoms after an apparently successful operation-may give rise to problems in these aspects of management and delay recovery.
MS-13 * NON-CONTIGUOUS LEPTOMENINGEAL METASTASIS OF OLFACTORY NEUROBLASTOMAS: A LONG-TERM MULTI-INSTITUTIONAL EXPERIENCE
Authors: B. Y. S. Kim, W. Jiang, P. Gullane, F. Gentili, F. DeMonte
Journal: Neuro-Oncology (2014)

BACKGROUND: Olfactory neuroblastoma (ONB) is a malignant neoplasm centered along the roof of the nasal cavity near the cribriform plate. Although distant metastasis of this tumor has been reported in extra-cranial site, non-contiguous spread to the dura is rare. Here, we report the largest series of intracranial leptomeningeal distant metastasis of ONBs from multiple institutions over a twenty year period. Using imaging analysis, we identified that these lesions preferentially home to specific dural regions that share a common vascular supply, suggesting a similar mechanism of tumor spread. METHOD: This study was conducted under M.D. Anderson Cancer Center and the University of Toronto IRB-approved protocols. Image analyses were obtained using preoperative and postoperative MR images. Statistical analyses were performed with IBM SPSS Statistics v21.0.0. RESULTS: A total of 10 patients with non-contiguous dural-based metastasis of ONBs were identified from both institutions. The mean age of diagnosis was 50.4 ± 11.56 years, with median time to distant dural metastasis of 73.03 ± 3.32 months. The median overall survival was 133.93 ± 8.2 months. Nine out of ten patients harbored their first dural metastasis in the perisylvian region. Radiographically, dural ONB metastasis initially present with focal dural thickening that becomes progressively nodular in shape. With time, the nodular component change in the signal intensity with progressive cystic appearance demonstrated with hyperintense central core on T2 weighted MR imaging with peripheral contrast enhancement. CONCLUSION: Here, we present the first and largest series of non-contiguous dural-based metastasis of ONBs. The unique natural history and geographical distribution of these metastatic lesions suggest a common mechanism of tumor spread that target specific regions within the dura. More detailed investigation into this phenomenon will provide greater insight into the progression and the pathophysiological features that underlying this unique disease process.
Diet for Malnourished Prisoners of War
Authors: S. Kenny
Journal: BMJ (1945)

A brief record has been made of 24 recently released British P.O.W.s admitted to hospital in this country for malnutrition and other conditions.The majority had done a long forced march and had been liberated only for periods varying from 2 to 7 days.Before admission 21 had suffered from severe diarrhoea, either during the march or after their liberation, on a sudden return to a full diet.On receiving the first group one was appalled by their emaciation.However, since enteritis was also an urgent symptom, it was felt that caution in feeding was necessary.No literature on the subject of malnutrition was immediately avail- able, but a decision about the diet had to be made quickly.The problem was to find one which, while suitable for the intestinal tract of men suffering from prolonged starvation, would also restore the depleted body tissues.A simple method was adopted which has, on the whole, proved satisfactory.progress.. Half the adult dose of vitamins, cod-liver oil, and iron was considered advisable for the first week, with an in- crease to the adult dose by the second week.Fersolate tablets